Facile synthesis of bicyclic and tricyclic skeletons by cycloisomerizations of hept-1-en-6-ynes and 4,9-diheteradodeca-1,11-dien-6-ynes, followed by [4+2] cycloadditions

Palladium-catalyzed intramolecular cross coupling of various 4-substituted hept-1-en-6-ynes, followed by intermolecular [4+2] cycloaddition with methy l acrylate and 2-chloro-2-cyclopropylideneacetate yielded both all-carbon a nd heteroanalogous bicyclic derivatives 8, 9, 18, 19, and 24 (24-71%). Cycl oisomerization of the hydroxymethyl- and hydroxyethyl-substituted hept-1-en -6-ynes 5 and 15, followed by Diels-Alder reaction with methyl acrylate, oc curred with intramolecular transesterification to give the tricyclic lacton es 11 (37%) and 16 (15%), respectively. Tricyclic systems containing up to three heteroatoms could be obtained from the corresponding dodeca-1,11-dien -6-ynes, by palladium-catalyzed cycloisomerization followed by intramolecul ar [4 + 2] cycloaddition. The scope and limitations of this single-operatio n tricyclization were evaluated. Symmetrically disubstituted dienynes with two nitrogen or two oxygen atoms reacted efficiently (41-90%) in this way, producing 5-6-5 ring-size combinations. Diastereoselectivities were poor in all cases (1:1 to 3.4:1). Unsymmetrically disubstituted dodecal,11-dien-6- ynes 44 and 48 underwent tricyclization with little or no regioselectivity to give 49/50 (7:3) and 51/52 (1:1).