Asymmetric Hydrogenation of Nonaromatic Cyclic Substrates

Review pubs.acs.org/CR

Asymmetric Hydrogenation of Nonaromatic Cyclic Substrates Zhenfeng Zhang,†,§ Nicholas A. Butt,†,§ and Wanbin Zhang*,†,‡ †

School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China ABSTRACT: Chiral cyclic structures are found in numerous natural products, pharmaceutical compounds, and important synthetic intermediates. Asymmetric hydrogenation, allowing for the preparation of these complex targets in an environmentally benign and efficient manner, has received much attention over the past few years. This review summarizes the advances in the construction of chiral heterocycles and carbocycles (including cyclic amines, ethers, alcohols, and alkanes) via the asymmetric hydrogenation of nonaromatic cyclic substrates (including prochiral cyclic imines, ketones, and alkenes) using appropriate transition-metal complexes.

CONTENTS 1. Introduction 2. Synthesis of Chiral Cyclic Amines 2.1. Via Asymmetric Hydrogenation of Cyclic Enamines Bearing an Exocyclic Vinyl Group and Endocyclic Nitrogen Atom 2.1.1. Ru-Catalyzed Asymmetric Hydrogenation 2.1.2. Rh-Catalyzed Asymmetric Hydrogenation 2.1.3. Ir-Catalyzed Asymmetric Hydrogenation 2.2. Via Asymmetric Hydrogenation of Cyclic Enamines Bearing an Endocyclic Vinyl Group and Endocyclic Nitrogen Atom 2.2.1. Ru-Catalyzed Asymmetric Hydrogenation 2.2.2. Rh-Catalyzed Asymmetric Hydrogenation 2.2.3. Ir-Catalyzed Asymmetric Hydrogenation 2.3. Via Asymmetric Hydrogenation of Other Cyclic Vinyl Amines 2.3.1. Rh-Catalyzed Asymmetric Hydrogenation 2.3.2. Ru-Catalyzed Asymmetric Hydrogenation 2.3.3. Ir-Catalyzed Asymmetric Hydrogenations 2.4. Via Asymmetric Hydrogenation of Endocyclic Imines 2.4.1. Ir-Catalyzed Asymmetric Hydrogenation 2.4.2. Ru-Catalyzed Asymmetric Hydrogenation 2.4.3. Rh-Catalyzed Asymmetric Hydrogenation 2.4.4. Pd-Catalyzed Asymmetric Hydrogenation 2.4.5. Ti-Catalyzed Asymmetric Hydrogenation 2.5. Summary 3. Synthesis of N-Substituted Chiral Cycloalkanes © 2016 American Chemical Society

3.1. Via Asymmetric Hydrogenation of Cyclic Enamines Bearing an Endocyclic Vinyl Group and Exocyclic Nitrogen Atom 3.1.1. Ru-Catalyzed Asymmetric Hydrogenation 3.1.2. Rh-Catalyzed Asymmetric Hydrogenation 3.1.3. Ir-Catalyzed Asymmetric Hydrogenation 3.2. Via Asymmetric Hydrogenation of Exocyclic Imines 3.2.1. Ru-Catalyzed Asymmetric Hydrogenation 3.2.2. Ir-Catalyzed Asymmetric Hydrogenation 3.2.3. Rh-Catalyzed Asymmetric Hydrogenation 3.2.4. Pd-Catalyzed Asymmetric Hydrogenation 3.3. Summary 4. Synthesis of Chiral Cyclic Ethers 4.1. Via Asymmetric Hydrogenation of Cyclic Enol Ethers Bearing an Endocyclic Oxygen Atom 4.1.1. Ru-Catalyzed Asymmetric Hydrogenation 4.1.2. Ir-Catalyzed Asymmetric Hydrogenation 4.2. Via Asymmetric Hydrogenation of Other Cyclic Vinyl Ethers 4.2.1. Ru-Catalyzed Asymmetric Hydrogenation 4.2.2. Ir-Catalyzed Asymmetric Hydrogenation 4.2.3. Ni-Catalyzed Asymmetric Hydrogenation 4.3. Summary 5. Syntheses of O-Substituted Chiral Cycloalkanes 5.1. Via Asymmetric Hydrogenation of Cyclic Enol Ethers/Esters Bearing an Exocyclic Oxygen Atom

14770 14771

14771 14771 14772 14773

14774 14774 14775 14776 14776 14776 14777 14777 14777 14778 14780 14782 14782 14782 14783 14783

14783 14784 14785 14789 14790 14790 14790 14791 14791 14792 14792 14792 14792 14792 14793 14793 14793 14794 14794 14794

14794

Received: August 19, 2016 Published: November 22, 2016 14769

DOI: 10.1021/acs.chemrev.6b00564 Chem. Rev. 2016, 116, 14769−14827

Chemical Reviews 5.1.1. Rh-Catalyzed Asymmetric Hydrogenation 5.1.2. Ir-Catalyzed Asymmetric Hydrogenation 5.1.3. Ru-Catalyzed Asymmetric Hydrogenation 5.2. Via Asymmetric Hydrogenation of Cyclic Ketones 5.2.1. Ru-Catalyzed Asymmetric Hydrogenation 5.2.2. Ir-Catalyzed Asymmetric Hydrogenation 5.2.3. Rh-Catalyzed Asymmetric Hydrogenation 5.2.4. Fe-Catalyzed Asymmetric Hydrogenation 5.3. Summary 6. Synthesis of Chiral Cyclic Sulfanes, Sulfones, and Sulfamides 6.1. Via Asymmetric Hydrogenation of Cyclic Vinyl Sulfanes 6.1.1. Ru-Catalyzed Asymmetric Hydrogenation 6.1.2. Ir-Catalyzed Asymmetric Hydrogenation 6.2. Asymmetric Hydrogenation of Cyclic Vinyl Sulfones 6.3. Asymmetric Hydrogenation of Cyclic Sulfimides 6.3.1. Ru-Catalyzed Asymmetric Hydrogenation 6.3.2. Rh-Catalyzed Asymmetric Hydrogenation 6.3.3. Pd-Catalyzed Asymmetric Hydrogenation 6.3.4. Ni-Catalyzed Asymmetric Hydrogenation 6.4. Summary 7. Synthesis of Chiral Cyclic Carbonyl Compounds 7.1. Via Asymmetric Hydrogenation of Cyclic Unsaturated Carbonyl Compounds 7.1.1. Ru-Catalyzed Asymmetric Hydrogenation 7.1.2. Rh-Catalyzed Asymmetric Hydrogenation 7.1.3. Ir-Catalyzed Asymmetric Hydrogenation 7.1.4. Cu-Catalyzed Asymmetric Hydrogenation 7.2. Via Asymmetric Hydrogenation of Cyclic α,βUnsaturated Carbonyl Compounds Bearing an Exocyclic Carbonyl Group 7.2.1. Rh-Catalyzed Asymmetric Hydrogenation 7.2.2. Ir-Catalyzed Asymmetric Hydrogenation 7.3. Summary 8. Synthesis of Unfunctionalized Chiral Cycloalkanes 8.1. Via Asymmetric Hydrogenation of Endocyclic Alkenes 8.1.1. Ir-Catalyzed Asymmetric Hydrogenation 8.1.2. Rh-Catalyzed Asymmetric Hydrogenation 8.1.3. Ru-Catalyzed Asymmetric Hydrogenation 8.1.4. Zr- and Co-Catalyzed Asymmetric Hydrogenation

Review

8.2. Via Asymmetric Hydrogenation of Exocyclic Alkenes 8.2.1. Rh-Catalyzed Asymmetric Hydrogenation 8.2.2. Ru-Catalyzed Asymmetric Hydrogenation 8.2.3. Ir-Catalyzed Asymmetric Hydrogenation 8.2.4. Co- and Ni-Catalyzed Asymmetric Hydrogenation 8.3. Summary 9. Conclusion Author Information Corresponding Author Author Contributions Notes Biographies Acknowledgments References

14794 14795 14795 14795 14795 14800 14801 14801 14801 14802

14814 14814 14815 14815 14816 14816 14817 14817 14817 14817 14817 14817 14817 14817

14802

1. INTRODUCTION Chiral cyclic structures such as chiral cyclic amines, ethers, alkanes, etc., are commonly found in numerous bioactive natural products and important pharmaceuticals. Among the various synthetic methods toward the preparation of such valuable molecules, asymmetric hydrogenation of cyclic substrates bearing unsaturated bonds (CC, CN, CO, etc.) is one of the most powerful, economical, and environmentally benign procedures. These procedures typically rely on transition-metal catalysis (particularly rhodium, ruthenium, and iridium) assisted by chiral ligands. Most commonly, transition-metal-catalyzed asymmetric hydrogenation is performed on acyclic molecules.1−7 However, the asymmetric hydrogenation of unsaturated cyclic substrates has gained increasing interest because it allows for the synthesis of chiral heterocycles and carbocycles that are difficult to obtain by other means. Two types of cyclic substrates are commonly used in asymmetric hydrogenation reactions: aromatic compounds and nonaromatic unsaturated cyclic compounds, i.e., cyclic systems bearing either exocyclic or endocyclic double bonds. The hydrogenation of arene and heteroarene compounds has been well documented, and reviews describing such methodologies have been provided by Y.-G Zhou and co-workers.8,9 In contrast, the asymmetric hydrogenation of nonaromatic cyclic substrates has received less attention. This is in part due to difficulties encountered when attempting to hydrogenate such substrates with high enantioselectivity. Over recent years, however, great progress has been made in this area. A number of challenging cyclic nonaromatic substrates have been reduced with high yields and selectivities using a variety of ligands and metal catalysts. Nonaromatic cyclic substrates used in asymmetric hydrogenations can possess either endocyclic double bonds or exocyclic double bonds. The hydrogenation of these substrates can lead to the synthesis of chiral heterocycles and carbocycles including cyclic amines, (thio)ethers, carbonyl compounds, and functionalized or unfunctionalized alkanes. The nature of the double bonds is not limited to the CC double bonds of cyclic alkenes; cyclic imines, ketones, and related onium salts bearing CN and CO double bonds are also prevalent (Figure 1). As this review will describe, the nature of the unsaturated bond greatly influences its reactivity toward hydrogenation, and thus, different catalyst systems based on different transition metals have been designed in order to ensure compatibility with a broad

14802 14802 14802 14802 14802 14803 14803 14804 14804 14804 14804 14804 14805 14805 14808

14808 14809 14809 14809 14809 14809 14809 14813 14813 14813

14770


Chemical Reviews

Review

Figure 1. Nonaromatic cyclic substrates used in asymmetric hydrogenation for the synthesis of chiral cyclic compounds.

2. SYNTHESIS OF CHIRAL CYCLIC AMINES

range of substrates. The rigidity of the double bond in cyclic systems also introduces extra complexity into the reaction system, preventing certain functional groups chelating with the catalyst’s metal center and thus reducing reactivity and selectivity. In addition to the type of transition metals used in hydrogenation reactions, the type of ligand also plays a pivotal role in inducing enantioselectivity. To this end, a myriad of ligands have been designed and employed in hydrogenation reactions. Originally, hydrogenation reactions often relied on P,P-chelating ligands such as BINAP. However, since these initial discoveries more exotic ligands have been developed allowing for a broader range of substrates to be hydrogenated with high enantioselectivities. This review aims to shed light on the rapidly evolving area of the asymmetric hydrogenation of functionalized and unfunctionalized nonaromatic cyclic substrates and describes how problems such as the ones mentioned above are being addressed. This review concerns only the transition-metal-catalyzed asymmetric hydrogenation (AH) and asymmetric transfer hydrogenation (ATH) of nonaromatic cyclic substrates; hydroboration, hydrosilylation, and other similar enantioselective reductions catalyzed by organocatalysts are not discussed. To the best of our knowledge, no current reviews which summarize the advances solely in the area of the asymmetric hydrogenation of nonaromatic unsaturated cyclic compounds have been published. However, several review articles do briefly mention the hydrogenation of simple cyclic alkenes and imines. In particular, Q.-L. Zhou and co-workers published an excellent review concerning the enantioselective hydrogenation of enamines and imines, which contain several examples related to the asymmetric hydrogenation of some cyclic substrates.6 Thus, inevitably, there will be a slight overlap with other book chapters and review articles.

2.1. Via Asymmetric Hydrogenation of Cyclic Enamines Bearing an Exocyclic Vinyl Group and Endocyclic Nitrogen Atom

The hydrogenation of cyclic enamines bearing an exocyclic vinyl group and endocyclic nitrogen atom is an effective methodology for the synthesis of chiral cyclic amines (Figure 2). Asymmetric

Figure 2. Asymmetric hydrogenation of cyclic enamines bearing an exocyclic vinyl group and endocyclic nitrogen atom for the synthesis of chiral cyclic amines.

hydrogenation of these substrates predominantly uses Ru and Rh catalysts for N-acyl enamines (enamides) and Ir catalysts for Naryl/alkyl enamines. P,P-Chelating ligands are most commonly employed. 2.1.1. Ru-Catalyzed Asymmetric Hydrogenation. Noyori et al. were some of the original pioneers in the area of asymmetric hydrogenation with the development of the wellknown BINAP (L1) ligand for the reduction of simple alkenes (Figure 3).10 Since this ground-breaking discovery, BINAP and derivatives have found broad use for the asymmetric hydrogenations of various substrates.11,12 In 1986, Noyori, Takaya, and co-workers utilized a [Ru(OAc)2((R or S)-BINAP)] catalyst for the asymmetric synthesis of chiral isoquinoline alkaloids via the asymmetric hydrogenation of N-acyl-1-alkylidenetetrahydroisoquinolines. Even in these early studies, the tetrahydroisoquinolines S1 and S2 bearing NCOMe or N-CHO groups could be hydrogenated with excellent enantioselectivities (96% to >99.5% ee) (Figure 4).13,14 However, the (E)-isomer of S1a showed no activity under the same conditions. 14771


Chemical Reviews

Review

and (R)-BINAP (L1R) complex to give the corresponding product with 90% ee (Figure 6).17

Figure 3. BINAP ligands. Figure 6. BINAP−Ru-catalyzed AH of a (E)-6-membered cyclic βenamidoester S5.

2.1.2. Rh-Catalyzed Asymmetric Hydrogenation. The earliest Rh-catalyzed asymmetric hydrogenation of exocyclic enamides bearing an endocyclic nitrogen atom was also reported by Noyori, Takaya, and co-workers in 1986. Using the rhodium complex [Rh((R)-BINAP)(MeOH)2]ClO4, the N-Ac-1-alkylidenetetrahydroisoquinolines S1a and S2a were hydrogenated with lower enantioselectivities (up to 76% ee and 60% ee, respectively) than that obtained by the analogous Ru catalyst.13,14 In 1995, Achiwa and co-workers developed a 1,4bisphosphine ligand MOCBP (L3) bearing a cyclobutane framework for the hydrogenation of S2a with 81% ee.18 In 2002, the enantioselectivity for the asymmetric hydrogenation of S2a was improved to 97% ee by X. Zhang and co-workers using chiral 1,2-bisphosphane ligand (SP,RC)-TangPhos (L4) and Rhcatalyst precursor [Rh(nbd)2]SbF6 (Figure 7).19

Figure 4. BINAP−Ru-catalyzed AH of N-acyl-1-alkylidene-1,2,3,4tetrahydroisoquinolines S1 and S2.

Using a similar catalyst [Ru(OCOCF3)2((S)-BINAP)], the 5membered enecarbamates S3 with (Z)-configuration could be hydrogenated to give chiral 2-(arylmethyl)pyrrolidines in high yields and with moderate enantioselectivities (18−57% ee) (Figure 5).15 The corresponding substrate with (E)-configuration could not be reduced under these reaction conditions.

Figure 5. BINAP−Ru-catalyzed AH of (Z)-5-membered cyclic enecarbamates S3.

Ruthenium complexes of axially chiral diphosphine ligands (S)-BINAP (L1S) and (S)-MeO-BIPHEP (L2S) (Scheme 1) were able to successfully hydrogenate structurally related (E)-2(pyrrolidin-2-ylidene)acetate S4 with 94% and 97% ee, respectively.16 The asymmetric hydrogenation of a 6-membered cyclic βenamidoester S5 was also examined using a [RuCl2(p-cymene)]2

Figure 7. P,P-Rh-catalyzed AH of a N-Ac-1-methylene-1,2,3,4tetrahydroisoquinoline S2a.

In 2004, Lee and co-workers applied new 1,4-bisphosphine ligands bearing an imidazolidin-2-one backbone, (S,S)-BDPMI, to the Rh-catalyzed asymmetric hydrogenation of 5-membered cyclic β-enamidoesters S4. The R substituent in the ligand influences the hydrogenation. Using (S,S)-Me-BDPMI (L5) and Rh-catalyst precursor [Rh(cod)2]BF4, the optically active homoproline derivatives P4 were obtained with complete conversions and with 87−96% ee (Scheme 2).20 The use of the ligand (R,R)-Me-DuPhos (L6) afforded the chiral homoproline derivative P4 (R1 = R2 = Me) with >99% ee but only with 37% conversion under 1 atm hydrogen pressure.20 The Rhcatalyzed asymmetric hydrogenation of 6-membered cyclic βenamidoesters S5 was also studied using various diphosphine ligands. The ligand (R,R)-Me-DuPhos (L6) was successfully applied to the reaction to give the corresponding products P5 with 96% ee but with only 30% conversion under 3 atm hydrogen pressure (Figure 8).16

Scheme 1. MeO-BIPHEP−Ru-Catalyzed AH of a (E)-5Membered Cyclic β-Enamidoester S4

14772


Chemical Reviews

Review

Scheme 2. BDPMI−Rh-Catalyzed AH of (E)-5-Membered Cyclic β-Enamidoesters S4

Scheme 3. P,P-Rh-Catalyzed AH of a Dihydro-β-carboline S7

Scheme 4. Tol-BINAP−Ir-Catalyzed AH of Cyclic Oxo-βenamidoesters S8 Figure 8. DuPhos−Rh-catalyzed AH of cyclic β-enamidoesters S4 and S5.

A [Rh((R,R)-Me-DuPhos)(cod)]BF4 complex has also been successfully used for the asymmetric hydrogenation of (Z)-3arylidene-4-acetyl-3,4-dihydro-2H-1,4-benzoxazines S6 (Figure 9).21 High enantioselectivities (91−99% ee) were obtained

unprotected cyclic enamines S9. With the aid of I2, the products were obtained with good to excellent enantioselectivities (78− 96% ee) (Figure 10).23

Figure 9. DuPhos−Rh-catalyzed AH of (Z)-3-arylidene-4-acetyl-3,4dihydro-2H-1,4-benzoxazines S6.

irrespective of the R or Ar substituents. Replacement of the N-Ac group with a N-Bz group reduced the enantioselectivity from 97% to 91% ee. Substrates bearing a N-Ts protecting group were inert to the reaction conditions. After the screening of numerous bidentate and monodentate phosphorus ligands, a DuPhos-like ligand L7a in combination with a [Rh(cod)2]BF4 catalyst precursor was found to hydrogenate dihydro-β-carboline derivatives S7 to give the related tetrahydro-β-carboline P7 with 99% ee. The chiral isoquinoline P2c was also synthesized from S2c with 96% ee using the related ligand L7b (Scheme 3).22 2.1.3. Ir-Catalyzed Asymmetric Hydrogenation. In addition to using Ru and Rh catalysts, Pousset and co-workers also attempted the Ir-catalyzed asymmetric hydrogenation of cyclic oxo-β-enamidoesters S8 to give the corresponding 3carboxymethyl morpholines P8. The reduced products were obtained with moderate enantioselectivities (up to 86% ee) using the axially chiral diphosphine ligand (S)-Tol-BINAP (L8) (Scheme 4).16 Ru and Rh catalysts only produce the ringopened byproducts. A similar iridium catalyst system that uses an axially chiral diphosphine ligand, (S)-MeO-BIPHEP (L2S), was developed and applied to the asymmetric hydrogenation of N-

Figure 10. MeO-BIPHEP−Ir-catalyzed AH of N-unprotected cyclic enamines S9.

In 2008, Andersson and co-workers applied a bicyclesupported phosphine−oxazoline ligand L9a to the Ir-catalyzed asymmetric hydrogenation of a 5-membered cyclic enamine S10. The product P10 was obtained with complete conversion but with only 20% ee (Scheme 5).24 In 2009, Q.-L. Zhou and co-workers were able to successfully apply spiro phosphoramidite ligands L10S to that of the Ircatalyzed asymmetric hydrogenation of N-alkyl enamines bearing an exocyclic double bond (Scheme 6).25 Under the optimized reaction conditions shown, a series of N-alkyl isoquinolines S11 could be reduced to chiral N-alkyl tetrahydroisoquinolines P11 with high enantioselectivities (58−98% ee). An alkyl group on the nitrogen atom was required 14773


Chemical Reviews

Review

Scheme 5. P,N-Ir-Catalyzed AH of a 5-Membered Cyclic Enamine S10

Scheme 7. Proposed Catalytic Cycle for Ir-Catalyzed AH of 2Methyl-1-methylene-1,2,3,4-tetrahydroisoquinoline S1125

Scheme 6. Phosphoramidite−Ir-Catalyzed AH of 6Membered Cyclic Enamines S11

elimination gives the desired product P11 and regenerates Ir(I) complex I. 2.2. Via Asymmetric Hydrogenation of Cyclic Enamines Bearing an Endocyclic Vinyl Group and Endocyclic Nitrogen Atom

The asymmetric hydrogenation of cyclic enamines bearing an endocyclic vinyl group and nitrogen atom also presents a valid synthetic route toward the synthesis of chiral cyclic amines (Figure 11). Rh complexes derived from diphosphine ligands are most commonly employed.

for high enantioselectivity. Changing the N-alkyl group from a methyl group to ethyl, benzyl, and isopropyl groups led to a reduction in enantioselectivity. Addition of strong electrondonating substituents to the phenyl ring resulted in a slight decrease in enantioselectivity. Increasing the steric bulk of this substituent significantly reduced the ee. The catalyst could also be used to reduce substrates which were prepared as a Z/E mixture, i.e., those in which the R group on the terminal carbon of the double bond was not hydrogen. A large reduction in ee was observed for substrates possessing large R groups. Phenylsubstituted substrates required high pressure (50 atm H2) in order to react, and comparatively lower enantioselectivities were obtained. Mechanistic investigations involving 31P NMR experiments showed that the catalytic reaction consists of an active iridium species that contains two phosphoramidite ligands coordinated to an iridium ion to form [IrI2Cl(L10S)2] (Scheme 7).25 Interestingly, deuterium-labeling experiments showed that the hydrogenation of S11 (Alk = Me, R = R1 = H) with D2 was faster than that with H2, thus indicating the presence of an inverse isotope effect. According to this datum, the authors proposed a Ir(I)−Ir(III)−Ir(I) catalytic cycle involving a Ir−dihydride species for the hydrogenation of unfunctionalized cyclic enamines. Excess I2 or KI leads to the formation of Ir(I) complex I (or dimer I′) which possesses two phosphoramidite ligands. Ir(III)−dihydride intermediate II is formed via oxidative addition of H2 to Ir(I) complex I. η2-Complexation of the emanine to the metal center of II gives rise to complex III. Complex IV is subsequently formed via hydride transfer from the metal to the adjacent unsaturated carbon atom. Reductive

Figure 11. Asymmetric hydrogenation of cyclic enamines bearing an endocyclic vinyl group and endocyclic nitrogen atom for the synthesis of chiral cyclic amines.

2.2.1. Ru-Catalyzed Asymmetric Hydrogenation. As with the asymmetric hydrogenation of cyclic enamines bearing an exocyclic vinyl group, the earliest investigations in this area also depended on the use of BINAP ligands. In 1995, Comins and co-workers utilized a [RuCl2((R)-BINAP)] catalyst for the hydrogenation of a 6-membered 2-acyl enecarbamate S12 (R1 = Ph, R2 = OMe) with good yield and enantioselectivity (80% ee). Poorer enantioselectivities (99% ee) but with only 29% conversion to the desired product P16. Using carbonyl protecting groups instead of carboxyl protecting groups leads to reduced enantioselectivities. Substrates bearing a 3-caybonyl substituent were reduced with excellent chemoselectivity (100%) and good enantioselectivity (66−69% ee). In 2012, the asymmetric hydrogenation of 2-phenylsubstituted tetrahydropyridines was also studied using several chiral diphosphine−Rh and −Ir catalysts; however, the

In 1998, Nicolaou and co-workers utilized a [Rh((R,R)-EtDuPhos)(cod)]OTf complex (Rh−L11) for the synthesis of cyclic α-aminoesters P15 from cyclic α-acyl enecarbamates S15. The reaction conditions were suitable for 7−16-membered ring systems. Five- and six-membered cyclic enamines could be reduced with good yields but poor enantioselectivities (Scheme 10).30 In 1999, Ito and co-workers reported the asymmetric hydrogenation of similar substrates using a rhodium catalyst with (S,S)-(Rp,Rp)-PhTRAP (L12) (Scheme 11).31 The methodology was suitable for the hydrogenation of 5-, 6-, and 7membered 1-aza-2-cycloalkene-2-carboxylates S15. The 5- and 7-membered cyclic enamines could be hydrogenated with good enantioselectivities (86% and 11−87%), with 6-membered substrates being hydrogenated with 73−93% ee. The hydrogenation of a 6-membered benzo substrate gave the highest ee of 14775


Chemical Reviews

Review

Scheme 14. P,N-Ir-Catalyzed AH of N-Ts Tetrahydropyridines S18

Scheme 12. TangPhos−Rh-Catalyzed AH of 3-Acyl Tetrahydropyridines S16

corresponding products were obtained with very poor enantioselectivities (99:1 er (Scheme 15).37 The amount of catalyst could be lowered by isolating the HCl salt of S19a via recrystallization to depress

reaction mixture is essential for reactivity, possibly due to the generation of a reactive Ir(III) complex. The alkyl group on the nitrogen does not significantly affect the reaction outcome; however, a 2-aryl group is required for good enantioselectivity (82−97% ee was observed for S17a but only 72% ee for a 2-nBusubstituted substrate S17b). Substituents at the ortho position of the aryl ring slightly reduced the enantioselectivity. The size of the N-alkyl group had no noticeable impact on the reaction, with N-Me-, N-Et-, and N-iPr-substituted enamines providing their corresponding tertiary amine products with similar enantioselectivities. However, 6-membered cyclic enamine S17c was reduced poorly using this catalyst system (21% ee). Other attempts to hydrogenate similar 6-membered cyclic enamines using diphosphine−Ir complexes also failed.33,35 In 2012, Andersson and co-workers utilized P,N-chelating iridium complexes for the hydrogenation of several 6-membered, 2,3-unsaturated hetero- and carbocycles. Among these, N-Tsprotected tetrahydropyridines were hydrogenated with moderate enantioselectivities using the reaction conditions shown in Scheme 14.36 Ligand L9b proved to be the most suitable for the hydrogenation of 3-substituted cyclic enamines S18a,b, whereas ligand L13a was most suitable for the reduction of 2-substituted cyclic enamine S18c.

Scheme 15. WalPhos−Rh-Catalyzed AH of a 3-Fluoro1,2,5,6-tetrahydropyridine S19a

14776


Chemical Reviews

Review

hydrogenation of 3,4-unsaturated 5- and 6-membered Nheterocycles S22 using their P,N-chelating Ir catalysts. This was achieved by employing two classes of ligands, the previously mentioned L9 and L13, which bear a 5-membered aromatic heterocyclic moiety with a coordinating nitrogen atom (Scheme 17).36 The 6-membered cyclic amines were obtained with 66−

catalyst poisons. Deuterium-labeling experiments showed that other catalyst and ligand combinations led to high levels of defluorination and that the reaction is highly dependent upon the acidic additive. 2.3.2. Ru-Catalyzed Asymmetric Hydrogenation. Several examples of the asymmetric hydrogenation of unsaturated N-heterocyclic compounds have been reported. Indeed, the Rucatalyzed asymmetric hydrogenation of such substrates (tetrahydropyridines S19b,c and dihydropyrrole S20) utilizing suitable diphosphine JosiPhos-type and MeO-BIPHEP-like ligands (L15a, L15b, and L16) is a key step in the synthesis of biologically active compounds (Figure 14).38−40

Scheme 17. Ir-Catalyzed AH of 3,4-Unsaturated NHeterocycles S22

Figure 14. P,P-Ru-catalyzed AH of 3,4-unsaturated N-heterocycles S19b,c and S20.

In 2015, Lefort et al. reported an interesting one-pot tandem metathesis−asymmetric hydrogenation methodology in which metathesis is used to construct a prochiral olefin that is then hydrogenated by a chiral ruthenium catalyst formed in situ (Scheme 16).41 Upon treatment with Ru catalyst G-II, the diene

99% ee. Reduction of the 5-membered substrates occurred more rapidly than their 6-membered counterparts but less selectively. Ligand L9c was more suitable for reduction of dihydropyrroles bearing a 3-methyl group and 3-benzyl group (44% and 54% ee, respectively). A 3-phenyl-substituted N-Ts-protected dihydropyrrole was reduced with 85% ee using ligand L13d. A dihydropyrrole bearing a bulky diphenylacetyl protecting group was reduced with 80% ee using ligand L13d, whereas L9c provided little improvement (47% ee) over the corresponding NTs substrate (44% ee). In 2013, Q.-L. Zhou and co-workers were also able to utilize spiro P,N-chelating ligands SIPHOX (L18) for the asymmetric hydrogenation of carboxylic acid-substituted unsaturated Nheterocycles (Scheme 18).42 In the presence of [Ir(L18)(cod)]BArF and Cs2CO3 as an additive, 5-, 6-, and 7-membered substrates S23 were hydrogenated with high yields and enantioselectivities, including a tertiary amine and a secondary amine.

Scheme 16. PhanePhos−Ru-Catalyzed One-Pot Tandem Metathesis−AH

2.4. Via Asymmetric Hydrogenation of Endocyclic Imines

The asymmetric hydrogenation of imine substrates provides an attractive pathway to the synthesis of amine compounds (Figure 15). Although a significant amount of research has been carried out on the reduction of acyclic imines, fewer reactions concerning the asymmetric hydrogenation of cyclic imines have been reported. Of the cyclic systems which have been reduced, the hydrogenation of 3,4-dihydroisoquinolines remains most popular because they provide an efficient synthetic route toward important chiral tetrahydroisoquinoline compounds.

compound is converted to the 3,4-unsaturated heterocycle S21. This heterocycle is subsequently reduced to a 3-substituted piperidine P21 via the aid of the bisphosphine ligand, (S)PhanePhos (L17), with 86% ee. The reaction is carried out in one pot using a DCM/iPrOH (1:1) solvent mixture. 2.3.3. Ir-Catalyzed Asymmetric Hydrogenations. In 2012, Andersson and co-workers reported the asymmetric 14777


Chemical Reviews

Review

Scheme 18. SIPHOX−Ir-Catalyzed AH of Unsaturated NHeterocyclic Acids S23

Figure 16. P,P-Ir-catalyzed AH of 2,3,3-trimethylindolenine S24.

phthalimide additive, S24 was reduced at 0 °C to afford the desired product with 95% ee. In 2012, Reek and co-workers successfully hydrogenated the same substrate S24 using an iridium complex derived from the supramolecular ligand L23, a combination of two different monodentate METAMORPhos ligands (Figure 16).52 This ligand was identified using a high-throughput screen of catalyst combinations and optimizations. Under optimal reaction conditions, S24 was reduced with 96% ee and with only 49% conversion. The reaction was carried out in the presence of a [IrCl(cod)]2/L23 catalyst with a H2 pressure of 50 bar. The reaction was found to be second order in iridium, first order in hydrogen, and zero order in substrate. 2.4.1.2. Dihydroisoquinolines. After initial studies employing Ir−L21 (28% ee)46 and Ir−L1R (89% ee),53 the asymmetric hydrogenation of 1-substituted 3,4-dihydroisoquinolines S25 has also gained much attention. Several catalytic systems have been developed for these types of reductions. In 2011, X. Zhang and co-workers discovered that the iridium complex of (S,S)-fBinaphane (L24) was suitable for the hydrogenation of 1substituted 3,4-dihydroisoquinolines with the substrates being reduced with 79−99% ee and with up to 10 000 TON (Scheme 19).54 Several 1-aryl/alkyl-3,4-dihydroisoquinoline imines were reduced with high selectivity irrespective of the position and electronic properties of the substituents. However, a substrate bearing a 1-substituted 2-MeC6H4 group could only be reduced with 79% ee and required a higher catalyst loading. In 2012, Ratovelomanana-Vidal and co-workers were also able to prepare 1-aryl-tetrahydroisoquinolines P25 with high enantioselectivities (81−94% ee) using an axially chiral diphosphine ligand, (R)-Xyl-SynPhos (L25) (Figure 17).55 Reactions were performed in the presence of a TsCl activator and a proton sponge. Additionally, Ružič, Zanotti-Gerosa, and co-workers successfully applied another axially chiral diphosphine ligand, (S)-P-Phos (L26), to the asymmetric hydrogenation of S25 (R = Ph, R1 = H) for the synthesis of a urinary antispasmodic, Solifenacin (Figure 17).56 With the aid of H3PO4 as an additive, large-scale experiments were performed at 60 °C to give the reduced product with up to 97% ee and >1000 TON. Monodentate phosphoramidite ligands have also been applied to the asymmetric hydrogenation of S25.57,58 As mentioned

Figure 15. Asymmetric hydrogenation of endocyclic imines for the synthesis of chiral cyclic amines.

