Issue 11, 2014

Computational investigations on the phosphine-ligated CuH-catalyzed conjugate reduction of α-β unsaturated ketones: regioselectivity and stereoselectivity

Abstract

Computational investigations on the phosphine-ligated CuH-catalyzed conjugate reduction of α-β unsaturated ketones were performed with the DFT method. Two phosphine-ligated CuH catalysts, Ph3P–CuH and (R)-SEGPHOS–CuH, were employed to probe the reaction mechanism with the emphasis on regioselectivity and stereoselectivity. The calculations on the Ph3P–CuH system indicate that there exist two competing reaction pathways: the 1,4- and 1,2-path. The 1,4-path is predicted to be energy-favoured among these reaction paths. The mechanism of the 1,4-path includes two steps: (1) the first step is predicted to be the rate-determining step (RDS), corresponding to the delivery of the hydrogen atom of the CuH catalyst to the β-carbon atom of the substrate, with the formation of the enolate; (2) in the second step, the enolate undergoes a σ-bond metathesis with the hydride source to liberate the final product and regain the catalysts. In the chiral (R)-SEGPHOS–CuH system, the first step of CuH to the unsaturated bond is vital for the distribution of products and therefore responsible for the stereoselectivity of the 1,4-addition. The calculations on the (R)-SEGPHOS–CuH system reproduce the major product in the R-configuration, which is consistent with the experimental observation. The steric hindrance between the bulky substituent moiety of the substrate and the P-phenyl ring of the SEGPHOS–CuH catalyst is identified as the origin of the stereoselectivity for the titled reaction.

Graphical abstract: Computational investigations on the phosphine-ligated CuH-catalyzed conjugate reduction of α-β unsaturated ketones: regioselectivity and stereoselectivity

Supplementary files

Article information

Article type
Paper
Submitted
30 Jul 2013
Accepted
11 Nov 2013
First published
11 Nov 2013

RSC Adv., 2014,4, 5726-5733

Computational investigations on the phosphine-ligated CuH-catalyzed conjugate reduction of α-β unsaturated ketones: regioselectivity and stereoselectivity

H. Liu, W. Zhang, L. He, M. Luo and S. Qin, RSC Adv., 2014, 4, 5726 DOI: 10.1039/C3RA44015J

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