Functionalized carbocycles by tandem dealkoxycarbonylation-Michael addition reactions

Abstract

A tandem dealkoxycarbonylation-Michael addition reaction has been developed as a synthetic route to highly functionalized carbocycles. Methyl esters, activated toward decarboxylation by an electron-withdrawing group at C-2 and tethered by a three- or four-carbon chain to an acrylate Michael acceptor, have been prepared and used as the cyclization substrates. Treatment of these compounds with LiCl in HMPA at 120 o C for 4 h results in selective S N 2 dealkylation of the methyl esters, decarboxylation, and cyclization of the intermediate anions by a Michael addition to the pendant acrylate moiety. This affords 45-90% of the cyclopentane- and cyclohexaneacetic esters substituted at C-2 by an electron-withdrawing group. Moderate to excellent selectivity (3:1-99:1) in favor of the product having the electron-withdrawing group trans to the acetic ester side chain is observed. The reaction works best for the preparation of five-membered rings, and cyclizations proceed most cleanly from substrates which cyclize through a tertiary carbanion. Synthetic and mechanistic details as well as optimization studies and product structure proofs are presented