The most common procedures utilize Ru and Ir catalysis; however, some Rh- and Pd-catalyzed reactions do exist. Several Ti-based reductions have also been reported. 2.4.1. Ir-Catalyzed Asymmetric Hydrogenation. Iridium complexes derived from diphosphine and phosphine−oxazoline ligands are commonly employed catalysts for the asymmetric hydrogenation of cyclic imines. 2,3,3-Trimethylindolenine, dihydroisoquinolines, and simple endocyclic imines are the most studied substrates. 2.4.1.1. 2,3,3-Trimethylindolenine. In 1990, Osborn and coworkers reported the first Ir-catalyzed asymmetric hydrogenation of endocyclic imines using various diphosphine ligands. Using an iridium complex derived from the diphosphine ligand BDPP (L19), 5-membered endocyclic imine 2,3,3-trimethylindolenine S24 was reduced with modest enantioselectivities (up to 80% ee).43 Similarly, simple diphosphine-based ligands such as DIOP (L20) and BCPM (L21) and their derivatives have also been employed in hydrogenation reactions of S24, initially with modest to good results (Figure 16).44−50 However, since these discoveries, significant advances have been made in the asymmetric hydrogenation of endocyclic imines providing the desired products with high enantioselectivities. In 1998, X. Zhang and co-workers employed the ligand (R,R)BICP (L22) to the hydrogenation of 2,3,3-trimethylindolenine S24 (Figure 16).51 In the presence of 0.5 mol % of [IrCl(cod)]2 catalyst precursor, 1.2 mol % of L22, and 4.0 mol % of 14778


Chemical Reviews

Review

Scheme 19. f-Binaphane−Ir-Catalyzed AH of 3,4Dihydroisoquinolines S25

Scheme 20. BINAP−Ir-Catalyzed AH of Simple Endocyclic Imines S26

Later in 2010, X. Zhang and co-workers applied iridium complexes derived from a variety of bisphosphine ligands to the hydrogenation of substrates S26. In particular, an Ir complex derived from (S,S)-f-Binaphane ligand, L24, catalyzed the hydrogenation of 2-aryl dihydropyrroles, 2-butyl dihydropyrrole, 2-phenyl tetrahydropyridine, and 2-phenyl-tetrahydroazepine to give their related products with 50−88%, 58%, 89%, and 75% ee, respectively (Scheme 21).61 Substituents at the meta and ortho Scheme 21. f-Binaphane−Ir-Catalyzed AH of Simple Endocyclic Imines S26

Figure 17. P,P-Ir-catalyzed AH of 1-aryl-tetrahydroisoquinolines S25.

previously, the iridium complexes of chiral spiro phosphoramidite ligands L10 were successfully applied to the hydrogenation of cyclic enamines.25,34 Such complexes were also found to be suitable catalysts for the hydrogenation of endocyclic imines.58 A series of 1-alkyl-3,4-dihydroisoquinolines S25 was reduced with high yields and high enantioselectivities (85−99% ee) using [IrCl(cod)]2 and chiral spiro phosphoramidite ligand L10R. The addition of an iodine source was found to be essential for the reaction. Using KI, the hydrogen pressure could be significantly lowered depending on the substrate. The bulk of the 1-alkyl group has a large influence on the reaction rate and enantioselectivity. Increasing the bulk of the 1-alkyl groups leads to a lower reaction rate and enantioselectivity; greater catalyst loadings and hydrogen pressure are required. Electron-donating and electron-withdrawing substituents on the aromatic ring reduce enantioselectivity. 1-Benzyl-3,4-dihydroisoquinoline and 1-benzyloxymethyl-3,4-dihydroisoquinoline could also be hydrogenated with high enantioselectivities. 2.4.1.3. Simple Endocyclic Imines. Simple endocyclic imines such as S26 have proven to be challenging substrates to hydrogenate. In initial studies reported by Tani and co-workers, iridium(I) complexes of (S)-BINAP (L1S) and (S)-Tol-BINAP (L8) were tested to give the reduced product P26 (n = 1, R = Ph) with 87% and 90% ee.59 According to mechanistic investigations, an Ir(III)−L1S complex was also found to be useful for the asymmetric hydrogenation of 5-, 6-, and 7-membered cyclic imines with up to 89%, 91%, and 69% ee, respectively (Scheme 20).60

positions affected enantioselectivity as did increasing ring size. However, this particular catalyst system was incompatible with substrates bearing alkyl substituents. In addition to P,P-chelating ligands, P,N-chelating ligands were also successfully employed for the Ir-catalyzed asymmetric hydrogenation of endocyclic imines. In 1997, Pfaltz and coworkers reported the asymmetric hydrogenation of endocyclic imines S26. Using an iridium complex derived from PHOX ligand L27, the 2-phenyl-substituted 5- and 6-membered endocyclic imines were reduced with 57% and 64% ee, respectively. No reactions have been reported for 2-methyl pyrroline or 2-acyl tetrahydropyridine (Figure 18).62 In 2015, Q.-L. Zhou and co-workers discovered that the iridium complex derived from SIPHOX L18c42 was sufficient for

Figure 18. P,N-Ir-catalyzed AH of simple endocyclic imines S26. 14779


Chemical Reviews

Review

good yields and with good enantioselectivities irrespective of the position or the electronic properties of the substituent on the phenyl ring. Enantioselectivities decreased slightly when a longer ethyl or propyl chain in the R1 position was used. When R1 was a phenyl group or a benzyl group, lower reactivities and only moderate enantioselectivities were observed. In 2012, Y.-G. Zhou and co-workers investigated the asymmetric hydrogenation of similar 7-membered cyclic imines S29 using (R,S,S)-C3*-TunePhos (L28R). The corresponding products were obtained with up to 96% ee (Figure 19).66 2.4.2. Ru-Catalyzed Asymmetric Hydrogenation. 2.4.2.1. Asymmetric Transfer Hydrogenation. Transfer hydrogenation, in which hydrogenation occurs via the transfer of hydrogen from a source other than H2, is commonly employed with Ru catalysis. The use of a nongaseous hydrogen has the advantages of reduced cost and minimizes the inconvenience of handling H2 gas. One of the earliest methodologies for the transfer hydrogenation of endocyclic imines was reported by Noyori and co-workers in 1996. The methodology involved the hydrogenation of 3,4-dihydroisoquinolines S25 and dihydro-βcarbolines S30 using a ruthenium catalyst derived from Narylsulfonyl 1,2-diamine ligands and formic acid (Scheme 23).67

the asymmetric hydrogenation of 2-(pyridine-3-yl) endocyclic imines S27 in high yields and with 75−99% ee (Scheme 22).63 Scheme 22. SIPHOX−Ir-Catalyzed AH of 2-(Pyridine-3-yl) Endoyclic Imines S27

Scheme 23. TsDPEN−Ru-Catalyzed ATH of Endocyclic Imines S25 and S30 The presence of an electron-withdrawing group at the 6 position of the pyridine ring led to a slight reduction in enantioselectivity. The 6- and 7-membered endocyclic imines could also be reduced to their corresponding products with good enantioselectivities, although larger ring systems afforded lower enantioselectivities. 2.4.1.4. Other Endocyclic Imines. Chan and co-workers reduced several other less common substrates using Ir catalysis and a chiral-bridged atropisomeric diphosphine ligand C3*TunePhos (L28).64 In 2011, Y.-G. Zhou, X. Zhang, and coworkers successfully applied Ir−(S,S,S)-C3*-Xyl-TunePhos (L28S) complex to the hydrogenation of 7-membered cyclic imines, substituted dibenzo[b,f ][1,4]oxazepines S28, as shown in Figure 19.65 Interestingly, the addition of a morpholine salt, in particular, morpholine−HCl, improved reaction activity and enantioselectivity. The corresponding products were obtained in

The η6-arene and 1,2-diamine ligands influence the rate and enantioselectivity of the reaction. Enantioselectivity relies on the chirality of the N-sulfonylated 1,2-diamine, the presence of the polar functional groups, and the alkyl substituents of the η6-arene ligand. TsDPEN (L29) proved to be most suitable. Triethylamine is required for the reaction to proceed; in its absence the Ru complexes catalyze the decomposition of formic acid, and so the substrate imine is not reduced. Noyori’s catalysts have also been employed in the asymmetric transfer hydrogenation of other 1-aryl-3,4-dihydroisoquinolines with good success.68,69 Several water-soluble catalyst systems have been developed for the reduction of imines. In 2006, Zhu, Deng, and co-workers prepared a water-soluble ruthenium complex derived from o,o′disulfonated N-tosyl-1,2-diphenylethylene ligand L30. A catalyst system consisting of [RuCl2(p-cymene)]2/L30, cetyltrimethylammonium bromide (CTAB), and sodium formate proved to be the most compatible with a number of 1-alkyl-3,4-dihydroisoquinolines S25. The 1-substituent had an effect on enantiose-

Figure 19. C3*-TunePhos−Ir-catalyzed AH of 7-membered endocyclic imines S28 and S29. 14780


Chemical Reviews

Review

lectivity, with longer alkyl chains giving slightly lower enantioselectivities (90−95% ee). Dihydro-β-carbolines S30 were reduced with 98−99% ee, even with low S/C ratios. A cyclic iminium S31 derived from S25 was also reduced under these reaction conditions to afford the related cyclic tertiary amine P31 with 90−95% ee (Scheme 24).70

Scheme 25. TsDPEN−Ru-Catalyzed ATH of Endocyclic Iminiums S32 in Water

Scheme 24. Ru-Catalyzed ATH of Endocyclic Iminium S31 in Water

via a transition state which minimizes contact between the N-R groups and the substrate. Further investigations proved the importance of the N−H bond in the transition state.75 For hydrogenations using [RuH(TsDPEN-H)(arene)] catalysts, it was found that the presence of the N−H is advantageous for formation of the ruthenium hydride species, necessary for the transfer of hydrogen to ketones in the reduction step, and advantageous for the transfer of hydrogen to imines. Extra alkyl groups on the nitrogen atom led to a reduction in enantioselectivities for TsDPEN−Ru-catalyzed reactions. In 2013, Ratovelomanana-Vidal and co-workers reported a highly enantioselective Ru-catalyzed asymmetric transfer hydrogenation of 1-aryl-tetrahydroisoquinolines S25 (R = Ar) with enantioselectivities of 82−99%.76 TsDPEN−Ru complex [RuCl(L29S)(benzene)], in the presence of formic acid, trimethylamine, and iPrOH solvent, was suitable for the hydrogenation procedure. A temperature of 30 °C was essential for high catalytic activity and selectivity. The enantioselectivity of the reaction is affected by the type and substitution pattern on the aromatic rings. The reaction conditions are tolerable to electronwithdrawing and electron-donating substituents; however, substituents at the para position provide their corresponding products with slightly lower yields compared to meta-substituted species. Ortho-substituted 6,7-dimethoxy isoquinoline substrates gave their desired products in excellent yields and enantioselectivities. Reaction activity gradually increases with increased steric bulk at the ortho position. Transfer hydrogenation reactions with imines lacking substituents on the benzene ring of the isoquinoline motif gave lower conversions and enantioselectivities than 2,7-dimethoxy-substituted substrates. Additionally, isoquinolines bearing only a single substituent on the benzene ring could be reacted with high yields and enantioselectivities. Conversions and stereoselectivities of substrates bearing electron-withdrawing groups were less affected than those bearing electron-donating groups. 2.4.2.2. Asymmetric Hydrogenation. Asymmetric hydrogenation of endocyclic imine S25 (R = Me) using Ru− diphosphine/diamine combinations have been successfully developed but with low enantioselectivities (79% and 89% ee).77,78 A transfer hydrogenation mechanism for these reactions cannot be ruled out due to the use of isopropyl alcohol and a base. In 2011, Fan and co-workers reported an asymmetric hydrogenation of endocyclic imines of the type S26 using the ruthenium complex of (R,R)-MsDPEN (Ru−L32), in which the commonly used Cl counterion is replaced with BArF. The reduced products were obtained with 67−98% ee (Scheme 26).79 The electronic properties of the substituents at the para or meta positions have little effect on activity and enantioselectivity.

In 2007, Süss-Fink and co-workers applied water-soluble ruthenium catalysts bearing N,N-chelating ligands to the asymmetric transfer hydrogenation of imines in aqueous solution. Using sodium formate as the hydrogen source, a modified version of Noyori’s catalyst [Ru((R,R)-TsCYDN)(pcymene)(H2O)]BF4 (Ru−L31) that employs a cyclohexyl diamine backbone was found to be the most suitable for the hydrogenation of 1-substituted 6,7-dimethoxy-3,4-dihydroisoquinoline S25, with modest enantioselectivity (Figure 20).71

Figure 20. TsCYDN−Ru-catalyzed ATH of endocyclic imines S25 in water.

In 2008, Pihko and co-workers were able to successfully utilize Noyori’s catalyst in aqueous media for the asymmetric transfer hydrogenation of polycyclic iminium salts. A modified procedure using sodium formate in the presence of a Ru complex derived from L29R, CTAB, and AgSbF6 successfully reduced iminium salts S32a and S32b in good yields and enantioselectivities (Scheme 25).72 The previously studied substrates S25 and S30 were also hydrogenated to their corresponding products with excellent enantioselectivities (99% ee). To elucidate the mechanism of the asymmetric transfer hydrogenation of imines, the Wills group prepared a series of Nalkylated TsDPEN ligands.73,74 The same (S)-configuration product was formed from each of the TsDPEN ligands. Enantiosectivities are generally lower than those reported by Noyori for TsDPEN-derived Ru catalysts, possibly due to the use of benzene rather than p-cymene or hexamethylbenzene as the η6-arene. The N-methylated catalyst gave the best results out of the catalysts screened. The hydrogenation is envisaged to occur 14781


Chemical Reviews

Review

of the cosolvent for the transfer hydrogenation process for the reduction of 3,4-dihydro-6,7-dimethoxyisoquinolines S25. Hydrogen transfer can follow either an outer-sphere pathway (similar to that proposed for carbonyl reductions) or an innersphere mechanism (the imine coordinates to the metal before hydrogen transfer). Using their DFT studies and prior investigations carried out by the groups of Wills et al.,75 a mechanism has been proposed (Scheme 27).82 The rhodium precatalyst is formed in situ from [RhCl2(Cp*)]2 and (S,S)TsDPEN in water. The complex reacts with sodium formate to give I. Reduction of intermediate I and subsequent decarboxylation gives the Rh−hydride species II. The reduction of the imine proceeds through transition state III via the antimechanism proposed by Wills et al.75 (although the imine is activated by the N−H bond of the catalyst, the methanol solvent may lower the theromodynamic free energy of the hydrogen transfer). The precatalyst I is subsequently regenerated through intermediate IV. 2.4.3.2. Asymmetric Hydrogenation. In 2008, Xiao and coworkers reported an asymmetric hydrogenation of endocyclic imines using the same [RhCl((R,R)-TsDPEN)(Cp*)] complex Rh−L29R. The generation of the complex using AgSbF6 was essential for high reaction activity and enantioselectivity in the asymmetric hydrogenation of 1-alkyl-3,4-dihydroisoquinolines S25 (83−99% ee) and tricyclic imines S30 (20−99% ee).83 Yields and enantioselectivities are comparable to that of Rubased hydrogenations. Hydrogenation of the tricyclic substrates was carried out in methanol to improve solubility. Additionally, reduction of these substrates bearing alkyl groups proceeded with better activity and enantioselectivity than that of imines bearing alkyl substituents. In 2014, a HCl salt of 3,4-dihydroquinoline S33 was hydrogenated using a rhodium complex of bis(phosphine)− thiourea ligand L34. The tetrahydroquinoline P33 was obtained with 97% yield and with 82% ee under 5 atm H2 (Scheme 28).84 2.4.4. Pd-Catalyzed Asymmetric Hydrogenation. In 2015, Y.-G. Zhou and co-workers successfully developed a Pdcatalyzed asymmetric hydrogenation of trifluoromethyl-substituted hydrazones S34. A catalyst system consisting of Pd(OCOCF3)2 and (S)-SegPhos (L35), in the presence of H2 and TFA in TFE solvent, reduced the cyclic hydrazone substrates with up to 97% ee. Higher reaction temperatures and prolonged reaction times gave the corresponding products with high yields. Aryl substituents bearing electron-donating and electron-withdrawing substituents were all amenable to the reaction conditions, Scheme 29.85 2.4.5. Ti-Catalyzed Asymmetric Hydrogenation. Some of the earliest reports of the asymmetric hydrogenation of endoyclic imines relied on Ti catalysis. Building on previous research in which chiral titanocene-based catalysts were used for hydrosilylation reactions, the same catalysts Ti−L36 could be applied to the asymmetric hydrogenation of endocyclic imines (Figure 22).86−88 Only a small effect was observed when 6,7dimethoxy-3,4-dihydro-1-methylisoquinoline S25 (R = Me) was hydrogenated at a low pressure (2000 psi, 98% ee and 80 psi, 95% ee). The endocyclic imines S26 were insensitive to hydrogen pressure. Cyclic imines bearing various functional groups were compatible with the reaction conditions, with the reduced products being obtained with up to 97−99% ee, even for substrates possessing additional olefin groups (although some reduction and isomerization were observed in some cases). Interestingly, cyclic imines bearing heteroarene groups were not reduced under these conditions due to either steric reasons or

Scheme 26. MsDPEN−Ru-Catalyzed AH of Endocyclic Imines S26

Conversely, substituents at the ortho positions reduced both the reactivity and the selectivity. The 6- and 7-membered cyclic imines were also hydrogenated to give the reduced products with 95% and 92% ee, respectively. 2.4.3. Rh-Catalyzed Asymmetric Hydrogenation. Rhodium-catalyzed asymmetric hydrogenation of endocyclic imines is much less common than those involving iridium and ruthenium. Rh-catalyzed methods commonly employ Rh analogues of Noyori’s Ru−TsDPEN complexes. These catalysts afford slightly lower enantioselectivities than their Ru counterparts but nonetheless are another tool in the synthetic chemists’ arsenal. 2.4.3.1. Asymmetric Transfer Hydrogenation. In 1999, Baker and co-workers prepared a Rh(III) complex of (R,R)-TsDPEN ([RhCl(L29R)(Cp*)]) for the asymmetric transfer hydrogenation of 1-substituted 3,4-dihydroisoquinolines S25 (Figure 21).80 1-Alkyl-3,4-dihydroisoquinolines could be reduced with

Figure 21. N,N-Rh-catalyzed ATH of endocyclic imines S25 and S30.

83−99% ee by using a 5:2 formic acid−triethylamine azeotrope as the hydrogen source. However, 1-aryl-3,4-dihydroisoquinolines showed very poor results. Similarly, Wills and co-workers developed Rh(III) analogues of their Ru(II) systems. Hydrogenation of various cyclic imines S25 (R = Me) and S30 (R = Me, Ph) using a “tethered” complex Rh−L33 afforded the corresponding products with 87%, 88%, and 96% ee, respectively (Figure 21).81 Kelkar, Vanka, and co-workers carried out mechanistic studies for the asymmetric transfer hydrogenation of imines in a water/ methanol cosolvent system. DFT studies showed the importance 14782


Chemical Reviews

Review

Scheme 27. Proposed Mechanism for TsDPEN−Rh-Catalyzed ATH of 1-Methyl-3,4-dihydro-6,7-dimethoxyisoquinoline82

Scheme 28. P,P-Rh-Catalyzed AH of 2-Methyl-3,4dihydroquinoline S33

Figure 22. Ti-catalyzed AH of endocyclic imines.

Scheme 29. SegPhos−Pd-Catalyzed AH of TrifluoromethylSubstituted Cyclic Hydrazones S34

2.5. Summary

A number of catalyst systems have been developed which are suitable for the asymmetric hydrogenation of a broad range of cyclic enamines and endocyclic imines. Rh catalysts, in combination with P,P-ligands (such as BINAP, TangPhos, and DuPhos), reduced cyclic enamides bearing endocyclic vinyl groups with high enantioselectivities. Ir-derived catalysts constituting P,P or N,P ligands (such as spiro phosphoramidite, f-Binaphane, and SIPHOX) have been proven to be particularly effective for the asymmetric hydrogenation of cyclic enamines and endocyclic imines. Additionally, derivatives of Noyori’s Ru/ Rh−TsDPEN catalysts have also been successfully applied to the reduction of various endocyclic imines using asymmetric transfer hydrogenation.

3. SYNTHESIS OF N-SUBSTITUTED CHIRAL CYCLOALKANES product inhibition of the catalyst.88 Mechanistic studies showed that the enantiomeric excess remains constant independent of the reaction conditions, differing from the hydrogenation of acyclic substrates which show a dependence on hydrogen pressure. Hydrogenation with cyclic substrates was shown to be first order with respect to hydrogen and catalyst.89

3.1. Via Asymmetric Hydrogenation of Cyclic Enamines Bearing an Endocyclic Vinyl Group and Exocyclic Nitrogen Atom

A large number of procedures for the asymmetric hydrogenation of cyclic enamines bearing an endocyclic vinyl group and exocyclic nitrogen atom have been reported (Figure 23). 14783


Chemical Reviews

Review

= Ph), a cyclic enamide bearing a 7-OMe substituent was hydrogenated with up to 98% and 95% ee, respectively.97,98 In 2001, Bruneau and co-workers also utilized a ruthenium complex of (R,R)-Me-DuPhos (L6) to hydrogenate the tetrasubstituted cyclic enamides S37. The nature of the benzylic substituent has a large influence on enantioselectivity, with the best results being obtained for sterically hindered 1-[(o,o)dimethylbenzoyl]-2-amintotetraline derivatives (Scheme 32).99

Rhodium catalysts are commonly employed in such reactions, typically with P,P-chelating ligands.

Figure 23. Asymmetric hydrogenation of cyclic enamines bearing an endocyclic vinyl group and exocyclic nitrogen atom for the synthesis of N-substituted chiral cycloalkanes.

Scheme 32. DuPhos−Ru-Catalyzed AH of Tetrasubstituted Cyclic Enamides S37

3.1.1. Ru-Catalyzed Asymmetric Hydrogenation. Bisphosphine ligands are commonly employed in asymmetric hydrogenation of enamides bearing an endocyclic vinyl group and exocyclic nitrogen atom. For example, some of the first methodologies used the ever versatile BINAP ligand to prepare chiral cyclic products with an exocyclic amido group and an endocyclic carboxyl group.90,91 In 1995, en route to the synthesis of the antiarrhthymia agent MK0499, Tschaen and co-workers reported an asymmetric hydrogenation of enamide S35 with 98% ee using a [RuCl((S)-BINAP)(benzene)] catalyst (Scheme 30).92

Interestingly, the addition of a halogen atom at the 2 position of the benzyl group effects enantioselectivity, with enantioselectivity increasing with halogen size. Additionally, methanol was found to be essential for high catalyst activity, as too was the type of acidic additive such as HBF4. In 2003, X. Zhang and co-workers reported a highly enantioselective Ru-catalyzed synthesis of chiral cyclic β-amino acids via the asymmetric hydrogenation of tetrasubstituted cyclic β-(acylamino)acrylates S38 (Scheme 33).100 A catalytic system

Scheme 30. BINAP−Ru-Catalyzed AH of a Cyclic Enamide S35

Scheme 33. C3-TunaPhos−Ru-Catalyzed AH of Cyclic β(Acylamino)acrylates S38 In 1999, Bruneau and co-workers reported the hydrogenation of trisubstituted cyclic enamides derived from 2-tetralone and 3chromanone and investigated the effect different acetamido protecting groups had on the hydrogenation reaction (Scheme 31).93−96 The mononuclear catalyst [Ru(OCOCF3)2((R or S)Scheme 31. BINAP−Ru-Catalyzed AH of Trisubstituted Cyclic Enamides S36

consisting of [Ru(2-Me-allyl)2(cod)] and a chiral diphosphine ligand with 2 equiv of HBF4 was utilized to hydrogenate a series of tetrasubstituted olefins. The best ligand for the asymmetric hydrogenation of tetrasubstituted olefins was found to be (S)-C3TunaPhos L37, which allowed for the asymmetric hydrogenation of a series of cyclic β-(acylamino)acrylates with high enantiomeric excess (44−99% ee). Ring size influenced the enantioselectivity of the reactions, with increasingly larger ring systems being detrimental to stereoselectivity. The preparation method of the ruthenium catalyst was shown to be of particular importance, with protic alcohol solvents (MeOH and EtOH) proving superior to solvents such as THF, CH2Cl2, and toluene. The cis-hydrogenated products could subsequently be epimerized to their trans analogues. The Ru−L37 catalyst was also

BINAP)] proved to be sufficient for hydrogenation of the enamide substrates S36. Substrates S36a bearing a Bz group on the nitrogen atom could be hydrogenated with the highest enantioselectivities (up to 96% ee). Enamides S36b bearing an oxygen atom in the ring system could be converted to their corresponding amines products with up to 80% ee. A similar method was also utilized by Agbossou and RatovelomananaVidal for the synthesis of an atypical β-adrenergic phenylethanolaminotetraline agonist SR58611A. Using a ruthenium complex of (R)-MeO-BIPHEP (L2R) or (R)-SynPhos (L25, Ar 14784


Chemical Reviews

Review

suitable for the hydrogenation of cyclic β-keto enamide substrates with modest to good enantioselectivities.101 In 2012, Kajiwara and co-workers applied this method to the large-scale preparation of chiral 2-(N-benzoylamino)cyclohexanecarboxylic ester P39 (Scheme 34).102 Initial

Scheme 35. BPE−Rh-Catalyzed AH of Cyclic Enamides S40

Scheme 34. DTBM-BINAP−Ru-Catalyzed AH of Cyclic β(Acylamino)acrylates S39

membered cyclic enamides S40a and S40b both with up to >99% ee. The oxa-substituted substrate S40c gave a comparatively lower enantioselectivity (90% ee). A tetrasubstituted 5membered cyclic enamide S41a was hydrogenated with 98% ee, while the corresponding 6-membered compound, S41b, was reduced with only 73% ee. A cyclic enamide, S36a (R1 = H), derived from β-tetralone, was also reduced but with only 71% ee. The same group also developed (S)-o-Ph-MeO-BIPHEP (L41) ligands,106,107 a C1-symmetric diphosphane ligand L42,108 and (SP, RC)-DuanPhos (L43)109 for the hydrogenation of related substrates (Figure 24). These ligands provided high enantioselectivities and showed similar trends. Later, X. Zhang and co-workers studied the Rh-catalyzed asymmetric hydrogenation of cyclic dienamides S42 for the synthesis of chiral cyclic allylic amines P42. After screening various diphosphine ligands, (SP,RC)-DuanPhos (L43) proved to be the best ligand with the desired products being obtained with 91−99% ee (Scheme 36).110 They also studied the Rh-catalyzed asymmetric hydrogenation of cyclic β-acetylamino acrylonitriles and o-alkoxy tetrasubstituted cyclic enamides using JosiPhostype ligands. However, only moderate to low enantioselectivities were obtained.111,112 In 2013, Tang and co-workers made considerable progress in developing bisphosphorus ligands possessing both P-chirality and C-chirality. The newly designed ligands, WingPhos (L44), were able to hydrogenate a number of cyclic enamides with excellent enantioselectivities (Scheme 37).113 Deeper chiral pockets are created by the bulky R groups present in L44 with the R groups being directed toward the substrate coordination site. This leads to increased conformational variation of the chiral pocket and also increases its rigidity. In particular, Rh catalyst Rh−L44 was found to be effective for not only the asymmetric hydrogenation of acyclic species but also chiral substrates. A number of chiral N-Ac 2-aminotetralines P36a and 3-aminochromanes P36b were prepared with high enantioselectivities. One noteworthy example was the hydrogenation of N-(5methoxy-3,4-dihydronaphthalen-2-yl)acetamide, which could be reduced with 96% ee and with up to 2000 TON. During these studies by the X. Zhang group, substrates such as those above have been used as model templates for investigating the catalytic performance of new ligands possessing only Pchirality. Preliminary studies involving the asymmetric hydrogenation of cyclic enamides using P-stereogenic diphosphine ligands were carried out by Ohashi and Hoge with moderate enantioselectivity.114,115 In 2010, Vardaguer, Riera, and coworkers developed a new class of P-stereogenic ligands for use in Rh-catalyzed asymmetric hydrogenations.116,117 A rhodium complex of C1-symmetric aminophosphine MaxPHOS (L45)

attempts at the reduction of its precursor, S39a (R = H), were carried out using (S)-BINAP (L1S) and (S)-C3-TunaPhos (L37) with a [Ru(2-Me-allyl)2(cod)] catalyst precursor. The reduced product P39a could be obtained with 97% conversion and with 71% and 70% ee using L1S and L37, respectively, when the hydrogenation was carried out at 50 °C. The asymmetric hydrogenation of S39b (R = OCF2H) was also examined, of which bears a difluoromethoxy group at the para position of the benzoyl substituent. (S)-C3-TunaPhos L37 showed slightly better enantioselectivity with the reduced product P39b being obtained with 90% ee. Further optimization of reaction conditions led to the discovery of a [Ru(OAc2)((S)-DTBMBINAP)] catalyst (Ru−L38) providing the best enantioselectivity (up to 95% ee) and diastereoselectivity. On an 18 kg scale, the optimized reaction could be used to reduce S39b with 100% conversion, 96% de, and 92% ee. 3.1.2. Rh-Catalyzed Asymmetric Hydrogenation. Although initial studies with Ru catalysis for the asymmetric hydrogenation of such substrates occurred earlier than investigations involving Rh catalysis, it is the latter which has attracted more attention both for the development of new ligands and for their application to the hydrogenation of new substrates. 3.1.2.1. Bisphosphorus Ligands. Bisphosphorus ligands have been used extensively in conjunction with Rh catalysis for the hydrogenation of cyclic enamides bearing an endocyclic vinyl group and exocyclic nitrogen atom. In 1998, Burk and coworkers reported the first Rh-catalyzed asymmetric hydrogenation of such substrates with good results. Catalyzed by a [Rh((S,S)-Me-BPE)(cod)]BF4 catalyst (Rh−L39), the 5- and 6membered cyclic enamides S40 were reduced to related products P40 with >99% and 92% ee, respectively (Scheme 35).103 The X. Zhang group is one of the most active research teams in this area. Several ligands have been developed and applied in these reactions. After initial unsatisfactory attempts using a rhodium complex of (R,R)-BICP (L22),104 X. Zhang and coworkers developed a Rh-catalyzed asymmetric hydrogenation of cyclic enamides using conformationally rigid chiral bisphosphanes (R,S,R,S)-Me-PennPhos (L40).105 Me-PennPhos ligand was suitable for the asymmetric hydrogenation of 5- and 614785


Chemical Reviews

Review

Figure 24. Diphosphine ligands used for Rh-catalyzed AH of cyclic enamides developed by the X. Zhang group.

Scheme 36. DuanPhos−Rh-Catalyzed Regioselective AH of Cyclic Dienamides S42

Scheme 37. WingPhos−Rh-Catalyzed AH of Cyclic Enamides S36 Figure 25. MaxPhos−Rh-catalyzed AH of cyclic enamides.

provided moderate enantioselectivities for the hydrogenation of S40 (Figure 26).118 In 2013, a new P-stereogenic ligand, t-Bu-SMS-Phos (L49), was developed by Mohar and Stephan and applied in Rhcatalyzed asymmetric hydrogenations. For cyclic enamides S40a and S40b, the reduced products were obtained with 99% and 87% ee, respectively, when the hydrogenation was conducted at 0 °C (Figure 26).119 In 2015, W. Zhang and co-workers successfully utilized (S)tert-butylmethyl(di-tert-butylphosphinomethyl)phosphino ((S)TCFP)(L50) for the Rh-catalyzed asymmetric hydrogenation of cyclic α-dehydroamino ketones S43 (Scheme 38).120 Catalyst Rh−L50 was capable of reducing a range of N-(1-oxo-1H-inden2-yl)acetamide substrates S43 with excellent enantioselectivities (97−99% ee). (S)-TCFP provided better enantioselectivities compared to other ligands such as (R)-BINAP and (R,R)QuinoxP*. Ethyl acetate was found to be the optimal solvent with nonpolar solvents such as toluene giving low enantioselectivities. Excellent product yields and enantioselectivities were obtained irrespective of the electronic character of the substituents on the aromatic ring. The reaction conditions were also highly chemoselective with no reduction of the ketone

was utilized for the asymmetric hydrogenation of cyclic enamides S40b and S36a (R1 = H) with 75% and 33% ee, respectively (Figure 25).117 In 2012, Imamoto and co-workers developed a series of new Pstereogenic diphosphine ligands for the hydrogenation of a number of functionalized olefins. Each enantiomer of the Pstereogenic diphosphine ligands was prepared from enantiopure (S)- and (R)-tert-butylmethylphosphine-boranes. Acyclic enamides were successfully reduced with high ee’s using these ligands; however, cyclic enamide S40 was significantly more difficult to reduce. As expected, these substrates required higher H2 pressures (20 atm) than that used for the hydrogenation of acyclic enamides. The rhodium complexes of (R,R)-QuinoxP* (L46), (R,R)-BenzP* (L47), and (R,R)-DioxyBenzP* (L48) 14786


Chemical Reviews

Review

Scheme 39. 3H-QuinoxP*−Rh-Catalyzed Sequential AH of Cyclic α-Dehydroamino Ketones S43

hydrogenation proceeds first via reduction of the CC bond, followed by reduction of the CO bond. A number of other P,P-chelating ligands have been developed, but these rely primarily on the use of acyclic substrates (Figure 27). The Vidal-Ferran group developed modular phosphine−

Figure 26. P-Stereogenic diphosphine ligands used for Rh-catalyzed AH of cyclic enamides S40.

Scheme 38. TCFP−Rh-Catalyzed Chemoselective AH of Cyclic α-Dehydroamino Ketones S43

Figure 27. Other diphosphine ligands used for Rh-catalyzed AH of cyclic enamides.

being observed. Products with an S-configuration are favored due to lower steric hindrance in their transition states. Using similar methodology, the W. Zhang group was also able to apply a rhodium catalyst derived from the ligand (R)-3HQuinoxP* (L51) to the sequential reduction of both the ketone and the alkene functional groups of the above substrates. In this manner, chiral β-amino alcohols P43′ with unusual trans configurations could be prepared (Scheme 39).121 The highest enantioselectivities (89−99% ee) and diastereoselectivities (3/ 1−16/1 dr) were obtained when the reaction was carried out in dioxane solvent and with a H2 pressure of 20 atm. Substrates bearing electron-donating substituents on the phenyl rings gave the desired products with the highest diastereoselectivities (9/ 1−16/1 dr). Electron-withdrawing substituents had the opposite affect, leading to products with lower diastereoselectivities (3/1− 7/1 dr). Mechanistic studies showed that the sequential

phosphite ligands L52, which in combination with a [Rh(nbd)2]BF4 catalyst precursor hydrogenated enamides S40b with up to 88% ee.122−124 Pizzano and co-workers reported the asymmetric hydrogenation of cyclic enamides S36a with a rhodium complex bearing a phosphine−phosphite ligand L53 to obtain chiral cyclic amides with 83−93% ee.125,126 Coordination studies with enamide S36a showed a preference for η6-arene coordination in a Rh(I) complex. Additionally, deuteriumlabeling experiments showed that there was a clean cis addition to the double bond.125 Reek and co-workers developed a catalyst system in which the chirality of a Rh−diphosphine complex Rh− L54 is derived utilizing a chiral cofactor. Cyclic enamides S40b and S36a were reduced with enantioselectivities of 79% and 43% ee, respectively. 127 Ferrocene-based bisphosphorus li14787


Chemical Reviews

Review

gands128−131 and others132−135 have also shown promising activity with low to moderate enantioselectivities. 3.1.2.2. Monodentate Phosphorus Ligands. Several methodologies utilizing monodentate phosphoramidites,136−142 phosphites,143−145 and phosphanes146−148 have also been developed for the asymmetric hydrogenation of cyclic enamides (Figure 28). Phosphoramidites and phosphites have proved to be more

Figure 29. Supraphos ligand used for Rh-catalyzed AH of cyclic enamides.

experiments showed that the bidentate nature of the ligands was important. The metal-to-ligand ratio as well as the ratio of L60a/ L60b was also important for optimal catalysis. High ligand loadings increased ee, but activity was reduced. Reek and co-workers also devised a dinuclear catalyst system for the asymmetric hydrogenation of cyclic enamides, which also mimics the mechanistic features that are encountered in natural metallocene enzymes. The binuclear catalyst system is formed via the use of P,N-bridging ligands L61 based on a sulfonamido− phosphoramidite scaffold, which creates a neutral boat-shaped Rh−P−N−Rh-bridged dinuclear species (Scheme 40).152 The Figure 28. Phosphoramidite and phosphite ligands used for Rhcatalyzed AH of cyclic enamides.

