Accessible Bifunctional Oxy-Tethered Ruthenium(II) Catalysts for

Letter Cite This: Org. Lett. 2018, 20, 5213−5218

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Accessible Bifunctional Oxy-Tethered Ruthenium(II) Catalysts for Asymmetric Transfer Hydrogenation Asuka Matsunami,† Marika Ikeda,‡ Hitomi Nakamura,‡ Minori Yoshida,‡ Shigeki Kuwata,‡ and Yoshihito Kayaki*,‡ †

Org. Lett. 2018.20:5213-5218. Downloaded from pubs.acs.org by UNIV OF SOUTH DAKOTA on 09/08/18. For personal use only.

Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, 5-10-1 Fuchinobe, Chuo-ku, Sagamihara 252-5258, Japan ‡ Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1-E4-1 O-okayama, Meguro-ku, Tokyo 152-8552, Japan S Supporting Information *

ABSTRACT: A concise synthesis of new oxy-tethered ruthenium complexes effective for the asymmetric transfer hydrogenation of aromatic ketones is described. The oxy-tether was constructed via a defluorinative etherification arising from an intramolecular nucleophilic substitution of a perfluorinated phenylsulfonyl substituent. The obtained tethered complexes exhibited desirable catalytic activity and selectivity, especially in the asymmetric transfer hydrogenation of functionalized aromatic ketones. The robustness and rigidity of the tether contribute to their superior catalytic performance relative to the nontethered prototype complex.

T

made the tether bridge easily accessible; however, multistep processes involving activation and protection/deprotection procedures are still required, as shown in Scheme 1a and 1b.6a−c,7 In the course of our synthetic studies on half-sandwich Ru, Ir, and Rh complexes derived from N-sulfonyl-1,2-diamines,9 the coordination of N-pentafluorobenzenesulfonyl-1,2diphenylethylene-1,2-diamine (FsDPEN) was found to facilitate unique transformations.10 As illustrated by an example in Scheme 2, the carbon−fluorine bond at the ortho position of the Fs group was selectively cleaved by an incoming hydroxide via nucleophilic aromatic substitution to afford an oxaruthenacycle.10a Inspired by this cyclization, we designed a straightforward synthesis of new oxy-tethered Ru complexes by intramolecular substitution of the FsDPEN ligand in hydroxyalkylated arene−Ru(II) dimers (Scheme 1c). Following the established synthesis of the FsDPENcoordinated Ru(η6-p-cymene) complex (6),10a chlorido(amine)−Ru complexes (7a and 7b) modified with a hydroxyethyl or hydroxypropyl chain on the arene moiety were isolated in high yields of 85% and 91% by mixing the corresponding [RuCl2(η6-arene)]2 and (S,S)-FsDPEN in the presence of an equimolar amount of triethylamine in refluxing THF for 2 h (Scheme 3). Analogously to that of prototype complex 6, the 19F NMR spectra of 7a and 7b in CD2Cl2 displayed a set of three signals with relative intensities of 2:1:2, i.e., −135.9, −153.3, and −162.7 ppm for 7a and −136.8,

he asymmetric transfer hydrogenation (ATH) of ketones offers an invaluable and operationally simple approach to chiral alcohols using 2-propanol or formic acid/formate salts as promising reducing agents.1 Since the trailblazing work by Noyori, Ikariya, and co-workers in the mid-1990s,2 halfsandwich Ru(η6-arene) complexes bearing chiral protic amine ligands and their analogues have received considerable attention as powerful bifunctional catalysts.1f,3 As a further advancement of the practical applications, Wills introduced innovatively designed modified Ru complexes (14a and 24b in Figure 1), in which the N-sulfonyl-1,2-diamine ligand is

Figure 1. Examples of bifunctional tethered Ru complexes.

