Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Letter
Accessing Axially Chiral Biaryls via Organocatalytic Enantioselective Dynamic-Kinetic Resolution-Semipinacol Rearrangement Yi Liu, Ying-Lung Steve Tse, Fuk Yee Kwong, and Ying-Yeung Yeung ACS Catal., Just Accepted Manuscript • Publication Date (Web): 26 May 2017 Downloaded from http://pubs.acs.org on May 26, 2017
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 7
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis
Accessing Axially Chiral Biaryls via Organocatalytic Enantioselective Dynamic-Kinetic Resolution-Semipinacol Rearrangement Yi Liu,† Ying-Lung Steve Tse,‡ Fuk Yee Kwong,‡ Ying-Yeung Yeung*,†,‡ † ‡
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 Department of Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)
ABSTRACT: We have developed a synthetic strategy to access axially chiral biaryls through a semipinacol rearrangement/ringexpansion/dynamic-kinetic resolution process. The axial chirality together with a sp3 quaternary carbon can be introduced in a single chemical operation. The products can be further ring-expanded to yield biologically relevant 7-membered dibenzolactams with inverted axial chirality.
KEYWORDS: axial chirality, biaryl, dynamic-kinetic resolution, organocatalysis, semipinacol rearrangement
Axially chiral biaryl systems are widely present as the fundamental units of chiral ligands as well as structural cores of many bioactive natural products.1 Due to the high rotation barrier in the structurally hindered biaryl compounds, the atropisomers are configurationally stable and not readily interchangeable. The structurally unique features of atropisomers with axial chirality attract much attention from synthetic chemists. As compared to the synthesis of stereogenic sp3 carbons, introduction of axial chirality remains highly challenging.2 Over the past decades, significant efforts have been devoted to the construction of axially chiral biaryl molecules. Kinetic resolution of racemic biaryl compounds is an important and classical strategy.3 Dynamic-kinetic resolution (DKR) of freely rotatable biaryl compounds is an attractive approach since the substrate can be effectively utilized, although it is non-trivial and comparatively less reported.4 A remarkable approach using the DKR strategy is the atroposelective ringopening of Bringmann’s lactones to give the configurationally stable axially chiral biaryls.4a-e Transition metal-catalyzed atroposelective cross-coupling5-8 and asymmetric cycloaddition9 reactions have been employed in the synthesis of axially chiral biaryl compounds. In sharp contrast, method using organocatalyst is sporadic.10 Point-to-axial chirality transfer, which involves the internal transfer of stereochemical information from a sp3 carbon to the chiral axis, is an uncommon but emerging strategy that allows for the introduction of axial chirality in certain structurally complex molecules.11 Herein we are pleased to describe a novel approach in the construction of axially chiral compounds through a dynamic-kinetic resolution (DKR)/point-to-axial chirality transfer of fluorene
systems to 9,10-dihydrophenanthrenes. Unlike the common point-to-axial chirality transfer strategy,11 this approach starts from the formation of a stereogenic center from a racemic compound followed by the induction of an axial chirality simultaneously, which allows us to introduce a stereogenic quaternary carbon and a chiral axis in a single chemical operation. In the 4,5-dimethylfluorene system, the two methyl units are more remote than a typical biaryl system due to bond angle perturbations caused by being constrained in a 5-membered ring system. The low rotation barrier in the 4,5dimethylfluorene system could result in a rapid racemization of the atropisomers.12 We hypothesize that ring-expansion of the 4,5-dimethylfluorene through asymmetric transformation might bring the two methyl groups close proximity and give configurationally stable atropisomer of the 4,5dimethylphenanthrene system (Scheme 1).