Scheme 40. Dinuclear Catalyst System for Asymmetric Hydrogenation of Cyclic Enamides152

useful than phosphanes for the hydrogenation of S40. Chan and co-workers successfully reduced S40b with 84% ee using a catalyst system consisting of [Rh(cod)2]BF4 and phosphoramidite ligand S-MonoPhos (L55) in dichloromethane solvent at different temperatures.136 Feringa and co-workers developed a series of BINOL-based phosphoramidites, PipPhos, and its analogues (L56). These ligands, in combination with a [Rh(cod)2]BF4 catalyst precursor, reduced cyclic enamides S40a, S40b, S40c, and S36a with up to 98%, 98%, >99%, and 34% ee.141 Monodentate phosphoramidite SIPHOS (L57) developed by Q.-L. Zhou et al.140 and monodentate phosphite L58 developed by Zheng et al.,144 in combination with a [Rh(cod)2]BF4 catalyst precursor, reduced cyclic enamides S40a with 88−95% and 96% ee, respectively. Pfaltz and co-workers also developed an efficient monodentate phosphite ligand L59 derived from BINOL to reduce S40b with up to 97% ee.145 3.1.2.3. Supramolecular Ligands. Inspired by nature, Reek and co-workers designed several “supramolecular ligands” for the reduction of cyclic enamides. A zinc(II) porphyrin−pyridyl interaction was used as an assembly motif to prepare a library of bidendate phosphorus-based ligands.149−151 This library of supraphos ligands was expanded for use in the asymmetric Rhcatalyzed hydrogenation of trisubstituted cyclic enamides. Two components form the supraphos ligands, which are brought together by coordination of the nitrogen donor atom of ligands L60a to the zinc atom of L60b (Figure 29).149 High-throughput screening of a number of supraphos ligands yielded ligand L60a/ L60b to be the most effective for the hydrogenation of cyclic enamide S36a when used with a cationic rhodium catalyst precursor ([Rh(cod)2]BF4). Supraphos ligands based on BINOL porphyrin phosphites induced higher enantioselectivities (up to 94% ee) than TADDOL-based porphyrin phosphites. Additional

dinuclear species [Rh2(L61)2(nbd)2] is formed in the presence of 1 equiv of [Rh(nbd)2]BF4 and ligands L61. According to density functional theory (DFT) calculations performed by the Reek group, the complex forms a six-membered ring system in which the two bridging anionic ligands adopt a boat conformation (5 kcal/mol lower in energy than the chair conformation). Surprisingly, in contrast to cationic Rh complexes which are commonly used in asymmetric hydrogenation reactions, neutral binuclear catalyst Rh2(L61)2(L61H)2 worked exceptionally well for the asymmetric hydrogenation of the trisubstituted acetamide S36a (83% ee) and even for the tetrasubstituted substrate N-(1-benzyl-3,4-dihydronaphthalene2-yl-acetamide S37 (>99% ee). 14788


Chemical Reviews

Review

Kinetic studies carried out by Reek and co-workers relating to the above reactions revealed the rate equation: rate = kobs[catalyst][substrate]0.9[PH2]0.5, indicating that the binuclear catalyst does not dissociate into mononuclear species for catalyst activation; neutral, dinculear Rh2(μ2-P,N-L61)2(μ2-P,O-L61H)2 is the active species in the asymmetric hydrogenation. The mechanistic pathway for the reaction is shown in Scheme 41. Scheme 41. Catalytic Mechanism of AH Using Binuclear Catalyst152

Figure 30. Other supramolecular ligands used for Rh-catalyzed AH of cyclic enamides.

3.1.2.4. Heterobidentate P,X Ligands. Of course, P,Pchelating ligands are not the only type of ligands that are used in hydrogenation of cyclic enamides. Evans and co-workers reported a mixed P,S-chelating ligand L65 for the enantioselective Rh-catalyzed hydrogenation of dehydroamino acids. In particular, L65 was capable of hydrogenating 5-membered cyclic enamide S40a with 92% ee (Figure 31).156 Reek and co-workers

Ethylene is used as a substrate, and the binaphthol groups of the ligand have been replaced with −OCH2−CH2O− fragments. In its resting state I, the catalyst adopts a chair conformation. The possibility of cooperative substrate activation by dinuclear complex I may occur due to the weak Rh−Rh metal bond (3.23 Å in length). Bishydride species III, which possesses one terminal and one bridging hydride, is formed from II via cooperative H2 splitting over Rh. The Rh−Rh bond distance in III decreases to 3.16 Å, resulting in the elongation of the O−Rh bond of the neutral sulfonamide fragment. This creates a vacant coordination site which has a high affinity for π-accepting alkenes. IV is formed via the binding of ethylene to the vacant site of III. The alkyl species V is formed via migratory insertion of the alkene species, which rearranges to the lower energy species VI in which the alkyl functionality is cis to the bridging hydride. Reductive elimination of the alkene products regenerates the catalyst. Genari and co-workers utilized a different approach to develop chiral supramolecular ligands for Rh-catalyzed asymmetric hydrogenation reactions.153−155 The Genari group developed a novel class of chiral monodentate phosphite ligand, PhthalaPhos L62, which contains a phthalic acid primary diamide moiety (Figure 30).153 The phthalamide motif possesses both hydrogenbond donor and acceptor functionalities, which can give rise to supramolecular interactions between the ligands and the reaction substrate. A [Rh(cod)2]BF4/L62 catalyst system successfully reduced N-(3,4-dihydronaphthalen-1-yl)-acetamide substrate S40b in the presence of 12 bar H2 with a conversion of 99% and 96% ee. In comparison, monodentate phosphite ligand L63 showed substantially lower activity though similar enantioselectivity.154 On the basis of these results, structurally related supramolecular ligands BenzaPhos L64 were also developed to give improved enantioselectivity (98% ee) for the asymmetric hydrogenation of S40b.155

Figure 31. P,X-Ligands used for Rh-catalyzed AH of cyclic enamides.

reported the hydrogenation of cyclic enamides using rhodium complexes derived from P,O-bidentate coordinated ligands. The ureaphosphane ligand L66 successfully reduced enamide S36a with up to 88% ee (Figure 31).157,158 3.1.3. Ir-Catalyzed Asymmetric Hydrogenation. Pfaltz and co-workers disclosed an asymmetric hydrogenation of unfunctionalized cyclic enamines using P,N-Ir complexes (Scheme 42).159 Cyclic enamine S44a could be reduced with >99% conversion and with an enantioselectivity of 87% using an iridium complex derived from Cy-ThrePHOX (L67) in tert-butyl methyl ether (TBME) solvent. Compared to acyclic enamides, a higher pressure of 50 bar was required to reduce the cyclic substrate. Hydrogenation of substrate S44b required an Ir complex derived from L68. Performing the reaction at 0 °C in CH2Cl2 under 50 bar H2 pressure gave the reduced product with 71% ee. Q.-L. Zhou and co-workers utilized a spiro phosphoramidite ligand L69 for the asymmetric hydrogenation of N,N-dialkylenamines S45 (Scheme 43).160 These substrates were reduced using an [IrCl(cod)]2 catalyst precursor in combination with L69 and iodine additive. The iodine additive was essential for 14789


Chemical Reviews

Review

Scheme 42. P,N-Ir-Catalyzed AH of Cyclic Enamines S44

Figure 32. Phosphoramidite ligands used for Ir-catalyzed AH of cyclic enamides.

Figure 33. Asymmetric hydrogenation of exocyclic imines for the synthesis of N-substituted chiral cycloalkanes.

Scheme 43. Phosphoramidite−Ir-Catalyzed AH of Cyclic Enamines S45

3.2.1. Ru-Catalyzed Asymmetric Hydrogenation. Ruthenium catalysis has proven to be effective for the hydrogenation of exocyclic imine substrates. Initially, P,Pchelating ligand (R)-BINAP (L1R) was applied to the Rucatalyzed asymmetric hydrogenation of N-tosyl ketimine S46. The 6-membered chiral amine P46 was obtained with 82% ee and 78% yield (Scheme 44).163 Scheme 44. BINAP−Ru-Catalyzed AH of Exocyclic Imines S46

In 2011, Fan and co-workers applied a phosphine-free, chiral, cationic Ru−MsDPEN catalyst Ru−L32 to the asymmetric reduction of N-alkyl exocyclic imines S47 (Scheme 45).164,165 Scheme 45. MsDPEN−Ru-Catalyzed AH of Exocyclic Imines S47

reactivity. Enantioselectivity increased with increasing ring size and compares favorably with other procedures. Beller and co-workers also used a monodentate 3,3′substituted phosphoramidite L70 derived form H8-BINOL for the asymmetric hydrogenation of various enamides, including cyclic enamide S40b. However, the ligand complex derived from L70 and [IrCl(cod)]2 could only reduce enamide S40b with 60% ee and 17% conversion.161 Reek and co-workers had greater success using phosphorylated sulfonimidamides SIAPhos (L71). The iridium complex of L71 was capable of reducing tetrasubstituted cyclic substrates S37 with 85−92% ee (Figure 32).162

The reduced products were obtained with enantioselectivities in excess of that of previously reported methods. This procedure was successfully applied to the synthesis of Setraline, a chiral antidepressant drug. 3.2.2. Ir-Catalyzed Asymmetric Hydrogenation. Only a handful of procedures have been reported for the asymmetric hydrogenation of cyclic systems bearing exocyclic imines with Ir catalysis. N-Aryl exocyclic imines S48 are more commonly targeted than the N-allkyl analogues S47.

3.2. Via Asymmetric Hydrogenation of Exocyclic Imines

The asymmetric hydrogenation of exocyclic imines is not as well reported as that of the reduction of endocyclic imines. However, a number of catalyst systems have been employed (Figure 33). Iridium complexes derived from P,N ligands have been shown to be particularly promising catalysts. 14790


Chemical Reviews

Review

In 2005, a phosphine−sulfoximine ligand L72, together with an Ir-catalyst precursor [IrCl(cod)]2, was successfully used for the hydrogenation of tetralone-derived N-aryl exocyclic imine. With the aid of iodine, the 6-membered chiral cyclic amine S48b (Ar = PMP) was obtained with 91% ee (Scheme 46).166 Scheme 46. Ir-Catalyzed AH of Exocyclic Imines S48 Figure 35. Other ligands used for Ir-catalyzed AH of exocyclic imines S47.

prevents coordination of the basic lone pair of the secondary amine to the metal center. Scheme 47. JosiPhos−Rh-Catalyzed AH of Cyclic Imine/ Enamine S49

In 2014, Qu and co-workers developed air-stable P-chiral dihydrobenzooxaphosphole−oxazoline ligands LalithPhos (L73) for the asymmetric synthesis of unfunctionalized dialins. These LalithPhos ligands were capable of reducing several substrates, including N-aryl-dihydronaphthalene ketimines S48b, with high enantioselectivities (94−98% ee) (Figure 34).167 Other Ir complexes based on phosphine−oxazoline ligands (L74, L75, and L76) were also suitable for the hydrogenation of S48 (Figure 34).168−170

3.2.4. Pd-Catalyzed Asymmetric Hydrogenation. In 2006, a palladium catalyst utilizing a P- and C-chiral bisphosphane ligand TangPhos (L4) was applied to the asymmetric hydrogenation of N-tosyl cyclic ketimines S46. Both 5- and 6-membered substrates, S46a and S46b, were completely hydrogenated to their corresponding chiral amines with 98% and 94% ee, respectively.174 In 2011, a similar palladium catalyst containing an axially chiral diphosphine ligand (R)-C4-TunePhos (L78) was utilized for the asymmetric hydrogenation of N-aryl cyclic ketimines S48. Various substrates possessing different substituents were reduced to chiral amines with good enantioselectivities (Scheme 48).175 Exocyclic N-tosyl imines prepared in situ from N-tosyl cyclic aminoalcohols have been applied to Pd-catalyzed asymmetric hydrogenations. The axially chiral diphosphine ligand (R)DifluorPhos (L79) was found to be suitable for 5-membered benzoimines S50a with 89−94% ee. A 6-membered substrate S50b was hydrogenated to a chiral cyclic amine using DuanPhos

Figure 34. Phosphine−oxazoline ligands used for Ir-catalyzed AH of exocyclic imines S48.

Scheme 48. C4-TunePhos−Pd-Catalyzed AH of Cyclic Imines S48

A new class of chiral phosphine−oxazoline ligands, SpinPHOX (L77), was developed by Ding and co-workers for the asymmetric hydrogenation of the challenging 6-membered exocyclic N-alkyl ketimines S47b and S47c. Excellent enantioselectivities of 95−98% ee were obtained for the cyclic amine products using L77S (Figure 35).171 The monodentate phosphoramidite PipPhos (L56) was also used for the Ircatalyzed asymmetric hydrogenation of S47a. However, a NnBu-substituted substrate was reduced with only 40% ee (Figure 35).172 3.2.3. Rh-Catalyzed Asymmetric Hydrogenation. En route to the synthesis of a HIV integrase inhibitor, Zhong, Krska, and co-workers utilized a Rh catalyst for the hydrogenation of a key imine/enamine intermediate S49. The substrate was reduced with up to 90% ee with the aid of the ligand JosiPhos (L15b) and using TFA as an additive (Scheme 47).173 The TFA additive 14791


Chemical Reviews

Review

4. SYNTHESIS OF CHIRAL CYCLIC ETHERS

(L43) with lower enantioselectivity (79% ee). Using another axially chiral diphosphine ligand (S)-SegPhos (L35), the in-situgenerated 5-membered imines S50c were reduced with 93−97% ee while the 4-membered imines S50d were reduced with 89− 98% ee (Scheme 49).176,177 The in-situ-converting pathways and intermediates are also shown in Scheme 49.

4.1. Via Asymmetric Hydrogenation of Cyclic Enol Ethers Bearing an Endocyclic Oxygen Atom

The hydrogenation of cyclic enol ethers provides an efficient pathway to the synthesis of chiral cyclic ethers (Figure 36). These

Scheme 49. Pd-Catalyzed AH of Exocyclic Imines S50 in-Situ Generated from N-Ts Cyclic Aminoalcohols

Figure 36. Asymmetric hydrogenation of cyclic enol ethers bearing an endocyclic oxygen atom for the synthesis of chiral cyclic ethers.

structural motifs are challenging substrates to reduce with high yields and enantioselectivities. As such, only a handful of asymmetric hydrogenation reactions concerning these substrates have been reported. 4.1.1. Ru-Catalyzed Asymmetric Hydrogenation. One of the earliest attempts directed toward the hydrogenation of cyclic enol ethers was reported by the Takaya group in which BINAP−Ru complexes were used to reduce simple alkenyl cyclic ethers with modest enantioselectivities.178 2-Methylenetetrahydrofuran S51, 2-methyl-3,4-dihydrofuran S52, and 2-methyl benzopyran S53 were reduced with 91%, 87%, and 64% ee, respectively (Scheme 50). Scheme 50. BINAP−Ru-Catalyzed AH of Cyclic Enol Ethers S51, S52, and S53

3.3. Summary

Once again, a large number of catalyst systems have been designed for the hydrogenation of enamines bearing endocyclic vinyl groups and an exocyclic nitrogen atom as well as exocyclic imines. Ru/Rh-P,P catalysts have been extensively employed for the asymmetric hydrogenation of the former. For example, a C3TunaPhos−Ru catalyst successfully reduced cyclic tetrasubstitued enamines with enantioselectivities dependent on ring size. A number of chiral N-Ac 2-aminotetralines and 3aminochromanes were successfully prepared with up to 96% ee using Rh−WingPhos catalysts, higher than other Rh/Ru−P,Pligand complexes. High enantioselectivities could also be obtained using a monodentate phosphoramidite ligand such as PipPhos. Alternative catalyst systems have provided yet higher enantioselectivities for related enamine susbtrates. For example, the highest enantioselectivity for the asymmetric hydrogenation of N-(1-benzyl-3,4-dihydronaphthalene-2-yl-acetamide was reported by Reek and co-workers using a supramolecular catalyst. In contrast to procedures utilizing Rh and Ru catalysis, Ircatalyzed asymmetric hydrogenation reactions for endocyclic enamines are less prevalent and employ phosphoramidite ligands. The asymmetric hydrogenation of exocyclic imines is more challenging than their endocyclic counterparts. Ru− TsDPEN, Ir−P,N-ligand, and Pd−P,P-ligand complexes provided good to excellent enantioselectivities for the reduction of specific susbtrates.

4.1.2. Ir-Catalyzed Asymmetric Hydrogenation. A handful of Ir-catalyzed reactions have also been reported. Pfaltz et al. reported the first Ir-catalyzed asymmetric hydrogenation of endocyclic enol ethers. Using the phosphinite−oxazoline ligand Cy-ThrePHOX (L67), 2-aryl- and 2-alkyl-4H-chromenes S53 were reduced to their corresponding products with 91−99% ee (Scheme 51).179 Scheme 51. ThrePHOX−Ir-Catalyzed AH of Endocyclic Enol Ethers S53

14792


Chemical Reviews

Review

Andersson and co-workers also reported the hydrogenation of endocyclic enol ethers using P,N-ligated iridium catalysts (Scheme 52).36 The structurally related ligands presented in Scheme 52. P,N-Ir-Catalyzed AH of Endocyclic Enol Ethers S54

Figure 37. Asymmetric hydrogenation of other cyclic vinyl ethers for the synthesis of chiral cyclic ethers.

were added to the terminus of the olefin to increase reactivity. Thus, the catalyst system [RuCl2(p-cymene)]2/L80 successfully reduced O-heterocyclic olefins S56 with 83−89% ee (Scheme 54).180,181

Scheme 52 were suitable for the hydrogenation of 5- and 6membered cyclic vinyl ethers using the reaction conditions shown. Ligand L13b reduced the 5-membered substrate S54a (n = 0) with >99% conversion and 90% ee. The 6-membered substrate 5-phenyl-3,4-dihydo-2H-pyran S54b (n = 1) was reduced with low enantioselectivity (64% ee) with the catalyst system derived from L13c, although enantioselectivity was improved to 81% ee using ligand L13d. Q.-L. Zhou and co-workers developed a straightforward and efficient synthesis of chiral O-heterocyclic carboxylic acids P55 starting from their corresponding unsaturated precursors S55 (Scheme 53).42 This was achieved using the chiral iridium

Scheme 54. N,N-Ru-Catalyzed ATH of α,α-Dicyanoolefins S56

Scheme 53. SIPHOX−Ir-Catalyzed AH of Unsaturated OHeterocyclic Carboxylic Acids S55

4.2.2. Ir-Catalyzed Asymmetric Hydrogenation. In 2007, Y.-G. Zhou and co-workers studied the performance of a number of phosphite−pyridine ligands for the Ir-catalyzed asymmetric hydrogenation of (2H-chromen-3-yl)methanols S57. Using the ligand L81 bearing an axially chiral phosphite group, the 6-membered cyclic ethers P57 were obtained with 85−94% ee (Scheme 55).182

complex of a spiro phosphine−oxazoline ligand SIPHOX (L18b). Only low catalyst loadings were required; however, a basic additive (Na2CO3) was needed to obtain the product with a high conversion. The optimized reaction conditions were applicable to the asymmetric hydrogenation of a number of different ring-sized O-heterocyclic carboxylic acids. Enantioselectivities were largely unaffected by the ring size; however, reduction of benzopyrans occurred with lower selectivity. The carboxylic acid functional group is required for the hydrogenation of the cyclic olefins using Ir and SIPHOX complexes, and the mechanism differs from that of the Ir-catalyzed asymmetric hydrogenation of unfunctionalized olefins; no migration of the double bond occurs during the hydrogenation as proved by isotopic labeling experiments.

Scheme 55. Ir-Catalyzed AH of (2H-Chromen-3yl)methanols S57

4.2. Via Asymmetric Hydrogenation of Other Cyclic Vinyl Ethers

Unsaturated cyclic ethers in which the olefin double bond is distant from the oxygen atom have been successfully reduced (Figure 37). However, these are also challenging substrates, and the double bond usually requires activation with electronwithdrawing groups in order to be reduced. 4.2.1. Ru-Catalyzed Asymmetric Hydrogenation. In 2004, Deng and co-workers reported an asymmetric transfer hydrogenation of tetrasubstituted cyclic olefins using ruthenium complexes derived from TsDPEN-type ligands. Cyano groups

The Andersson group also reported the asymmetric hydrogenation of 3,4-unsaturated cyclic ether substrates S58 using their P,N-ligated Ir catalysts.36 This was achieved by employing two types of ligands: the previously mentioned L13 bearing a thiazole moiety with a coordinating nitrogen atom and the more sterically demanding ligand L9 which possesses a bicyclic backbone and P(o-tol)2 donor. Six-membered cyclic substrates could be reduced with high enantioselectivities. 5,6-Dihydro-314793


Chemical Reviews

Review

catalyzed asymmetric transfer hydrogenation of conjugated olefins using a series of bisphosphine ligands. (R,R)-Me-DuPhos (L6) was found to be the best ligand for the reduction of such substrates in combination with a NiBr2(DME) catalyst precursor. Among these substrates, ethyl (E)-2-(chroman-4ylidene)acetate S61 was reduced with 93% ee and 98% yield (Scheme 59).183

phenyl-2H-pyran was hydrogenated with excellent enantioselectivity using L13c. The bulky ligand L9c was found to be better for 3-benzyl and 3-hydroxymethyl analogues. The 5-membered 3-phenyl-2,5-dihydrofuran was best reduced with ligand L13d; however, the enantioselectivity was much lower than those reported for 6-membered species (Scheme 56). Scheme 56. Ir-Catalyzed AH of 3,4-Unsaturated Cyclic Ethers S58

Scheme 59. DuPhos−Ni-Catalyzed ATH of Ethyl (E)-2(Chroman-4-ylidene)acetate S61

4.3. Summary

Cyclic enol ethers bearing an endocyclic vinyl group are challenging substrates to hydrogenate with high enantioselectivities, especially compared to nitrogen-containing heterocycles. This is most likely due to the greater electronegativity of the oxygen atom reducing the electron density of the vinyl bond. Therefore, reactivity is lower, and higher catalyst loadings are required. In spite of this, several different types of substrates have been reduced with high enantioselectivity. 2-Aryl- and 2-alkyl4H-chromenes and various dihydropyrans have been reduced with high ee using P,N-ligands and an Ir catalyst. For example, Andersson’s imidazole and thiazole P,N-chelating ligands and Zhou’s SIPHOX ligand have proved particually useful for the asymmetric hydrogenation of such substrates. Ir catalysts derived from these ligands could also be applied to the asymmetric hydrogenation of other cyclic vinyl ethers with broader substrate scope than other ligands. Interestingly, Ni has also been shown to be a potentially useful transition metal for hydrogenation reactions, as exemplified by the work of Zhou and co-workers.

Q.-L. Zhou and co-workers found that their spiro-chiral IrSIPHOX complexes Ir−L18 were compatible with unsaturated O-heterocyclic-2/3-carboxylic acids S59 (Scheme 57).42 A range Scheme 57. SIPHOX−Ir-Catalyzed AH of Unsaturated OHeterocyclic Carboyxlic Acids S59

5. SYNTHESES OF O-SUBSTITUTED CHIRAL CYCLOALKANES

of O-heterocyclic olefins could be reduced with high enantioselectivities using similar conditions to that used for the reduction of N-heterocyclic olefins. Generally, slightly lower ee’s were obtained for 5-membered O-heterocycles, and low catalyst loading could be used without causing any adverse effects on yield or selectivity. Additionally, Qu and co-workers also applied the ligand LalithPhos (L73) to the asymmetric hydrogenation of 1-aryl-3,4dihydronaphthalenes. Using the iridium catalyst system [Ir(L73)(cod)]BArF, 4-phenylchromene S60 was reduced with 86% ee (Scheme 58).167 4.2.3. Ni-Catalyzed Asymmetric Hydrogenation. Despite the advantages of Ni (lower toxicity, reduced costs, etc.), few hydrogenations of cyclic substrates have been reported. However, in 2015, J. (Steve) Zhou and co-workers reported a Ni-

5.1. Via Asymmetric Hydrogenation of Cyclic Enol Ethers/Esters Bearing an Exocyclic Oxygen Atom

Only a few methodologies concerning the hydrogenation of substrates bearing endocyclic vinyl groups and exocyclic oxygen atoms have been reported (Figure 38).

Figure 38. Asymmetric hydrogenation of cyclic enol ethers/esters bearing an exocyclic oxygen atom for the synthesis of O-substituted chiral cycloalkanes.

Scheme 58. LalithPhos−Ir-Catalyzed AH of 4Phenylchromene S60

5.1.1. Rh-Catalyzed Asymmetric Hydrogenation. In 1999, X. Zhang and co-workers reported one of the first methodologies for the hydrogenation of 3,4-dihydronaphth-1-yl acetates utilizing a Rh−(R,S,R,S)-Me-PennPhos catalyst (Rh− L40) (Scheme 60).184 The catalyst is generated in situ with MeOH being the best solvent for the reaction. Several cyclic enol acetates S62 were reduced with high enantioselectivities (98− 14794


Chemical Reviews

Review

Scheme 62. Origin of High Enantioselectivity185,186

Scheme 60. PennPhos−Rh-Catalyzed AH of Cyclic Enol Esters S62

99%). The PennPhos-based catalyst was considerably more effective for the reduction of these substrates than BINAP and DuPhos-derived catalyst systems. The Genari group was also able to use their Rh-based system using supramolecular ligands for the hydrogenation of enol acetates; however, the reduced products were obtained with poor enantioselectivities.155 5.1.2. Ir-Catalyzed Asymmetric Hydrogenation. Using a sequential Birch reduction and asymmetric Ir-catalyzed hydrogenation strategy, Andersson et al. were able to prepare a range of chiral 1,3-substituted cyclohexane intermediates P63. A number of 1,3-disubstituted cyclohexadienes S63 obtained from the Birch reduction of 1,3-aromatic compounds could be reduced with the Ir catalyst Ir−L13 described previously. For the majority of substrates, high trans-to-cis ratios (>70:30) were observed, and the trans isomers were hydrogenated with excellent enantioselectivities (Scheme 61).185,186

Scheme 63. PhTRAP−Ru-Catalyzed AH of a Cyclic Alkenyl Ether S64

5.2. Via Asymmetric Hydrogenation of Cyclic Ketones

5.2.1. Ru-Catalyzed Asymmetric Hydrogenation. The most commonly used catalyst for the asymmetric hydrogenation of cyclic ketones are P,P-Ru complexes and P,P/N,N-Ru complexes. The former are mainly employed in the hydrogenation of racemic α-substituted cyclic ketones via dynamic kinetic resolution, while the latter are mainly used to reduce simple benzocycloalkanones via asymmetric hydrogenation and ATH. Some challenging cyclic enones have also been chemoselectively reduced, Figure 39.

Scheme 61. Ir-Catalyzed AH of 1,3-Disubstituted Cyclohexadienes S63

Figure 39. Asymmetric hydrogenation of cyclic ketones for the synthesis of O-substituted chiral cycloalkanes.

5.2.1.1. Racemic α-Substituted Cyclic Ketones. A number of transition-metal-catalyzed asymmetric hydrogenation of cyclic ketones have been reported and provide a succinct pathway to the preparation of racemic α-substituted cyclic alcohols (Figure 40). The earliest of such reactions utilizing the ever versatile Ru− The ee of the preferred trans isomer is enhanced at the expense of the ee of the minor cis isomer. Reduction of the double bond on the wrong face producing I is quickly remedied by the rapid reduction of II to the cis isomer. Therefore, the cis isomer is obtained with poor ee, whereas the major trans isomer is obtained with high ee (Scheme 62).185,186 5.1.3. Ru-Catalyzed Asymmetric Hydrogenation. In 2012, Kuwano and co-workers developed a ruthenium catalyst derived from PhTRAP (L12) for the asymmetric hydrogenation of substituted naphthalenes. To confirm the sequential pathway for the reduction of 2-ethoxynaphthalene, a cyclic alkenyl ether S64 was hydrogenated with 93% ee (Scheme 63).187 The hydrogenation was conducted using 10 mol % of additive TMG (1,1,3,3-tetramethylguanidine) under 50 atm hydrogen pressure and at 100 °C.

Figure 40. Asymmetric hydrogenation of racemic cyclic α-substituted cyclic ketones for the synthesis of O-substituted chiral cycloalkanes via dynamic kinetic resolution.

BINAP catalyst was reported by Noyori and co-workers in 1989. Using a [RuCl((R)-BINAP)(benzene)]Cl complex and a dynamic kinetic resolution strategy, the racemic cyclic keto ester S65a was reduced to give trans-hydroxy ester P65a selectively (99:1 dr, 92% ee) (Scheme 64).188 This methodology was utilized by Achiwa and co-workers for the synthesis of new diphosphine ligands.189 14795


Chemical Reviews

Review

Scheme 64. BINAP−Ru-Catalyzed AH of a Racemic Cyclic Keto Ester S65a via Dynamic Kinetic Resolution

Scheme 65. P,P/N,N-Ru-Catalyzed AH of Racemic 2-ArylSubstituted Cycloalkanones S66 via Dynamic Kinetic Resolution

The racemic cyclic keto esters S65 have subsequently been used as model substrates in Ru-catalyzed asymmetric hydrogenations for testing the performance of various diphosphine ligands (TetraMe-BITIANP (L82),190,191 iPr-BPE (L83),192 TaniaPhos (L84),193−195 L85,196 BisP* (L86),197 ClickFerroPhos (L87)198,199). Good to excellent trans selectivities and enantioselectivities have been obtained (Figure 41). A related methodology was applied by Minnaard and Ortiz et al. for the synthesis of several drug candidates.200,201

Q.-L. Zhou and co-workers also succeeded in developing an efficient diphosphine ligand SDP (L91) similar to Noyori’s BINAP (in which the binaphthalene is replaced by a spiro backbone) (Figure 42) and applied this methodology (asymmetric hydrogenation of racemic 2-aryl-substituted cycloalkanones) to the total synthesis of synthetically useful compounds.204−207

Figure 42. SDP ligands.

In 2007, Q.-L. Zhou and co-workers applied the [RuCl2((R)SDP)((R,R)-DPEN)] catalyst to the asymmetric hydrogenation of 2-amino-substituted cycloalkanones S67 via dynamic kinetic resolution (Scheme 66). Substrates with different ring sizes were compatible with these reaction conditions. Chiral cyclic amino alcohols with high cis selectivities and excellent enantioselectivities could be obtained.208,209 In 2010, the same catalyst system [RuCl2((R)-SDP)((R,R)DPEN)] was successfully applied to the asymmetric hydrogenation of 2-aryloxy-substituted cycloalkanones S68 using dynamic kinetic resolution (Scheme 67).210 The corresponding chiral cyclic β-aryloxy alcohols were obtained with high cis selectivities and excellent enantioselectivities. Later, this methodology was applied in the total synthesis of (−)-galanthamine and (−)-lycoramine.211

Figure 41. P,P-Ligands used for Ru-catalyzed AH of racemic cyclic keto esters S65 via dynamic kinetic resolution.

In 1995, Noyori and co-workers improved the above BINAP− Ru system by using the more hindered Tol-BINAP (L8) and XylBINAP (L88) and by adding a second diamine ligand (usually DPEN (L89) or DAIPEN (L90)).202 In 2004, asymmetric hydrogenation of racemic 2-aryl-substituted cycloalkanones S66 was achieved through dynamic kinetic resolution (Scheme 65).203 Differing from 2-acyl-substituted substrates which showed trans selectivity, excellent cis selectivity was obtained for 2-aryl-substituted ketones. The excellent enantioselectivity (up to 99% ee) and activity (up to 100 000 S/C) also allowed for the application of this methodology to the preparation of two useful azacyclohexanols. 14796


Chemical Reviews

Review

Scheme 66. SDP/DPEN−Ru-Catalyzed AH of Racemic 2Amino-Substituted Cycloalkanones S67 via Dynamic Kinetic Resolution

Scheme 69. Ru Catalysts Used for AH of Cyclohexenones S70

Scheme 67. SDP/DPEN−Ru-Catalyzed AH of Racemic 2Aryloxy-Substituted Cycloalkanones S68 via Dynamic Kinetic Resolution

applied another Ru catalyst, [RuCl2((S)-BINAP)((R)-IPHAN)] (Ru−L1S/L92), to the hydrogenation of these two substrates with 80% and 96% ee, respectively.217 In 2011, Ikaria and coworkers developed an oxo-tethered Ru amido complex [RuCl(S,S)-DPEN-O-η6-arene)] (Ru−L93) and applied it to the transfer hydrogenation of S70a. Using a formic acid/triethylamine azeotropic mixture as the hydrogen source, the product was obtained with 96% ee.218 In 2013, Santoro and co-workers reported an asymmetric hydrogenation of various ketones using ruthenium complexes of chiral tetradentate S,N,N,S-type ligands.219 In the presence of [Ru(2-Me-allyl)2(cod)], L94, and H2 in iPrOH, cyclic ketone S70b was hydrogenated with 95% ee. Using a combination of achiral DPEphos and BIDN ligands (L95a), Huang et al. successfully hydrogenated cyclic enones S70c (R1 = R3 = H, R2 = Ph) and S71 with excellent carbonyl selectivity and enantioselectivity (97% and 95% ee) (Figure 43). The transition state for the asymmetric hydrogenation likely involves the generation of a bugles-like chiral pocket which allows entry of the sterically hindered enone substrates.220

In 2013, three racemic 2-sulfonyl-substituted 1-tetralones and 1-indanone S69 were reduced by Wang and co-workers using a Ru-catalyzed asymmetric hydrogenation dynamic kinetic resolution (Scheme 68). Using the well-established ruthenium Scheme 68. TsDPEN−Ru-Catalyzed AH of Racemic Cyclic βKeto Sulfonamides/Sulfones S69 via Dynamic Kinetic Resolution

complex [Ru(OTf)((R,R)-TsDPEN)(p-cymene)] (Ru− L29R), the reduced products were obtained with very high diastereoselectivities (all >99:1) and excellent ee’s (all 98%).212 5.2.1.2. Cyclic Enones. After the discovery of the carbonylselective hydrogenation of cyclohexenone S70a utilizing a P,P/ N,N-Ru catalyst system,213 Noyori and co-workers developed an enantioselective version of this reaction (Scheme 69). The catalyst system Ru−L8/L89S formed from racemic RuCl2(TolBINAP)(dmf)n, (S,S)-DPEN, and KOH in a 7:1 mixture of 2propanol and toluene was able to selectively hydrogenate cyclohexenone S70b in 100% yield and with 95% ee.214,215 Similar reaction conditions were utilized for the quantitative asymmetric hydrogenation of (R)-carvone.216 Later, the group

Figure 43. Ru-catalyzed AH of cyclohexenones S70c and S71. 14797


Chemical Reviews

Review

experimental results, a combined hydrogenation and transfer hydrogenation mechanism was proposed.

Glorius and co-workers applied chiral NHC ligands to the Rucatalyzed sequential asymmetric hydrogenation of flavones (R1 = Ar) and chromones (R1 = Alk) S72. Using a ruthenium complex consisting of ligand precursor (R,R)-SINpEt-HBF4 (L96-HBF4), flavanols and chromanols P72 were synthesized with up to 98% ee (Scheme 70).221 An α-methyl-substituted substrate was also hydrogenated to its respective product but with only 62% ee and 8.3:1 dr.