covalently linked to the η6-arene ligand. Compared to the original nontethered complex, tethered complex 2 offers a longer lifetime and higher catalytic activity due to its enhanced stability from the three-point coordination. Thereafter, Wills,5 Mohar,6 and Takasago7 have each developed related tethered amine−Ru complexes (Figure 1).1f Among them, the oxytethered Ru complex (5) has been well utilized in the ATH of a range of ketonic substrates8 including simple alkyl aryl ketones,7a α-substituted alkyl aryl ketones,7c and unsymmetrical diaryl ketones.7b The heteroatom junction has indeed © 2018 American Chemical Society

Received: July 10, 2018 Published: August 13, 2018 5213

DOI: 10.1021/acs.orglett.8b02157 Org. Lett. 2018, 20, 5213−5218

Letter

Organic Letters Scheme 1. Synthetic Routes to Tethered Ru Complexes Having an Oxygen- or Nitrogen-Dope Linkage

Scheme 2. Oxydefluorination of FsDPEN via Intramolecular Nucleophilic Attack

Scheme 3. Synthesis of Chlorido(amine)−Ru Complexes 7a and 7b

−154.2, and −163.8 ppm for 7b. The 1H NMR spectrum of 7a showed signals for diastereomeric NH protons at 3.67 and 6.95 ppm, as well as the resonances attributable to the methylene protons on the tether at 2.96 and 4.05 ppm.

When the oxydefluorination of 7a was examined in the presence of K2CO3 (1.2 equiv) in THF under reflux conditions for 4 h (Scheme 4),11 the desired oxy-tethered Ru complex (8a) was successfully obtained as an orange powder in 63% isolated yield after reprecipitation from acetonitrile and diethyl ether. Treatment of 7b with K2CO3 in acetonitrile at 70 °C also afforded the corresponding oxy-tethered product (8b) in 85% isolated yield. Figure 2 shows the 19F NMR spectrum of 5214

DOI: 10.1021/acs.orglett.8b02157 Org. Lett. 2018, 20, 5213−5218

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Organic Letters

complex 8a derived from (S,S)-FsDPEN adopts a three-legged piano-stool structure around the (R)-Ru center which attaches to the η6-arene, NH2, sulfonylamido, and chlorido ligands.12 The η6-arene ligand connects to the ortho-position of the tetrafluorophenylsulfonyl moiety via the ethyl ether linkage. There is no significant change in the bond lengths around the Ru center, between the tethered and nontethered complexes; however, 8a exhibits a comparatively greater angle of 135.14(10)° between the sulfonamido−Ru bond and the vector passing from the Ru center to the centroid of the arene ligand than is seen in 6 (131.01(14)° and 130.39(13)°). Notably, the N2−S−C1−C2 dihedral angle (55.8(3)°) of 8a is smaller than that of 6 (60.5(2)° and 63.4(2)°), implying that the slightly tilted fluoroarene ring in 8a will compensate for the strain caused by the junction. The ATH of acetophenone (S1) using 0.1 mol % of oxytethered complex 8a in an azeotropic mixture of formic acid and triethylamine at 60 °C for 15 h gave (S)-1-phenylethanol (P1) in 97% yield with 96% ee (Table 1, run 1). Comparable activity with a slightly lower enantioselectivity of 94% ee was obtained with 8b (run 2). When nontethered (S,S)-FsDPEN analogue 6 was employed under the same conditions, the yield

Scheme 4. Synthesis of Oxy-Tethered Ru Complexes 8a and 8b

Table 1. Asymmetric Transfer Hydrogenation of Acetophenonesa

Figure 2. 19F NMR spectra of 7a (a) and 8a (b) in DMSO-d6.

8a, which exhibits four separated peaks as a result of the defluorination of the Fs unit. The 1H and two-dimensional NMR data (1H−1H COSY and 1H−13C HMQC) of 8a are also consistent with the defluorinated ethereal linkage (Figures S15, S16, and S19). The diastereotopic methylene protons on the alkyl chain appeared as four independent multiplet signals in the 2.69−5.09 ppm region in the spectrum of tethered complex 8a, which is unlike the set of two triplets observed for the nontethered complex 7a. For both 8a and 8b, a mixture of diastereomers with the opposite chirality at the Ru center were not observed. Recrystallization by slow diffusion of diethyl ether into an acetonitrile solution gave yellow crystals of oxy-tethered complexes 8a and 8b, that were suitable for X-ray crystallography. As shown in Figure 3, new oxy-tethered Ru

run

ketone

cat.