Scheme 1. Proposed strategy in introducing axial chirality through ring-expansion
ACS Paragon Plus Environment
ACS Catalysis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
As a proof-of-concept, we anticipated the ring-expansion reaction through asymmetric semipinacol rearrangement with an electrophilic bromination catalytic protocol. Biaryl compound 1a, which was found to be optically inactive at room temperature, was used as the substrate in the initial study together with N-bromosuccinimide (NBS) as the brominating agent. After a survey on some established catalytic protocols13 such as thiocarbamate 3a, BINOL-derived phosphoric acid 3b, and hydroquinidine 1,4-phthalazinediyl diether [(DHQD)2PHAL, (3c)] catalysts, it was realized that (DHQD)2PHAL (3c),14 an effective catalyst for asymmetric semipinacol rearrangement, could promote the rearrangement of 1a to give the ring-expanded product 2a in 75% yield with negligible enantioselectivity (Table 1, entries 1–3). Other DHQD-derived catalysts such as (DHQD)2Pyr (3d) and (DHQD)2AQN (3e) also gave good conversion of the rearrangement reaction but again no enantioselectivity was observed (entries 4 and 5). It has been reported that acid additive Table 1. Semipinacol rearrangement of 1aa
Page 2 of 7
can enhance the enantioselectivity in some of the asymmetric halogenation reactions.13 Hence, evaluation of a series of acid additives was conducted. No significant improvement of enantioselectivity was observed when employing BzOH, MsOH and AcOH as the additives (entries 6–8). Nonetheless, to our delight, the enantioselectivity of 2a was improved dramatically when using (±)-camphor-10-sulfonic acid (CSA) (entry 9). More importantly, the axial chirality was introduced successfully whereas 2a was obtained as a single diastereomer. The chirality of CSA displayed negligible influence on the enantioselectivity (entries 10 and 11). However, the combination of 3d or 3e with (±)-CSA did not display any chirality induction (entries 12 and 13). A brief survey on some halogen sources was also performed (Table 2). The use of N-bromophthalimide (NBP) provided an appreciable improvement on the enantioselectivity of 2a to 78:22 (Table 2, entry 1). On the other hand, the more reactive brominating reagent 1,3-dibromo-5,5’-dimethylhydantoin (DBDMH) reduced the enantioselectivity (Table 2, entry 2). N-chlorosuccinimide (NCS) was found to be not suitable for this type of reaction (Table 2, entry 3). Table 2. Ring-expansion of 1a using different halogen sourcesa
Entry
halogen source
yield (%)b
erc
1 2 3
NBP DBDMH NCS
88 92 trace
78:22 66:34 -
a
Reactions were conducted with 1a (0.1 mmol), 3c (0.02 mmol), (±)-CSA (0.024 mmol), halogen source (0.12 mmol) in CH2Cl2 (5.0 mL) at 25 oC in the absence of light. b Isolated yield. c The er ratios were determined by chiral HPLC. NBP = Nbromophthalimide; DBDHM = 1,3-dibromo-5,5’dimethylhydantoin; NCS = N-chlorosuccinimide. entry
catalyst
additive
yield (%)b
erc
1 2 3 4 5 6 7 8 9 10 11 12 13
3a 3b 3c 3d 3e 3c 3c 3c 3c 3c 3c 3d 3e
BzOH MsOH AcOH (±)-CSA (–)-CSA (+)-CSA (±)-CSA (±)-CSA
trace trace 75 81 79 88 89 82 90 89 86 85 87
50:50 50:50 51:49 50:50 50.5:49.5 50:50 50:50 51.5:48.5 71.5:28.5 71:29 73:27 50:50 50:50
a
Reactions were carried out with substrate 1a (0.1 mmol), catalyst (0.02 mmol), additive (0.024 mmol) and NBS (0.12 mmol) in CH2Cl2 (5.0 mL) at 25 oC in the absence of light. b Isolated yield. c The er ratios were determined by chiral HPLC. NBS = Nbromosuccinimide; CSA = camphor-10-sulfonic acid.
