A n + 1 Strategy for Macrocyclization Based on Free-Radical Carbonylation

Abstract

The synthesis of 10-17 membered 4-oxolactones 2 from alkyl iodides 1 having an acryloxy moiety at the termini, carbon monoxide, and TTMSS (or tin hydride) takes place cleanly in moderate to good yield under free radical conditions. Low concentrations of 1 (0.005-0.01 M) are favorable for both intermolecular trap of CO and intramolecular acyl radical addition to the C-C double bond.