S/C

temp (°C)

time (h)

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11 12 13d 14 15

S1

8a 8b 6 8a 6 8a 8a 8b 8a 8a 8a 8b 8a 8a 8a

1000 1000 1000 300 300 300 300 300 500 1000 1000 1000 500 1000 50

60 60 60 40 40 40 40 40 30 60 30 30 60 60 0

15 15 24 24 24 24 24 24 24 3 24 24 24 3 24

97 99 52 85 67 100 97 90 96 >99 79 88 100 100 100

96 94 94 86 92 86 88 90 96 80 90 90 96 45 60

S2 S3 S4 S5 S6

S7 S8

(S) (S) (S) (S) (S) (S) (S) (S) (S) (R) (R) (R) (R) (R) (R)

a

Standard reaction conditions (S/C = 1000): the reaction was carried out with substrate (2 mmol) and catalyst (0.002 mmol) in 1 mL of a 5:2 azeotropic mixture of HCO2H and Et3N. bDetermined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene (runs 1−5), durene (runs 6−13), or benzotrifluoride (runs 14 and 15) as internal standards. cThe ee values were determined by chiral HPLC analysis on Chiralcel OD-H and OJ-H columns and COSMOSIL CHiRAL 5A and 5B columns. dConditions: HCO2H (3 equiv) and HCO2K (1 equiv) were used in a mixed solvent of EtOAc (1.5 mL) and water (2 mL).

Figure 3. X-ray crystal structure of oxy-tethered Ru complex 8a. The hydrogen atoms, except for the coordinating amine protons, are omitted for clarity. Thermal ellipsoids are shown at the 30% probability level. 5215

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and functionalized acetophenones. The oxy-tethered structure could be easily obtained by a short synthesis involving a highly selective intramolecular defluorinative aromatic substitution. Comparison of their catalytic performance to that of nontethered analogue 6 demonstrated the practical utility of 8a and 8b as ATH catalysts. The catalytic properties could be finely tuned by altering the length of the tether. Further structural modifications of the tethered complexes and an exploration of their catalytic applications are in progress.

