Stereoretentive Suzuki–Miyaura and Kumada–Tamao–Corriu Cross-Couplings for Preparing (E)- and (Z)-Stereodefined, Fully Substituted α,β-Unsaturated Esters: Application for a Pharmacophore Synthesis

Dedicated to Professor Teruaki Mukaiyama on the celebration of his 90^th birthday (Sotuju)

Abstract

Substrate-general stereocomplementary Suzuki–Miyaura (SM) cross-coupling and relevant Kumada–Tamao–Corriu (KTC) cross-coupling reactions for preparing (E)- and (Z)-stereodefined, fully substituted α,β-unsaturated esters are described. The SM cross-coupling reactions were performed under Pd(OAc)₂/SPhos/iPr₂NEt catalysis (24 examples, 66–99% yield). The KTC cross-coupling reactions were also performed under similar Pd(OAc)₂/SPhos conditions (11 examples, 50–98% yield). Application to a useful pharmacophore containing a cyclopropane structure was investigated, wherein distinctive (E)- and (Z)-stereochemical difference between XPhos and SPhos was observed. A plausible mechanism for the stereoretention and stereoinversion cross-coupling reactions is proposed.

Key words

Suzuki–Miyaura cross-coupling - Kumada–Tamao–Corriu cross-coupling - fully substituted α,β-unsaturated esters - pharmaco­phore - stereoretention - XPhos - SPhos

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