Nonracemic Diarylmethanols From CuH-Catalyzed Hydrosilylation of Diaryl Ketones

Abstract

An efficient method for the synthesis of nonracemic diarylmethanols has been developed. The use of ( R)-(-)-(DTBM-SEGPHOS)CuH effects highly enantioselective 1,2-hydrosilylation of prochiral diaryl ketones.

Enantioselective Reduction of Diaryl Ketones Catalyzed by a Carbonyl Reductase from Sporobolomyces salmonicolor and its Mutant Enzymes

“…[15,19,22,24] For the reduction of para-substituted diaryl ketones, the enantioselectivity was increased in the order of F < Cl < CH 3 < CH 3 O, which was in agreement with the increasing size and electron-donating property of the para-substituent. It is worth noting that 4-methoxybenzophenone was reduced to the corresponding (R)-alcohol with excellent conversion (95%) and enantiomeric purity (99% ee) in buffer containing 10% of methanol.…”

“…Compared to the asymmetric hydrogenation and hydrosilylation of 4-chlorobenzophenone and 4-methylbenzophenone catalyzed by chiral metal catalysts, in which the enantiomeric purity for p-chlorobenzhydrol was 0-47% ee and the best result for p-methylbenzhydrol was 39% ee, [8,18,19,24] the carbonyl reductase SSCR-catalyzed reduction exhibited much higher stereoselectivity (up to 88 and 92% ee for 1b and 1c, respectively), and even higher than the best results of the commercially available ketoreductases (64 and 85% ee for 1b and 1c, respectively), [30] showing the promise of this enzyme toward the reduction of sterically bulky diaryl ketones.…”

“…The asymmetric chemical reductions of diaryl ketones involve chiral borane reduction, [15][16][17] transition metal-catalyzed hydrogenation, [18][19][20] hydrogen transfer reduction [21] , and hydrosilylation. [22][23][24] Although these chemical methods have provided a useful access to diarylmethanol with high enantiomeric purity in some cases, their common drawback is the limited substrate range. [1,25] For example, the degree of enantiofacial discrimination in Coreys CBS reduction of diaryl ketones is determined by both electronic and steric effects, requiring that the ketones have an electron donor substituent on one aromatic ring and an acceptor group on the other, [26] or an ortho-substituent on one of the aryl groups.…”

“…The reduction of diaryl ketones with only a para-or metasubstituent on one of the aryl groups affords the diarylA C H T U N G T R E N N U N G methanol in low enantiomeric purity (ee often being less than 50%). [18,19,22,24] Therefore, the highly enantioselective reduction of diaryl ketones without high electronic dissymmetry or an ortho-substituent on one of the aryl groups has proven to be a significant challenge. [1] Biocatalysts have been demonstrated to be highly enantioselective in the reduction of a wide range of ketones including some bulky ones.…”

Reduction of Sulfoxides to Sulfides in the Presence of Copper Catalysts

“…Besides molybdenum-, iron-, and zinc-based systems the application of copper can be beneficial. Indeed, the potential of copper catalyst in reduction techniques has been explored in the reduction of various functionalities [46][47][48][49][50][51][52][53][54][55][56][57][58]. However, the catalytic reduction of sulfoxides in the presence of copper has been so far unreported, while the converse process has been studied [59].…”