Preparation of O-Protected Cyanohydrins by Aerobic Oxidation of α-Substituted Malononitriles in the Presence of Diarylphosphine Oxides

Org Lett. 2019 Apr 19;21(8):2597-2601. doi: 10.1021/acs.orglett.9b00569. Epub 2019 Mar 28.

Abstract

A mild, reagent-cyanide-free, and efficient synthesis of O-phosphinoyl-protected cyanohydrins from readily available α-substituted malononitriles was realized using diarylphosphine oxides in the presence of O2. Mechanistic studies indicated that in addition to the initial aerobic oxidation of the malononitrile derivative notable features of this process include the formation of a tetrahedral intermediate and a subsequent intramolecular rearrangement. The phosphinoyl-protecting group can be removed by alcoholysis or by reduction with DIBAL-H.

Publication types

  • Research Support, Non-U.S. Gov't