Stereoselectivity in the intramolecular Pauson-Khand reaction: Towards a simple predictive model

The major product in the intramolecular Pauson-Khand reaction of 3,4-disubs tituted 1,6-heptenynes to form bicyclo[3.3.0]octenones is highly dependent on the relative configurations of the two stereocenters of the substrate. F or example, cycloaddition of the "syn,syn" stereoisomer of 3,5-dimethyl-4-p ropargyl-1,6-heptadiene gives predominantly an enone containing both substi tuents in more hindered endo orientations; the "syn,anti" stereoisomer, upo n reaction across the "syn" linkage similarly gives mostly endo product, bu t upon reaction across the "anti" portion of the molecule affords almost ex clusively an enone in which the C6 methyl group possesses exo stereochemist ry. Parallel results obtain from enynes built upon cyclohexane frameworks. Calculated energies of pre-cycloaddition enynes, metallacycles presumed to be the penultimate intermediates in the cyclization mechanism, and the fina l products are examined in order to develop a reasonable predictive model. (C) 1999 Elsevier Science Ltd. All rights reserved.