Scheme 72. TsDPEN−Ru-Catalyzed ATH/AH of meso-Epoxy Cyclic Diketones S74 via Desymmetrization

Scheme 70. NHC−Ru-Catalyzed Sequential AH of Flavones and Chromones S72

In addition to catalysts developed by Noyori et al., a number of other ligands have been used in conjunction with Ru catalysts in asymmetric transfer hydrogenation reactions, in particular, those derived from diamines and amino alcohols (Figure 44). Wills’

5.2.1.3. Benzocycloalkanones. (a) Asymmetric Transfer Hydrogenation (ATH). Early studies concerning Ru-catalyzed asymmetric hydrogenations of simple cyclic ketones S73 were reported by Noyori and co-workers in 1996 using the TsDPEN− Ru complex Ru−L29. A formic acid and triethylamine mixture was utilized as the hydrogen resource to give the desired chiral alcohols with 82−99% ee (Scheme 71).222 Scheme 71. TsDPEN−Ru-Catalyzed ATH of Benzocycloalkanones S73

Figure 44. Ligands and catalysts used for Ru-catalyzed ATH of benzocycloalkanones S73.

group is the most active in this area. In 1997, they reported a transfer hydrogenation of ketones using amino alcohol ligand L97.224 Using the ruthenium catalyst precursor [RuCl2(pcymene)]2 in conjunction with L97 and KOH in propan-2-ol, ketone S73b and S73c could be hydrogenated with 98% and 81% ee, respectively. In 2004, the same group reported the use of “tethered” ruthenium catalysts for asymmetric transfer hydrogenation reactions. Ru complex Ru−L98, in the presence of formic acid/Et3N in propan-2-ol, was able to hydrogenate S73a and S73b with 84% and 98% ee, respectively.225 In 2011, the proline-functionalized 1,2-diphenylethane-1,2diamine ligand L99 was successfully employed in the reduction of the previously mentioned benzocycloalkanones (Figure

In 2016, W. Zhang and co-workers studied the enantioselective reduction of meso-epoxy cyclic diketones S74 via asymmetric desymmetrization. Using a [RuCl(L29R)(p-cymene)] catalyst and EtOH/H2 as a combined hydrogen source, a series of chiral cis-epoxy naphthoquinols possessing three contiguous stereocenters P74 were successfully hydrogenated with excellent enantioselectivities (96−99% ee) and diastereoselectivities (8/1−15/1) (Scheme 72).223 On the basis of the 14798


Chemical Reviews

Review

44).226 Using a [RuCl2(p-cymene)]2 catalyst precursor in the presence of L99 and NaHCO2 in H2O, chiral alcohols P73a and P73b could be obtained with up to 91% and 98% ee via transfer hydrogenation. The 7-membered ketone S73d was also reduced with 89% ee. The presence of heteroatoms did not significantly reduce enantioselectivity (S73e, S73f); however, substituents at the 7 and 6 positions of the tetralone did cause a slight decrease in enantioselectivity. A furyl-fused substrate was also reduced with 85% ee. Wills’ group was also able to apply tethered Ru−amine complex Ru−L100 to the asymmetric transfer hydrogenation of hindered derivatives of S73b and S73c.227,228 Hindered substrates, especially the spiro derivative, showed higher enantioselectivities (99% ee) than unsubstituted S73c (88% ee), suggesting that the substituents reinforce the enantiocontrol of the reaction by the catalyst.227 As the substituent group gets larger, ee increases. An additional CH/π interaction between the Ru−η6-arene and the alkene or second aromatic ring may be responsible for the high enantioselectivities of the substrates. This phenomenon is further evidenced by the higher ee for the reduction of spiro substrates bearing a benzo group compared to the corresponding substrate without. The importance of an unsaturated functional group directing the asymmetric transfer hydrogenation can also be observed. Other tethered Ru complexes such as L101 have also shown to be useful for the reduction of benzocycloalkanone substrates. For example, substrates S73b and S73e were both transfer hydrogenated with 99% ee.229 Other groups have reported the reduction of similar substrates. Pericàs et al. employed proline-derived aminotriazole ligands L102 for the asymmetric transfer hydrogenation of various cyclic ketones.230 2-Triazolyl- and 2-triazolylmethylpyrrolidines were readily prepared from L-proline and L-trans-4-hydroxyproline. 1Tetralone S73b and 1-chromanone S73e were reduced with excellent enantioselectivities (94% and >99% ee, respectively) but poor conversions in the presence of [RuCl2(p-cymene)]2/ L102 catalyst system and KOH in iPrOH solvent. Xu and coworkers used the unsymmetrical vicinal diamine L103 as a ligand for the Ru-catalyzed asymmetric transfer hydrogenation of S73b with high enantioselectivity (97% ee).231 The use of O-tethered N,N-Ru−arene complexes has also been reported by Ikariya and co-workers. Chiral oxo-tethered ruthenium catalysts Ru−L93 (R = Ts or Ms) were prepared and applied to the asymmetric transfer hydrogenation of cyclic ketones to obtain the related chiral alcohols P73d and P73e with high enantioselectivities (98% and >99% ee, respectively).218 (b) Asymmetric Hydrogenation (AH). The first asymmetric hydrogenation of simple cyclic ketones was also reported by the Noyori group. In 2004 they reported a procedure for the reduction of 1-tetralones and analogues.217 Using the ruthenium complexes Ru−L1S/L92a, the cyclic ketones could be reduced quantitatively with up to 99% ee (Figure 45). The most suitable catalyst system for the substrate is dependent upon the substrate’s substitution pattern. For aryl-fused cyclohexanones S73b, substrates were obtained with 92−99% ee. Substrate S75 bearing a single methyl substituent at the α position only afforded the desired product with 87% ee. Noyori and co-workers also discovered that some complexes such as [RuCl2((S)-TolBINAP)(PICA)] (Ru−L8S/N,N) were capable of hydrogenating benzocycloalkanones S76 possessing double methyl groups at the α position with good to excellent enantioselectivities (Figure 45).232 The enantioselectivity for simple cyclohexanone

Figure 45. Pioneering work on Ru-catalyzed AH of benzocycloalkanones.

S77 (84% ee) was lower than that of benzocyclohexanone S76b (98% ee). Following this pioneering work, several other P,P/N,N-Ru catalyst systems (Ru−L104/L92b,233 Ru−L20/L105,234 Ru− P,P/L95b and its analogue235,236) were developed and applied to the asymmetric hydrogenation of benzocycloalkanones (Figure 46).

Figure 46. Ru catalysts used for AH of benzocycloalkanones S73.

In 2011, Ohkuma and co-workers proposed a mechanism for the asymmetric hydrogenation of cyclic ketones using P,P/N,NRu ruthenabicyclic complexes (Scheme 73).237 In an alcoholic solvent, X− dissociates from the precatalyst to give the cationic species I. Molecular hydrogen species II is formed via reaction of hydrogen with I. The rate-determining step is basic heterolysis of H2 to give the active Ru−H complex III. The ketone substrate is reduced by III to give the alcohol and the amide−Ru complex IV, which is in rapid equilibrium with I and the alkoxide complex V. I is the preferred species in polar alcohol solvents. The Ru−H species III is formed via reaction of the amide complex IV (formed also by treatment of the precatalyst with a strong base) with hydrogen when a less polar aprotic solvent was used for the hydrogenation. Using similar methodology to that described above, Rodriguez and co-workers developed a series of chiral bishydrobenzooxaphosphole BIBOP/diamine−Ru complexes Ru−L106 for the 14799


Chemical Reviews

Review

the opposite side of the complex, with the arene unit oriented away from the bulky tert-butyl group of the ligand. The R configuration of the secondary alcohol is generated via hydride transfer to the Si face of the prochiral ketone. Other frequently used ruthenium catalyst systems for asymmetric hydrogenation of benzocycloalkanones are N,N-Ru complexes (Figure 48). In 2008, Ikaria and co-workers developed

Scheme 73. Mechanism of Ru-Catalyzed AH with Bicyclic Diamine Complexes237

Figure 48. Ligands and complexes used for Ru-catalyzed AH of benzocycloalkanones S73.

triflamide-tethered Ru(TsDPEN)(arene) complex Ru−L107 and applied it to the asymmetric hydrogenation of S73a and S73b. These substrates were reduced with 95% and 98% ee, respectively.239 In 2011, they developed an additional oxotethered ruthenium complex Ru−L93 to hydrogenate benzocycloalkanones S73a, S73b, and S73e with 98%, >99%, and 99% ee, respectively.218 In 2012, Wills and co-workers applied Ru−L101 to this reaction to prepare the chiral cyclic alcohols P73a, P73b, and P73e with 98%, 99%, and 99% ee, respectively.228,229 In addition to P,P/N,N-Ru and N,N-Ru complexes, several other types of ruthenium catalysts have also been used in these reactions (Figure 48). Kitamura and co-workers utilized a N,N,N,N-Ru complex, (R)-R-BINAN-R′-Py (L108), for the hydrogenation of the cyclic ketones.240 Using a [Ru(2-Meallyl)2(cod)] catalyst precursor in the presence of tBuOK in iPrOH under 50 atm H2 pressure, cyclic substrates S73a, S73b, and S73c could be reduced with 93%, 99%, and 94% ee, respectively. P,N-Type ligands have also been employed to the asymmetric hydrogenation of various cyclic ketones (Figure 48). In 2012, W. Zhang and co-workers successfully utilized a C2-ruthenecyl phosphinooxazoline ligand RuPHOX (L109), in the presence of a Ru(PPh3)3Cl2 catalyst precursor, for the asymmetric hydrogenation of 1-indanone S73a and 1-tetralone S73b in quantitative conversions and >99% ee.241 Differing from the work published by Hidai and Umeura et al. using a RuCl2(PPh3)(oxazolinylferrocenylphosphine) catalyst,242 this reaction proceeds via hydrogenation with H2 rather than via asymmetric transfer hydrogenation. Santoro and co-workers reported an asymmetric hydrogenation of various ketones using chiral tetradentate S,N,N,Stype ligands and Ru catalysis.219 In the presence of [Ru(2-Meallyl)2(cod)], L96, and H2 in iPrOH, 1-tetralone S73b was hydrogenated with 95% ee. 5.2.2. Ir-Catalyzed Asymmetric Hydrogenation. Although less commonly used for the hydrogenation of cyclic ketones, Ir complexes have shown promise for several types of substrates. In 1993, Takaya and co-workers reported the first example of an Ir-catalyzed asymmetric hydrogenation of cyclic ketones. Using a new catalytic system consisting of [Ir(BINAP)(cod)]BF 4 and a mixed P,N-donor ligand, bis(o-(N,N-

asymmetric hydrogenation of cyclic ketones, in particular, heteroaryl-fused cycloalkanones.238 Screening of a series of diamine species led to diamines DPEN being the most reactive ligands. Using Ru complexes Ru−L106 in the presence of H2, and tBuOK in iPrOH, a number of cyclic ketones could be reduced with excellent enantioselectivities and yields (Figure 47). Complete inversion of stereoselectivity could be obtained

Figure 47. BIBOP/N,N-Ru-catalyzed AH of benzocycloalkanones.

using either of the complexes. The enantioselectivity induced by the Ru complexes can be explained as follows. The complex derived from precatalyst L106 containing the DPEN ligand is C2 symmetrical. The more sterically demanding side of the prochiral ketone is positioned away from the arene of the ligand framework by the axial hydrogen on the amine. This allows for hydride delivery to the Re face of the ketone, giving the S enantiomer. The Ru hydride complex derived from L106 positions the ketone on 14800


Chemical Reviews

Review

5.2.3. Rh-Catalyzed Asymmetric Hydrogenation. Compared to Ru and Ir catalysis, Rh catalysis is seldom used for the asymmetric hydrogenation of cyclic ketones (Figure 50).

dimethylamino)phenyl)-phenylphosphine, the 5- and 6-membered benzocycloalkanones S73a and S73b were reduced with up to 86% and 95% ee, respectively. The oxa and thio substrates S73e/f were also subjected to the reaction conditions and gave slightly lower enantioselectivities. A similar ligand, H8-BINAP (L110), was used for the hydrogenation of β-thiacycloalkanones S78 to give the desired products with up to 82% ee (Figure 49).243

Figure 50. Ligands and complexes used for Rh-catalyzed ATH of cyclic ketones.

Himeda and co-workers first utilized a rhodium complex for the asymmetric transfer hydrogenation of cyclic ketones. Using a Schiff base L112 as the ligand with [RhCl2(Cp*)]Cl as the catalyst precursor, cyclohexanone S77 was reduced with low yield and enantioselectivity (31% ee).248 The first truly promising result using rhodium catalysis for this reaction was reported by Wills and co-workers in 2006. A tethered Ru complex, Ru−L113, successfully hydrogenated 1-tetralone S73b with 100% conversion and 99% ee.249 5.2.4. Fe-Catalyzed Asymmetric Hydrogenation. Despite the advantages of iron for use in catalytic reactions (cost effectiveness, abundance, etc.), Fe catalysis has not been commonly employed for the reduction of cyclic ketones. In 2015, an example of Fe catalysis for the asymmetric hydrogenation of cyclic ketones was reported. Using a chiral (cyclopentadienone)iron complex Fe−L114, derived from (R)BINOL in the presence of a Me3NO activator and H2 (30 bar) in a iPrOH/H2O solvent mixture, the cyclic ketones S73a, S73b, and S73c were reduced to their respective cyclic alcohols with 59%, 77%, and 13% ee (Figure 51).250 The enantioselectivities decrease with increasing steric hindrance around the ketone functionality.

Figure 49. P,P-Ir-catalyzed AH of cyclic ketones S73 and S78.

Later, the Ir-TsDPEN-type complexes and aminophosphine ligands were applied by Wills and co-workers to the hydrogenation of 1-indanone S73a and 1-tetralone S73b. However, the reduced products were obtained with only moderate enantioselectivities.244,245 In 2010, Q.-L. Zhou and co-workers reported the chemoselective asymmetric hydrogenation of α,β-unsaturated ketones S79 using Ir complexes of chiral spiro aminophosphine ligand L111 (Scheme 74).246,247 β-Arylmethylene cyclohexanols P79 Scheme 74. Ir-Catalyzed AH of α,β-Unsaturated Ketones S79

Figure 51. Fe-catalyzed AH of cyclic ketones S73.

5.3. Summary

Similar to cyclic enol ethers bearing an endocyclic oxygen atom, cyclic enol ethers possessing an exocyclic oxygen atom are difficult to hydrogenate; thus, substrate scope is rather limited. However, 3,4-dihydronaphth-1-yl acetates have been reduced with high ee using Rh and Ru complexes derived from P,Pchelating ligands such as Rh−PennPhos and Ru−PhTRAP. In contrast to the hydrogenation of cyclic enol ethers, the asymmetric hydrogenation of cyclic ketones has been extensively

were prepared in high yields and with excellent enantioselectivities. Electron-donating and electron-withdrawing substituents on the phenyl ring of the substrate had no pronounced effect on reactivity or enantioselectivity. Five- and seven-membered substrates could also be hydrogenated with high enantioselectivities. 14801


Chemical Reviews

Review

1,5-benziothiazepine derivatives. In the presence of a [Ru(2-Meallyl)2(cod)] catalyst precursor and (R,R)-SINpEt-HBF4 (L96HBF4) preligand, a series of unsaturated N-methyl-protected 1,5benzothiazepinones S81 was reduced with 86−95% ee (Scheme 76).251 The reaction conditions were amenable to substrates

studied. The most common catalyst systems employ Ru complexes as the active catalyst species. Racemic ketones bearing α-carboxyl group can be reduced with high enantioselectivities using P,P-chelating ligands such as BINAP, (R)-TetraMeBITIANP, and (S,S)-iPr-BPE. Conversely, Noyori’s Ru− TsDPEN catalyst and derivatives exhibit excellent catalytic behavior for the asymmetric transfer hydrogenation of benzocycloalkanones. The most versatile P,P-N,N-Ru catalyst system proved to be suitable for asymmetric hydrogenation of a broad range of cyclic ketones. Only a handful of Ir, Rh, and Fe catalysts have been utilized for the asymmetric hydrogenation of cyclic enones, with Q.-L. Zhou and co-workers’ spiro aminophosphine ligand showing its versatility in the preparation of βarylmethylene cyclohexanols.

Scheme 76. NHC−Ru-Catalyzed AH of Cyclic Vinyl Sulfanes S81

6. SYNTHESIS OF CHIRAL CYCLIC SULFANES, SULFONES, AND SULFAMIDES Only a handful of procedures have been reported for the asymmetric hydrogenation of sulfur-containing heterocycles despite their prevalence in nature (Figure 52). However, the

bearing electron-donating and electron-withdrawing substituents on the aminothiophenol ring, with the former providing slightly higher enantioselectivities. A N-4-methoxybenzyl-protected substrate could also be reduced with high ee (93%). The aromatic substituent of the vinyl thioether bond could also be varied, with high ee’s being obtained irrespective of the electronic nature or position of substituents on the aromatic ring. 6.1.2. Ir-Catalyzed Asymmetric Hydrogenation. Pfaltz and co-workers reported the first Ir-catalyzed asymmetric hydrogenation of cyclic vinyl thioethers. Using an oxazolinebased P,N-ligand Cy-ThrePHOX (L67), 2-phenyl-4H-chromenes S82 was reduced to P82 with 73% conversion and 91% ee (Scheme 77).179 Scheme 77. ThrePHOX−Ir-Catalyzed AH of a Cyclic Vinyl Sulfane S82

Figure 52. Asymmetric hydrogenation for the synthesis of chiral cyclic sulfanes, sulfones, and sulfamides.

reduction of such species has been achieved using Ru and Ir catalysis. Cyclic sulfonylimines represent the largest group of sulfur heterocycles that can be reduced with transition-metal catalysts.

6.2. Asymmetric Hydrogenation of Cyclic Vinyl Sulfones

The Andersson group utilized their chiral oxazoline and thiazole ligands for the asymmetric hydrogenation of unsaturated cyclic sulfones (Scheme 78).252 Thiazole ligand L9c was found to be the best ligand for these reactions in the presence of an [Ir(cod)2]BArF catalyst precursor. β-Substituted β,γ-unsaturated seven-membered cyclic sulfones were hydrogenated to their corresponding products with excellent enantioselectivities. Aryl substituents bearing para groups had little influence on enantioselectivity; however, an o-methyl substituent gave lower conversion. A methyl-substituted sulfone was best reduced using ligand L9d. Ir complexes derived from ligand L9c also reduced sulfones of different ring sizes. Six- and seven-membered sulfones were reduced with high conversions and enantioselectivities. Ligand L9b provided the best ee and conversion for the reduction of five-membered sulfones. The reduced products were subsequently converted to chiral allylic and homoallylic compounds via a Ramberg−Backlund rearrangement.

6.1. Via Asymmetric Hydrogenation of Cyclic Vinyl Sulfanes

6.1.1. Ru-Catalyzed Asymmetric Hydrogenation. Deng and co-workers successfully applied Ru−TsDPEN-type complexes (Ru−L80) to the asymmetric transfer hydrogenation of 4methylenethiochromanones.180,181 The methylene group is activated via CN electron-withdrawing groups. Using the catalyst conditions described previously for the asymmetric transfer hydrogenation of 4-methylenechormans, the sulfur derivate S80 was reduced in 99% yield and with 82% ee, thus showing the diversity of Noyori-type catalysts to the reduction of heterocyclic substrates (Scheme 75). Recently, Glorius and co-workers employed N-heterocyclic carbine (NHC) ligands to the Ru-catalyzed preparation of chiral Scheme 75. Ru-Catalyzed ATH of Cyclic Vinyl Sulfanes S80

6.3. Asymmetric Hydrogenation of Cyclic Sulfimides

6.3.1. Ru-Catalyzed Asymmetric Hydrogenation. The earliest asymmetric hydrogenations of cyclic 2-alkyl-substituted cyclic benzosulfimides S84 were reported using Ru−BINAP catalysts.253 However, this methodology was quickly supplanted by Ru-catalyzed asymmetric transfer hydrogenation based on 14802


Chemical Reviews

Review

methylbenzo[d]isothiazole 1,1-dioxide S84 (Alk = Me) with 94% ee.174 Later in 2007, Y.-G. Zhou and co-workers studied the asymmetric hydrogenation of various N-sulfonylimines using Pd catalysis and P,P-chelating ligands (Figure 53).259 Cyclic N-

Scheme 78. P,N-Ir-Catalyzed AH of Cyclic Sulfones S83

Figure 53. P,P-Pd-catalyzed AH of cyclic N-sulfonylimines and enesulfonamides.

sulfonylimines S84 were successfully reduced using a Pd(OCOCF3)2/(S)-SegPhos (L35) catalyst system with high selectivities. Better reactivity and selectivity were observed when the ligand (S,S)-f-Binaphane ligand (L24) was used in place of (S)-SegPhos.260,261 The Pd(OCOCF3)2/(S,S)-f-Binaphane catalyst system reduced 5-membered N-sulfonylimines with up to 98% ee. Interestingly, this catalyst system was also able to successfully reduce 6-membered enesulfonamides and exocyclic-enesulfonamides via N-sulfonylimine intermediates.262,263 Y.-G. Zhou and co-workers also applied (SP,RC)-TangPhos (L4) to the Pd-catalyzed hydrogenolysis of N-sulfonyloxaziridines (Scheme 80).264 The reaction proceeds through breakage of the N−O bond and formation of a sulfonylimine in the presence of a Bronsted acid. In this case, L-camphorsulfonic acid (L-CSA) was found to be the best acid for this process. NSulfonyloxaziridines bearing aromatic groups could be reduced with excellent enantioselectivities (90−97% ee) irrespective of

TsDPEN-type ligands.254−256 For example, Fan and co-workers subjected 2-aryl/alkyl-substituted cyclic benzosulfimides S84 to hydrogenation using complex [RuOTf((R,R)-MsDPEN)(pcymene)] (Ru−L32). The reduced products were obtained with modest to good enantioselectivities (Scheme 79).255 Scheme 79. MsDPEN−Ru-Catalyzed AH of Cyclic NSulfonylimines S84

Scheme 80. TangPhos−Pd-Catalyzed AH of Cyclic NSulfonylimines S84 in-Situ Generated from NSulfonyloxaziridines

6.3.2. Rh-Catalyzed Asymmetric Hydrogenation. Few hydrogenations of N-sulfonylimines with Rh catalysis have been reported, and those that have are generally not as effective as those based on ruthenium catalysts. Products resulting from the reduction of 2-alkyl- and 2-aryl-substituted substrates have been obtained with 68−81% ee.80,257,258 6.3.3. Pd-Catalyzed Asymmetric Hydrogenation. In 2006, X. Zhang and co-workers applied a (SP,RC)-TangPhos-Pd catalyst (Pd−L4) to the asymmetric hydrogenation of 314803


Chemical Reviews

Review

the position or electronic character of the substituent on the aromatic ring. 6.3.4. Ni-Catalyzed Asymmetric Hydrogenation. Recently, Ni-catalyzed asymmetric transfer hydrogenations of cyclic N-sulfonylimines have been reported by J. (Steve) Zhou and coworkers. Using formic acid/Et3N as the hydrogen source, an asymmetric transfer hydrogenation of cyclic 2-methyl- and 2phenyl-substitued N-sulfonylimines S84 has been developed, with the corresponding products being obtained in 96% and 93% ee, respectively, in the presence of 5 mol % of [NiCl2(dme)] catalyst and 6 mol % of (R)-Ph-BPE ligand L115 (Scheme 81).265

Figure 54. Asymmetric hydrogenation of cyclic unsaturated carbonyl compounds for the synthesis of chiral cyclic carbonyl compounds.

Scheme 81. Ph-BPE−Ni-Catalyzed ATH of Cyclic NSulfonylimines S84

Scheme 82. P,P-Ru-Catalyzed AH of Cyclic Enones S85 and S86

6.4. Summary

The asymmetric hydrogenation of sulfur-containing heterocycles represents the smallest area of research in this field. Sulfur possesses the ability to poison the catalyst, thus making reduction of sulfur-heterocycles difficult. Cyclic sulfimides are the most amenable substrates of this type to asymmetric hydrogenation with transition-metal catalysts. The versatile Ru−TsDPEN complex is capable of reducing several sulfimides with high enantioselectivities. Success with other transition metals (Rh, Pd, and Ni) is achieved using P,P-chelating ligands such as SegPhos, f-Binaphane, TangPhos, and in the case of Ni Ph-BPE.

L20), the corresponding products P85 and P86 were obtained with poor to modest enantioselectivities. In 1992, Takaya and co-workers reported the hydrogenation of several cyclic enones and lactones bearing a vinyl group using BINAP−Ru complexes (Ru−L1S). The reduced products were obtained with good enantioselectivities (Figure 55).268,178 Cyclic enones bearing exocyclic vinyl groups are easier to hydrogenate than their endocyclic equivalents. Later in 2013, Koert and coworkers applied Takaya’s methodology to total synthesis.269

7. SYNTHESIS OF CHIRAL CYCLIC CARBONYL COMPOUNDS 7.1. Via Asymmetric Hydrogenation of Cyclic Unsaturated Carbonyl Compounds

Chiral cyclic carbonyl compounds can be prepared via the hydrogenation of cyclic unsaturated carbonyl substrates bearing CC bonds (Figure 54). Only a few methodologies have been reported for the asymmetric reduction of such species, especially for conjugated substrates. Obtaining products with high enantioselectivities has proved challenging. 7.1.1. Ru-Catalyzed Asymmetric Hydrogenation. The Ru-catalyzed hydrogenation of cyclic enones has been reported; however, most methodologies only give the corresponding products with poor enantioselectivities. In 1986, Simonneaux and co-workers reported the first studies concerning the asymmetric hydrogenation of cyclic enones S85 and S86 (Scheme 82).266,267 Utilizing diphosphine ruthenium complexes [HRuCl(TBPC)2] (Ru−L116) and [Ru2Cl4(DIOP)3] (Ru−

Figure 55. BINAP−Ru-catalyzed AH of cyclic unsaturated carbonyl compounds S85−S92. 14804


Chemical Reviews

Review

Scheme 83. BINAP−Ru-Catalyzed AH of 3-Alkylidene-2-piperidones S93

In 1995, Chung and co-workers reported the hydrogenation of alkyllidine piperidones S93 with good enantioselectivities using a [RuCl2((S)-BINAP)]2/NEt3 catalyst. Selectivity is highly dependent on the substituent at the nitrogen atom (Scheme 83).270 Similar P,P-Ru complexes, [RuCl((R or S)-BINAP)(pcymene)]Cl (Ru−L1) and [Ru(OAc)2((R)-3,5-tBu-MeO-BIPHEP)] (Ru−L117), have been applied to the asymmetric hydrogenation of derivatives of S87 (S87c,d). The corresponding products were obtained with excellent enantioselectivities (Figure 56).271,272 The analogous P,P-Rh complexes, [Rh((R or

Scheme 84. Rh-Catalyzed Chemoselective AH of 3-Alkyl-6isopropylidene-2-cyclohexen-1-ones S94

were found to be a suitable combination for the reduction of S85 with up to 90% ee (Figure 57).

Figure 56. Unsaturated lactones S87c and S87d used in Ru- and Rhcatalyzed AH.

S)-BINAP)(cod)]ClO4 (Ru−L1) and [RhCl(cod)]2/(S)TMBTP (Rh−L118), were also applied to the asymmetric hydrogenation of S87c and S87d with high enantioselectivities.271,272 7.1.2. Rh-Catalyzed Asymmetric Hydrogenation. Mashima and co-workers reported the asymmetric hydrogenation of various cyclic enones using SegPhos ligands.273 DTBM-SegPhos ligand L119 proved to be the most efficient for the selective hydrogenation of 3-alkyl-6-isopropylidene-2-cyclohexen-1-ones S94 (Scheme 84). The addition of a halogen source to the cationic rhodium complex has a large effect on selectivity, giving rise to P94 as the major product. The isopropylidene moiety is important for selectivity and can subsequently be removed to give the corresponding β-substituted ketones. The higher enantioselectivity obtained via use of a (S)-DTBM-SegPhos L119S compared to BINAP (L1), Tol-BINAP (L8), and SegPhos (L35) is thought to arise from the narrower dihedral angle in the chiral backbone and the bulkier substituents on the diarlyphosphine moiety. Jaekel and co-workers applied a typical hydroformylation catalyst to the asymmetric hydrogenation of cyclic enones.274 After screening of several diphosphine ligands, (R,R)-ChiraPhos (L120), together with a [Rh(acac)(CO)2] catalyst precursor

Figure 57. ChiraPhos−Rh-catalyzed AH of cyclic enones S85.

Ulgheri and co-workers reported the application of a [RhCl(cod)]2/TMBTP (L118) or ChiraPhos (L120) catalyst system to the asymmetric hydrogenation of a coumarin derivative for the synthesis of (S)- and (R)-tolterodine.275 In 2012, Wills and co-workers reported the asymmetric hydrogenation of α,β-unsaturated cyclic imides S95 using P,P-Rh complexes. [Rh((R,R)-Et-DuPhos)(cod)]BF4 ((Rh−L11)) proved to be the most suitable for the reduction giving the product P95 selectively with 89% conversion and 95% ee. A [RhCl(cod)]2/TaniaPhos (Rh−L84) catalyst system gave the reduced product P95′ with 100% conversion and 98% ee (Scheme 85).276 7.1.3. Ir-Catalyzed Asymmetric Hydrogenation. Encouraged by Chung’s work, Yue and Nugent prepared 3alkylpiperidines P96 via the hydrogenation of N-unsubstituted 3alklidene-2-piperidones S96 (Scheme 86).277,278 After the screening of 32 chiral phosphine ligands and 8 metal precursors, an Ir−BDPP (Ir−L19) catalyst system was chosen as the most promising metal−ligand complex. The reaction conditions shown in Scheme 86 were amenable to a number of N14805


Chemical Reviews

Review

Scheme 85. P,P-Rh-Catalyzed AH of α,β-Unsaturated Cyclic Imides S95

Scheme 86. BDPP−Ir-Catalyzed AH of α,β-Unsaturated Lactams S96

Scheme 87. Ir-Catalyzed AH of α-Substituted Cyclic Enones S97

unsubstituted 3-alklidene-2-piperidones substrates. Enantioselectivity was lower for pyrrolidinone substrates (n = 1) and alkylidenecaprolactam derivatives (n = 3). Substitution at the nitrogen with a methyl group dramatically reduced enantioselectivity; however, this procedure is an attractive approach for the large-scale and efficient synthesis of enantiopure 3-alkylpiperidines. In 2008, Bolm279 and Hou280,170 reported the hydrogenation of α-substituted cyclic enones using Ir−phosphine−oxazoline complex Ir−L121 and Ir−L75 and phosphine−sulfoximine complex Ir−L122 (Scheme 87). A series of cyclic substrates S97 could be hydrogenated, regardless of ring size or the position of the aryl ring. Lower enantioselectivities were observed for alkylsubstituted tetralone derivatives. In 2010, W. Zhang and co-workers utilized a new phosphine− oxazoline ligand, which possesses an axially unfixed biphenyl backbone, for the asymmetric hydrogenation of unsaturated cyclic enones. Coordination of ligand BiphPHOX (L123) to [Ir(cod)Cl]2 results in the formation of only one diastereomer. This complex was successfully applied to the asymmetric hydrogenation of a number of α-substituted cyclic enones S97, with quantitative conversions and up to excellent enantioselectivities (Scheme 88).281,282 Unlike the Ir catalyst system reported by Bolm et al., enantioselectivity decreased with increasing ring size, including for tetralone derivatives. The catalytic system could further be extended to the asymmetric hydrogenation of α,β-unsaturated lactones S98 and lactams S96 bearing an exocyclic vinyl group. Substrates could be hydrogenated with enantioselectivities of up to 98% ee and with quantitative conversions depending on ring size; 6-membered ring lactones and lactams provided lower enantioselectivities than their 5-membered ring counterparts. The W. Zhang group developed a succinct asymmetric hydrogenation of α-alkylidene succinimides S99 using BiphPHOX ligand L123 (Scheme 89).283 Substituents on the oxazoline ring had a strong influence on enantioselectivity. Asymmetric hydrogenation of α-alkylidene succinimide (R1 = Bn, R2 = Ph) using chiral ligand L123 gave the desired product in quantitative yield and with 99% ee. Use of other phosphine−

oxazoline ligands gave low conversions and ee. Additionally, hydrogenation of the aforementioned alkylidene could be carried out under low H2 pressures in dichloromethane solvent. The optimized reaction conditions shown in Scheme 89 could be applied to a number of alkylidene substrates with excellent stereoselectivities. Lower enantioselectivities were obtained for substrates bearing an alkyl R2 group. A similar catalytic system was also successfully used for the preparation of C3monosubstituted oxindoles via the asymmetric hydrogenation of 3-substituted unsaturated oxindoles.282 W. Zhang, Gridnev, and co-workers carried out further experiments using NMR and DFT studies to deduce the mechanism of the asymmetric hydrogenation of exocyclic α,βunsaturated carbonyl compounds using an Ir−BiPhPHOX complex (Scheme 90).284 At −18 °C this complex exists as a 5:1 mixture of two diastereomers of a pentahydride complex (Ia,b) with three bridging hydride ligands. Analysis of NMR spectra taken directly after low-temperature hydrogenation showed a number of other species were present in solution, thus indicating the initial formation of several diastereomers of dinuclear Ir tetrahydrides II, in equilibrium with monomer solvate complexes III. Computational analysis showed that the 14806


Chemical Reviews

Review

According to computational calculations, the reaction mechanism consists of an Ir(I)−Ir(III)−Ir(I) cycle and the enantio-determining step of the reaction is the migratory insertion. The migratory insertion takes place in the catalyst/ substrate/hydride (CSH) complex with the CCHPh group positioned coplanar to the trans-P−Ir−H fragment. There are a total of four possible transition states for the asymmetric hydrogenation of (E)-3-benzylidenedihydrofuran-2(3H)-one (Figure 58). The difference in the stabilities of the transition

Scheme 88. BiphPHOX−Ir-Catalyzed AH of Unsaturated Cyclic Carbonyl Compounds

Figure 58. Possible pathways with the α-alkylidene lactone coordinated coplanar to the P-Ir-H moiety.

Scheme 89. BiphPHOX−Ir-Catalyzed AH of α-Alkylidene Succinimides S99

states of migratory insertion for the S pathways and R pathways regulates the order of enantioselection. For the R1 and R2 pathways, the steric hindrance between the substrate and one of the phenyl groups of the ligand prevents the coordination of the substrate to the metal centre. One of the S pathways is comparatively more stable than the other due to an additional hydrogen bonding interaction between the axial hydride and the carbonyl group of the substrate. Further computational calculations on other α,β-unsaturated carbonyl compounds reliably predicted the same stereoselectivity and are in accordance with the experimental results. Several other P,N-chelating ligands have also been shown to be efficient ligands for the Ir-catalyzed asymmetric hydrogenation of similar substrates (Figure 59). Andersson and co-workers

Scheme 90. Equilibrium of Dimers Found at Low Temperature290

formation of the dimers II is exogonic, and the structure of the major isomer corresponds well to the most stable structure calculated using computational studies. Further computational studies precluded the formation of a dimeric catalyst, and thus, the hydrogenation is thought to occur via monomeric dihydride complexes III. The formation of pentahydrides I from tetrahydride dimers III is also reversible.

