Rhodium-Catalyzed Enantioselective Silylation of Arene C–H Bonds: Desymmetrization of Diarylmethanols

Abstract

We report a Rh-catalyzed, enantioselective silylation of arene C–H bonds directed by a (hydrido)silyl group. (Hydrido)silyl ethers that are formed in situ by hydrosilylation of benzophenone or its derivatives undergo asymmetric C–H silylation in high yield with excellent enantioselectivity in the presence of [Rh(cod)Cl]2 and a chiral bisphosphine ligand. The stereoselectivity of this process also allows enantioenriched diarylmethanols to react with site selectivity at one aryl group over the other. Enantioenriched benzoxasiloles from the silylation process undergo a range of transformations to form C–C, C–O, C–I, or C–Br bonds.

A Chiral Nitrogen Ligand for Enantioselective, Iridium‐Catalyzed Silylation of Aromatic C−H Bonds

“…[15] Although methods are known for the synthesis of chiral unsymmetrical diarylmethanols, such methods are not suitable for the synthesis of the corresponding unsymmetrical diarylmethanols containing one or two ortho-substituted aryl groups. [15][16] Moreover, rhodium catalysts that led to high site selectivity for reaction with enantioenriched, unsymmetrical diarylmethanols [10] did not lead to high selectivity for reaction with one enantiomer over another, even when one of the aryl groups was ortho substituted (see the supporting information for details).…”

“…[15] Although methods are known for the synthesis of chiral unsymmetrical diarylmethanols, such methods are not suitable for the synthesis of the corresponding unsymmetrical diarylmethanols containing one or two ortho-substituted aryl groups. [15][16] Moreover, rhodium catalysts that led to high site selectivity for reaction with enantioenriched, unsymmetrical diarylmethanols [10] did not lead to high selectivity for reaction with one enantiomer over another, even when one of the aryl groups was ortho substituted (see the supporting information for details).To determine if our newly developed catalyst system (L25-Ir) would resolve the two enantiomers of such diarylmethanols, rac-3a was subjected the catalyst system at 50 °C for 12 h. The desired silylation product 4a and the unreacted product 3a were obtained with 76% ee and 97% ee respectively, corresponding to a selectivity factor (s) [17] of 40 (SI, Table 2, entry 1). The reaction at 40 °C for 12 h occurred with an s value of 88, but only 20% of the product was obtained (SI, Table 2, entry 2).…”

“…It is well established that the resulting arylsilanes can be converted to diarylmethanols containing two ortho-substituted aryl groups. [10] A preliminary evaluation of the mechanism was conducted. The reaction under the conditions of the method development occurred with an induction period.…”

Rhodium‐Catalyzed Enantioselective Silylation of Cyclopropyl C−H Bonds

“…[8][9][10] Recently, we reported an enantioselective silylation of aryl C-H bonds to form enantioenriched benzoxasilole products with up-to 99% ee. [11] Although these reactions can occur with high enantioselectivity, they are limited to the functionalization of aryl C-H bonds. The only published set of enantioselective silylations of alkyl C-H bonds occurs with low ee (37-40% ee) and with limited scope (Scheme 1B).…”

“…(1) Having identified a simple synthesis of 2a, we sought conditions for the asymmetric, intramolecular silylation (Table 1). Based on previous reports of Rh-catalyzed silylations of C-H bonds, [9][10][11][12] we examined the Rh catalyst derived from [Rh(cod)Cl] 2 and (S)-DTBM-SEGPHOS (L1) with cyclohexene as a hydrogen acceptor [30] at 80 °C (entry 1). The functionalization of cyclopropyl C-H bonds occurred in 2 hours under these conditions, yielding the cyclized product 3a in 93% yield and 83% ee.…”