Further investigation on the parameters that could affect this type of DKR revealed the importance of solvent and temperature effects (Table 3). Other chlorinated solvents such as chloroform and 1,2-dichloroethane were tested (Table 3, entries 1 and 2). While chloroform gave only moderate enantioselectivity, an enhanced er of 86:14 was observed when employing 1,2-dichloroethane as the reaction media (entry 3). In contrast, only 59:41 er for the desired product 2a was obtained when using the relatively non-polar solvent toluene (entry 4). Since it has been reported that alcohol additive can offer positive effect on some asymmetric halogenation reactions,15 we also examined the effect of some alcohols on the DKR of 1a. Among MeOH, EtOH and iPrOH, the addition of EtOH (10:1 v/v) gave a significant improvement on the conversion (97% yield) and a slight enhancement on the enantioselectivity (er 87:13) (Table 3, entries 5–7). The reaction carried out at –30 o C afforded higher enantioselectivity up to 90:10 (Table 3, entry 8). Further optimizing the reaction by fine-tuning the amount to EtOH additive (50:1 v/v) provided 2a in 95:5 er (Table 3, entry 10).16
ACS Paragon Plus Environment
Page 3 of 7
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis
Table 3. Solvent and temperature effects on the dynamickinetic-resolution of 1aa
Me
O
Ph
HO
Me
3c (20 mol %), ( )-CSA (24 mol %) NBP, solvent temp, 48 h
Ph
Table 4. Substrate scope of the dynamic-kinetic resolution of 1a
Br HO
R1
Me Me 2a
( )-1a
O
R2
R1
3c (20 mol %), ( )-CSA (24 mol %) NBP, (CH2Cl) 2/EtOH (50:1 v/v) -30 oC, 48 h
R2
Br
R1 R1 2
( )-1
entry
solvent
temp (oC)
yield (%)b
erc
entry
product, R1, R2
yield (%)b
erc
dr
1 2 3 4 5
CH2Cl2 CHCl3 (CH2Cl)2 PhMe (CH2Cl)2/MeOH (10:1 v/v) (CH2Cl)2/EtOH (10:1 v/v) (CH2Cl)2/iPrOH (10:1 v/v) (CH2Cl)2/EtOH (10:1 v/v) (CH2Cl)2/EtOH (10:1 v/v) (CH2Cl)2/EtOH (50:1 v/v) (CH2Cl)2/MeOH (50:1 v/v) (CH2Cl)2/iPrOH (50:1 v/v) (CH2Cl)2/Et2O (50:1 v/v)
–15 –15 –15 –15 –15
85 89 73 70 80
84:16 57:43 86:14 59:41 84:16
1
2a, Me, Ph
72
>20:1
–15
97
87:13
–15
78
80:20
–30
70
90:10
–78
53
89:11
2 3 4 5 6 7 8 9 10 11 12e
2b, Me, 2-CH3-C6H4 2c, Me, 3-CH3-C6H4 2d, Me, 4-CH3-C6H4 2e, Me, 3-Cl-C6H4 2f, Me, 4-Cl-C6H4 2g, Me, 3-F-C6H4 2h, Me, 4-F-C6H4 2i, Me, 2-naphthyl 2j, Me, Me 2k, Ph, Ph 2a, Me, Ph
78 76 85 71 73 67 62 78 82 85 74
95:5 (>99:1)d 95:5 93:7 85:15 86:14 93:7 92:8 94:6 89:11 87:13 56:44 93:7
–30
72
95:5
–30
75
79:20
–30
69
75:25
–30
76
69:31
6
7 8 9 10 11 12 13
>20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1
a Reactions were carried out with alcohol 1 (0.1 mmol), 3c (0.02 mmol), NBP (0.12 mmol), and (±)-CSA (0.024 mmol) in 50:1 v/v of (CH2Cl)2/EtOH (5.0 mL) at –30 oC in the absence of light. b Isolated yields. c Determined by chiral HPLC. d The er after recrystallization. e The reaction was conducted at 5 mmol scale.
a
Reactions were carried out with alcohol 1a (0.1 mmol), catalyst 3c (0.02 mmol), (±)-CSA (0.024 mmol), and NBP (0.12 mmol) in the absence of light. b Isolated yield. c The er ratios were determined by chiral HPLC.