Figure 59. P,N-Ir-catalyzed AH of cyclic unsaturated carbonyl compounds. 14807


Chemical Reviews

Review

enantioselectivities were obtained for products containing 5membered ring systems. Compared to the exocyclic α,β-unsaturated carbonyl compounds, the corresponding endocyclic substrates are often difficult to hydrogenate;280 therefore, only a few examples have been reported and most with low enantioselectivities.291−293 For example, Pfaltz and co-workers reported the Ir-catalyzed asymmetric hydrogenation of a limited number of maleic anhydrides S100. A complex derived from the NeoPHOX ligand L126 proved to be the best catalyst. The corresponding succinic anhydrides could be obtained in good yields and with relatively high enantioselectivities (Scheme 91).293

developed an efficient iridium complex (Ir−L9d) for the asymmetric hydrogenation of acyclic α,β-unsaturated esters, which could also be applied to the hydrogenation of two 6membered α,β-unsaturated lactones with quantitative conversions to the reduced products and with excellent enantioselectivities (96−99% ee).285 Pfaltz and co-workers also developed a phosphinite−pyridine ligand L124 for the asymmetric hydrogenation of a 5-membered α,β-unsaturated lactone S98. However, the reduced product was only obtained with 89% ee.286 Kazmaier and co-workers developed a phosphinite−oxazoline ligand L125 and applied it to the hydrogenation of a 6membered exocyclic enone to give the corresponding product with up to 99% ee.287 Ding and co-workers were able to further develop this work by using a (S,S)-SpinPHOX−Ir catalyst (Ir−L77S) for the asymmetric hydrogenation of a wider range of α-alkylidine carbonyl compounds including α-alkylidene lactams S96 and lactones S98 as well as unsaturated cyclic ketones S97. Such substrates could be hydrogenated with up to 98% ee (Figure 60).288 Ir−SpinPHOX complexes have previously been used by

Scheme 91. NeoPHOX−Ir-Catalyzed AH of Maleic Anhydrides S100

7.1.4. Cu-Catalyzed Asymmetric Hydrogenation. A Cucatalyzed asymmetric hydrogenation of cyclic enone S85a and S94 was reported in 2009. Using the (R)-DTBM-SegPhos (L119R) ligand reported previously,273 the reduced products were obtained with moderate to good chemoselectivities depending on the reaction conditions (Scheme 92).294 Higher catalyst loadings and temperatures improved the conversion values. Scheme 92. DTBM-SegPhos−Cu-Catalyzed AH of Endocyclic Enones

Figure 60. SpinPHOX−Ir-catalyzed AH of cyclic unsaturated carbonyl compounds.

Ding and co-workers for the asymmetric hydrogenation of α,α′bis(2-hydroxyarylidene) cycloalkanones to synthesize aromatic spiroketals.289,290 These catalysts provided the desired piperidone products with excellent ee but as opposite enantiomers depending on the ligand used, thus showing the spirochirality of the ligand controls the sense of asymmetric induction in the catalysis. A number of aryl-substituted akylidenes substrates could be reduced with high ee irrespective of the substitution pattern on the phenyl ring or the electron-donating/withdrawing nature of the substituents. An Ir−L77R catalyst in combination with the optimized reaction conditions could be used to reduce a number of N-Boc-protected alklidenecaprolactams possessing a variety of aryl substituents. All hydrogenations proceeded with high conversions and ee. Additionally, the Ir catalysts could also be used for the asymmetric hydrogenation of 6- and 7-membered ring lactones, ketones, and lactams, although slightly lower

7.2. Via Asymmetric Hydrogenation of Cyclic α,β-Unsaturated Carbonyl Compounds Bearing an Exocyclic Carbonyl Group

Ring systems bearing α,β-unsaturated carbonyl groups, in which the C−C double bond is endocyclic with respect to the CO group, have proved difficult to hydrogenate (Figure 61). 14808


Chemical Reviews

Review

7.2.2. Ir-Catalyzed Asymmetric Hydrogenation. In 2010, Pfaltz, Mulzer, and co-workers studied the asymmetric hydrogenation of a cyclic α,β-unsaturated carboxyl ester S103 using several P,N-Ir complexes. The pyridine-based ligand L128 was found to be the best for this reaction (Scheme 95).297

Figure 61. Asymmetric hydrogenation of cyclic α,β-unsaturated carbonyl compounds bearing an exocyclic carbonyl group for the synthesis of chiral cyclic carbonyl compounds.

Scheme 95. Ir-Catalyzed AH of a Cyclic α,β-Unsaturated Carboxyl Ester S103

7.2.1. Rh-Catalyzed Asymmetric Hydrogenation. In 1988, ferrocene-derived ligands L127 were used for the asymmetric hydrogenation of exocyclic α,β-unsaturated carboxyl acids S101. Five- and six-membered substrates were reduced with 92% and 87% ee, respectively (Scheme 93).295 Scheme 93. Rh-Catalyzed AH of Cyclic α,β-Unsaturated Carboxyl Acids S101

7.3. Summary

A variety of cyclic α,β-unsaturated carbonyl compounds bearing an endocyclic carbonyl group have been successfully reduced using different catalyst systems. The greatest success has been achieved using Ir catalysts derived from P,N-chelating ligands. For example, BiPhPHOX and SpinPHOX have been successfully used for the hydrogenation of 5- and 6-membered substrates, respectively. However, the hydrogenation of cyclic α,βunsaturated carbonyl substrates bearing an exocyclic carbonyl group have been less successful. Rh catalysts derived from ferrocene ligands such as JosiPhos have shown some promising activity.

In 2012, May and co-workers reported an asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones S102 using a rhodium complex consisting of Josiphos L15c (Scheme 94).296 A variety of cyclic substrates were reduced with Scheme 94. JosiPhos−Rh-Catalyzed AH of Tetrasubstituted Cyclic α,β-Unsaturated Ketones S102

8. SYNTHESIS OF UNFUNCTIONALIZED CHIRAL CYCLOALKANES 8.1. Via Asymmetric Hydrogenation of Endocyclic Alkenes

Endocyclic alkenes are considered to be some of the most challenging substrates for asymmetric hydrogenation due to the lack of an extra coordinating group and their rigid structural properties (Figures 62).

Figure 62. Asymmetric hydrogenation of endocyclic alkenes for the synthesis of unfunctionalized chiral cycloalkanes.

8.1.1. Ir-Catalyzed Asymmetric Hydrogenation. The majority of procedures for the hydrogenation of cyclic alkenes rely on Ir catalysis. By far the most commonly used ligands for these hydrogenations are P,N-derived species. In particular, the groups of Pfaltz, Andersson, and Diéguez have reported numerous advances in this area of catalysis. The most commonly used cyclic substrates for these reactions are, as seen previously, 1-alkyl-3,4-dihydronaphthalenes such as S104 (Figure 63). 8.1.1.1. Pfaltz Group. In 2001, soon after the development of the P,N-chelating ligand PHOX L121, Pfaltz and co-workers reported the asymmetric hydrogenation of S104a using pyrrolederived phosphinooxazoline ligand PyrPHOX (L129) with a

high yields and enantioselectivities; however, higher catalyst loadings are needed as R2 changes from bulky to smaller alkyl groups. The substitution position on the aryl ring influences selectivity with 2-substituted substrates giving higher enantioselectivities. The addition of Zn(OTf)2 greatly increased the turnover number for the reaction, whereas other additives such as zinc chloride and zinc acetate did not. It is proposed that a mixed ketal can be formed in the presence of either Bronsted or Lewis acids, increasing the electron density of the alkene and the directing ability of the hydroxyl group of the mixed ketal. This may lead to an increase in the rate of substrate ligand complex formation. 14809


Chemical Reviews

Review

found to be efficient catalysts for the asymmetric hydrogenation of S104a, with the reduced products being obtained with up to 86% ee.292,304 Although the aforementioned ligands were effective for the hydrogenation of trisubstituted endocyclic olefins, more challenging tetrasubstituted olefins proved to be more problematic. To this end, simple and readily accessible phosphane− oxazoline ligands L136 were developed. Iridium complexes derived from these had previously proved to be useful for the hydrogenation of acyclic tetrasubstituted olefins. Through the screening of various ligands, SimplePHOX (L131), ThrePHOX (L134), and L136 in combination with an [Ir(cod)2]BArF precatalyst were found to be suitable candidates for the hydrogenation of a number of challenging tetrasubstituted olefins such as dihydronaphthalenes S105 (Scheme 96).305,306 Scheme 96. Ir-Catalyzed AH of Tetrasubstituted Endocyclic Alkenes S105

Figure 63. P,N-Chelating ligands used in the Pfaltz group for AH of endocyclic alkenes S104.

[IrCl(cod)]2 catalyst precursor and a NaBArF salt. The cyclic substrate S104a could be reduced with up to 92% ee, significantly higher than that achieved using iridium complexes derived from PHOX L121 (61% ee).298 The use of a tetrakis[5,5-bis(trifluoromethyl)phenyl]borate (TFPB or BArF) counterion greatly accelerates the reactions and allows for a lower substrate/ catalyst ratio. In a continuation of this research, the structurally related chiral phosphino−imidazoline ligands (L130) were developed.299 The additional nitrogen atom allows for “fine tuning” of the electronic properties of the ligand via the addition of extra substituents on the nitrogen atom. Indeed, ligand L130 bearing a Ph group (R3) on the nitrogen atom was able to reduce S104a with >99% conversion and with 91% ee. The enantioselectivity of the reduction could be further improved by employing a phosphinite analogue, SimplePHOX (L131). Performing the hydrogenation of S104a in the presence of an Ir− L131 complex (1 mol %), 50 bar H2, and in DCM gave the reduced product with 95% ee.300 En route to the synthesis of dimtheyl methoxycalamene, P,N-chelating ligand NeoPHOX L132 was used for the Ir-catalyzed asymmetric hydrogenation of S104a and 7-methoxy-4-isopropyl-1,2-dihydronaphthalene intermediate S104b.301 The desired products were obtained with 96% and 93% ee, respectively. Additionally, in 2001 Pfaltz and co-workers developed a new class of phosphinite−oxazoline ligands L133 possessing an endocyclic chiral center within the iridium complexes. The endocyclic substrate S104a was reduced with 85% ee.302 The similarly structured threonine-derived phosphinite−oxazoline ligand Ph-ThrePHOX L134 also proved to be quite versatile, successfully reducing S104a with 100% conversion and 85% ee.303 In 2005, Pfaltz and co-workers introduced an extra chiral element to the P group of the P,N-chelating ligands. The iridium complexes derived from bis(amino)phosphine−oxazoline ligands (L135) bearing cyclic diazaphosphoslidine rings were

In addition, Pfaltz et al. developed a series of pyridine-derived P,N-chelating ligands. High enantioselectivities could also be obtained with bicyclic phosphinite−pyridine complex Ir−L137. The addition of the extra ring system creates a structure with a more rigid conforrmation.307 Thus, S104a could be reduced with an enantioselectivity of 92% using an iridium complex derived from [IrCl(cod)]2 in the presence of a NaBArF additive. The enantioselectivity for S104a could be further increased to 98% ee using chiral pyridyl phosphinite complex Ir−L137.308 This catalyst system was also suitable for the reduction of dihydronaphthalene S104b and S104c with high enantioselectivities (Figure 64). 14810


Chemical Reviews

Review

plexes have shown to be excellent catalysts for the asymmetric hydrogenation of endocyclic alkenes. Early studies involving the hydrogenation of dinaphthalene S104a gave the corresponding reduced product with enantioselectivities of up to 94% (catalyst = Ir−L139) when the reaction was carried out under 30 bar H2 pressure in CH2Cl2 solvent.310 Changing the oxazole-based ligands to thiazole ligands and replacing the labile P−O bond with a more stable P−CH2 bond allowed for the formation of a more stable ligand structure. It also allows for the late-stage diversification of the ligand’s skeleton. Thus, thiazole ligands Ir−L13c showed excellent results for the hydrogenation of cyclic alkenes S104a, S106, and S107 (Figure 66).311 The activity of the catalyst is strongly dependent on the substitution pattern of the ligand, thus allowing for the pairing of particular ligands and substrates for optimal selectivity. Similar selectivities could be obtained using unfused thiazole-based iridium catalysts.312 Replacing the phosphine coordinating group with an NHC group led to a decrease in enantioselectivity for S106 (70% ee) but an increase in the enantioselectivity for S107 (70% ee).313 Similar imidazole-based ligands L13b and L13e were also developed and applied to the AH of endocyclic alkenes to reduce substrates S106 and S107 with 72% and 90% ee, respectively (Figure 66).314 With the excellent enantioselectivities shown by fused phosphine−oxazole and −thiazole ligands, Andersson et al. synthesized a new class of P,N-type ligand bearing a bicyclic C− N backbone. These have shown promising results for the asymmetric hydrogenation of endocyclic alkenes (Figure 67).315,316 Iridium complexes of phosphine−oxazoline ligands in DCM with 50 bar H2 successfully reduced endocyclic alkenes with varying degrees of success. Ir complex Ir−L9d gave the best result, reducing S104a, S106, and S107 with 95%, 38%, and 94% ee, respectively. An iridium catalyst generated with the corresponding phosphine−thiazole ligand L9c improved the enantioselectivity of S106 to 83% ee.316 Further modifications of the ligand backbone led to the development of the related complexes L140 and L141, which were able to reduce alkene S106 with an improved 51% and 89% ee, respectively.317,318 Andersson and co-workers also prepared the structurally similar pyridine-based ligands to determine if a pyridine group would still allow for the catalyst to retain its activity (Figure 68).319,320 In 2007, Andersson and co-workers reported the asymmetric hydrogenation of substrates S104a and 106 using an iridium complex derived from pinene-based diastereomeric ligand L142. Substrate 106 could be reduced with 97% ee at 100 bar H2 pressure using a [Ir(COD)2]BArF catalyst precursor.319 These ligands were further derivatized via removal of the O−P linker to give pyridine-derived N,P-ligands bearing a carbon linker. Ir complexes derived from five-membered ligand L143 gave superior results compared to their 6-membered counterparts. Cyclic alkene 106 was reduced with 91% ee using 1 mol % of Ir−L143 and H2 (50 bar) in DCM.320 Since 2008, several phosphite-derived Ir complexes have also been developed by Andersson, Diéguez, and co-workers, each with varying degrees of activity (Figure 69). An Ir complex derived from biaryl phosphite−oxazoline ligand L144 reduced S104a with 100% conversion and 96% ee.321 Similar thiazoline ligands, L145, also showed very good enantioselectivity for the hydrogenation of S104a.322 An Ir complex consisting of phosphite−thiazole ligand L146 was capable of hydrogenating S104a and S106 with 99% and 93% ee, respectively.323

Figure 64. Phosphinite−pyridine−Ir-catalyzed AH of endocyclic alkenes.

In an extension of the work involving phosphite−oxazoline ligands, Pfaltz and co-workers replaced the phosphite moiety of the ligands with a carbene functionality (Figure 65).309 The

Figure 65. NHC-pyridine−Ir complexes for AH of endocyclic alkene S104a.

NHC−Ir complexes Ir−L138, in the presence of H2 (50 bar) in CH2Cl2 were able to hydrogenate S104a with enantioselectivities (up to 96% ee) in excess of previously reported pyridine phosphinite complexes. Due to the lower acidity of the Ir− hydride complexes produced from NHC complexes, such catalysts are suitable for the asymmetric hydrogenation of acidsensitive substrates. 8.1.1.2. Andersson and Dieǵ uez Group. Andersson and coworkers also carried out pivotal work in this area of asymmetric catalysis. In particular, they developed a series of iridium− phosphine oxazole, thiazole, and imidazole complexes for use in numerous hydrogenation reactions (Figure 66). These com-

Figure 66. Ir-catalyzed AH of endocyclic alkenes using oxazole− phosphinite and thiazole− and imidazole−phosphine ligands. 14811


Chemical Reviews

Review

Figure 67. Ir-catalyzed AH of endocyclic alkenes using oxazoline− and thiazole−phosphine ligands.

respectively. These values are comparable to hydrogenations involving acyclic substrates. Phosphite−pyridine ligands L148 were applied to the asymmetric hydrogenation of endocyclic alkenes with excellent enantioselectivities (Figure 70). In the presence of 1 mol % of [IrCl(cod)]2 catalyst precursor and under 50 bar H2 pressure in CH2Cl2, dinaphthalenes S104a, S104b, S104c, and S106 were reduced with 95%, 95%, 98%, and 97% ee, respectively.325 Diegeuz and co-workers also incorporated pyridine rings into pyranoside ligands.326 However, S104a could only be reduced with 65% ee using an [Ir(cod)2]BArF catalyst precursor, L149, and 100 bar H2 pressure. Modular furanoside thioether− phosphite ligands L150 were also prepared but show lower efficiency for the reduction of the cyclic substrates S104a and S106 (86% and 75% ee, respectively) (Figure 70).327 8.1.1.3. Other Groups. Besides a few reports describing the asymmetric hydrogenation of 1-alkyl-3,4-dihydronaphthalenes such as S104a and S106 for the testing of new ligands,328−330 other groups have directed their efforts to the asymmetric hydrogenation of challenging substrates such as 1,2-disubstituted-3,4-dihydronaphthalenes S105 and 1-aryl-3,4-dihydronaphthalenes S108 (Figure 71). Asymmetric hydrogenation of 1,2-dimethyl-3,4-dinaphthalenes have been reported using chiral imidate ferrocenylphos-

Figure 68. Ir-catalyzed AH of endocyclic alkenes using pyridine− phosphine ligands.

Andersson and Dieguez also developed several phosphite− oxazoline ligands that incorporate a pyranoside moiety into their structures (Figure 69).324 Such ligands possess several advantages over more conventional P,N-ligands; sugars are readily available from cheap feedstocks and can be constructed relatively easily using a modular approach. The catalyst precursors can be readily prepared by addition of the ligands to 0.5 equiv of [IrCl(cod)]2 in refluxing dichloromethane followed by counterion exchange with NaBArF (1 equiv) in the presence of water. Among the series of phosphite−oxazoline ligands, L147 proved to be an excellent ligand for the asymmetric hydrogenation of dihydronaphthalene derivatives S104a and S106 affording the reduced products with 98% and 91% ee,

Figure 69. Ir-catalyzed AH of endocyclic alkenes using oxazoline−, thiazoline−, and thiazole−phosphite ligands. 14812


Chemical Reviews

Review

Figure 70. Ir-catalyzed AH of endocyclic alkenes using pyridine− and thioether−phosphite ligands.

for both 5- and 6-membered substrates.334 They subsequently prepared a similar phosphine−oxazoline ligand, LalithPhos (L73), for the hydrogenation of endocyclic alkenes.167 Under 1 atm hydrogen pressure, a series of 1-aryl-3,4-dihydronaphthalenes S108 was hydrogenated with good to excellent enantioselectivities. Substitution on the Ar group with electron-withdrawing and electron-donating groups affected selectivity. 8.1.2. Rh-Catalyzed Asymmetric Hydrogenation. In 2006, Kim and co-workers reported a Rh-catalyzed hydrogenation of 1-methyl-3,4-dihydronaphthalene using chiral ferrocence-based iminophosphorane ligands.331 6-Methoxy-1methyl-3,4-dihydronaphthalene S104a was successfully reduced in quantitative yield and with 97% ee using ferrocence ligand L151 with a Rh(cod)BF4 catalyst precursor. In 2011, the asymmetric hydrogenation of 5-membered trisubstituted alkenes S109 functionalized by a hydroxyl group were used for the synthesis of several chiral compounds including (R)-tolterodine. The hydroxyl group was found to be essential for high enantioselectivity. Using rhodium complexes derived from the diphosphine ligands DuanPhos (L43) and JosiPhos (L15d), the reduced products were obtained with up to 99% ee (Scheme 97).335,336 8.1.3. Ru-Catalyzed Asymmetric Hydrogenation. One of the only methodologies concerning the hydrogenation of 5membered endocyclic alkenes with a ruthenium catalyst was reported by Glorius and co-workers in 2012 (Scheme 98).337 While investigating the asymmetric reduction of benzofurans, 3methyl-indene S110 was reduced to determine the influence the oxygen atom had on the reaction. A Ru−NHC complex derived from (R,R)-SINpEt-HBF4 (L96-HBF4) was only capable of reducing S110 with 16% ee, whereas benzofuran was reduced with 94% ee. This is most likely due to the ability of the oxygen atom to coordinate to the ruthenium catalyst; thus, the oxygen atom is essential for a high level of enantioselectivity. 8.1.4. Zr- and Co-Catalyzed Asymmetric Hydrogenation. Although the asymmetric hydrogenation of cyclic substrates bearing exocyclic olefins relies predominantly on the more traditionally used transition metals, a handful of methodologies employing Zr and Co catalysis have been employed in several reactions. In 1999, Buchwald and co-workers reported the asymmetric hydrogenation of tetrasbstituted endocyclic un-

Figure 71. Ir-catalyzed AH of tetrasubstituted endocyclic alkenes S105 and 1-aryl-3,4-dihydronaphthalenes S108.

phanes. In 2006, Kim and co-workers employed the N,N-type ligands, chiral (iminophosphoryanyl)ferrocences L151, to the hydrogenation of S105a. Moderate enantioselectivities (83% ee) were observed (Figure 71).331 The trisubstituted substrate S104a was also hydrogenated with 97% ee. In 2013, Busacca and co-workers developed two types of phosphine−imidazoline ligands L152 and L153 for the asymmetric hydrogenation of dinaphthalenes. The reduction of S105 and S108 was performed under 1 bar hydrogen pressure in CH2Cl2 with good enantioselectivities (Figure 71).332,333 In 2014, Qu and co-workers developed a dihydrobenzooxaphosphole−pyridine ligand BoqPhos (L154) for the hydrogenation of S105 and S108. Moderate ee values were obtained 14813


Chemical Reviews

Review

Scheme 97. Rh-Catalyzed AH of 5-Membered Trisubstituted Alkenes S109

Figure 73. Co-catalyzed AH of trisubstituted endocyclic alkenes.

lectivities of up to 99% ee under H2 (4 atm) in toluene solvent. Seven-membered substrates were reduced with lower ee than the corresponding 5- and 6-membered alkenes. Mechanistic studies and deuterium-labeling experiments suggest that the reaction proceeds via a 1,2-alkene insertion which is the enantiodetermining and rate-limiting step. The formation of the preferred enantiomeric product is influenced by the achiral aryl imine substituent on the Co catalyst.

Scheme 98. Ru-Catalyzed AH of 3-Methyl-indene S110

8.2. Via Asymmetric Hydrogenation of Exocyclic Alkenes

Similar to the asymmetric hydrogenation of endocyclic alkenes, the majority of procedures involving hydrogenation of exocyclic alkenes utilize iridium catalysis. Rh- and Ru-catalyzed hydrogenations of endocyclic alkene substrates provide the corresponding products with relatively low yields but high enantioselectivities (Figure 74).

functionalized alkenes using a cationic zirconocene catalyst (Zr− L36) in aromatic hydrocarbon solvents. Similar to its Ti analogue (Ti−L36), the enantioselectivities are influenced by hydrogen pressure with higher pressures (1000−2000 psi) providing higher selectivity. Five- and six-membered substrates S105 were hydrogenated to chiral cycloalkanes P105 with 52−99% ee (Figure 72).338 Chirik and co-workers reported a Co-catalyzed hydrogenation of trisubstituted endocyclic alkenes (Figure 73).339 Using a C1symmetric bis(imino)pyridine cobalt complex, Co−L155a, the substrates shown in Figure 73 were reduced with enantiose-

Figure 74. Asymmetric hydrogenation of exocyclic alkenes for the synthesis of unfunctionalized chiral cycloalkanes.

8.2.1. Rh-Catalyzed Asymmetric Hydrogenation. In 1995, Takaya and co-workers reported the first asymmetric hydrogenation of exocyclic alkenes S111 using a [RhI(cod)]/ (R)-BINAP] catalyst system (Scheme 99). The desired products P111 were obtained with better enantioselectivities compared to similar hydrogenations using Ru catalyst [Ru(OAc)2((R)BINAP)]. Increasing ring size led to a decrease in enantioselectivity, and addition of an electron-donating methoxy group in Scheme 99. BINAP−Rh- and BINAP−Ru-Catalyzed AH of Exocyclic Alkenes S111

Figure 72. Zr-catalyzed AH of tetrasubstituted endocyclic alkenes S105. 14814


Chemical Reviews

Review

Scheme 102. BINAP−Ru-Catalyzed AH of Exocyclic N-Acyl Allylamines S114

different positions greatly influences selectivity. For example, 5methoxy-1-methylene-1,2,3,4-tetrahydronaphthalene was reduced with only 47% ee.340 In 2006, Kim and co-workers reported a Rh-catalyzed hydrogenation of 6-methoxy-1-methylene-1,2,3,4-tetrahydronaphthalene S111b (R1 = R3 = H, R2 = OMe).331 Using a chiral ferrocence-based iminophosphorane ligand L151 and Rh(cod)BF4 catalyst precursor, S111b could be reduced with 94% ee but in only 7% yield. In 2009, Yamashita and co-workers applied various ferrocenebased diphosphine ligands to the Rh-catalyzed asymmetric hydrogenation of an exocyclic allylic amine S112. The JosiPhostype ligand L15b reduced S112 to its corresponding product with 92% ee (Scheme 100).341

substrates S115 (Scheme 103).180,181 The hydrogen source for the reaction is derived from the azeotrope of formic acid and Scheme 103. Ru-Catalyzed ATH of Dicyano-Substituted Exocyclic Alkenes S115

Scheme 100. JosiPhos−Rh-Catalyzed AH of Exocyclic Allylamines S112

triethylamine. Prior to these studies, such reaction conditions had been used for the transfer hydrogenation of α,β-acetylenic ketones to give chiral propargylic alcohols with high enantioselectivities. This reactivity can be switched to reduce the olefinic double bond by replacing the ketone functionality with sufficiently strong electron-withdrawing groups, e.g., cyano and aromatic groups. α,α-Dicyanoolefin substrates S115 were found to be sufficiently reactive to be hydrogenated by the Ru− TsDPEN complexes. The greatest enantioselectivity for the asymmetric hydrogenation of substrates was achieved using the bulky ligand L80. Addition of electron-withdrawing groups to the aromatic rings of the TsDPEN ligand (e.g., a NO2) results in a decrease in enantioselectivity. The substituents on the Ru− arene ring also influenced catalytic performance, with [RuCl2(pcymene)]2 providing the highest enantioselectivity for the hydrogenation of substrates S115. Using the reaction conditions shown in Scheme 103, high enantioselectivities could be obtained for the majority of the substrates, irrespective of the substituents on the aromatic ring. 8.2.3. Ir-Catalyzed Asymmetric Hydrogenation. One of the first attempts to asymmetrically hydrogenate exocyclic alkenes using Ir catalysis was reported in 2001 by Kündig and co-workers. Using a phosphino benzoxazine ligand L157, a tetrasubstituted 6-membered exocyclic alkene S116 was reduced but with only 10% yield and 5% ee (Scheme 104).344 In addition to the asymmetric hydrogenation of arylsubstituted endocyclic alkenes, Kim and co-workers were able to apply their Ir−(iminophosphoranyl)ferrocene catalyst system to that of the reduction of exocyclic derivatives. 6-Methoxy-1methylene-1,2,3,4-tetrahydronaphthalene S111b (R1 = R3 = H, R2 = OMe) could be reduced quantitatively with Ir catalysis. An iridium catalyst derived from ligand L151 proved to be the most effective, giving the corresponding product in 99% yield and 88% ee.331 Börner, Andersson, Dieguez, and co-workers utilized a modular library of phosphite−oxazoline ligands L158 for the Ir-catalyzed asymmetric hydrogenation of unfunctionalized 1,1disubstituted terminal alkenes.345,346 Although most substrates were acyclic, 1-methylene-1,2,3,4-tetrahydronaphthalene S111b (R1 = R2 = R3 = H) was successfully reduced with 99% yield and 87% ee (Figure 75).346 Difficulty arises from hydrogenation due to the substrate’s propensity to isomerize to the trisubstituted

In 2012, Hu, Duan and co-workers synthesized β-chiral cyclic alkylphosphonates via a Rh−(S,Rp)-WalPhos (Rh−L14) catalyzed asymmetric hydrogenation of β,β′-disubstituted α,βunsaturated phosphonate. The cyclic substrate S113 could be reduced with 93% ee, higher than previous studies involving a Rh−(R,Sa)-FAPhos (Rh−L156) catalyst (Scheme 101).342 Scheme 101. Rh-Catalyzed AH of Exocyclic α,β-Unsaturated Phosphonate S113

8.2.2. Ru-Catalyzed Asymmetric Hydrogenation. In 1995, Takaya et al. reported the hydrogenation of 5-, 6-, and 7membered endocyclic alkenes S111 with 45−78%, 61−75%, and 23% ee using a [Ru(OAc)2((R)-BINAP)] catalyst system.340 This catalyst system was applied by Yamano and co-workers to the asymmetric hydrogenation of exocyclic N-acyl allylamines S114 for the synthesis of the nonbenzodiazepine hypnotic drug Ramelteon (Scheme 102).343 In 2004, Deng and co-workers developed an asymmetric transfer hydrogenation of activated dicyano-substituted exocyclic olefins catalyzed by ruthenium complexes. The Deng group utilized a catalyst derived from [RuCl2(p-cymene)]2 and a TsDPEN-like ligand (L80) to hydrogenate α,α-dicyanoolefin 14815


Chemical Reviews

Review

Scheme 104. Ir-Catalyzed AH of Tetrasubstituted Exocyclic Alkenes S116

Scheme 105. Ir-Catalyzed AH of 5-Membered Exocyclic Alkene S117

Scheme 106. Ir-Catalyzed AH of 8-Methylene-5,6,7,8tetrahydronaphthalene-1-carboxylic Acid S118

Scheme 107. f-SpiroPhos−Ir-Catalyzed AH of Exocyclic Nitroalkene S119

Figure 75. Ir-catalyzed AH of exocyclic alkenes using oxazoline-based ligands.

endocyclic olefin under certain reaction conditions. Nonetheless, the use of propylene carbonate (PC) as a solvent significantly reduces isomerization, allowing 1-methylene-1,2,3,4-tetrahydronaphthalene to be hydrogenated with high enantioselectivity. Higher hydrogen pressure and a longer reaction time were required to effect this transformation. Govendar and co-workers also reported the hydrogenation of S111b using tetrahydroisoquinoline-based phosphine−oxazoline ligand L140 with slightly better results than L159 (48% vs 46% ee) (Figure 75).317 Chiral imidate−ferrocenylphosphanes have also been used as P,N-chelating ligands for the Ir-catalyzed hydrogenation of unfunctionalized olefins. Among these substrates, a 5-membered exocyclic alkene S117 could be reduced with 86% conversion and 40% ee using Ir/ferrocenyl complex Ir−L160 in the absence of additional additives. This result is similar to that obtained for the reduction of substrates bearing endocyclic olefins (Scheme 105).347 In 2014, Q.-L. Zhou and co-workers employed spiro phosphine−oxazoline Ir complexes to the hydrogenation of 8methylene-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid S118. Ir−SIPHOX (Ir−L18a) successfully reduced S118 in 99% yield and with 91% ee using the reaction conditions shown in Scheme 106. The carboxyl group aids in the enantioselective induction.348 In 2015, Hou and co-workers studied the asymmetric hydrogenation of β,β-disubstituted nitroalkenes catalyzed by various diphosphine−Ir complexes. Using an iridium complex of (S,S)-f-SpiroPhos (L161), a exocyclic substrate S119 was reduced with 98% ee (Scheme 107). 8.2.4. Co- and Ni-Catalyzed Asymmetric Hydrogenation. Chirik and co-workers reported a Co-catalyzed hydro-

genation of geminal-disubstituted olefins.349 The C1-symmetric bis(imino)pyridine cobalt complexes, Co−L155, were able to reduce a series of substituted styrenes, including 3-methylene1H-indene S111a. The reduced product was obtained in >98% yield but with only 39% ee using L155a. Use of L155b improved the enantioselectivity to 96% ee but reduced the yield to 44% (Scheme 108). In 2014, J. (Steve) Zhou and co-workers reported a Nicatalyzed asymmetric transfer hydrogenation of α,β-unsaturated carboxyl esters using a series of bisphosphine ligands. (R)-MeDuphos (L6) was found to be the best ligand for the reduction of such substrates in combination with a NiBr2(DME) catalyst precursor. Among these substrates, exocyclic S120 was reduced with 98% ee (Scheme 109). 8.3. Summary

The hydrogenation of endo- and exocyclic alkenes is challenging with the alkene often requiring activation with other substituents. Research in this area is dominated by Ir catalysis and relies predominantly on the use of P,N-ligands developed by the Pfaltz and Andersson groups. Their respective ligands are able to 14816


Chemical Reviews

Review

show that such problems can eventually be overcome by developing new catalytic systems.

Scheme 108. Co-Catalyzed AH of Exocyclic Alkene S111a

AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]. Author Contributions §

Z.Z. and N.B. contributed equally.

Notes

The authors declare no competing financial interest. Biographies Zhenfeng Zhang received his B.S. and M.S. degrees from Shanghai Jiao Tong University (SJTU) in 2003 and East China University of Science and Technology (ECUST) in 2006, respectively. From 2006 to 2010 he carried out Ph.D. research at SJTU under the supervision of Professor Wanbin Zhang. From 2010 to 2011 he carried out postdoctoral research at Nippon Chemical Industrial Co. Ltd. with Professor Tsuneo Imamoto. In 2012 he became a research assistant at SJTU. His current research interests consist of asymmetric catalysis and pharmaceutical process chemistry.

Scheme 109. DuPhos-Ni-Catalyzed ATH of Exocyclic α,βUnsaturated Carboxyl Ester S120

Nicholas A. Butt received his M.S. degree from the University of Warwick in 2007. From 2007 to 2011 he carried out Ph.D. research at the University of Nottingham under the supervision of Professor Christopher Moody. From 2011 to 2013 he carried out postdoctoral research at Shanghai Jiao Tong University in the group of Professor Zhang. In 2014 he became a research assistant at the same university. His current research interests consist of asymmetric catalysis and organometallic chemistry.

reduce 1-alkyl-3,4-dihydronaphthalene and related substrates with similar enantioselectivities. Of particular note is the use of SimplePHOX, ThrePHOX, and other oxazoline ligands for the asymmetric hydrogenation of challenging tetrasubstituted dihydronaphthalenes with good to excellent enantioselectivities. Earlier hydrogenations of such substrates relied on Zr and Co catalysis. In contrast to the above, exocyclic alkenes are far more challenging substrates to hydrogenate. Although several examples exist, the catalyst systems are only specific to certain substrates, no matter the type of transition metal; thus, more research in this area is required.