of the alcohol product decreased dramatically to 52% (run 3); however the enantioselectivity was almost identical (94% ee). Although there are limited studies about FsDPENcomplexes,10 some positive effects of FsDPEN compared to the original tosyl analogue have been disclosed, particularly in the ATH of functionalized ketones.13 Desirable results were also obtained in the ATH of substituted acetophenones using fluorinated oxy-tethered Ru complexes 8a and 8b. In the reduction of sterically congested acetophenone derivatives of 2-methoxy-, 2-chloro-, and 2-bromoacetophenone (S2−S4), which usually exhibit difficulty in being enantioselectively reduced,5b,14 the oxy-tethered complexes (8a and 8b) provided the corresponding (S)-alcohols (P2−P4) in excellent yields with satisfactory enantioselectivities (86−92% ee; runs 4 and 6−8) after the reaction with a substrate/catalyst ratio of 300 at 40 °C for 24 h. In contrast, the ATH of S2 using alkyl-tethered complex 2 was reported to give P2 with a somewhat lower enantioselectivity (79% ee) under identical conditions.5b The yield of P2 decreased to 67% when nontethered complex 6, which has an η6-p-cymene ligand, was used for the ATH of S2 (run 5). These results highlight the vital contribution of oxytethered catalysts with appropriate structural tuning for achieving high activities and enantioselectivities. Other functionalized ketones including α-cyano-, αhydroxy-, and α-chloroacetophenone (S5−S7) were also transformed into the desired alcohols in a good enantioselective manner using tethered complexes 8a and 8b (runs 9− 13). The enantioselectivity of the ATH of α-cyanoacetophenone (S5) with 8a (run 9; 96% ee, S form) was modestly better than that with the related nontethered FsDPEN−Ir complex (94% ee)13f and oxy-tethered complex 5 (95% ee).7a The ATH of α-hydroxyacetophenone (S6) using 8a proceeded slightly faster (quantitative yield after 3 h) than that with commercial oxy-tethered complex 5 (98% yield after 5 h) and resulted in good enantioselectivity of 80% ee (R) at 60 °C (run 10). The enantioselectivity was increased to 90% ee when the reaction was performed at 30 °C (run 11). Related complex 8b with a longer tether provided a similar stereochemical result with a higher yield (88% yield and 90% ee; run 12). αHaloketone S7 was reduced by a combination of HCO2H and HCO2K in a mixed solvent of EtOAc/H2O using the established method7c to prevent side reactions accompanied by formylation of the halogenated substrate in the azeotropic mixture of HCO2H and Et3N. The ATH of 1,1,1-trifluoroacetophenone (S8) usually gives 1-phenyl-2,2,2-trifluoroethanol (P8) with relatively low enantioselectivity due to poor discrimination of the prochiral face of fluoroalkyl ketone.5b,15 By using 0.1 mol % of 8a as the catalyst at 60 °C, (R)-P8 was obtained quantitatively after 3 h with a moderate ee of 45% (run 14), and the enantioselectivity was significantly lower (22% ee) when nontethered FsDPENcomplex 6 was used. The reaction proceeded even at 0 °C, leading to a higher ee of 60% (run 15). In the ATH with a nontethered original TsDPEN−Ru complex under the same conditions, the enantioselectivity remained below 45% ee.15 For the ATH reactions of S8 with modified-DPEN catalysts reported to date, the maximum enantioselectivity of 56% ee was achieved by using an alkyl-tethered complex;5b thus, the present fluorinated oxy-tethered complex 8a was convincingly shown to be effective for the ATH. In summary, we have developed a new synthetic route to oxy-tethered Ru complexes utilizing (S,S)-FsDPEN derivatives as highly efficient and reliable catalysts for the ATH of simple

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b02157. Experimental details, characterization data, and copies of NMR spectra of the products (PDF) Accession Codes

CCDC 1855028−1855029 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Shigeki Kuwata: 0000-0002-3165-9882 Yoshihito Kayaki: 0000-0002-4685-8833 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This study was financially supported by JSPS KAKENHI Grant Number 18K14225 and in part by a Grant for Basic Science Research Projects from The Sumitomo Foundation and by a Grant for Engineering Research from Mizuho Foundation for the Promotion of Sciences and by a Sasakawa Scientific Research Grant from the Japan Science Society. We also acknowledge Takasago International Corporation for the generous gifts of (S,S)-1,2-diphenylethylenediamine.

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REFERENCES

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DOI: 10.1021/acs.orglett.8b02157 Org. Lett. 2018, 20, 5213−5218