With the optimal conditions in hand, the substrate scope was investigated and the results are summarized in Table 4. In general, good yields and er together with excellent dr were obtained. Enantiopure 2a could be obtained after a simple recrystallization of product 2a right after the DKR (Table 4, entry 1). Among the substrates 1b–1d with electron-donating substituents, the sterically bulkier 2-methylphenyl substituted substrate 1b gave better enantioselectivity (entries 2–4). The electron-withdrawing groups substituted substrates 1e–1h were also well-tolerated in the DKR reaction, giving the corresponding ring-expanded products 2e–2h in high enantioselectivity (entries 5–8). The enantioselectivity was slightly diminished when the 2-naphthyl or methyl substituted substrate was used (entries 9 and 10). Nonetheless, the excellent dr was retained. Unfortunately, a poor enantioselectivity was observed when changing the methyl substitutions with phenyl groups (entry 11). Finally, the reaction was found to be readily scalable (entry 12). The absolute configuration of the axially chiral biaryl products were determined based on an X-ray crystallographic study on 2a (Figure 1). The stereochemistry of the tetrasubstituted carbon (C2) and axial chirality (C9 and C10) were assigned as R and S, respectively.
Figure 1. X-Ray structure of 2a The axially chiral products 2 from the newly developed DKR protocol could be further ring-expanded through an in-
ACS Paragon Plus Environment
ACS Catalysis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
tramolecular Schmidt reaction to give the 7-membered dibenzolactam 4 (Scheme 2). By the treatment of 2a with sodium azide and methanesulfonic acid at 60 oC, 4a was obtained smoothly in 83% yield. Dibenzolactam 4f and 4h could also be obtained readily from 2f and 2h using the same strategy. The stereochemistry of products 4 were assigned based on the X-ray diffraction analysis on a single crystal of 4a (Scheme 2). Interestingly, the configuration of the product 4a was determined to be R (the sp3 stereogenic center) and R (the chiral axis) based on the X-ray diffraction analysis. The torsion angle was found to be 54.4o. As a matter of fact, the 5H,7Hdibenzo[b,d]azepin-6-one core 4 is the fundamental building block of γ-secretase inhibitors.17 O O
Br
NaN3, MsOH 60 o C, 10 h 83%
HN
Br
Me Me (90:10 er; >20:1 dr) 4a
Me Me (90:10 er; >20:1 dr) 2a Cl
O
Cl
O Br
NaN3, MsOH 60 o C, 10 h 72%
Me Me (93:7 er; >20:1 dr) 2f F
HN
Br
Me Me (93:7 er; >20:1 dr) 4f F
O O
Br
Me Me (94:6 er; >20:1 dr) 2h
NaN 3, MsOH 60 oC, 10 h 79%
HN
Br
Me Me (94:6 er; >20:1 dr) 4h
X -Ray of 4a
Scheme 2. Intramolecular Schmidt reaction of 2 It is interesting to realize that the axial chirality was inverted after the Schmidt reaction. To get a better understanding on this aspect, density functional theory (DFT) calculation was conducted in order to shed light on the mechanistic picture. DFT calculations for both the geometry optimization and the
Page 4 of 7