Wanbin Zhang received his B.S. and M.S. degrees from East China University of Science and Technology (ECUST) in 1985 and 1988, respectively. From 1993 to 1997 he undertook Ph.D. studies at Osaka University under the supervision of Professor Isao Ikeda. He then worked as an assistant professor at Osaka University until 2001 and then as a research fellow at the Specialty Chemicals Research Centre of the Mitsubishi Chemical Corp. Since 2003 he has worked as a professor in the School of Chemistry and Chemical Engineering at Shanghai Jiao Tong University. In 2013 he was promoted to the position of Distinguished Professor. His current research interests include organometallic chemistry, asymmetric catalysis, and pharmaceutical process chemistry.

9. CONCLUSION Over recent years great progress has been made in the area of transition-metal-catalyzed asymmetric hydrogenations of cyclic alkenes, ketones, and imines. Such procedures allow for efficient synthesis of complex chiral carbocycles and heterocycles from simple starting materials. A number of challenging nonaromatic cyclic substrates have been reduced with high yields and selectivities using a variety of ligands and metal catalysts. However, despite these advances, several challenges still remain: (1) tetrasubstituted cyclic alkenes are still challenging substrates to hydrogenate with high reactivity, stereoselectivity, and diversity; (2) unfunctionalized cycloalkenes are also difficult to reduce with high enantioselectivities; (3) ligands are often highly specific to certain substrates; privileged ligands that are able to hydrogenate a greater variety of substrates are highly desired; and (4) more environmentally benign procedures would be beneficial to both industry and academia, for example, the development of catalytic systems using inexpensive and abundant transition metals such as nickel, cobalt, and iron. The challenges mentioned above provide an exciting opportunity for chemists to develop novel reactions to further promote the use of asymmetric hydrogenation reactions for the synthesis of complex molecules. Recent advances in this field

ACKNOWLEDGMENTS This work was supported by the Natural Science Foundation of China (Nos. 21232004 and 21572131) and Science and Technology Commission of Shanghai Municipality (Nos. 14XD1402300 and 15Z111220016). REFERENCES (1) Cui, X.; Burgess, K. Catalytic Homogeneous Asymmetric Hydrogenations of Largely Unfunctionalized Alkenes. Chem. Rev. 2005, 105, 3272−3296. (2) Källström, K.; Munslow, I.; Andersson, P. G. Ir-Catalysed Asymmetric Hydrogenation: Ligands, Substrates and Mechanism. Chem. - Eur. J. 2006, 12, 3194−3200. (3) Church, T. L.; Andersson, P. G. Iridium Catalysts for the Asymmetric Hydrogenation of Olefins with Nontraditional Functional Substituents. Coord. Chem. Rev. 2008, 252, 513−531. (4) Pàmies, O.; Andersson, P. G.; Diéguez, M. Asymmetric Hydrogenation of Minimally Functionalised Terminal Olefins: An Alternative Sustainable and Direct Strategy for Preparing Enantioenriched Hydrocarbons. Chem. - Eur. J. 2010, 16, 14232−14240. 14817


Chemical Reviews

Review

(5) Woodmansee, D. H.; Pfaltz, A. Asymmetric Hydrogenation of Alkenes Lacking Coordinating Groups. Chem. Commun. 2011, 47, 7912−7916. (6) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Transition Metal-Catalyzed Enantioselective Hydrogenation of Enamines and Imines. Chem. Rev. 2011, 111, 1713−1760. (7) Hopmann, K. H.; Bayer, A. Enantioselective Imine Hydrogenation with Iridium-Catalysts: Reactions, Mechanisms and Stereocontrol. Coord. Chem. Rev. 2014, 268, 59−82. (8) Lu, S.-M.; Han, X.-W.; Zhou, Y.-G. Recent Advances in Asymmetric Hydrogenation of Heteroaromatic Compounds. Youji Huaxue 2005, 25, 634−641. (9) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.; Zhou, Y.-G. Asymmetric Hydrogenation of Heteroarenes and Arenes. Chem. Rev. 2012, 112, 2557−2590. (10) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. Synthesis of 2,2′-Bis(diphenylphosphino)-1,1′-Binaphthyl (BINAP), an Atropisomeric Chiral Bis(triaryl)phosphine, and Its Use in the Rhodium(I)-Catalyzed Asymmetric Hydrogenation of α(Acylamino)acrylic Acids. J. Am. Chem. Soc. 1980, 102, 7932−7934. (11) Noyori, R.; Takaya, H. BINAP: An Efficient Chiral Element for Asymmetric Catalysis. Acc. Chem. Res. 1990, 23, 345−350. (12) Berthod, M.; Mignani, G.; Woodward, G.; Lemaire, M. Modified BINAP: The How and The Why. Chem. Rev. 2005, 105, 1801−1836. (13) Noyori, R.; Ohta, M.; Hsiao, Y.; Kitamura, M.; Ohta, T.; Takaya, H. Asymmetric Synthesis of Isoquinoline Alkaloids by Homogeneous Catalysis. J. Am. Chem. Soc. 1986, 108, 7117−7119. (14) Kitamura, M.; Hsiao, Y.; Ohta, M.; Tsukamoto, M.; Ohta, T.; Takaya, H.; Noyori, R. General Asymmetric Synthesis of Isoquinoline Alkaloids. Enantioselective Hydrogenation of Enamides Catalyzed by BINAP-Ruthenium(II) Complexes. J. Org. Chem. 1994, 59, 297−310. (15) Couture, A.; Deniau, E.; Lebrun, S.; Grandclaudon, P.; Carpentier, J.-F. A New Route to Ene Carbamates, Precursors to Benzoindolizinones through Sequential Asymmetric Hydrogenation and Cyclization. J. Chem. Soc., Perkin Trans. 1 1998, 1403−1407. (16) Pousset, C.; Callens, R.; Marinetti, A.; Larchevêque, M. An Efficient Synthesis of Chiral Cyclic β-Amino Acids via Asymmetric Hydrogenation. Synlett 2004, 2004, 2766−2770. (17) Karamé, I.; Nemra-Baydoun, G.; Abdallah, R.; Kanj, A.; Börner, A. Highly Regioselective Synthesis of Ethyl 2-(N-Methylformate-1,4,5,6Tetrahydropyridin-2-yl) Acetate and Its Conversion into Corresponding (R)-Ethyl Homopepicolate by Asymmetric Hydrogenation. Synth. Commun. 2011, 41, 583−588. (18) Morimoto, T.; Nakajima, N.; Achiwa, K. Synthesis of a New Chiral Bisphosphine Ligand, MOCBP, and Its Use in Rhodium(I)Catalyzed Asymmetric Hydrogenation of a Cyclic Enamide. Tetrahedron: Asymmetry 1995, 6, 75−78. (19) Tang, W.; Zhang, X. A Chiral 1,2-Bisphospholane Ligand with a Novel Structural Motif: Applications in Highly Enantioselective RhCatalyzed Hydrogenations. Angew. Chem., Int. Ed. 2002, 41, 1612−1614. (20) Zhang, Y. J.; Park, J. H.; Lee, S. Asymmetric Synthesis of Homoproline Derivatives via Rh(I)-Catalyzed Hydrogenation Using Chiral Bisphosphines as Ligands. Tetrahedron: Asymmetry 2004, 15, 2209−2212. (21) Zhou, Y.-G.; Yang, P.-Y.; Han, X.-W. Synthesis and Highly Enantioselective Hydrogenation of Exocyclic Enamides: (Z)-3Arylidene-4-Acetyl-3,4-Dihydro-2H-1,4-Benzoxazines. J. Org. Chem. 2005, 70, 1679−1683. (22) Enthaler, S.; Erre, G.; Junge, K.; Addis, D.; Kadyrov, R.; Beller, M. Synthesis of Enantiomerically Pure 1,2,3,4-Tetrahydro-β-Carbolines and N-Acyl-1-Aryl Ethylamines by Rhodium-Catalyzed Hydrogenation. Chem. - Asian J. 2008, 3, 1104−1110. (23) Wang, X.-B.; Wang, D.-W.; Lu, S.-M.; Yu, C.-B.; Zhou, Y.-G. Highly Enantioselective Ir-Catalyzed Hydrogenation of Exocyclic Enamines. Tetrahedron: Asymmetry 2009, 20, 1040−1045. (24) Cheruku, P.; Church, T. L.; Trifonova, A.; Wartmann, T.; Andersson, P. G. Access to Chiral Tertiary Amines via the IridiumCatalyzed Asymmetric Hydrogenation of Enamines. Tetrahedron Lett. 2008, 49, 7290−7293.

(25) Yan, P.-C.; Xie, J.-H.; Hou, G.-H.; Wang, L.-X.; Zhou, Q.-L. Enantioselective Synthesis of Chiral Tetrahydroisoquinolines by Iridium-Catalyzed Asymmetric Hydrogenation of Enamines. Adv. Synth. Catal. 2009, 351, 3243−3250. (26) Foti, C. J.; Comins, D. L. Synthesis and Reactions of α(Trifluromethanesulfonyloxy) Enecarbamates Prepared from N-Acyllactams. J. Org. Chem. 1995, 60, 2656−2657. (27) Wilkinson, T. J.; Stehle, N. W.; Beak, P. Enantioselective Syntheses of 2-Alkyl- and 2,6-Dialkylpiperidine Alkaloids: Preparations of the Hydrochlorides of (−)-Coniine, (−)-Solenopsin A, and (−)-Dihydropinidine. Org. Lett. 2000, 2, 155−158. (28) Lim, S. H.; Ma, S.; Beak, P. Asymmetric Syntheses of Fused Bicyclic Lactams. J. Org. Chem. 2001, 66, 9056−9062. (29) Rossen, K.; Weissman, S. A.; Sager, J.; Reamer, R. A.; Askin, D.; Volante, R. P.; Reider, P. J. Asymmetric Hydrogenation of Tetrahydropyrazines: Synthesis of (S)-Piperazine-2-tert-Butylcarboxamide, an Intermediate in the Preparation of the HIV Protase Inhibitor Indinavir. Tetrahedron Lett. 1995, 36, 6419−6422. (30) Nicolaou, K. C.; Shi, G.-Q.; Namoto, K.; Bernal, F. Synthesis of NHeterocycles via Lactam-Derived Ketene Aminal Phosphates. Asymmetric Synthesis of Cyclic Amino Acids. Chem. Commun. 1998, 1757− 1758. (31) Kuwano, R.; Karube, D.; Ito, Y. Catalytic Asymmetric Hydrogenation of 1-Aza-2-Cycloalkene-2-Carboxylates Catalyzed by a Trans-Chelating Chiral Diphosphine PhTRAP-Rhodium Complex. Tetrahedron Lett. 1999, 40, 9045−9049. (32) Lei, A.; Chen, M.; He, M.; Zhang, X. Asymmetric Hydrogenation of Pyridines: Enantioselective Synthesis of Nipecotic Acid Derivatives. Eur. J. Org. Chem. 2006, 2006, 4343−4347. (33) Sallio, R.; Lebrun, S.; Agbossou-Niedercorn, F.; Michon, C.; Deniau, E. Alternative Strategies for the Stereoselective Synthesis of Enantioenriched 6-Arylated Piperidin-2-Ones. Tetrahedron: Asymmetry 2012, 23, 998−1004. (34) Hou, G.-H.; Xie, J.-H.; Yan, P.-C.; Zhou, Q.-L. Iridium-Catalyzed Asymmetric Hydrogenation of Cyclic Enamines. J. Am. Chem. Soc. 2009, 131, 1366−1367. (35) Ye, Z.-S.; Guo, R.-N.; Cai, X.-F.; Chen, M.-W.; Shi, L.; Zhou, Y.-G. Enantioselective Iridium-Catalyzed Hydrogenation of 1- and 3Substituted Isoquinolinium Salts. Angew. Chem., Int. Ed. 2013, 52, 3685−3689. (36) Verendel, J. J.; Li, J.-Q.; Quan, X.; Peters, B.; Zhou, T.; Gautun, O. R.; Govender, T.; Andersson, P. G. Chiral Hetero- and Carbocyclic Compounds from the Asymmetric Hydrogenation of Cyclic Alkenes. Chem. - Eur. J. 2012, 18, 6507−6513. (37) Krska, S. W.; Mitten, J. V.; Dormer, P. G.; Mowrey, D.; Machrouhi, F.; Sun, Y.; Nelson, T. D. Enantioselective Synthesis of a Chiral Fluoropiperidine via Asymmetric Hydrogenation of a Vinyl Fluoride. Tetrahedron 2009, 65, 8987−8994. (38) Stumpf, A.; Reynolds, M.; Sutherlin, D.; Babu, S.; Bappert, E.; Spindler, F.; Welch, M.; Gaudino, J. Kilogram-Scale Asymmetric Ruthenium-Catalyzed Hydrogenation of a Tetrasubstituted Fluoroenamide. Adv. Synth. Catal. 2011, 353, 3367−3372. (39) Campeau, L.-C.; Dolman, S. J.; Gauvreau, D.; Corley, E.; Liu, J.; Guidry, E. N.; Ouellet, S. G.; Steinhuebel, D.; Weisel, M.; O’Shea, P. D. Convergent Kilo-Scale Synthesis of a Potent Renin Inhibitor for the Treatment of Hypertension. Org. Process Res. Dev. 2011, 15, 1138−1148. (40) Chen, J.; Chen, T.; Hu, Q.; Püntener, K.; Ren, Y.; She, J.; Du, Z.; Scalone, M. Practical Asymmetric Hydrogenation-Based Synthesis of a Class-Selective Histone Deacetylase Inhibitor. Org. Process Res. Dev. 2014, 18, 1702−1713. (41) Renom-Carrasco, M.; Gajewski, P.; Pignataro, L.; de Vries, J. G.; Piarulli, U.; Gennari, C.; Lefort, L. Assisted Tandem Catalysis: Metathesis Followed by Asymmetric Hydrogenation from a Single Ruthenium Source. Adv. Synth. Catal. 2015, 357, 2223−2228. (42) Song, S.; Zhu, S.-F.; Pu, L.-Y.; Zhou, Q.-L. Iridium-Catalyzed Enantioselective Hydrogenation of Unsaturated Heterocyclic Acids. Angew. Chem., Int. Ed. 2013, 52, 6072−6075. 14818


Chemical Reviews

Review

(43) Ng Cheong Chan, Y.; Osborn, J. A. Iridium(III) Hydride Complexes for the Catalytic Enantioselective Hydrogenation of Imines. J. Am. Chem. Soc. 1990, 112, 9400−9401. (44) Morimoto, T.; Nakajima, N.; Achiwa, K. Efficient Asymmetric Hydrogenation of Imines Catalyzed by a Neutral Iridium(I) Complex of (4R,5R)-MOD-DIOP. Chem. Pharm. Bull. 1994, 42, 1951−1953. (45) Morimoto, T.; Achiwa, K. An Improved Diphosphine-Iridium(I) Catalyst System for the Asymmetric Hydrogenation of Cyclic Imines: Phthalimide as an Efficient Co-Catalyst. Tetrahedron: Asymmetry 1995, 6, 2661−2664. (46) Morimoto, T.; Nakajima, N.; Achiwa, K. Asymmetric Hydrogenation of Cyclic Ketimines Catalyzed by Iridium(I)-Complexes of BCPM and Its Analog. Synlett 1995, 1995, 748−750. (47) Sablong, R.; Osborn, J. A. Asymmetric Hydrogenation of Imines Catalysed by Carboxylato(diphosphine)iridium(III) Complexes. Tetrahedron: Asymmetry 1996, 7, 3059−3062. (48) Reetz, M. T.; Beuttenmüller, E. W.; Goddard, R.; Pastó, M. A New Class of Chiral Diphosphines Having Planar Chirality. Tetrahedron Lett. 1999, 40, 4977−4980. (49) Blaser, H.-U.; Buser, H.-P.; Häusel, R.; Jalett, H.-P.; Spindler, F. Tunable Ferrocenyl Diphosphine Ligands for the Ir-Catalyzed Enantioselective Hydrogenation of N-Aryl Imines. J. Organomet. Chem. 2001, 621, 34−38. (50) Liu, D.; Li, W.; Zhang, X. Development of DIOP Derivatives as Efficient Ligands for Asymmetric Hydrogenation: Factors Controlling the Reactivities and Enantioselectivities. Tetrahedron: Asymmetry 2004, 15, 2181−2184. (51) Zhu, G.; Zhang, X. Additive Effects in Ir-BICP Catalyzed Asymmetric Hydrogenation of Imines. Tetrahedron: Asymmetry 1998, 9, 2415−2418. (52) Kluwer, A. M.; Detz, R. J.; Abiri, Z.; van der Burg, A. M.; Reek, J. N. H. Evolutionary Catalyst Screening: Iridium-Catalyzed Imine Hydrogenation. Adv. Synth. Catal. 2012, 354, 89−95. (53) Morimoto, T.; Suzuki, N.; Achiwa, K. Enantioselective Synthesis of (S)-Calycotomine Employing Catalytic Asymmetric Hydrogenation with an Iridium(I)−(R)-BINAP−Phthalimide Complex. Tetrahedron: Asymmetry 1998, 9, 183−187. (54) Chang, M.; Li, W.; Zhang, X. A Highly Efficient and Enantioselective Access to Tetrahydroisoquinoline Alkaloids: Asymmetric Hydrogenation with an Iridium Catalyst. Angew. Chem., Int. Ed. 2011, 50, 10679−10681. (55) Berhal, F.; Wu, Z.; Zhang, Z.; Ayad, T.; Ratovelomanana-Vidal, V. Enantioselective Synthesis of 1-Aryl-Tetrahydroisoquinolines through Iridium Catalyzed Asymmetric Hydrogenation. Org. Lett. 2012, 14, 3308−3311. (56) Ružič, M.; Pecavar, A.; Prudič, D.; Kralj, D.; Scriban, C.; ZanottiGerosa, A. The Development of an Asymmetric Hydrogenation Process for the Preparation of Solifenacin. Org. Process Res. Dev. 2012, 16, 1293− 1300. (57) Mršić, N.; Panella, L.; Ijpeij, E. G.; Minnaard, A. J.; Feringa, B. L.; de Vries, J. G. Methylaluminoxane as an Alternative for BArF in the Iridium-Catalyzed Asymmetric Hydrogenation of Imines. ChemCatChem 2011, 3, 1139−1142. (58) Xie, J.-H.; Yan, P.-C.; Zhang, Q.-Q.; Yuan, K.-X.; Zhou, Q.-L. Asymmetric Hydrogenation of Cyclic Imines Catalyzed by Chiral Spiro Iridium Phosphoramidite Complexes for Enantioselective Synthesis of Tetrahydroisoquinolines. ACS Catal. 2012, 2, 561−564. (59) Tani, K.; Onouchi, J.; Yamagata, T.; Kataoka, Y. Iridium(I)Catalyzed Asymmetric Hydrogenation of Prochiral Imines; Protic Amines as Catalyst Improvers. Chem. Lett. 1995, 24, 955−956. (60) Yamagata, T.; Tadaoka, H.; Nagata, M.; Hirao, T.; Kataoka, Y.; Ratovelomanana-Vidal, V.; Genet, J. P.; Mashima, K. Oxidative Addition of RCO2H and HX to Chiral Diphosphine Complexes of Iridium(I): Convenient Synthesis of Mononuclear Halo-Carboxylate Iridium(III) Complexes and Cationic Dinuclear Triply Halogen-Bridged Iridium(III) Complexes and Their Catalytic Performance in Asymmetric Hydrogenation of Cyclic Imines and 2-Phenylquinoline. Organometallics 2006, 25, 2505−2513.

(61) Chang, M.; Li, W.; Hou, G.; Zhang, X. Iridium-Catalyzed Enantioselective Hydrogenation of Cyclic Imines. Adv. Synth. Catal. 2010, 352, 3121−3125. (62) Schnider, P.; Koch, G.; Prétôt, R.; Wang, G.; Bohnen, F. M.; Krüger, C.; Pfaltz, A. Enantioselective Hydrogenation of Imines with Chiral (Phosphanodihydrooxazole)iridium Catalysts. Chem. - Eur. J. 1997, 3, 887−892. (63) Guo, C.; Sun, D.-W.; Yang, S.; Mao, S.-J.; Xu, X.-H.; Zhu, S.-F.; Zhou, Q.-L. Iridium-Catalyzed Asymmetric Hydrogenation of 2-Pyridyl Cyclic Imines: A Highly Enantioselective Approach to Nicotine Derivatives. J. Am. Chem. Soc. 2015, 137, 90−93. (64) Qiu, L.; Kwong, F. Y.; Wu, J.; Lam, W. H.; Chan, S.; Yu, W.-Y.; Li, Y.-M.; Guo, R.; Zhou, Z.; Chan, A. S. C. A New Class of Versatile ChiralBridged Atropisomeric Diphosphine Ligands: Remarkably Efficient Ligand Syntheses and Their Applications in Highly Enantioselective Hydrogenation Reactions. J. Am. Chem. Soc. 2006, 128, 5955−5965. (65) Gao, K.; Yu, C.-B.; Li, W.; Zhou, Y.-G.; Zhang, X. Synthesis and Enantioselective Hydrogenation of Seven-Membered Cyclic Imines: Substituted Dibenzo[b,f ][1,4]oxazepines. Chem. Commun. 2011, 47, 7845−7847. (66) Gao, K.; Wu, B.; Yu, C.-B.; Chen, Q.-A.; Ye, Z.-S.; Zhou, Y.-G. Iridium Catalyzed Asymmetric Hydrogenation of Cyclic Imines of Benzodiazepinones and Benzodiazepines. Org. Lett. 2012, 14, 3890− 3893. (67) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R. Asymmetric Transfer Hydrogenation of Imines. J. Am. Chem. Soc. 1996, 118, 4916−4917. (68) Vedejs, E.; Trapencieris, P.; Suna, E. Substituted Isoquinolines by Noyori Transfer Hydrogenation: Enantioselective Synthesis of Chiral Diamines Containing an Aniline Subunit. J. Org. Chem. 1999, 64, 6724− 6729. (69) Williams, G. D.; Pike, R. A.; Wade, C. E.; Wills, M. A One-Pot Process for the Enantioselective Synthesis of Amines via Reductive Amination under Transfer Hydrogenation Conditions. Org. Lett. 2003, 5, 4227−4230. (70) Wu, J.; Wang, F.; Ma, Y.; Cui, X.; Cun, L.; Zhu, J.; Deng, J.; Yu, B. Asymmetric Transfer Hydrogenation of Imines and Iminiums Catalyzed by a Water-Soluble Catalyst in Water. Chem. Commun. 2006, 1766− 1768. (71) Canivet, J.; Süss-Fink, G. Water-Soluble Arene Ruthenium Catalysts Containing Sulfonated Diamine Ligands for Asymmetric Transfer Hydrogenation of α-Aryl Ketones and Imines in Aqueous Solution. Green Chem. 2007, 9, 391−397. (72) Evanno, L.; Ormala, J.; Pihko, P. M. A Highly Enantioselective Access to Tetrahydroisoquinoline and β-Carboline Alkaloids with Simple Noyori-Type Catalysts in Aqueous Media. Chem. - Eur. J. 2009, 15, 12963−12967. (73) Martins, J. E. D.; Clarkson, G. J.; Wills, M. Ru(II) Complexes of N-Alkylated TsDPEN Ligands in Asymmetric Transfer Hydrogenation of Ketones and Imines. Org. Lett. 2009, 11, 847−850. (74) Martins, J. E. D.; Redondo, M. A. C.; Wills, M. Applications of N′Alkylated Derivatives of TsDPEN in the Asymmetric Transfer Hydrogenation of CO and CN Bonds. Tetrahedron: Asymmetry 2010, 21, 2258−2264. (75) Soni, R.; Cheung, F. K.; Clarkson, G. C.; Martins, J. E. D.; Graham, M. A.; Wills, M. The Importance of the N-H Bond in Ru/ TsDPEN Complexes for Asymmetric Transfer Hydrogenation of Ketones and Imines. Org. Biomol. Chem. 2011, 9, 3290−3294. (76) Wu, Z.; Perez, M.; Scalone, M.; Ayad, T.; Ratovelomanana-Vidal, V. Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of 1Aryl-Substituted Dihydroisoquinolines: Access to Valuable Chiral 1Aryl-Tetrahydroisoquinoline Scaffolds. Angew. Chem., Int. Ed. 2013, 52, 4925−4928. (77) Cobley, C. J.; Henschke, J. P. Enantioselective Hydrogenation of Imines Using a Diverse Library of Ruthenium Dichloride(diphosphine)(diamine) Precatalysts. Adv. Synth. Catal. 2003, 345, 195−201. (78) Jackson, M.; Lennon, I. C. 1,2-Bis(2,5-diphenylphospholano)methane, a New Ligand for Asymmetric Hydrogenation. Tetrahedron Lett. 2007, 48, 1831−1834. 14819


Chemical Reviews

Review

(79) Chen, F.; Ding, Z.; Qin, J.; Wang, T.; He, Y.; Fan, Q.-H. Highly Effective Asymmetric Hydrogenation of Cyclic N-Alkyl Imines with Chiral Cationic Ru-MsDPEN Catalysts. Org. Lett. 2011, 13, 4348−4351. (80) Mao, J.; Baker, D. C. A Chiral Rhodium Complex for Rapid Asymmetric Transfer Hydrogenation of Imines with High Enantioselectivity. Org. Lett. 1999, 1, 841−843. (81) Matharu, D. S.; Martins, J. E. D.; Wills, M. Asymmetric Transfer Hydrogenation of CO and CN Bonds by Tethered Rh(III) Catalysts. Chem. - Asian J. 2008, 3, 1374−1383. (82) Shende, V. S.; Shingote, S. K.; Deshpande, S. H.; Kuriakose, N.; Vanka, K.; Kelkar, A. A. Asymmetric Transfer Hydrogenation of Imines in Water/Methanol Co-Solvent System and Mechanistic Investigation by DFT Study. RSC Adv. 2014, 4, 46351−46356. (83) Li, C.; Xiao, J. Asymmetric Hydrogenation of Cyclic Imines with an Ionic Cp*Rh(III) Catalyst. J. Am. Chem. Soc. 2008, 130, 13208− 13209. (84) Zhao, Q.; Wen, J.; Tan, R.; Huang, K.; Metola, P.; Wang, R.; Anslyn, E. V.; Zhang, X. Rhodium-Catalyzed Asymmetric Hydrogenation of Unprotected NH Imines Assisted by a Thiourea. Angew. Chem., Int. Ed. 2014, 53, 8467−8470. (85) Chen, Z.-P.; Hu, S.-B.; Zhou, J.; Zhou, Y.-G. Synthesis of Chiral Trifluoromethyl-Substituted Hydrazines via Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination. ACS Catal. 2015, 5, 6086− 6089. (86) Willoughby, C. A.; Buchwald, S. L. Asymmetric TitanoceneCatalyzed Hydrogenation of Imines. J. Am. Chem. Soc. 1992, 114, 7562− 7564. (87) Willoughby, C. A.; Buchwald, S. L. Synthesis of Highly Enantiomerically Enriched Cyclic Amines by the Catalytic Asymmetric Hydrogenation of Cyclic Imines. J. Org. Chem. 1993, 58, 7627−7629. (88) Willoughby, C. A.; Buchwald, S. L. Catalytic Asymmetric Hydrogenation of Imines with a Chiral Titanocene Catalyst: Scope and Limitations. J. Am. Chem. Soc. 1994, 116, 8952−8965. (89) Willoughby, C. A.; Buchwald, S. L. Catalytic Asymmetric Hydrogenation of Imines with a Chiral Titanocene Catalyst: Kinetic and Mechanistic Investigations. J. Am. Chem. Soc. 1994, 116, 11703− 11714. (90) Buser, H. P.; Pugin, B.; Spindler, F.; Sutter, M. Two Enantioselective Synthesis of a Precusor of the Biologically Most Active Isomer of CGA 80000 (Clozylacon). Tetrahedron 1991, 47, 5709−5716. (91) Armstrong, J. D., III; Eng, K. K.; Keller, J. L.; Purick, R. M.; Hartner, F. W., Jr.; Choi, W.-B.; Askin, D.; Volante, R. P. An Efficient Asymmetric Synthesis of (R)-3-Amino-2,3,4,5-Tetrahydro-1H-[1]Benzazapin-2-One. Tetrahedron Lett. 1994, 35, 3239−3242. (92) Tschaen, D. M.; Abramson, L.; Cai, D.; Desmond, R.; Dolling, U.H.; Frey, L.; Karady, S.; Shi, Y.-J.; Verhoeven, T. R. Asymmetric Synthesis of MK-0499. J. Org. Chem. 1995, 60, 4324−4330. (93) Dupau, P.; Bruneau, C.; Dixneuf, P. H. New Route to Optically Active Amine Derivatives: Ruthenium-Catalyzed Enantioselective Hydrogenation of Ene Carbamates. Tetrahedron: Asymmetry 1999, 10, 3467−3471. (94) Dupau, P.; Le Gendre, P.; Bruneau, C.; Dixneuf, P. H. Optically Active Amine Derivatives: Ruthenium-Catalyzed Enantioselective Hydrogenation of Enamides. Synlett 1999, 1999, 1832−1834. (95) Dupau, P.; Hay, A.-E.; Bruneau, C.; Dixneuf, P. H. Synthesis of Optically Active 2-Aminotetraline Derivatives via Enantioselective Ruthenium-Catalyzed Hydrogenation of Ene Carbamates. Tetrahedron: Asymmetry 2001, 12, 863−867. (96) Renaud, J. L.; Dupau, P.; Hay, A.-E.; Guingouain, M.; Dixneuf, P. H.; Bruneau, C. Ruthenium-Catalysed Enantioselective Hydrogenation of Trisubstituted Enamides Derived from 2-Tetralone and 3Chromanone: Influence of Substitution on the Amide Arm and the Aromatic Ring. Adv. Synth. Catal. 2003, 345, 230−238. (97) Devocelle, M.; Mortreux, A.; Agbossou, F.; Dormoy, J.-R. Alternative Synthesis of the Chiral Atypical β-Adrenergic Phenylethanolaminotetraline Agonist SR58611A Using Enantioselective Hydrogenation. Tetrahedron Lett. 1999, 40, 4551−4554. (98) Pautigny, C.; Debouit, C.; Vayron, P.; Ayad, T.; RatovelomananaVidal, V. Asymmetric Hydrogenation of Trisubstituted N-Acetyl

Enamides Derived from 2-Tetralones Using Ruthenium-SYNPHOS Catalysts: A Practical Synthetic Approach to the Preparation of β3Adrenergic Agonist SR58611A. Tetrahedron: Asymmetry 2010, 21, 1382−1388. (99) Dupau, P.; Bruneau, C.; Dixneuf, P. H. Enantioselective Hydrogenation of the Tetrasubstituted CC Bond of Enamides Catalyzed by a Ruthenium Catalyst Generated in situ. Adv. Synth. Catal. 2001, 343, 331−334. (100) Tang, W.; Wu, S.; Zhang, X. Enantioselective Hydrogenation of Tetrasubstituted Olefins of Cyclic β-(Acylamino)acrylates. J. Am. Chem. Soc. 2003, 125, 9570−9571. (101) Huang, K.; Guan, Z.-H.; Zhang, X. Synthesis of Chiral Cyclic βAmino Ketones by Ru-Catalyzed Asymmetric Hydrogenation. Tetrahedron Lett. 2014, 55, 1686−1688. (102) Kajiwara, T.; Konishi, T.; Yamano, M. Asymmetric Catalytic Hydrogenation for Large Scale Preparation of Optically Active 2-(NBenzoylamino) Cyclohexanecarboxylic Acid Derivatives. Catal. Sci. Technol. 2012, 2, 2146−2152. (103) Burk, M. J.; Casy, G.; Johnson, N. B. A Three-Step Procedure for Asymmetric Catalytic Reductive Amidation of Ketones. J. Org. Chem. 1998, 63, 6084−6085. (104) Zhu, G.; Zhang, X. Asymmetric Rh-Catalyzed Hydrogenation of Enamides with a Chiral Diphenylphosphino Groups. J. Org. Chem. 1998, 63, 9590−9593. (105) Zhang, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Zhang, X. Highly Enantioselective Hydrogenation of Cyclic Enamides Catalyzed by a RhPennPhos Catalyst. J. Org. Chem. 1999, 64, 1774−1775. (106) Tang, W.; Chi, Y.; Zhang, X. An Ortho-Substituted BIPHEP Ligand and Its Applications in Rh-Catalyzed Hydrogenation of Cyclic Enamides. Org. Lett. 2002, 4, 1695−1698. (107) Wu, S.; He, M.; Zhang, X. Synthesis of Ortho-Phenyl Substituted MeO-BIPHEP Ligand and Its Application in Rh-Catalyzed Asymmetric Hydrogenation. Tetrahedron: Asymmetry 2004, 15, 2177−2180. (108) Dai, Q.; Li, W.; Zhang, X. Development of a New Class of C1Symmetric Bisphosphine Ligands for Rhodium-Catalyzed Asymmetric Hydrogenation. Tetrahedron 2008, 64, 6943−6948. (109) Guan, Z.-H.; Huang, K.; Yu, S.; Zhang, X. Synthesis of Enamides via Rh/C-Catalyzed Direct Hydroacylation of Ketoximes. Org. Lett. 2009, 11, 481−483. (110) Zhou, M.; Liu, T.-L.; Cao, M.; Xue, Z.; Lv, H.; Zhang, X. Highly Enantioselective Synthesis of Chiral Cyclic Allylic Amines via RhCatalyzed Asymmetric Hydrogenation. Org. Lett. 2014, 16, 3484−3487. (111) Ma, M.; Hou, G.; Wang, J.; Zhang, X. Rhodium-Catalyzed Asymmetric Hydrogenation of β-Acetylamino Acrylonitriles. Tetrahedron: Asymmetry 2011, 22, 506−511. (112) Meng, J.; Gao, M.; Lv, H.; Zhang, X. Highly Enantioselective Hydrogenation of o-Alkoxy Tetrasubstituted Enamides Catalyzed by a Rh/(R,S)-JosiPhos Catalyst. Org. Lett. 2015, 17, 1842−1845. (113) Liu, G.; Liu, X.; Cai, Z.; Jiao, G.; Xu, G.; Tang, W. Design of Phosphorus Ligands with Deep Chiral Pockets: Practical Synthesis of Chiral β-Arylamines by Asymmetric Hydrogenation. Angew. Chem., Int. Ed. 2013, 52, 4235−4238. (114) Ohashi, A.; Kikuchi, S.; Yasutake, M.; Imamoto, T. Unsymmetrical P-Chirogenic Bis(phosphane) Ligands: Their Preparation and Use in Rhodium-Catalyzed Asymmetric Hydrogenation. Eur. J. Org. Chem. 2002, 2002, 2535−2546. (115) Wu, H.-P.; Hoge, G. Highly Enantioselective Asymmetric Hydrogenation of β-Acetamido Dehydroamino Acid Derivatives Using a Three-Hindered Quadrant Rhodium Catalyst. Org. Lett. 2004, 6, 3645−3647. (116) Revés, M.; Ferrer, C.; León, T.; Doran, S.; Etayo, P.; VidalFerran, A.; Riera, A.; Verdaguer, X. Primary and Secondary Aminophosphines as Novel P-Stereogenic Building Blocks for Ligand Synthesis. Angew. Chem., Int. Ed. 2010, 49, 9452−9455. (117) Cristóbal-Lecina, E.; Etayo, P.; Doran, S.; Revés, M.; MartínGago, P.; Grabulosa, A.; Costantino, A. R.; Vidal-Ferran, A.; Riera, A.; Verdaguer, X. MaxPHOS Ligand: PH/NH Tautomerism and RhodiumCatalyzed Asymmetric Hydrogenations. Adv. Synth. Catal. 2014, 356, 795−804. 14820