Letter

Organic Letters Iridium Catalyst Modified for Persistent Hydrogen Generation from Formic Acid: Understanding Deactivation via Cyclometalation of a 1,2-Diphenylethylenediamine Motif. ACS Catal. 2017, 7, 4479−4484. (10) (a) Dub, P. A.; Wang, H.; Matsunami, A.; Gridnev, I. D.; Kuwata, S.; Ikariya, T. C−F Bond Breaking through Aromatic Nucleophilic Substitution with a Hydroxy Ligand Mediated via Water Bifunctional Activation. Bull. Chem. Soc. Jpn. 2013, 86, 557−568. (b) Matsunami, A.; Kayaki, Y.; Kuwata, S.; Ikariya, T. Nucleophilic Aromatic Substitution in Hydrodefluorination Exemplified by Hydridoiridium(III) Complexes with Fluorinated Phenylsulfonyl1,2-diphenylethylenediamine Ligands. Organometallics 2018, 37, 1958−1969. (11) The intramolecular oxidefluorination in Scheme 4 should be conducted in the absence of water to prevent the formation of oxaruthenacycles, as demonstrated in ref 10a. (12) The crystal structure of the oxy-tethered complex 8b is shown in Figure S1 of the Supporting Information. (13) (a) Mohar, B.; Valleix, A.; Desmurs, J.-R.; Felemez, M.; Wagner, A.; Mioskowski, C. Highly enantioselective synthesis via dynamic kinetic resolution under transfer hydrogenation using Ru(η6arene)-N-perfluorosulfonyl-1,2-diamine catalysts: a first insight into the relationship of the ligand’s pKa and the catalyst activity. Chem. Commun. 2001, 24, 2572−2573. (b) Limanto, J.; Krska, S. W.; Dorner, B. T.; Vazquez, E.; Yoshikawa, N.; Tan, L. Dynamic Kinetic Resolution: Asymmetric Transfer Hydrogenation of α-Alkyl-Substituted β-Ketoamides. Org. Lett. 2010, 12, 512−515. (c) Liu, Z.; Shultz, C. S.; Sherwood, C. A.; Krska, S.; Dormer, P. G.; Desmond, R.; Lee, C.; Sherer, E. C.; Shpungin, J.; Cuff, J.; Xu, F. Highly enantioselective synthesis of anti aryl β-hydroxy α-amino esters via DKR transfer hydrogenation. Tetrahedron Lett. 2011, 52, 1685−1688. (d) Villacrez, M.; Somfai, P. Enantioselective synthesis of anti-βamido-α-hydroxy esters via asymmetric transfer hydrogenation coupled with dynamic kinetic resolution. Tetrahedron Lett. 2013, 54, 5266−5268. (e) Soltani, O.; Ariger, M. A.; Carreira, E. M. Transfer Hydrogenation in Water: Enantioselective, Catalytic Reduction of (E)-β,β-Disubstituted Nitroalkenes. Org. Lett. 2009, 11, 4196−4198. (f) Soltani, O.; Ariger, M. A.; Vázquez-Villa, H.; Carreira, E. M. Transfer Hydrogenation in Water: Enantioselective, Catalytic Reduction of α-Cyano and α-Nitro Substituted Acetophenones. Org. Lett. 2010, 12, 2893−2895. (14) (a) Zheng, L.-S.; Llopis, Q.; Echeverria, P.-G.; Férard, C.; Guillamot, G.; Phansavath, P.; Ratovelomanana-Vidal, V. Asymmetric Transfer Hydrogenation of (Hetero)arylketones with Tethered Rh(III)-N-(p-Tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine Complexes: Scope and Limitations. J. Org. Chem. 2017, 82, 5607−5615. (b) Zimbron, J. M.; Dauphinais, M.; Charette, A. B. Noyori-Ikariya catalyst supported on tetraarylphosphonium salt for asymmetric transfer hydrogenation in water. Green Chem. 2015, 17, 3255−3259. (c) Echeverria, P.-G.; Férard, C.; Phansavath, P.; RatovelomananaVidal, V. Synthesis, characterization and use of a new tethered Rh(III) complex in asymmetric transfer hydrogenation of ketones. Catal. Commun. 2015, 62, 95−99. (15) (a) Slungård, S. V.; Krakeli, T.-A.; Thvedt, T. H. K.; Fuglseth, E.; Sundby, E.; Hoff, B. H. Investigation into the enantioselection mechanism of ruthenium-arene-diamine transfer hydrogenation catalysts using fluorinated substrates. Tetrahedron 2011, 67, 5642− 5650. (b) Š terk, D.; Stephan, M.; Mohar, B. Highly Enantioselective Transfer Hydrogenation of Fluoroalkyl Ketones. Org. Lett. 2006, 8, 5935−5938.

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DOI: 10.1021/acs.orglett.8b02157 Org. Lett. 2018, 20, 5213−5218