potential energy were carried out at B3LYP with 6-311G** basis set using the Firefly quantum chemistry package.18 Potential energy of the rotation barrier and the torsion angle of 2a were found to be 40.5 kcal/mol and 43.8o, respectively (Scheme 3). The potential energy of 2a was found to be only slightly higher than 2a’ (R = Ph) by 2.5 kcal/mol. For compound 4a, potential energy of the rotation barrier (65.1 kcal/mol) and the torsion angle (55.9o) were found to be even higher. As a comparison, potential energy of the rotation barrier of a structurally related Bringmann’s type lactone was found to be 21 kcal/mol with the torsion angle 33.0o.19 These values indicate that the axial chirality in 2 and 4 should be considerably stable. Next, substrate 1l that has no methyl substitutions at the C(4) and C(5) was subjected to the reaction and the corresponding product 2l was obtained in good er (Scheme 3). However, the axial chirality in 2l was found to be relatively unstable as compared with that in 2a and 4a based on computational study (potential energy of the rotation barrier was found to be 2.8 kcal/mol) and the variable temperature NMR study,20 suggesting that the diastereotopic methyl groups might play a role in stabilizing the axial chirality. In addition, debromination of a chiral sample of 2j was performed using Zn in AcOH at 50 oC, which could destroy the point chirality and gave rise to 2m containing only the axial chirality. While good yield was obtained, the product 2m was found to be racemic. This result indicates that the point chirality in 2 might also play a role in stabilizing the axial chirality.21 Since an excellent diastereoselectivity was observed in the formation of 2, we speculate that the biaryl system might be pre-organized at low energy geometry (with the help of the catalyst) before the rearrangement process. Among the four possible ring-expansion pathways (Scheme 3, 1→2; 1→ 2’; ent-1→2; ent-1→2’), we believe that the 1→2 pathway might be the most energetically favorable one, which could result in the formation of atropisomer 2. A plausible mechanism is depicted in Scheme 3. We speculate that NBP could be activated by the protonated quinuclidine while the basic nitrogen of phthalazine in catalyst 3c could deprotonate the hydroxyl hydrogen of substrate 1 to give intermediate A.10,14,23 Subsequently, semipinacol rearrangement triggered by the electrophilic Br could yield the atropisomer 2. ent-1 could adapt a similar pathway to give intermediate B. However, we suspect that ent-1 could encounter a higher steric stress, potentially between the aryl system in 1 and the catalyst substituent; the postulation could rationalize the excellent dr even though 1 and ent-1 are readily interchangeable. We also suspect that pathways 1→2’ and ent-1→2 might be even less energetically favorable since both the stereocenter and inversion of the axial chirality are involved in a single transformation. Based on these aspects and the abovementioned studies, we suspect that inversion of the axial chirality might happen during the Schmidt reaction, potentially during the C-C bond breaking process. On the other hand, the inversion of axial chirality could be explained by the possibility that 2 could be the thermodynamically controlled product due to the existence of the point chirality.21 The formation of 4 might then proceed through the inversion from 2 to 2’ followed by the Schmidt rearrangement. However, a more detailed study is needed in order to elucidate a clearer mechanistic picture and the role of the alcohol additive.22
ACS Paragon Plus Environment
Page 5 of 7
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis ring expansion (Schmidt reactions) to give axially chiral lactams which are biologically relevant synthetic intermediates.
