title: 2,2,3-Trisubstituted Tetrahydrofurans and 2H-Tetrahydropyrans by Tandem Demethoxycarbonylation-Michael Addition Reactions.
abstract: A tandem demethoxycarbonylation-Michael addition reaction has been developed as a synthetic route to highly functionalized five- and six-membered oxygen heterocycles. Methyl esters, activated toward decarboxylation by a C-2 ethoxycarbonyl group and tethered by a three- or four-atom chain to an acrylate Michael acceptor, have been prepared and used as the cyclization substrates. Treatment of these compounds with lithium chloride in DMEU (1,3-dimethyl-2-imidazolidinone) at 120 degrees C for 4-8 h results in chemoselective S(N)2 dealkylation of the methyl esters, decarboxylation, and cyclization of the intermediate enolates by a Michael addition to the pendent acrylate moiety. This affords tetrahydrofuran and 2H-tetrahydropyran derivatives in 60-90% yields with diastereoselectivities up to 7.5:1 in favor of the product having the C-2 ethoxycarbonyl group trans to the C-3 acetic ester side chain. The reaction works best for the preparation of five- and six-membered rings, and cyclizations proceed most cleanly from substrates which cyclize through a tertiary enolate. Synthetic and mechanistic details are presented.
authors.affiliation: Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078-3071.
authors.forename: Richard A.
authors.initials: RA
authors.lastname: Bunce
authors.forename: Eric D.
authors.initials: ED
authors.lastname: Dowdy
authors.forename: R. Shawn
authors.initials: RS
authors.lastname: Childress
authors.forename: Paul B.
authors.initials: PB
authors.lastname: Jones