Chemical Reviews

Review

Monodentate Phosphoramidite Complex. Tetrahedron Lett. 2002, 43, 5541−5544. (137) van den Berg, M.; Haak, R. M.; Minnaard, A. J.; de Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. Rhodium/MonoPhos-Catalysed Asymmetric Hydrogenation of Enamides. Adv. Synth. Catal. 2002, 344, 1003−1007. (138) Li, X.; Jia, X.; Lu, G.; Au-Yeung, T. T. L.; Lam, K.-H.; Lo, T. W. H.; Chan, A. S. C. Highly Enantioselective Hydrogenation of Enamides Catalyzed by Rhodium-Monodentate Phosphoramidite Complex Derived from H8-BINOL. Tetrahedron: Asymmetry 2003, 14, 2687− 2691. (139) Hoen, R.; van den Berg, M.; Bernsmann, H.; Minnaard, A. J.; de Vries, J. G.; Feringa, B. L. Catechol-Based Phosphoramidites: A New Class of Chiral Ligands for Rhodium-Catalyzed Asymmetric Hydrogenations. Org. Lett. 2004, 6, 1433−1436. (140) Fu, Y.; Guo, X.-X.; Zhu, S.-F.; Hu, A.-G.; Xie, J.-H.; Zhou, Q.-L. Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized Olefins Using Monodentate Spiro Phosphoramidite Ligands. J. Org. Chem. 2004, 69, 4648−4655. (141) Bernsmann, H.; van den Berg, M.; Hoen, R.; Minnaard, A. J.; Mehler, G.; Reetz, M. T.; de Vries, J. G.; Feringa, B. L. PipPhos and MorfPhos: Privileged Monodentate Phosphoramidite Ligands for Rhodium-Catalyzed Asymmetric Hydrogenation. J. Org. Chem. 2005, 70, 943−951. (142) Breuil, P.-A. R.; Reek, J. N. H. Amino Acid Based Phosphoramidite Ligands for the Rhodium-Catalyzed Asymmetric Hydrogenation. Eur. J. Org. Chem. 2009, 2009, 6225−6230. (143) Hannen, P.; Militzer, H.-C.; Vogl, E. M.; Rampf, F. A. New Monodentate Chiral Phosphite Ligands for Asymmetric Hydrogenation. Chem. Commun. 2003, 2210−2211. (144) Huang, H.; Zheng, Z.; Luo, H.; Bai, C.; Hu, X.; Chen, H. A Novel Class of P-O Monophosphite Ligands Derived from D-Mannitol: Broad Applications in High Enantioselective Rh-Catalyzed Hydrogenations. J. Org. Chem. 2004, 69, 2355−2361. (145) Frank, D. J.; Franzke, A.; Pfaltz, A. Asymmetric Hydrogenation Using Rhodium Complexes Generated from Mixtures of Monodentate Neutral and Anionic Phosphorus Ligands. Chem. - Eur. J. 2013, 19, 2405−2415. (146) Guillen, F.; Rivard, M.; Toffano, M.; Legros, J.-Y.; Daran, J.-C.; Fiaud, J.-C. Synthesis and First Applications of a New Family of Chiral Monophosphine Ligand: 2,5-Diphenylphosphospholanes. Tetrahedron 2002, 58, 5895−5904. (147) Enthaler, S.; Hagemann, B.; Junge, K.; Erre, G.; Beller, M. Enantioselective Rhodium-Catalyzed Hydrogenation of Enamides in the Presence of Chiral Monodentate Phosphanes. Eur. J. Org. Chem. 2006, 2006, 2912−2917. (148) Enthaler, S.; Erre, G.; Junge, K.; Holz, J.; Börner, A.; Alberico, E.; Nieddu, I.; Gladiali, S.; Beller, M. Development of Practical Rhodium Phosphine Catalysts for the Hydrogenation of β-Dehydroamino Acid Derivatives. Org. Process Res. Dev. 2007, 11, 568−577. (149) Jiang, X.-B.; Lefort, L.; Goudriaan, P. E.; de Vries, A. H. M.; van Leeuwen, P. W. N. M.; de Vries, J. G.; Reek, J. N. H. Screening of a Supramolecular Catalyst Library in the Search for Selective Catalysts for the Asymmetric Hydrogenation of a Difficult Enamide Substrate. Angew. Chem., Int. Ed. 2006, 45, 1223−1227. (150) Sandee, A. J.; van der Burg, A. M.; Reek, J. N. H. UREAphos: Supramolecular Bidentate Ligands for Asymmetric Hydrogenation. Chem. Commun. 2007, 864−866. (151) Meeuwissen, J.; Kuil, M.; van der Burg, A. M.; Sandee, A. J.; Reek, J. N. H. Application of a Supramolecular-Ligand Library for the Automated Search for Catalysts for the Asymmetric Hydrogenation of Industrially Relevant Substrates. Chem. - Eur. J. 2009, 15, 10272−10279. (152) Patureau, F. W.; de Boer, S.; Kuil, M.; Meeuwissen, J.; Breuil, P.A. R.; Siegler, M. A.; Spek, A. L.; Sandee, A. J.; de Bruin, B.; Reek, J. N. H. Sulfonamido-Phosphoramidite Ligands in Cooperative Dinuclear Hydrogenation Catalysis. J. Am. Chem. Soc. 2009, 131, 6683−6685. (153) Pignataro, L.; Carboni, S.; Civera, M.; Colombo, R.; Piarulli, U.; Gennari, C. Phthalaphos: Chiral Supramolecular Ligands for

(118) Imamoto, T.; Tamura, K.; Zhang, Z.; Horiuchi, Y.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; Gridnev, I. D. Rigid P-Chiral Phosphine Ligands with tert-Butylmethylphosphino Groups for Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized Alkenes. J. Am. Chem. Soc. 2012, 134, 1754−1769. (119) Mohar, B.; Stephan, M. Practical Enantioselective Hydrogenation of α-Aryl- and α-Carboxyamidoethylenes by Rhodium(I)-{1,2Bis[(o-tert-butoxyphenyl)(phenyl)phosphino]ethane}. Adv. Synth. Catal. 2005, 355, 594−600. (120) Zhang, Z.; Hu, Q.; Wang, Y.; Chen, J.; Zhang, W. Rh-Catalyzed Asymmetric Hydrogenation of Cyclic α-Dehydroamino Ketones. Org. Lett. 2015, 17, 5380−5383. (121) Hu, Q.; Chen, J.; Zhang, Z.; Liu, Y.; Zhang, W. Rh-Catalyzed One-Pot Sequential Asymmetric Hydrogenation of α-Dehydroamino Ketones for the Synthesis of Chiral Cyclic trans-β-Amino Alcohols. Org. Lett. 2016, 18, 1290−1293. (122) Fernández-Pérez, H.; Donald, S. M. A.; Munslow, I. J.; BenetBuchholz, J.; Maseras, F.; Vidal-Ferran, A. Highly Modular P-OP Ligands for Asymmetric Hydrogenation: Synthesis, Catalytic Activity, and Mechanism. Chem. - Eur. J. 2010, 16, 6495−6508. (123) Fernández-Pérez, H.; Benet-Buchholz, J.; Vidal-Ferran, A. Small Bite-Angle P-OP Ligands for Asymmetric Hydroformylation and Hydrogenation. Org. Lett. 2013, 15, 3634−3637. (124) Fernández-Pérez, H.; Benet-Buchholz, J.; Vidal-Ferran, A. Enantiopure Narrow Bite-Angle P-OP Ligands: Synthesis and Catalytic Performance in Asymmetric Hydroformylations and Hydrogenations. Chem. - Eur. J. 2014, 20, 15375−15384. (125) Arribas, I.; Rubio, M.; Kleman, P.; Pizzano, A. Rhodium Phosphine-Phosphite Catalysts in the Hydrogenation of Challenging N(3,4-Dihydronaphthalen-2-yl) Amide Derivatives. J. Org. Chem. 2013, 78, 3997−4005. (126) Kleman, P.; Vaquero, M.; Arribas, I.; Suárez, A.; Á lvarez, E.; Pizzano, A. Asymmetric Hydrogenation Reactions with Rh and Ru Complexes Bearing Phosphine-Phosphites with an Oxymethylene Backbone. Tetrahedron: Asymmetry 2014, 25, 744−749. (127) Dydio, P.; Rubay, C.; Gadzikwa, T.; Lutz, M.; Reek, J. N. H. Cofactor”-Controlled Enantioselective Catalysis. J. Am. Chem. Soc. 2011, 133, 17176−17179. (128) Argouarch, G.; Samuel, O.; Kagan, H. B. Synthesis of Some Ferrocene-Based 1,3-Bis(phosphanes) with Planar Chirality as the Sole Source of Chirality. Eur. J. Org. Chem. 2000, 2000, 2885−2891. (129) Argouarch, G.; Samuel, O.; Riant, O.; Daran, J.-C.; Kagan, H. B. A New Class of Ferrocene-Based 1,2-Bis(phosphanes) Possessing Only Planar Chirality. Eur. J. Org. Chem. 2000, 2000, 2893−2899. (130) Lennon, I. C.; Ramsden, J. A.; Brear, C. J.; Broady, S. D.; Muir, J. C. Asymmetric Enamide Hydrogenation in the Synthesis of NAcetylcolchinol: A Key Intermediate for ZD6126. Tetrahedron Lett. 2007, 48, 4623−4626. (131) Zirakzadeh, A.; Groß, M. A.; Wang, Y.; Mereiter, K.; Spindler, F.; Weissensteiner, W. Biferrocene-Based Diphosphine Ligands: Synthesis and Application of Walphos Analogues in Asymmetric Hydrogenations. Organometallics 2013, 32, 1075−1084. (132) Yonehara, K.; Ohe, K.; Uemura, S. Highly Enantioselective Hydrogenation of Enamides and Itaconic Acid in Water in the Presence of Water-Soluble Rhodium(I) Catalyst and Sodium Dodecyl Sulfate. J. Org. Chem. 1999, 64, 9381−9385. (133) Stemmler, R. T.; Bolm, C. Asymmetric Enamide Hydrogenation Using Planar-Chiral Cyrhetrenes. Tetrahedron Lett. 2007, 48, 6189− 6191. (134) Rankic, D. A.; Hopkins, J. M.; Parvez, M.; Keay, B. A. Synthesis and Resolution of 3,3′-Disubstituted XyLBINAP Derivatives and Their Application in Rhodium-Catalyzed Asymmetric Hydrogenation. Synlett 2009, 2009, 2513−2517. (135) Bravo, M. J.; Ceder, R. M.; Muller, G.; Rocamora, M. New Enantiopure P,P-Bidentate Bis(diamidophosphite) Ligands. Application in Asymmetric Rhodium-Catalyzed Hydrogenation. Organometallics 2013, 32, 2632−2642. (136) Jia, X.; Guo, R.; Li, X.; Yao, X.; Chan, A. S. C. Highly Enantioselective Hydrogenation of Enamides Catalyzed by Rhodium14821


Chemical Reviews

Review

Enantioselective Rhodium-Catalyzed Hydrogenation Reactions. Angew. Chem., Int. Ed. 2010, 49, 6633−6637. (154) Pignataro, L.; Boghi, M.; Civera, M.; Carboni, S.; Piarulli, U.; Gennari, C. Rhodium-Catalyzed Asymmetric Hydrogenation of Olefins with PhthalaPhos, a New Class of Chiral Supramolecular Ligands. Chem. - Eur. J. 2012, 18, 1383−1400. (155) Pignataro, L.; Bovio, C.; Civera, M.; Piarulli, U.; Gennari, C. A Library Approach to the Development of BenzaPhos: Highly Efficient Chiral Supramolecular Ligands for Asymmetric Hydrogenation. Chem. Eur. J. 2012, 18, 10368−10381. (156) Evans, D. A.; Michael, F. E.; Tedrow, J. S.; Campos, K. R. Application of Chiral Mixed Phosphorus/Sulfur Ligands to Enantioselective Rhodium-Catalyzed Dehydroamino Acid Hydrogenation and Ketone Hydrosilylation Processes. J. Am. Chem. Soc. 2003, 125, 3534− 3543. (157) Meeuwissen, J.; Detz, R. J.; Sandee, A. J.; de Bruin, B.; Reek, J. N. H. Rhodium-P,O-Bidentate Coordinated Ureaphosphine Ligands for Asymmetric Hydrogenation Reactions. Dalton Trans. 2010, 39, 1929− 1931. (158) Meeuwissen, J.; Detz, R.; Sandee, A. J.; de Bruin, B.; Siegler, M. A.; Spek, A. L.; Reek, J. N. H. Ureaphosphanes as Hybrid, Anionic or Supramolecular Bidentate Ligands for Asymmetric Hydrogenation Reactions. Eur. J. Inorg. Chem. 2010, 2010, 2992−2997. (159) Baeza, A.; Pfaltz, A. Iridium-Catalyzed Asymmetric Hydrogenation of Unfunctionalized Enamines. Chem. - Eur. J. 2009, 15, 2266− 2269. (160) Yan, P.-C.; Xie, J.-H.; Zhou, Q.-L. Asymmetric Hydrogenation of Unfunctionalized Enamines Catalyzed by Iridium Complexes of Chiral Spiro N,N-Diarylphosphoramidites. Chin. J. Chem. 2010, 28, 1736− 1742. (161) Erre, G.; Enthaler, S.; Junge, K.; Addis, D.; Beller, M. IridiumCatalysed Asymmetric Hydrogenation of Enamides in the Presence of 3,3′-Substituted H8-Phosphoramidites. Adv. Synth. Catal. 2009, 351, 1437−1441. (162) Patureau, F. W.; Worch, C.; Siegler, M. A.; Spek, A. L.; Bolm, C.; Reek, J. N. H. SIAPhos: Phosphorylated Sulfonimidamides and Their Use in Iridium-Catalyzed Asymmetric Hydrogenations of Sterically Hindered Cyclic Enamides. Adv. Synth. Catal. 2012, 354, 59−64. (163) Charette, A. B.; Giroux, A. Asymmetric Hydrogenation of NTosylimines Catalyzed by BINAP-Ruthenium(II) Complexes. Tetrahedron Lett. 1996, 37, 6669−6672. (164) Chen, F.; Wang, T.; He, Y.; Ding, Z.; Li, Z.; Xu, L.; Fan, Q.-H. Asymmetric Hydrogenation of N-Alkyl Ketimines with Phosphine-Free, Chiral, Cationic Ru-MsDPEN Catalysts. Chem. - Eur. J. 2011, 17, 1109− 1113. (165) Chen, F.; Ding, Z.; He, Y.; Qin, J.; Wang, T.; Fan, Q.-H. Asymmetric Hydrogenation of N-Alkyl and N-Aryl Ketimines Using Chiral Cationic Ru(diamine) Complexes as Catalysts: The Counteranion and Solvent Effects, and Substrate Scope. Tetrahedron 2012, 68, 5248−5257. (166) Moessner, C.; Bolm, C. Diphenylphosphanylsulfoximines as Ligands in Iridium-Catalyzed Asymmetric Imine Hydrogenations. Angew. Chem., Int. Ed. 2005, 44, 7564−7567. (167) Qu, B.; Samankumara, L. P.; Ma, S.; Fandrick, K. R.; Desrosiers, J.-N.; Rodriguez, S.; Li, Z.; Haddad, N.; Han, Z. S.; McKellop, K.; Pennino, S.; Grinberg, N.; Gonnella, N. C.; Song, J. J.; Senanayake, C. H. A Mild Dihydrobenzooxaphosphole oxazoline/Iridium Catalytic System for Asymmetric Hydrogenation of Unfunctionalized Dialins. Angew. Chem., Int. Ed. 2014, 53, 14428−14432. (168) Trifonova, A.; Diesen, J. S.; Andersson, P. G. Asymmetric Hydrogenation of Imines and Olefins Using Phosphine-Oxazoline Iridium Complexes as Catalysts. Chem. - Eur. J. 2006, 12, 2318−2328. (169) Baeza, A.; Pfaltz, A. Iridium-Catalyzed Asymmetric Hydrogenation of Imines. Chem. - Eur. J. 2010, 16, 4003−4009. (170) Lu, W. J.; Chen, Y.-W.; Hou, X.-L. Highly Enantioselective Iridium-Catalyzed Hydrogenation of Trisubstituted Olefins, α,βUnsaturated Ketones and Imines with Chiral Benzylic Substituted P,N Ligands. Adv. Synth. Catal. 2010, 352, 103−107.

(171) Han, Z.; Wang, Z.; Zhang, X.; Ding, K. Spiro[4,4]-1,6Nonadiene-Based Phosphine-Oxazoline Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of Ketimines. Angew. Chem., Int. Ed. 2009, 48, 5345−5349. (172) Mršić, N.; Minnaard, A. J.; Feringa, B. L.; de Vries, J. G. Iridium/ Monodentate Phosphoramidite Catalyzed Asymmetric Hydrogenation of N-Aryl Imines. J. Am. Chem. Soc. 2009, 131, 8358−8359. (173) Zhong, Y.-L.; Krska, S. W.; Zhou, H.; Reamer, R. A.; Lee, J.; Sun, Y.; Askin, D. Catalytic Asymmetric Synthesis of an HIV Integrase Inhibitor. Org. Lett. 2009, 11, 369−372. (174) Yang, Q.; Shang, G.; Gao, W.; Deng, J.; Zhang, X. A Highly Enantioselective, Pd−TangPhos-Catalyzed Hydrogenation of NTosylimines. Angew. Chem., Int. Ed. 2006, 45, 3832−3835. (175) Zhou, X.-Y.; Bao, M.; Zhou, Y.-G. Palladium-Catalyzed Asymmetric Hydrogenation of Simple Ketimines Using a Brønsted Acid as Activator. Adv. Synth. Catal. 2011, 353, 84−88. (176) Yu, C.-B.; Zhou, Y.-G. Palladium-Catalyzed Asymmetric Hydrogenolysis of N-Sulfonyl Aminoalcohols via Achiral Enesulfonamide Intermediates. Angew. Chem., Int. Ed. 2013, 52, 13365−13368. (177) Yu, C.-B.; Huang, W.-X.; Shi, L.; Chen, M.-W.; Wu, B.; Zhou, Y.G. Asymmetric Hydrogenation via Capture of Active Intermediates Generated from Aza-Pinacol Rearrangement. J. Am. Chem. Soc. 2014, 136, 15837−15840. (178) Ohta, T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Takaya, H. Asymmetric Hydrogenation of Olefins with Aprotic Oxygen Functionalities Catalyzed by BINAP-Ru(II) Complexes. J. Org. Chem. 1995, 60, 357−363. (179) Valla, C.; Baeza, A.; Menges, F.; Pfaltz, A. Enantioselective Synthesis of Chromanes by Iridium-Catalyzed Asymmetric Hydrogenation of 4H-Chromenes. Synlett 2008, 2008, 3167−3171. (180) Chen, Y.-C.; Xue, D.; Deng, J.-G.; Cui, X.; Zhu, J.; Jiang, Y.-Z. Efficient Asymmetric Transfer Hydrogenation of Activated Olefins Catalyzed by Ruthenium Amido Complexes. Tetrahedron Lett. 2004, 45, 1555−1558. (181) Xue, D.; Chen, Y.-C.; Cui, X.; Wang, Q.-W.; Zhu, J.; Deng, J.-G. Transfer Hydrogenation of Activated CC Bonds Catalyzed by Ruthenium Amido Complexes: Reaction Scope, Limitation, and Enantioselectivity. J. Org. Chem. 2005, 70, 3584−3591. (182) Liu, Q.-B.; Zhou, Y.-G. Iridium-Catalyzed Asymmetric Hydrogenation of (2H-Chrmen-3-yl)methanols. Cuihua Xuebao 2007, 28, 847−849. (183) Guo, S.; Yang, P.; Zhou, J. (Steve). Nickel-Catalyzed Asymmetric Transfer Hydrogenation of Conjugated Olefins. Chem. Commun. 2015, 51, 12115−12117. (184) Jiang, Q.; Xiao, D.; Zhang, Z.; Cao, P.; Zhang, X. Highly Enantioselective Hydrogenation of Cyclic Enol Acetates Catalyzed by a Rh-PennPhos Complex. Angew. Chem., Int. Ed. 1999, 38, 516−518. (185) Paptchikhine, A.; Itto, K.; Andersson, P. G. Sequential Birch Reaction and Asymmetric Ir-Catalyzed Hydrogenation as a Route to Chiral Building Blocks. Chem. Commun. 2011, 47, 3989−3991. (186) Cadu, A.; Paptchikhine, A.; Andersson, P. G. Birch Reaction Followed by Asymmetric Iridium-Catalysed Hydrogenation. Synthesis 2011, 2011, 3796−3800. (187) Kuwano, R.; Morioka, R.; Kashiwabara, M.; Kameyama, N. Catalytic Asymmetric Hydrogenation of Naphthalenes. Angew. Chem., Int. Ed. 2012, 51, 4136−4139. (188) Noyori, R.; Ikeda, T.; Ohkuma, T.; Widhalm, M.; Kitamura, M.; Takaya, H.; Akutagawa, S.; Sayo, N.; Saito, T. Stereoselective Hydrogenation via Dynamic Kinetic Resolution. J. Am. Chem. Soc. 1989, 111, 9134−9135. (189) Inoguchi, K.; Achiwa, K. Development of a New Six-Membered Chelating [Bisphosphine]rhodium Catalyst and Efficient Asymmetric Hydrogenatnion of (Z)-2-Acetamidocinnamic Acid. Synlett 1991, 1991, 49−51. (190) Benincori, T.; Brenna, E.; Sannicolo, F.; Trimarco, L.; Antognazza, P.; Cesarotti, E. (Diphenylphosphino)-Biheteroaryls: The First Example of a New Class of Chiral Atropisomeric Chelating Diphosphine Ligands for Transition Metal Catalysed Stereoselective Reactions. J. Chem. Soc., Chem. Commun. 1995, 685−686. 14822


Chemical Reviews

Review

(191) Benincori, T.; Piccolo, O.; Rizzo, S.; Sannicolo, F. 3,3′Bis(diphenylphosphino)-1,1′-Disubstituted-2,2′-Biindoles: Easily Accessible, Electron-Rich, Chiral Diphosphine Ligands for Homogeneous Enantioselective Hydrogenation of Oxoesters. J. Org. Chem. 2000, 65, 8340−8347. (192) Burk, M. J.; Harper, T. G. P.; Kalberg, C. S. Highly Enantioselective Hydrogenation of β-Keto Esters under Mild Conditions. J. Am. Chem. Soc. 1995, 117, 4423−4424. (193) Ireland, T.; Grossheimann, G.; Wieser-Jeunesse, C.; Knochel, P. Ferrocenyl Ligands with Two Phosphanyl Substituents in the α,ε Positions for the Transition Metal Catalyzed Asymmetric Hydrogenation of Functionalized Double Bonds. Angew. Chem., Int. Ed. 1999, 38, 3212−3215. (194) Ireland, T.; Tappe, K.; Grossheimann, G.; Knochel, P. Synthesis of a New Class of Chiral 1,5-Diphosphanylferrocene Ligands and Their Use in Enantioselective Hydrogenation. Chem. - Eur. J. 2002, 8, 843− 852. (195) Tappe, K.; Knochel, P. New Efficient Synthesis of Taniaphos Ligands: Application in Ruthenium- and Rhodium-Catalyzed Enantioselective Hydrogenations. Tetrahedron: Asymmetry 2004, 15, 91−102. (196) Reetz, M. T.; Li, X. Asymmetric Hydrogenation of β-Keto Esters Using Chiral Diphosphonites. Adv. Synth. Catal. 2006, 348, 1157−1160. (197) Yamano, T.; Taya, N.; Kawada, M.; Huang, T.; Imamoto, T. Enantioselective Hydrogenation of β-Keto Esters Catalyzed by P-Chiral Bis(dialkylphosphino)ethanes-Ru(II). Tetrahedron Lett. 1999, 40, 2577−2580. (198) Fukuzawa, S.; Oki, H.; Hosaka, M.; Sugasawa, J.; Kikuchi, S. ClickFerrophos: New Chiral Ferrocenyl Phosphine Ligands Synthesized by Click Chemistry and the Use of Their Metal Complexes as Catalysts for Asymmetric Hydrogenation and Allylic Substitution. Org. Lett. 2007, 9, 5557−5560. (199) Oki, H.; Oura, I.; Nakamura, T.; Ogata, K.; Fukuzawa, S. Modular Synthesis of the ClickFerrophos Ligand Family and Their Use in Rhodium- and Ruthenium-Catalyzed Asymmetric Hydrogenation. Tetrahedron: Asymmetry 2009, 20, 2185−2191. (200) Madduri, A. V. R.; Minnaard, A. J. Formal Synthesis of the AntiAngiogenic Polyketide (−)-Borrelidin under Asymmetric Catalytic Control. Chem. - Eur. J. 2010, 16, 11726−11731. (201) Ortiz, A.; Young, I. S.; Sawyer, J. R.; Hsiao, Y.; Singh, A.; Sugiyama, M.; Corbett, R. M.; Chau, M.; Shi, Z.; Conlon, D. A. Synthetic Approaches to a Chiral 4-Amino-3-Hydroxy Piperidine with Pharmaceutical Relevance. Org. Biomol. Chem. 2012, 10, 5253−5257. (202) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. Practical Enantioselective Hydrogenation of Aromatic Ketones. J. Am. Chem. Soc. 1995, 117, 2675−2676. (203) Ohkuma, T.; Li, J.; Noyori, R. Asymmetric Hydrogenation of 2Arylated Cycloalkanones through Dynamic Kinetic Resolution. Synlett 2004, 2004, 1383−1386. (204) Cheng, L.-J.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. Enantioselective Synthesis of (−)-CP-55940 via Ruthenium-Catalyzed Asymmetric Hydrogenation of Ketones. Adv. Synth. Catal. 2012, 354, 1105− 1113. (205) Liu, C.; Xie, J.-H.; Li, Y.-L.; Chen, J.-Q.; Zhou, Q.-L. Asymmetric Hydrogenation of α,α′-Disubstituted Cycloketones through Dynamic Kinetic Resolution: An Efficient Construction of Chiral Diols with Three Contiguous Stereocenters. Angew. Chem., Int. Ed. 2013, 52, 593− 596. (206) Li, G.; Xie, J.-H.; Hou, J.; Zhu, S.-F.; Zhou, Q.-L. Catalytic Asymmetric Hydrogenation of α-Arylcyclohexanones and Total Synthesis of (−)-α-Lycorane. Adv. Synth. Catal. 2013, 355, 1597−1604. (207) Cheng, L.-J.; Xie, J.-H.; Chen, Y.; Wang, L.-X.; Zhou, Q.-L. Enantioselective Total Synthesis of (−)-Δ8-THC and (−)-Δ9-THC via Catalytic Asymmetric Hydrogenation and SNAr Cyclization. Org. Lett. 2013, 15, 764−767. (208) Liu, S.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. Dynamic Kinetic Resolution Allows a Highly Enantioselective Synthesis of cis-αAminocycloalkanols by Ruthenium-Catalyzed Asymmetric Hydrogenation. Angew. Chem., Int. Ed. 2007, 46, 7506−7508.

(209) Liu, S.; Xie, J.-H.; Li, W.; Kong, W.-L.; Wang, L.-X.; Zhou, Q.-L. Highly Enantioselective Synthesis of Chiral Cyclic Amino Alcohols and Conhydrine by Ruthenium-Catalyzed Asymmetric Hydrogenation. Org. Lett. 2009, 11, 4994−4997. (210) Bai, W.-J.; Xie, J.-H.; Li, Y.-L.; Liu, S.; Zhou, Q.-L. Enantioselective Synthesis of Chiral β-Aryloxy Alcohols by Ruthenium-Catalyzed Ketone Hydrogenation via Dynamic Kinetic Resolution (DKR). Adv. Synth. Catal. 2010, 352, 81−84. (211) Chen, J.-Q.; Xie, J.-H.; Bao, D.-H.; Liu, S.; Zhou, Q.-L. Total Synthesis of (−)-Galanthamine and (−)-Lycoramine via Catalytic Asymmetric Hydrogenation and Intramolecular Reductive Heck Cyclization. Org. Lett. 2012, 14, 2714−2717. (212) Huang, X.-F.; Zhang, S.-Y.; Geng, Z.-C.; Kwok, C.-Y.; Liu, P.; Li, H.-Y.; Wang, X.-W. Asymmetric Hydrogenation of β-Keto Sulfonamides and β-Keto Sulfones with a Chiral Cationic Ruthenium Diamine Catalyst. Adv. Synth. Catal. 2013, 355, 2860−2872. (213) Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. Preferential Hydrogenation of Aldehydes and Ketones. J. Am. Chem. Soc. 1995, 117, 10417−10418. (214) Ohkuma, T.; Doucet, H.; Pham, T.; Mikami, K.; Korenaga, T.; Terada, M.; Noyori, R. Asymmetric Activation of Racemic Ruthenium(II) Complexes for Enantioselective Hydrogenation. J. Am. Chem. Soc. 1998, 120, 1086−1087. (215) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. trans[RuCl2(phosphane)2(1,2-diamine)] and Chiral trans[RuCl2(diphosphane)(1,2-diamine)]: Shelf-Stable Precatalysts for the Rapid, Productive, and Stereoselective Hydrogenation of Ketones. Angew. Chem., Int. Ed. 1998, 37, 1703−1707. (216) Ohkuma, T.; Ikehira, H.; Ikariya, T.; Noyori, R. Asymmetric Hydrogenation of Cyclic α,β-Unsaturated Ketones to Chiral Allylic Alcohols. Synlett 1997, 1997, 467−468. (217) Ohkuma, T.; Hattori, T.; Ooka, H.; Inoue, T.; Noyori, R. BINAP/1,4-Diamine-Ruthenium(II) Complexes for Efficient Asymmetric Hydrogenation of 1-Tetralones and Analogues. Org. Lett. 2004, 6, 2681−2683. (218) Touge, T.; Hakamata, T.; Nara, H.; Kobayashi, T.; Sayo, N.; Saito, T.; Kayaki, Y.; Ikariya, T. Oxo-Tethered Ruthenium(II) Complex as a Bifunctional Catalyst for Asymmetric Transfer Hydrogenation and H2 Hydrogenation. J. Am. Chem. Soc. 2011, 133, 14960−14963. (219) Patchett, R.; Magpantay, I.; Saudan, L.; Schotes, C.; Mezzetti, A.; Santoro, F. Asymmetric Hydrogenation of Ketones with H2 and Ruthenium Catalysts Containing Chiral Tetradentate S2N2 Ligands. Angew. Chem., Int. Ed. 2013, 52, 10352−10355. (220) Chen, X.; Zhou, H.; Zhang, K.; Li, J.; Huang, H. Highly Enantioselective Hydrogenation of Steric Hindrance Enones Catalyzed by Ru Complexes with Chiral Diamine and Achiral Phosphane. Org. Lett. 2014, 16, 3912−3915. (221) Zhao, D.; Beiring, B.; Glorius, F. Ruthenium-NHC-Catalyzed Asymmetric Hydrogenation of Flavones and Chromones: General Access to Enantiomerically Enriched Flavanones, Flavanols, Chromanones, and Chromanols. Angew. Chem., Int. Ed. 2013, 52, 8454−8458. (222) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation of Ketones Using a Formic Acid-Triethylamine Mixture. J. Am. Chem. Soc. 1996, 118, 2521−2522. (223) Hong, Y.; Chen, J.; Zhang, Z.; Liu, Y.; Zhang, W. Ru-Catalyzed Asymmetric Hydrogenative/Transfer Hydrogenative Desymmetrization of Meso-Epoxy Diketones. Org. Lett. 2016, 18, 2640−2643. (224) Palmer, M.; Walsgrove, T.; Wills, M. (1R,2S)-(+)-cis-1-Amino2-Indanol: An Effective Ligand for Asymmetric Catalysis of Transfer Hydrogenations of Ketones. J. Org. Chem. 1997, 62, 5226−5228. (225) Hannedouche, J.; Clarkson, G. J.; Wills, M. A New Class of “Tethered” Ruthenium(II) Catalyst for Asymmetric Transfer Hydrogenation Reactions. J. Am. Chem. Soc. 2004, 126, 986−987. (226) Manville, C. V.; Docherty, G.; Padda, R.; Wills, M. Application of Proline-Functionalized 1,2-Diphenylethane-1,2-Diamine (DPEN) in Asymmetric Transfer Hydrogenation of Ketones. Eur. J. Org. Chem. 2011, 2011, 6893−6901. 14823


Chemical Reviews

Review

(227) Soni, R.; Collinson, J.-M.; Clarkson, G. C.; Wills, M. An Unexpected Directing Effect in the Asymmetric Transfer Hydrogenation of α,α-Disubstituted Ketones. Org. Lett. 2011, 13, 4304−4307. (228) Jolley, K. E.; Zanotti-Gerosa, A.; Hancock, F.; Dyke, A.; Grainger, D. M.; Medlock, J. A.; Nedden, H. G.; Le Paih, J. J. M.; Roseblade, S. J.; Seger, A.; Sivakumar, V.; Prokes, I.; Morris, D. J.; Wills, M. Application of Tethered Ruthenium Catalysts to Asymmetric Hydrogenation of Ketones, and the Selective Hydrogenation of Aldehydes. Adv. Synth. Catal. 2012, 354, 2545−2555. (229) Soni, R.; Jolley, K. E.; Clarkson, G. J.; Wills, M. Direct Formation of Tethered Ru(II) Catalysts Using Arene Exchange. Org. Lett. 2013, 15, 5110−5113. (230) Cambeiro, X. C.; Pericàs, M. A. Proline-Derived Aminotriazole Ligands: Preparation and Use in the Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation. Adv. Synth. Catal. 2011, 353, 113−124. (231) Zhang, B.; Wang, H.; Lin, G.-Q.; Xu, M.-H. Ruthenium(II)Catalyzed Asymmetric Transfer Hydrogenation Using Unsymmetrical Vicinal Diamine-Based Ligands: Dramatic Substituent Effect on Catalyst Efficiency. Eur. J. Org. Chem. 2011, 2011, 4205−4211. (232) Ohkuma, T.; Sandoval, C. A.; Srinivasan, R.; Lin, Q.; Wei, Y.; Muñiz, K.; Noyori, R. Asymmetric Hydrogenation of tert-Alkyl Ketones. J. Am. Chem. Soc. 2005, 127, 8288−8289. (233) Grasa, G. A.; Zanotti-Gerosa, A.; Medlock, J. A.; Hems, W. P. Asymmetric Hydrogenation of Isobutyrophenone Using a [(Diphosphine)RuCl2(1,4-diamine)] Catalyst. Org. Lett. 2005, 7, 1449−1451. (234) Li, Y.; Zhou, Y.; Shi, Q.; Ding, K.; Noyori, R.; Sandoval, C. A. An Efficient Diphosphine/Hybrid-Amine Combination for Ruthenium(II)Catalyzed Asymmetric Hydrogenation of Aryl Ketones. Adv. Synth. Catal. 2011, 353, 495−500. (235) Zhu, Q.; Shi, D.; Xia, C.; Huang, H. Ruthenium Catalysts Containing Rigid Chiral Diamines and Achiral Diphosphanes for Highly Enantioselective Hydrogenation of Aromatic Ketones. Chem. - Eur. J. 2011, 17, 7760−7763. (236) Zhou, H.; Huang, H. A Ruthenium Catalyst with Simple Triphenylphosphane for the Enantioselective Hydrogenation of Aromatic Ketones. ChemCatChem 2013, 5, 2253−2257. (237) Matsumura, K.; Arai, N.; Hori, K.; Saito, T.; Sayo, N.; Ohkuma, T. Chiral Ruthenabicyclic Complexes: Precatalysts for Rapid, Enantioselective, and Wide-Scope Hydrogenation of Ketones. J. Am. Chem. Soc. 2011, 133, 10696−10699. (238) Rodríguez, S.; Qu, B.; Fandrick, K. R.; Buono, F.; Haddad, N.; Xu, Y.; Herbage, M. A.; Zeng, X.; Ma, S.; Grinberg, N.; Lee, H.; Han, Z. S.; Yee, N. K.; Senanayake, C. H. Amine-Tunable Ruthenium Catalysts for Asymmetric Reduction of Ketones. Adv. Synth. Catal. 2014, 356, 301−307. (239) Ito, M.; Endo, Y.; Ikariya, T. Well-Defined TriflylamideTethered Arene-Ru(Tsdpen) Complexes for Catalytic Asymmetric Hydrogenation of Ketones. Organometallics 2008, 27, 6053−6055. (240) Huang, H.; Okuno, T.; Tsuda, K.; Yoshimura, M.; Kitamura, M. Enantioselective Hydrogenation of Aromatic Ketones Catalyzed by Ru Complexes of Goodwin-Lions-Type sp2N/sp3N Hybrid Ligands RBINAN-R′-Py. J. Am. Chem. Soc. 2006, 128, 8716−8717. (241) Guo, H.; Liu, D.; Butt, N. A.; Liu, Y.; Zhang, W. Efficient Ru(II)Catalyzed Asymmetric Hydrogenation of Simple Ketones with C2Symmetric Planar Chiral Metallocenyl Phosphinooxazoline Ligands. Tetrahedron 2012, 68, 3295−3299. (242) Nishibayashi, Y.; Takei, I.; Uemura, S.; Hidai, M. Extremely High Enantioselective Redox Reaction of Ketones and Alcohols Catalyzed by RuCl2(PPh3)(oxazolinylferrocenylphosphine). Organometallics 1999, 18, 2291−2293. (243) Zhang, X.; Taketomi, T.; Yoshizumi, T.; Kumobayashi, H.; Akutagawa, S.; Mashima, K.; Takaya, H. Asymmetric Hydrogenation of Cycloakanones Catalyzed by BINAP-Ir(I)-Aminopbosphine Systems. J. Am. Chem. Soc. 1993, 115, 3318−3319. (244) Martins, J. E. D.; Morris, D. J.; Wills, M. Asymmetric Hydrogenation of Ketones Using Ir(III) Complexes of N-Alkyl-N′Tosyl-1,2-Ethanediamine Ligands. Tetrahedron Lett. 2009, 50, 688−692.