ASSOCIATED CONTENT Supporting Information Available: [Experimental details of the synthesis and characterization of compounds; CIF files of X-ray data; copies of 1H NMR and 13C NMR spectra of all new compounds.] This material is available free of charge via the internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author *
[email protected] Notes The authors declare no competing financial interest.
ACKNOWLEDGMENT We thank the National University of Singapore (grant no. 143000-605-112) and The Chinese University of Hong Kong Direct Grant (grant no. 4053203) for financial support.
REFERENCES
Scheme 3. Proposed reaction mechanism In summary, we have described a new approach in the construction of axially chiral biaryl compounds via a semipinacol rearrangement/ring-expansion/dynamic kinetic resolution process. This report also opens a new avenue for the introduction of axial chirality and sp3 quaternary carbon in single chemical transformation. Notably, the chiral biaryls can further undergo
(1) For selected reviews on axially chiral biaryl natural products and bioactive compounds, see: (a) Bringmann, G.; Gulder, T.; Gulder, T. A.; Breuning, M. Chem. Rev. 2010, 111, 563-639. (b) Kozlowski, M. C.; Morgan, B. J.; Linton, E. C. Chem. Soc. Rev. 2009, 38, 31933207. (c) Bringmann, G.; Menche, D. Acc. Chem. Res. 2001, 34, 615624. For selected reviews on axially chiral ligands, see: (d) Chen, Y.; Yekta, S.; Yudin, A. K. Chem. Rev. 2003, 103, 3155-3212. (e) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809-3844. (2) Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser, M. J.; Garner, J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384-5427. (3) For selected recent reports on the preparation of axially chiral biaryls through kinetic resolution, see: (a) Aoyama, H.; Tokunaga, M.; Kiyosu, J.; Iwasawa, T.; Obora, Y.; Tsuji, Y. J. Am. Chem. Soc. 2005, 127, 10474-10475. (b) Shirakawa, S.; Wu, X.; Maruoka, K. Angew. Chem., Int. Ed. 2013, 52, 14200-14203. (c) Lu, S.; Poh, S. B.; Zhao, Y. Angew. Chem., Int. Ed. 2014, 53, 11041-11045. (4) For selected recent reports on dynamic kinetic resolution in the synthesis of axially chiral biaryls, see (a) Bringmann, G.; Tasler, S.; Pfeifer, R.-M.; Breuning, M. J. Organomet. Chem. 2002, 641, 49-65. (b) Bringmann, G.; Hartung, T. Angew. Chem., Int. Ed. 1992, 31, 761762. (c) Bringmann, G.; Breuning, M.; Walter, R.; Wuzik, A.; Peters, K.; Peters, E.-M. Eur. J. Org. Chem. 1999, 3047-3055. (d) Pellissier, H. Tetrahedron 2003, 59, 8291-8327. (e) Bringmann, G.; Breuning, M.; Pfeifer, R.-M.; Schenk, W. A.; Kamikawa, K.; Uemura, M. J. Organomet. Chem. 2002, 661, 31-47. (f) Yu, C.; Huang, H.; Li, X.; Zhang, Y.; Wang, W. J. Am. Chem. Soc. 2016, 138, 6956-6959. (g) Miyaji, R.; Asano, K.; Matsubara, S. J. Am Chem. Soc. 2015, 137, 6766-6769. (h) Diener, M. E.; Metrano, A. J.; Kusano, S.; Miller, S. J. J. Am. Chem. Soc. 2015, 137, 12369-12377. (i) Gustafson, J. L.; Lim, D.; Miller, S. J. Science 2010, 328, 1251-1255. (5) For selected reviews on the synthesis of axially chiral biaryls using asymmetric cross-coupling reactions, see: (a) Loxq, P.; Manoury, E.; Poli, R.; Deydier, E.; Labande, A. Coord. Chem. Rev. 2016, 308, 131-190. (b) Zhang, D.; Wang, Q. Coord. Chem. Rev. 2015, 286, 1-16. (6) For selected publications on asymmetric Kumada cross coupling reactions to access axially chiral biaryls, see: (a) Tamao, K.; Minato, A.; Miyake, N.; Matsuda, T.; Kiso, Y.; Kumada, M. Chem. Lett. 1975, 4, 133-136. (b) Hayashi, T.; Hayashizaki, K.; Kiyoi, T.; Ito, Y. J. Am. Chem. Soc. 1988, 110, 8153-8156. (c) Kamikawa, T.; Hayashi, T. Tetrahedron 1999, 55, 3455-3466. (d) Wu, L.; Salvador, A.; Ou, A.; Shi, M. W.; Skelton, B. W.; Dorta, R. Synlett 2013, 24,
