Functionalized Carbocycles by Tandem Dealkoxycarbonylation-Michael Addition Reactions

Article abstract of DOI:10.1021/jo00077a043

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 deg C for 4 h results in selective S_N2 dealkylation of the methyl esters, decarboxylation, and cyclization of the intermediate anions by a Michael addition to the pendant acrylate moiety.This affords 45-90percent 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.