Dialkyl Phosphite-Initiated Cyclopropanation of α,β-Unsaturated Ketones Using α-Ketoesters or Isatin Derivatives

J Org Chem. 2017 Mar 17;82(6):3252-3261. doi: 10.1021/acs.joc.6b03009. Epub 2017 Mar 2.

Abstract

Efficient cyclopropanation of α,β-unsaturated ketones using α-ketoesters or isatin derivatives is reported. The cyclopropanation reaction occurs via a cascade transformation that starts with addition of deprotonated dialkyl phosphite to the keto groups of α-ketoesters or isatin derivatives, followed by [1,2]-phosphonate/phosphate rearrangement to generate α-phosphonyloxyenolate intermediates, which are trapped by α,β-unsaturated ketones via Michael addition/ring closure. This protocol was used to synthesize tetra-substituted cyclopropanes with a 1,2-cis-1,3-trans configuration in high yield with excellent diastereoselectivity.

Publication types

  • Research Support, Non-U.S. Gov't