Mechanistic Studies on the Copper‐Catalyzed Hydrosilylation of Ketones

Abstract

The copper‐catalyzed asymmetric hydrosilylation of ketones is an efficient method for the synthesis of chiral enantiopure secondary alcohols. Herein, we present a detailed computational study (DFT/B3LYP) of the copper(I)‐catalyzed reaction. In particular, the two transition states involved in the catalytic cycle have been determined. The insertion of the ketone into the Cu–H bond was found to have a lower activation barrier than the reaction of the copper alkoxy intermediate with the silane, which regenerates Cu–H along with the silyl ether product. Our findings also reveal the importance of the copper hydride dimer in controlling the reactivity toward the ketone. The conclusions are supported by experimental mechanistic investigations including kinetic studies, kinetic isotope effect, and isotope labeling measurements.

Mechanistic Studies Lead to Dramatically Improved Reaction Conditions for the Cu-Catalyzed Asymmetric Hydroamination of Olefins

“…Corroborating our full kinetic analysis, initial-rate kinetics demonstrated that the reaction was zero-order in styrene and amine electrophile 3 across a range of concentrations for each component. In addition, a clear first-order dependence was observed for diethoxymethylsilane (DEMS) and an apparent fractional-order 11 was observed while simultaneously changing the concentration of Cu(OAc) 2 and DTBM-SEGPHOS.…”

“…30 In addition, these results are consistent with previous reports that β-hydride elimination most likely does not occur during the CuH-catalyzed hydrosilylation of ketones. 11 , 31 …”

Application of a C2-Symmetric Copper Carbenoid in the Enantioselective Hydrosilylation of Dialkyl and Aryl–Alkyl Ketones

“…7,20 The importance of aggregation of the copper hydride active catalyst has been established, and it is possible that the extraordinary activity of CuPhEt may be attributable in part to diminished ability to aggregate due to its steric bulk. 19 The kinetics and mechanism of CuPhEt-catalyzed hydrosilylations are under current investigation and will be reported in due course.…”

Nickel-Mediated Hydrogenolysis of C–O Bonds of Aryl Ethers: What Is the Source of the Hydrogen?

“…The increased isotopic incorporation from Et 3 SiH vs Et 3 SiD is consistent with normal isotope effects for β-H elimination (conversion of 3b to 4b ) and transmetallation between 3b and silane to generate 4b . 42–44,48,49 …”