Lili Zong, Shuaidong Huo | ACS Catalysis: Enantioselectivity and Reactivity Enhancement by 1,1,3,3-Tetramethylguanidine in Bisguanidinium-Catalyzed Asymmetric Alkylation for Construction of Indole Alkaloid Marine Natural Products

Abstract

Catalytic 1,1,3,3-tetramethylguanidine (TMG)-mediated enhancement of enantioselectivity and reactivity was revealed in bisguanidinium-catalyzed asymmetric prenylation, propargylation, and benzylation of 3-substituted oxindoles. Preliminary mechanistic studies indicate that protonated TMG not only assists enolate intermediate formation as a phase-transfer agent but also activates electrophiles in the transition state. The resulting 3,3-disubstituted oxindoles with high enantioselectivities were readily transformed to pharmaceutically valuable molecules. A mild and efficient methodology for synthesizing (−)-flustramine B, (−)-debromoflustramine B and their triazole analogues with antibiofilm potentials was established.

Link: https://pubs.acs.org/doi/10.1021/acscatal.3c03812