ACS Paragon Plus Environment
ACS Catalysis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
1215-1220. (e) Shimada, T.; Cho, Y.-H.; Hayashi, T. J. Am. Chem. Soc. 2002, 124, 13396-13397. (7) For review on asymmetric Suzuki cross coupling to access axially chiral biaryls, see: Baudoin, O. Eur. J. Org. Chem. 2005, 42234229. (8) For selected reports on asymmetric Negishi coupling reactions to access axially chiral biaryls, see: (a) Genov, M.; Fuentes, B.; Espinet, P.; Pelaz, B. Tetrahedron: Asymmetry 2006, 17, 2593-2595. (b) Genov, M.; Almorín, A.; Espinet, P. Tetrahedron: Asymmetry 2007, 18, 625-627. (9) For selected reports on asymmetric cycloaddition reactions to access axially chiral biaryls, see: (a) Gutnov, A.; Heller, B.; Fischer, C.; Drexler, H. J.; Spannenberg, A.; Sundermann, B.; Sundermann, C. Angew. Chem., Int. Ed. 2004, 43, 3795-3797. (b) Shibata, T.; Fujimoto, T.; Yokota, K.; Takagi, K. J. Am. Chem. Soc. 2004, 126, 8382-8383. (c) Tanaka, K.; Nishida, G.; Wada, A.; Noguchi, K. Angew. Chem., Int. Ed. 2004, 43, 6510-6512. (d) Heller, B.; Gutnov, A.; Fischer, C.; Drexler, H. J.; Spannenberg, A.; Redkin, D.; Sundermann, C.; Sundermann, B. Chem.-Eur. J. 2007, 13, 1117-1128. (e) Onodera, G.; Suto, M.; Takeuchi, R. J. Org. Chem. 2011, 77, 908920. (f) Tanaka, K.; Suda, T.; Noguchi, K.; Hirano, M. J. Org. Chem. 2007, 72, 2243-2246. (g) Garcia, L.; Roglans, A.; Laurent, R.; Majoral, J.-P.; Pla-Quintana, A.; Caminade, A.-M. Chem. Commun. 2012, 48, 9248-9250. (10) For selected references of organocatalytic reactions to access axially chiral biaryls, see: (a) Moliterno, M.; Cari, R.; Puglisi, A.; Antenucci, A.; Sperandio, C.; Moretti, E.; Di Sabato, A.; Salvio, R.; Bella, M. Angew. Chem., Int. Ed. 2016, 55, 6525-6529. (b) Chen, Y.H.; Cheng, D.-J.; Zhang, J.; Wang, Y.; Liu, X.-Y.; Tan, B. J. Am. Chem. Soc. 2015, 137, 15062-15065. (c) Wang, J.-Z.; Zhou, J.; Xu, C.; Sun, H.; Kürti, L.; Xu, Q.-L. J. Am. Chem. Soc. 2016, 138, 52025205. (d) Zhang, L.; Zhang, J.; Ma, J.; Cheng, D.-J.; Tan, B. J. Am. Chem. Soc. 2017, 139, 1714-1717. (e) Gao, H.; Xu, Q.-L.; Keene, C.; Yousufuddin, M.; Ess, D. H.; Kürti, L. Angew. Chem., Int. Ed. 2016, 55, 566-571. (f) Shirakawa, S.; Maruoka, K. Chem. 2017, 2, 329-331. (g) Zhang, J.-W.; Xu, J.-H.; Cheng, D.-J.; Shi, C.; Liu, X.-Y.; Tan, B. Nat. Commun. 2016, 7, 10677. (h) Shirakawa, S.; Wu, X.; Liu, S.; Maruoka, K. Tetrahedron 2016, 72, 5163-5171. (i) Mori, K.; Itakura, T.; Akiyama, T. Angew. Chem., Int. Ed. 2016, 55, 11642-11646. Also see reference 3. (11) For selected references on point-to-axial chirality transfer, see: (a) Qin, T.; Skraba-Joiner, S. L.; Khalil, Z. G.; Johnson, R. P.; Capon, R. J.; Porco, J. A., Jr. Nat. Chem. 2015, 7, 234-240. (b) De, C. K.; Pesciaioli, F.; List, B. Angew. Chem., Int. Ed. 2013, 52, 9293-9295. (c) Guo, F.; Konkol, L. C.; Thomson, R. J. J. Am. Chem. Soc. 2011, 133, 18-20. (d) Li, G.-Q.; Gao, H.; Keene, C.; Devonas, M.; Ess, D. H.; Kürti, L. J. Am. Chem. Soc. 2013, 135, 7414-7417. (12) Shuklov, I. A.; Dubrovina, N. V.; Jiao, H.; Spannenberg, A.; Börner, A. Eur. J. Org. Chem. 2010, 1669-1680. (13) (a) Tan, C. K.; Zhou, L.; Yeung, Y.-Y. Synlett 2011, 13351339. (b) Hennecke, U. Chem. Asian. J. 2012, 7, 456-465. (c) Denmark, S. E.; Kuester, W. E.; Burk, M. T. Angew. Chem., Int. Ed. 2012, 51, 10938-10953. (d) Chemler, S. R.; Bovino, M. T. ACS Catal. 