FUNCTIONALIZED CARBOCYCLES BY TANDEM DEALKOXYCARBONYLATION MICHAEL ADDITION-REACTIONS

A tandem dealkoxycarbonylation-Michael addition reaction has been deve loped as a synthetic route to highly functionalized carbocycles. Methy l esters, activated toward decarboxylation by an electron-withdrawing group at C-2 and tethered by a three- or four-carbon chain to an acryl ate Michael acceptor, have been prepared and used as the cyclization s ubstrates. Treatment of these compounds with LiCl in HMPA at 120-degre es-C or 4 h results in selective S(N)2 dealkylation of the methyl este rs, decarboxylation, and cyclization of the intermediate anions by a M ichael addition to the pendant acrylate moiety. This affords 45-90% of the cyclopentane- and cyclohexaneacetic esters substituted at C-2 by an electron-with drawing group. Moderate to excellent selectivity (3:1 -99:1) in favor of the product having the electron-withdrawing group t rans to the acetic ester side chain is observed. The reaction works be st for the preparation of five-membered rings, and cyclizations procee d most cleanly from substrates which cyclize through a tertiary carban ion. Synthetic and mechanistic details as well as optimization studies and product structure proofs are presented.