Brønsted Acid Catalyzed Asymmetric Silylation of Biaryl Diols

Abstract

We report a Brønsted acid catalyzed enantioselective silylation of biaryl diols with an allylsilane as a silicon source. This process enables facile access to enantioenriched biaryl silyl ethers with an axial stereogenicity. A control experiment supports a mechanism proceeding by desymmetrization followed by kinetic resolution.

Key words

Brønsted acid - imidodiphosphorimidate - silylation - axial chirality - desymmetrization - kinetic resolution

The silylation of alcohols is a commonly used protecting group operation in chemical synthesis.[1] Since the first enantioselective variant reported by Ishikawa,[2] several catalytic enantioselective approaches have been developed during the past two decades.[3] The majority of these methods use a chiral Lewis base catalyst in conjunction with a stoichiometric amount of an achiral base and a silyl chloride (Scheme [1a]).[4] Transition-metal-catalyzed silylations of alcohols with hydrosilanes via kinetic resolution have also been developed.[5] Recently, we reported a Brønsted acid catalyzed enantioselective silylation of alcohols with hexamethyldisilazane (HMDS) (Scheme [1b]).[6] Inspired by our studies on silicon–hydrogen exchange reactions, we recently found that strong and confined imidodiphosphorimidate (IDPi) Brønsted acids catalyze the enantioselective silylation of phenol derivatives with allylsilanes.[7] We envisioned that our silylation strategy could be applied to biaryl diols to yield axially chiral biaryl silyl ethers. Indeed, we herein report a Brønsted acid catalyzed atroposelective silylation of biaryl diols (Scheme [1c]).

Scheme 1 Catalytic asymmetric silylation of alcohols

We commenced our investigation by examining the silylation of biaryl diol 1a in the presence of different IDPi catalysts 4 and allyl(tert-butyl)dimethylsilane (2) (Table [1]). Catalyst 4a afforded the desired mono-silylated product, but with poor enantioselectivity (54:46 er; entry 1). While catalysts 4b–e revealed low enantioselectivities (54:46 to 62:38 er; entries 2–5), catalyst 4f resulted in promising enantioselectivity (71:29 er; entry 6). A modification of the m,m-substituents on the 3,3′-phenyl groups of the BINOL backbone from trifluoromethyl to pentafluorosulfanyl further enhanced the enantioselectivity (77:23 er; entry 7). At –50 °C, the reaction proceeded with 86:14 er (entry 8). Finally, high enantioselectivity was achieved by increasing the amount of allylsilane 2 (95:5 er; entry 9).

Table 1 Optimization of the Reaction Conditions^a

Entry	IDPi	Temp (°C)	Conv. (%)	er
1	4a	rt	70	54:46
2	4b	rt	67	54:46
3	4c	rt	70	61:39
4	4d	rt	71	56:44
5	4e	rt	55	62:38
6	4f	rt	66	71:29
7	4g	rt	70	77:23
8b	4g	–50	70	86:14
9b,c	4g	–50	full	95:5

^a Reactions were performed with substrate 1a (0.025 mmol), allylsilane 2 (1.5 equiv.) and IDPi 4 (2.5 mol%) in CHCl₃ (0.25 mL); conversions (conv.) were determined by ¹H NMR analysis with dibromomethane as an internal standard; enantiomeric ratios (er) were measured by HPLC analysis.

^b Reaction time: 5 days.

^c 2 equivalents of 2 were used.

We next conducted the reactions on a 0.1 mmol scale (Scheme [2]). The reaction of 1a gave the desired product 3a without loss of enantioselectivity. Employing naphthyl substrate 1b required catalyst 4b to furnish product 3b with high enantioselectivity (91.5:8.5 er). The absolute configuration of 3b was determined by comparing experimental and computational circular dichroism (CD) spectra (see the Supporting Information for details).[8]

Scheme 2 Asymmetric silylation of biaryl diols. Reactions were performed on a 0.1 mmol scale. ^a Reaction was conducted with catalyst 4g and allylsilane 2 (2 equiv.) in CHCl₃ (0.1 M) at –50 °C for 5 days. ^b Reaction was conducted with catalyst 4b and allylsilane 2 (1.5 equiv.) in CH₂Cl₂ (0.2 M) at –30 °C for 3 days.

We performed a control experiment that confirmed that a kinetic resolution takes place during a second silylation (Scheme [3]). Upon subjecting racemic mono-silylated product 3a to Brønsted acid catalyzed silylation conditions, bis-silylated product 5a was obtained and the remaining 3a showed an er of 68:32. This result is consistent with the desymmetrizing silylation of 1a to initially provide the enantioenriched mono-silylated product 3a, the enantioselectivity of which is further improved in the second silylation via kinetic resolution. Although several catalysts (4b, 4e, and 4f) were further examined for the kinetic resolution, they did not afford the bis-silylated product 5a.

Scheme 3 Control experiment

In summary, we have developed a Brønsted acid catalyzed asymmetric silylation of biaryl diols that provides access to axially chiral biaryl silyl ethers.[9] A simple mechanistic investigation has revealed that the reaction proceeds via a desymmetrization–kinetic resolution sequence. Efforts to develop other useful silylation methods are currently underway in our laboratory. During our studies, Professor Martin Oestreich kindly shared a manuscript with us describing his independent and advanced investigation of the same transformation.[10] Our own studies on the asymmetric silylation of biaryl diols have since been terminated at the reported stage.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We thank the technicians of our group and the members of our mass spectrometry (MS) group for their excellent service.

