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 SynthesisThis research was partially supported by Grants-in-Aid for Scientific Research on Basic Areas (B) ‘18350056’, Priority Areas (A) ‘17035087’ and ‘18037068’, (C) ‘15K05508’, and Exploratory Research ‘17655045’ from the Ministry of Education, Culture, Sports, Science and Technology (MEXT).
Received: 05 June 2018
Accepted after revision: 12 July 2018
23 August 2018 (online)
Dedicated to Professor Teruaki Mukaiyama on the celebration of his 90th birthday (Sotuju)
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 wordsSuzuki–Miyaura cross-coupling - Kumada–Tamao–Corriu cross-coupling - fully substituted α,β-unsaturated esters - pharmacophore - stereoretention - XPhos - SPhos
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