(245) Martins, J. E. D.; Wills, M. Ir(III) Complexes of Diamine Ligands for Asymmetric Ketone Hydrogenation. Tetrahedron 2009, 65, 5782− 5786. (246) Xie, J.-B.; Xie, J.-H.; Liu, X.-Y.; Kong, W.-L.; Li, S.; Zhou, Q.-L. Highly Enantioselective Hydrogenation of α-Arylmethylene Cycloalkanones Catalyzed by Iridium Complexes of Chiral Spiro Aminophosphine Ligands. J. Am. Chem. Soc. 2010, 132, 4538−4539. (247) Xie, J.-B.; Xie, J.-H.; Liu, X.-Y.; Zhang, Q.-Q.; Zhou, Q.-L. Chiral Iridium Spiro Aminophosphine Complexes: Asymmetric Hydrogenation of Simple Ketones, Structure, and Plausible Mechanism. Chem. - Asian J. 2011, 6, 899−908. (248) Himeda, Y.; Onozawa-komatsuzaki, N.; Sugihara, H.; Arakawa, H.; Kasuga, K. Transfer Hydrogenation of a Variety of Ketones Catalyzed by Rhodium Complexes in Aqueous Solution and Their Application to Asymmetric Reduction Using Chiral Schiff Base Ligands. J. Mol. Catal. A: Chem. 2003, 195, 95−100. (249) Matharu, D. S.; Morris, D. J.; Clarkson, G. J.; Wills, M. An Outstanding Catalyst for Asymmetric Transfer Hydrogenation in Aqueous Solution and Formic Acid/Triethylamine. Chem. Commun. 2006, 3232−3234. (250) Gajewski, P.; Renom-Carrasco, M.; Facchini, S. V.; Pignataro, L.; Lefort, L.; de Vries, J. G.; Ferraccioli, R.; Forni, A.; Piarulli, U.; Gennari, C. Chiral (Cyclopentadienone)iron Complexes for the Catalytic Asymmetric Hydrogenation of Ketones. Eur. J. Org. Chem. 2015, 2015, 1887−1893. (251) Li, W.; Schlepphorst, C.; Daniliuc, C.; Glorius, F. Asymmetric Hydrogenation of Vinylthioethers: Access to Optically Active 1,5Benzothiazepine Derivatives. Angew. Chem., Int. Ed. 2016, 55, 3300− 3303. (252) Zhou, T.; Peters, B.; Maldonado, M. F.; Govender, T.; Andersson, P. G. Enantioselective Synthesis of Chiral Sulfones by IrCatalyzed Asymmetric Hydrogenation: A Facile Approach to the Preparation of Chiral Allylic and Homoallylic Compounds. J. Am. Chem. Soc. 2012, 134, 13592−12595. (253) Oppolzer, W.; Wills, M.; Starkemann, C.; Bernardinelli, G. Chiral Toluene-2,α-Sultam Auxiliaries: Preparation and Sturcture of Enantiomerically Pure (R)- and (S)-Ethyl-2−1′-Sultam. Tetrahedron Lett. 1990, 31, 4117−4120. (254) Ahn, K. H.; Ham, C.; Kim, S.-K.; Cho, C.-W. Practical Synthesis of Chiral Sultam Auxiliaries: 3-Substituted 1,2-Benzisothiazoline 1,1Dioxides. J. Org. Chem. 1997, 62, 7047−7048. (255) Chen, F.; Li, Z.; He, Y.; Fan, Q.-H. Asymmetric Hydrogenation of Cyclic N-Sulfonylimines with Phosphine-Free Chiral Cationic RuMsDPEN Catalysts. Chin. J. Chem. 2010, 28, 1529−1532. (256) Vilhanová, B.; Václavík, J.; Šot, P.; Pechácě k, J.; Zápal, J.; Pažout, R.; Maixner, J.; Kuzma, M.; Kačer, P. Enantioselective Hydrogenation of Cyclic Imines Catalysed by Noyori-Ikariya Half-Sandwich Complexes and Their Analogues. Chem. Commun. 2016, 52, 362−365. (257) Wang, L.; Zhou, Q.; Qu, C.; Wang, Q.; Cun, L.; Zhu, J.; Deng, J. Efficient Asymmetric Transfer Hydrogenation of N-Sulfonylimines on Water. Tetrahedron 2013, 69, 6500−6506. (258) Shende, V. S.; Deshpande, S. H.; Shingote, S. K.; Joseph, A.; Kelkar, A. A. Asymmetric Transfer Hydrogenation of Imines in Water by Varying the Ratio of Formic Acid to Triethylamine. Org. Lett. 2015, 17, 2878−2881. (259) Wang, Y.-Q.; Lu, S.-M.; Zhou, Y.-G. Highly Enantioselective PdCatalyzed Asymmetric Hydrogenation of N-Diphenylphosphinyl Ketimines. J. Org. Chem. 2007, 72, 3729−3734. (260) Wang, Y.-Q.; Yu, C.-B.; Wang, D.-W.; Wang, X.-B.; Zhou, Y.-G. Enantioselective Synthesis of Cyclic Sulfamidates via Pd-Catalyzed Hydrogenation. Org. Lett. 2008, 10, 2071−2074. (261) Yu, C.-B.; Wang, D.-W.; Zhou, Y.-G. Highly Enantioselective Synthesis of Sultams via Pd-Catalyzed Hydrogenation. J. Org. Chem. 2009, 74, 5633−5635. (262) Yu, C.-B.; Gao, K.; Wang, D.-S.; Shi, L.; Zhou, Y.-G. Enantioselective Pd-Catalyzed Hydrogenation of Enesulfonamides. Chem. Commun. 2011, 47, 5052−5054. (263) Yu, C.-B.; Gao, K.; Chen, Q.-A.; Chen, M.-W.; Zhou, Y.-G. Enantioselective Pd-Catalyzed Hydrogenation of Tetrasubstituted 14824


Chemical Reviews

Review

Olefins of Cyclic β-(Arylsulfonamido)acrylates. Tetrahedron Lett. 2012, 53, 2560−2563. (264) Song, B.; Yu, C.-B.; Huang, W.-X.; Chen, M.-W.; Zhou, Y.-G. Formal Palladium-Catalyzed Asymmetric Hydrogenolysis of Racemic N-Sulfonyloxaziridines. Org. Lett. 2015, 17, 190−193. (265) Xu, H.; Yang, P.; Chuanprasit, P.; Hirao, H.; Zhou, J. (Steve). Nickel-Catalyzed Asymmetric Transfer Hydrogenation of Hydrazones and Other Ketimines. Angew. Chem., Int. Ed. 2015, 54, 5112−5116. (266) Massonneau, V.; Le Maux, P.; Simonneaux, G. Catalytic Asymmetric Hydrogenation of α,β-Unsaturated Ketones Using Chiral Ruthenium Hydride Complexes. Tetrahedron Lett. 1986, 27, 5497− 5498. (267) Massonneau, V.; Le Maux, P.; Simonneaux, G. Catalytic Asymmetric Synthesis II. Hydrogenation of α,β-Unsaturated Ketones Using Chiral Ruthenium Complexes. J. Organomet. Chem. 1987, 327, 269−273. (268) Ohta, T.; Miyake, T.; Seido, N.; Kumohayashi, H. Asymmetric Hydrogenation of Unsaturated Carbonyl Compounds Catalyzed by BINAP-Ru(II) Complexes. Enantioselective Synthesis of γ-Butyrolactones and Cyclopentanones. Tetrahedron Lett. 1992, 33, 635−638. (269) Bartholomäus, R.; Dommershausen, F.; Thiele, M.; Karanjule, N. S.; Harms, K.; Koert, U. Total Synthesis of the Postulated Structure of Fulicineroside. Chem. - Eur. J. 2013, 19, 7423−7436. (270) Chung, J. Y. L.; Zhao, D.; Hughes, D. L.; McNamara, J. M.; Grabowski, E. J. J.; Reider, P. J. Asymmetric Hydrogenation of 3Alkylidene-2-Piperidones Using Noyori’s Catalyst. Effect of NSubstituents on the Enantioselectivity. Tetrahedron Lett. 1995, 36, 7379−7382. (271) Bronze-Uhle, E. S.; de Sairre, M. I.; Donate, P. M.; Frederico, D. Enantioselective Hydrogenation of 4-(Hydroxymethyl)furan-2(5H)One Derivatives. J. Mol. Catal. A: Chem. 2006, 259, 103−107. (272) Adam, J.-M.; Foricher, J.; Hanlon, S.; Lohri, B.; Schmid, R.; Stahr, H.; Weber, M.; Wirz, B.; Zutter, U. Development of a Scalable Synthesis of (S)-3-Fluoromethyl-γ-Butyrolactone, Building Block for Carmegliptin’s Lactam Moiety. Org. Process Res. Dev. 2011, 15, 515− 526. (273) Ohshima, T.; Tadaoka, H.; Hori, K.; Sayo, N.; Mashima, K. Highly Enantio- and s-trans CC Bond Selective Catalytic Hydrogenation of Cyclic Enones: Alternative Synthesis of (−)-Menthol. Chem. - Eur. J. 2008, 14, 2060−2066. (274) Scheuermann née Taylor, C. J. S.; Jaekel, C. Enantioselective Hydrogenation of Enones with a Hydroformylation Catalyst. Adv. Synth. Catal. 2008, 350, 2708−2714. (275) Ulgheri, F.; Marchetti, M.; Piccolo, O. Enantioselective Synthesis of (S)- and (R)-Tolterodine by Asymmetric Hydrogenation of a Coumarin Derivative Obtained by a Heck Reaction. J. Org. Chem. 2007, 72, 6056−6059. (276) Bisset, A. A.; Shiibashi, A.; Desmond, J. L.; Dishington, A.; Jones, T.; Clarkson, G. J.; Ikariya, T.; Wills, M. Synthesis and Asymmetric Hydrogenation of (3E)-1-Benzyl-3-[(2-Oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-Dione. Chem. Commun. 2012, 48, 11978− 11980. (277) Yue, T.-Y.; Nugent, W. A. Enantioselective Hydrogenation of 3Alkylidenelactams: High-Throughput Screening Provides a Surprising Solution. J. Am. Chem. Soc. 2002, 124, 13692−13693. (278) Yue, T.-Y.; McLeod, D. D.; Albertson, K. B.; Beck, S. R.; Deerberg, J.; Fortunak, J. M.; Nugent, W. A.; Radesca, L. A.; Tang, L.; Xiang, C. D. Stereoselective Process for a CCR3 Antagonist. Org. Process Res. Dev. 2006, 10, 262−271. (279) Lu, S.-M.; Bolm, C. Highly Enantioselective Synthesis of Optically Active Ketones by Iridium-Catalyzed Asymmetric Hydrogenation. Angew. Chem., Int. Ed. 2008, 47, 8920−8923. (280) Lu, W.-J.; Chen, Y.-W.; Hou, X.-L. Iridium-Catalyzed Highly Enantioselective Hydrogenation of the CC Bond of α,β-Unsaturated Ketones. Angew. Chem., Int. Ed. 2008, 47, 10133−10136. (281) Tian, F.; Yao, D.; Liu, Y.; Xie, F.; Zhang, W. Iridium-Catalyzed Highly Enantioselective Hydrogenation of α,β-Unsaturated Carbonyl Compounds. Adv. Synth. Catal. 2010, 352, 1841−1845.

(282) Liu, Y.; Yao, D.; Li, K.; Tian, F.; Xie, F.; Zhang, W. IridiumCatalyzed Asymmetric Hydrogenation of 3-Substituted Unsaturated Oxindoles to Prepare C3-Mono Substituted Oxindoles. Tetrahedron 2011, 67, 8445−8450. (283) Liu, Y.; Zhang, W. Iridium-Catalyzed Asymmetric Hydrogenation of α-Alkylidene Succinimides. Angew. Chem., Int. Ed. 2013, 52, 2203−2206. (284) Liu, Y.; Gridnev, I. D.; Zhang, W. Mechanism of the Asymmetric Hydrogenation of Exocyclic α,β-Unsaturated Carbonyl Compounds with an Iridium/BiphPhox Catalyst: NMR and DFT Studies. Angew. Chem., Int. Ed. 2014, 53, 1901−1905. (285) Li, J.-Q.; Quan, X.; Andersson, P. G. Highly Enantioselective Iridium-Catalyzed Hydrogenation of α,β-Unsaturated Esters. Chem. Eur. J. 2012, 18, 10609−10616. (286) Woodmansee, D. H.; Müller, M.-A.; Tröndlin, L.; Hörmann, E.; Pfaltz, A. Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Esters with Chiral Iridium N,P Ligand Complexes. Chem. - Eur. J. 2012, 18, 13780−13786. (287) Maurer, F.; Huch, V.; Ullrich, A.; Kazmaier, U. Development of Catalysts for the Stereoselective Hydrogenation of α,β-Unsaturated Ketones. J. Org. Chem. 2012, 77, 5139−5143. (288) Liu, X.; Han, Z.; Wang, Z.; Ding, K. SpinPhox/Iridium(I)Catalyzed Asymmetric Hydrogenation of Cyclic α-Alkylidene Carbonyl Compounds. Angew. Chem., Int. Ed. 2014, 53, 1978−1982. (289) Wang, X.; Han, Z.; Wang, Z.; Ding, K. Catalytic Asymmetric Synthesis of Aromatic Spiroketals by Spinphox/Iridium(I)-Catalyzed Hydrogenation and Spiroketalization of α,α′-Bis(2-hydroxyarylidene) Ketones. Angew. Chem., Int. Ed. 2012, 51, 936−940. (290) Wang, X.; Guo, P.; Wang, X.; Wang, Z.; Ding, K. Practical Asymmetric Catalytic Synthesis of Spiroketals and Chiral Diphosphine Ligands. Adv. Synth. Catal. 2013, 355, 2900−2907. (291) Kamlage, S.; Sefkow, M.; Zimmermann, N.; Peter, M. G. Concise Synthesis of (+)-β-Benzyl γ-Butyrolactones from Butynediol. Synlett 2002, 2002, 77−80. (292) Hilgraf, R.; Pfaltz, A. Chiral Bis(N-sulfonylamino)phosphineand TADDOL-Phosphite-Oxazoline Ligands: Synthesis and Application in Asymmetric Catalysis. Adv. Synth. Catal. 2005, 347, 61−77. (293) Bernasconi, M.; Müller, M.-A.; Pfaltz, A. Asymmetric Hydrogenation of Maleic Acid Diesters and Anhydrides. Angew. Chem., Int. Ed. 2014, 53, 5385−5388. (294) Shimizu, H.; Nagano, T.; Sayo, N.; Saito, T.; Ohshima, T.; Mashima, K. Asymmetric Hydrogenation of Heteroaromatic Ketones and Cyclic and Acyclic Enones Mediated by Cu(I)-Chiral Diphosphine Catalysts. Synlett 2009, 2009, 3143−3146. (295) Hayashi, T.; Kawamura, N.; Ito, Y. Catalytic Asymmetric Hydrogenation of β-Disubstituted α-Phenylacrylic Acids. Asymmetric Synthesis of Carboxylic Acids Containing Two Vicinal Chiral Carbon Centers. Tetrahedron Lett. 1988, 29, 5969−5972. (296) Calvin, J. R.; Frederick, M. O.; Laird, D. L. T.; Remacle, J. R.; May, S. A. Rhodium-Catalyzed and Zinc(II)-Triflate-Promoted Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones. Org. Lett. 2012, 14, 1038−1041. (297) Tiefenbacher, K.; Tröndlin, L.; Mulzer, J.; Pfaltz, A. An Expeditious Asymmetric Formal Synthesis of the Antibiotic Platensimycin. Tetrahedron 2010, 66, 6508−6513. (298) Cozzi, P. G.; Zimmermann, N.; Hilgraf, R.; Schaffner, S.; Pfaltz, A. Chiral Phosphinopyrrolyl-Oxazolines: A New Class of Easily Prepared, Modular P,N-Ligands. Adv. Synth. Catal. 2001, 343, 450−454. (299) Menges, F.; Neuburger, M.; Pfaltz, A. Synthesis and Application of Chiral Phosphino-Imidazoline Ligands: Ir-Catalyzed Enantioselective Hydrogenation. Org. Lett. 2002, 4, 4713−4716. (300) Smidt, S. P.; Menges, F.; Pfaltz, A. SimplePHOX, a Readily Available Chiral Ligand System for Iridium-Catalyzed Asymmetric Hydrogenation. Org. Lett. 2004, 6, 2023−2026. (301) Schrems, M. G.; Pfaltz, A. NeoPHOX−an Easily Accessible P,NLigand for Iridium-Catalyzed Asymmetric Hydrogenation: Preparation, Scope and Application in the Synthesis of Demethyl Methoxycalamenene. Chem. Commun. 2009, 6210−6212. 14825


Chemical Reviews

Review

(302) Blankenstein, J.; Pfaltz, A. A New Class of Modular PhosphiniteOxazoline Ligands: Ir-Catalyzed Enantioselective Hydrogenation of Alkenes. Angew. Chem., Int. Ed. 2001, 40, 4445−4447. (303) Menges, F.; Pfaltz, A. Threonine-Derived Phosphinite-Oxazoline Ligands for the Ir-Catalyzed Enantioselective Hydrogenation. Adv. Synth. Catal. 2002, 344, 40−41. (304) Schönleber, M.; Hilgraf, R.; Pfaltz, A. Chiral Bis(N-arylamino)phosphine-Oxazolines: Synthesis and Application in Asymmetric Catalysis. Adv. Synth. Catal. 2008, 350, 2033−2038. (305) Schrems, M. G.; Neumann, E.; Pfaltz, A. Iridium-Catalyzed Asymmetric Hydrogenation of Unfunctionalized Tetrasubstituted Olefins. Angew. Chem., Int. Ed. 2007, 46, 8274−8276. (306) Schumacher, A.; Schrems, M. G.; Pfaltz, A. Enantioselective Synthesis of cis-1,2-Disubstituted Cyclopentanes and Cyclohexanes by Suzuki−Miyaura Cross-Coupling and Iridium-Catalyzed Asymmetric Hydrogenation. Chem. - Eur. J. 2011, 17, 13502−13509. (307) Kaiser, S.; Smidt, S. P.; Pfaltz, A. Iridium Catalysts with Bicyclic Pyridine-Phosphinite Ligands: Asymmetric Hydrogenation of Olefins and Furan Derivatives. Angew. Chem., Int. Ed. 2006, 45, 5194−5197. (308) Woodmansee, D. H.; Müller, M.-A.; Neuburger, M.; Pfaltz, A. Chiral Pyridyl Phosphinites with Large Aryl Substituents as Efficient Ligands for the Asymmetric Iridium-Catalyzed Hydrogenation of Difficult Substrates. Chem. Sci. 2010, 1, 72. (309) Schumacher, A.; Bernasconi, M.; Pfaltz, A. Chiral NHeterocyclic Carbene/Pyridine Ligands for the Iridium-Catalyzed Asymmetric Hydrogenation of Olefins. Angew. Chem., Int. Ed. 2013, 52, 7422−7425. (310) Källström, K.; Hedberg, C.; Brandt, P.; Bayer, A.; Andersson, P. G. Rationally Designed Ligands for Asymmetric Iridium-Catalyzed Hydrogenation of Olefins. J. Am. Chem. Soc. 2004, 126, 14308−14309. (311) Hedberg, C.; Källström, K.; Brandt, P.; Hansen, L. K.; Andersson, P. G. Asymmetric Hydrogenation of Trisubstituted Olefins with Iridium-Phosphine Thiazole Complexes: A Further Investigation of the Ligand Structure. J. Am. Chem. Soc. 2006, 128, 2995−3001. (312) Cheruku, P.; Paptchikhine, A.; Ali, M.; Neudö rfl, J.-M.; Andersson, P. G. Development of New Thiazole-Based Iridium Catalysts and Their Applications in the Asymmetric Hydrogenation of Trisubstituted Olefins. Org. Biomol. Chem. 2008, 6, 366−373. (313) Källström, K.; Andersson, P. G. Asymmetric Hydrogenation of Tri-Substituted Alkenes with Ir-NHC-Thiazole Complexes. Tetrahedron Lett. 2006, 47, 7477−7480. (314) Kaukoranta, P.; Engman, M.; Hedberg, C.; Bergquist, J.; Andersson, P. G. Iridium Catalysts with Chiral Imidazole-Phosphine Ligands for Asymmetric Hydrogenation of Vinyl Fluorides and Other Olefins. Adv. Synth. Catal. 2008, 350, 1168−1176. (315) Trifonova, A.; Diesen, J. S.; Chapman, C. J.; Andersson, P. G. Application of Phosphine-Oxazoline Ligands in Ir-Catalyzed Asymmetric Hydrogenation of Acyclic Aromatic N-Arylimines. Org. Lett. 2004, 6, 3825−3827. (316) Li, J.-Q.; Paptchikhine, A.; Govender, T.; Andersson, P. G. Bicyclic Phosphine-Thiazole Ligands for the Asymmetric Hydrogenation of Olefins. Tetrahedron: Asymmetry 2010, 21, 1328−1333. (317) Chakka, S. K.; Peters, B. K.; Andersson, P. G.; Maguire, G. E. M.; Kruger, H. G.; Govender, T. Iridium-Catalyzed Asymmetric Hydrogenation of Olefins Using TIQ Phosphine-Oxazoline Ligands. Tetrahedron: Asymmetry 2010, 21, 2295−2301. (318) Yotapan, N.; Paptchikhine, A.; Bera, M.; Avula, S. K.; Vilaivan, T.; Andersson, P. G. Simple Proline-Derived Phosphine-Thiazole Iridium Complexes for Asymmetric Hydrogenation of Trisubstituted Olefins. Asian J. Org. Chem. 2013, 2, 674−680. (319) Verendel, J. J.; Andersson, P. G. Development of Pinene-Derived N,P Ligands and Their Ultility in Catalytic Asymmetric Hydrogenation. Dalton Trans. 2007, 5603−5610. (320) Quan, X.; Parihar, V. S.; Bera, M.; Andersson, P. G. Iridium Catalysts with Chiral Bicyclic Pyridine-Phosphane Ligands for the Asymmetric Hydrogenation of Olefins. Eur. J. Org. Chem. 2014, 2014, 140−146. (321) Diéguez, M.; Mazuela, J.; Pàmies, O.; Verendel, J. J.; Andersson, P. G. Biaryl Phosphite-Oxazolines from Hydroxyl Aminoacid

Derivatives: Highly Efficient Modular Ligands for Ir-Catalyzed Hydrogenation of Alkenes. Chem. Commun. 2008, 3888−3890. (322) Mazuela, J.; Pàmies, O.; Diéguez, M. Expanded Scope of the Asymmetric Hydrogenation of Minimally Functionalized Olefins Catalyzed by Iridium Complexes with Phosphite−Thiazoline Ligands. ChemCatChem 2013, 5, 2410−2417. (323) Mazuela, J.; Paptchikhine, A.; Pàmies, O.; Andersson, P. G.; Diéguez, M. Adaptative Biaryl Phosphite-Oxazole and PhosphiteThiazole Ligands for Asymmetric Ir-Catalyzed Hydrogenation of Alkenes. Chem. - Eur. J. 2010, 16, 4567−4576. (324) Mazuela, J.; Norrby, P.-O.; Andersson, P. G.; Pàmies, O.; Diéguez, M. Pyranoside Phosphite-Oxazoline Ligands for the Highly Versatile and Enantioselective Ir-Catalyzed Hydrogenation of Minimally Functionalized Olefins. A Combined Theoretical and Experimental Study. J. Am. Chem. Soc. 2011, 133, 13634−13645. (325) Mazuela, J.; Pàmies, O.; Diéguez, M. A Phosphite-Pyridine/ Iridium Complex Library as Highly Selective Catalysts for the Hydrogenation of Minimally Functionalized Olefins. Adv. Synth. Catal. 2013, 355, 2569−2583. (326) Margalef, J.; Lega, M.; Ruffo, F.; Pàmies, O.; Diéguez, M. The Application of Pyranoside Phosphite-Pyridine Ligands to Enantioselective Ir-Catalyzed Hydrogenations of Highly Unfunctionalized Olefins. Tetrahedron: Asymmetry 2012, 23, 945−951. (327) Coll, M.; Pàmies, O.; Diéguez, M. A Modular Furanoside Thioether-Phosphite/Phosphinite/ Phosphine Ligand Library for Asymmetric Iridium-Catalyzed Hydrogenation of Minimally Functionalized Olefins: Scope and Limitations. Adv. Synth. Catal. 2013, 355, 143−160. (328) Xu, G.; Gilbertson, S. R. Asymmetric Hydrogenation of Aromatic Olefins Catalyzed by Iridium Complexes of Proline Derived Phosphine-Oxazoline Ligands. Tetrahedron Lett. 2003, 44, 953−955. (329) Li, X.; Kong, L.; Gao, Y.; Wang, X. Enantioselective Hydrogenation of Olefins with Axial Chiral Iridium QUINAP Complex. Tetrahedron Lett. 2007, 48, 3915−3917. (330) Li, X.; Li, Q.; Wu, X.; Gao, Y.; Xu, D.; Kong, L. Enantioselective Hydrogenation of Olefins with Planar Chiral Iridium Ferrocenyloxazolinylphosphine Complexes. Tetrahedron: Asymmetry 2007, 18, 629− 634. (331) Co, T. T.; Kim, T.-J. Chiral (Iminophosphoranyl)ferrocenes: Highly Efficient Ligands for Rhodium- and Iridium-Catalyzed Enantioselective Hydrogenation of Unfunctionalized Olefins. Chem. Commun. 2006, 3537−3539. (332) Busacca, C. a; Qu, B.; Farber, E.; Haddad, N.; Grět, N.; Saha, A. K.; Eriksson, M. C.; Wu, J.-P.; Fandrick, K. R.; Han, S.; Grinberg, N.; Ma, S.; Lee, H.; Li, Z.; Spinelli, M.; Gold, A.; Wang, G.; Wopf, P.; Senanayake, C. H. Hydrophosphination of Propargylic Alcohols and Amines with Phosphine Boranes. Org. Lett. 2013, 15, 1132−1135. (333) Busacca, C. A.; Qu, B.; Grět, N.; Fandrick, K. R.; Saha, A. K.; Marsini, M.; Reeves, D.; Haddad, N.; Eriksson, M.; Wu, J. P.; Grinberg, N.; Lee, H.; Li, Z.; Lu, B.; Chen, D.; Hong, Y.; Ma, S.; Senanayake, C. H. Tuning the Peri Effect for Enantioselectivity: Asymmetric Hydrogenation of Unfunctionalized Olefins with the BIPI Ligands. Adv. Synth. Catal. 2013, 355, 1455−1463. (334) Qu, B.; Samankumara, L. P.; Savoie, J.; Fandrick, D. R.; Haddad, N.; Wei, X.; Ma, S.; Lee, H.; Rodriguez, S.; Busacca, C. a; Yee, N. K.; Song, J. J.; Senanayake, C. H. Synthesis of Pyridyl-Dihydrobenzooxaphosphole Ligands and Their Application in Asymmetric Hydrogenation of Unfunctionalized Alkenes. J. Org. Chem. 2014, 79, 993− 1000. (335) Caille, S.; Crockett, R.; Ranganathan, K.; Wang, X.; Woo, J. C. S.; Walker, S. D. J. Org. Chem. 2011, 76, 5198−5206. (336) Wang, X.; Guram, A.; Caille, S.; Hu, J.; Preston, J. P.; Ronk, M.; Walker, S. Org. Lett. 2011, 13, 1881−1883. (337) Ortega, N.; Beiring, B.; Urban, S.; Glorius, F. Highly Asymmetric Synthesis of (+)-Corsifuran A. Elucidation of the Electronic Requirements in the Ruthenium-NHC Catalyzed Hydrogenation of Benzofurans. Tetrahedron 2012, 68, 5185−5192. (338) Troutman, M. V.; Appella, D. H.; Buchwald, S. L. Asymmetric Hydrogenation of Unfunctionalized Tetrasubstituted Olefins with a 14826


Chemical Reviews

Review

Cationic Zirconocene Catalyst. J. Am. Chem. Soc. 1999, 121, 4916− 4917. (339) Friedfeld, M. R.; Shevlin, M.; Margulieux, G. W.; Campeau, L.C.; Chirik, P. J. Cobalt-Catalyzed Enantioselective Hydrogenation of Minimally Functionalized Alkenes: Isotopic Labeling Provides Insight into the Origin of Stereoselectivity and Alkene Insertion Preferences. J. Am. Chem. Soc. 2016, 138, 3314−3324. (340) Ohta, T.; Ikegami, H.; Miyake, T.; Takaya, H. BINAP-Ru(II) and BINAP-Rh(I)-Catalyzed Asymmetric Hydrogenation of Olefins without Heteroatom-Functionalities. J. Organomet. Chem. 1995, 502, 169−176. (341) Yamashita, M.; Yamano, T. Synthesis of Melatonin Receptor Agonist Ramelteon via Rh-Catalyzed Asymmetric Hydrogenation of an Allylamine. Chem. Lett. 2009, 38, 100−101. (342) Duan, Z. C.; Wang, L. Z.; Song, X. J.; Hu, X. P.; Zheng, Z. Enantioselective Synthesis of Optically Active Alkylphosphonates via Rh-Catalyzed Asymmetric Hydrogenation of β-Substituted α,βUnsaturated Phosphonates. Tetrahedron: Asymmetry 2012, 23, 508− 514. (343) Yamano, T.; Yamashita, M.; Adachi, M.; Tanaka, M.; Matsumoto, K.; Kawada, M.; Uchikawa, O.; Fukatsu, K.; Ohkawa, S. Approach to the Stereoselective Synthesis of Melatonin Receptor Agonist Ramelteon via Asymmetric Hydrogenation. Tetrahedron: Asymmetry 2006, 17, 184−190. (344) Bernardinelli, G. H.; Kundig, E. P.; Meier, P.; Pfaltz, A.; Radkowski, K.; Zimmermann, N.; Neuburger-Zehnder, M. Chiral Bidentate (Phosphinophenyl)benzoxazine Ligands in Asymmetric Catalysis. Helv. Chim. Acta 2001, 84, 3233−3246. (345) Bayardon, J.; Holz, J.; Schäffner, B.; Andrushko, V.; Verevkin, S.; Preetz, A.; Börner, A. Propylene Carbonate as a Solvent for Asymmetric Hydrogenations. Angew. Chem., Int. Ed. 2007, 46, 5971−5974. (346) Mazuela, J.; Verendel, J. J.; Coll, M.; Schäffner, B.; Börner, A.; Andersson, P. G.; Pàmies, O.; Diéguez, M. Iridium Phosphite-Oxazoline Catalysts for the Highly Enantioselective Hydrogenation of Terminal Alkenes. J. Am. Chem. Soc. 2009, 131, 12344−12353. (347) Bert, K.; Noël, T.; Kimpe, W.; Goeman, J. L.; van der Eycken, J. Chiral Imidate-Ferrocenylphosphanes: Synthesis and Application as P,N-Ligands in Iridium(I)-Catalyzed Hydrogenation of Unfunctionalized and Poorly Functionalized Olefins. Org. Biomol. Chem. 2012, 10, 8539−8550. (348) Yang, S.; Zhu, S.-F.; Guo, N.; Song, S.; Zhou, Q.-L. CarboxyDirected Asymmetric Hydrogenation of α-Alkyl-α-Aryl Terminal Olefins: Highly Enantioselective and Chemoselective Access to a Chiral Benzylmethyl Center. Org. Biomol. Chem. 2014, 12, 2049−2052. (349) Monfette, S.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J. Enantiopure C1-Symmetric Bis(imino)pyridine Cobalt Complexes for Asymmetric Alkene Hydrogenation. J. Am. Chem. Soc. 2012, 134, 4561− 4564.

14827


Asymmetric Hydrogenation of Nonaromatic Cyclic Substrates

Recommend Documents