• References and Notes

• 1 Greene TW, Wuts PG. M. Protection for the Hydroxyl Group, Including 1,2- and 1,3-Diols. In Protective Groups in Organic Synthesis, 3rd ed. John Wiley & Sons; New York: 1999: 17-245
• 2 Isobe T, Fukuda K, Araki Y, Ishikawa T. Chem. Commun. 2001; 243
• 3a Xu L.-W, Chen Y, Lu Y. Angew. Chem. Int. Ed. 2015; 54: 9456
• 3b Seliger J, Oestreich M. Chem. Eur. J. 2019; 25: 9358
• 4a Zhao Y, Rodrigo J, Hoveyda AH, Snapper ML. Nature 2006; 443: 67
• 4b Zhao Y, Mitra AW, Hoveyda AH, Snapper ML. Angew. Chem. Int. Ed. 2007; 46: 8471
• 4c Sheppard CI, Taylor JL, Wiskur SL. Org. Lett. 2011; 13: 3794
• 4d Manville N, Alite H, Haeffner F, Hoveyda AH, Snapper ML. Nat. Chem. 2013; 5: 768
• 5a Weickgenannt A, Mewald M, Muesmann TW. T, Oestreich M. Angew. Chem. Int. Ed. 2010; 49: 2223
• 5b Dong X, Weickgenannt A, Oestreich M. Nat. Commun. 2017; 8: 15547
• 5c Dong X, Kita Y, Oestreich M. Angew. Chem. Int. Ed. 2018; 57: 10728
• 5d Seliger J, Dong X, Oestreich M. Angew. Chem. Int. Ed. 2019; 58: 1970
• 6a Hyodo K, Gandhi S, van Gemmeren M, List B. Synlett 2015; 26: 1093
• 6b For an example of asymmetric silylation of alcohols using BINOL-based polyether catalyst, see: Park SY, Lee J.-W, Song CE. Nat. Commun. 2015; 6: 7512
• 7a Kaib PS. J, Schreyer L, Lee S, Properzi R, List B. Angew. Chem. Int. Ed. 2016; 55: 13200
• 7b Schreyer L, Properzi R, List B. Angew. Chem. Int. Ed. 2019; 58: 12761
• 7c Zhou H, Bae HY, Leutzsch M, Kennemur JL, Bécart D, List B. J. Am. Chem. Soc. 2020; 142: 13695
• 7d Zhou H, Han JT, Nöthling N, Lindner MM, Jenniches J, Kühn C, Tsuji N, Zhang L, List B. J. Am. Chem. Soc. 2022; 144: 10156
• 7e Zhou H, Properzi R, Leutzsch M, Belanzoni P, Bistoni G, Tsuji N, Han JT, Zhu C, List B. J. Am. Chem. Soc. 2023; 145: 4994
• 8 Li XC, Ferreira D, Ding Y. Curr. Org. Chem. 2010; 14: 1678
• 9 Silylation of Biaryl Diols; General Procedure A GC vial equipped with a Teflon-coated magnetic stir bar was charged with catalyst 4 (2.5 mol%), biaryl diol 1 (0.1 mmol) and solvent (CHCl₃ or CH₂Cl₂), and the resulting mixture was cooled to –50 or –30 °C in a cryostat. After 10 min, allylsilane 2 (2 or 1.5 equiv.) was slowly added and the reaction mixture was stirred for 3–5 d at the same temperature. After complete conversion as indicated by TLC, the reaction was quenched with trimethylamine. The solvent was removed in vacuo and the mixture was purified by column chromatography on silica gel to afford the desired silyl ether 3. (S)-6-((tert-Butyldimethylsilyl)oxy)-2′-methyl-[1,1′-biphenyl]-2-ol [(S)-3a] Yield: 12.6 mg (40%); white solid; [α]_D ²⁵ –25.5 (c 0.53, CHCl₃. ¹H NMR (501 MHz, CD₂Cl₂): δ = 7.34–7.24 (m, 3 H), 7.16 (dd, J = 7.4, 1.7 Hz, 1 H), 7.12 (t, J = 8.2 Hz, 1 H), 6.60 (dd, J = 8.2, 1.0 Hz, 1 H), 6.50 (dd, J = 8.1, 1.0 Hz, 1 H), 4.75 (s, 1 H), 2.12 (s, 3 H), 0.65 (s, 9 H), 0.07 (s, 3 H), –0.06 (s, 3 H). ¹³C NMR (126 MHz, CD₂Cl₂): δ = 154.4, 154.0, 139.2, 132.7, 131.5, 130.9, 129.1, 128.8, 126.5, 120.2, 111.7, 108.5, 25.3, 19.8, 18.0, –4.3, –4.6. EI-HRMS: m/z [M]^+• calcd for C₁₉H₂₆O₂Si: 314.1695; found: 314.1697. HPLC (IA-3, heptane/isopropanol = 95:5, 0.5 mL/min, 298 K, 220 nm): t_R1 = 8.6 min, t_R2 = 10.8 min; er = 95:5.
• 10 Zhu M, Jiang H.-J, Sharanov I, Irran E, Oestreich M. Angew. Chem. Int. Ed. 2023; 62: in press DOI: 10.1002/anie.202304475.

Publication History

Received: 30 April 2023

Accepted after revision: 23 May 2023

Accepted Manuscript online:
25 May 2023

Article published online:
12 July 2023