(3 + 2) Annulation of Cyclopropanone Acetal with Silyl Enol Ether toward the Synthesis of Polysubstituted Cyclopentanones

Org Lett. 2026 Jan 9;28(1):450-455. doi: 10.1021/acs.orglett.5c04864. Epub 2025 Dec 22.

Abstract

A (3 + 2) annulation to access the structurally diverse polysubtituted cyclopentanones bearing two adjacent quaternary stereogenic centers is reported. This reaction is proposed to proceed through a domino Mukaiyama aldol/homoaldol reaction of silyl enol ethers with commercially available (1-ethoxycyclopropoxy)trimethylsilane, which serves as a cyclopropanone surrogate. The synthetic utilities of this methodology have been demonstrated by the diverse derivatizations of the annulated products and the synthesis of an analogue of natural product α-cuparenone.