2013, 3, 1076-1091. (e) Murai, K.; Fujioka, H. Heterocycles 2013, 87, 763-805. (f) Tan, C. K.; Yeung, Y.-Y. Chem. Commun. 2013, 49, 7985-7996. (g) Tan, C. K.; Yu, W. Z.; Yeung, Y. Y. Chirality 2014, 26, 328-343. (h) Cheng, Y. A.; Yu, W. Z.; Yeung, Y.-Y. Org. Biomol. Chem. 2014, 12, 2333-2343. (14) For selected references on asymmetric semipinacol rearrangement using (DHQD)2PHAL as the catalyst, see: (a) Wang, S.-H.; Li, B.-S.; Tu, Y.-Q. Chem. Commun. 2014, 50, 2393-2408. (b) Chen, Z.-M.; Zhang, Q.-W.; Chen, Z.-H.; Li, H.; Tu, Y.-Q.; Zhang, F.-M.; Tian, J.-M. J. Am. Chem. Soc. 2011, 133, 8818-8821. (c) Chen, Z. M.; Yang, B. M.; Chen, Z. H.; Zhang, Q. W.; Wang, M.; Tu, Y.-Q. Chem.-Eur. J. 2012, 18, 12950-12954. (d) Li, H.; Zhang, F.-M.; Tu, Y.-Q.; Zhang, Q.-W.; Chen, Z.-M.; Chen, Z.-H.; Li, J. Chem. Sci. 2011, 2, 1839-1841. (e) Romanov-Michailidis, F.; Pupier, M.; Guenee, L.; Alexakis, A. Chem. Commun. 2014, 50, 13461-13464. (f)
Page 6 of 7
Romanov-Michailidis, F.; Romanova-Michaelides, M.; Pupier, M.; Alexakis, A. Chem.-Eur. J. 2015, 21, 5561-5583. (15) Cheng, Y. A.; Yu, W. Z.; Yeung, Y.-Y. Angew. Chem., Int. Ed. 2015, 54, 12102-12106. (16) It appears that both a suitable steric demand and the proton in the additive were curcial for the high enantioselectivity (Table 3, entries 10–13). We speculate that the additive EtOH might be involved in the enantiodetermining step, potentially through hydrogen bond interaction. However, a more detailed investigation is underway to elucidate the exact mode of interaction. For relevant study on using alcohol additive in asymmetric halogenation, see reference 15. (17) Andersson, E. R.; Lendahl, U. Nat. Rev. Drug Discovery 2014, 13, 357-378. (18) Firefly quantum chemistry package, which is partially based on the GAMESS (US) source code, was used in the computational studies. For references, see: (a) Granovsky, A. A. Firefly version 8.2.0. http://classic.chem.msu.su/gran/firefly/index.html (date of access: 3 Feb 2017). (b) Schmidt, M. W.; Baldridge, K. K.; Boatz, J. A.; Elbert, S. T.; Gordon, M. S.; Jensen, J. H.; Koseki, S.; Matsunaga, N.; Nguyen, K. A.; Su, S.; Windus, T. L.; Dupuis, M.; Montgomery, J. A. J. Comput. Chem. 1993, 14, 1347-1363. (19) For detail of the calculation, see SI. For references of Bringmann’s type lactones, see: (a) Bringmann, G.; Busse, H.; Dauer, U.; Güssregen, S.; Stahl, M. Tetrahedron 1995, 51, 3149-3158. (b) Bringmann, G.; Hartung, T.; Göbel, L.; Schupp, O.; Ewers, Ch. L. J.; Schöner, B.; Zagst, R.; Peters, K.; von Schnering, H. G.; Burschka, Ch. Liebigs Ann. Chem. 1992, 225-232. (20) For detail, see SI. (21) It has been reported that stereo-centers in the biaryl systems might influcence stability of the axial chirality. For example, colchicine does not show mutarotation and it is believed that the point chirality is playing a role in controlling the axial chirality. For reference, see: Pietra, E. J. Phy. Org. Chem. 2007, 20, 1102-1107. Also see reference 2 for the examples of Bringmann’s lactones. (22) A full calculation is underway to elucidate the whole picture and the results will be reported in due course. (23) Niu, W.; Yeung, Y.-Y. Org. Lett. 2015, 17, 1660-1663.
ACS Paragon Plus Environment
Page 7 of 7
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis
semi-pinacol rearrangement HO
R2
O
R2
chiral organocatalyst
r acemic
chiral quat er nary car bon Br axial chirality
one-step R1
R1
dynamic-kinetic resolution
R1
R1
up to 95:5 er > 20:1 dr
ACS Paragon Plus Environment
7
