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The major product in the intramolecular Pauson-Khand reaction of 3,4-disubstituted 1,6-heptenynes to form bicyclo[3.3.0]octenones is highly dependent on the relative configurations of the two stereocenters of the substrate. For example, cycloaddition of the “syn,syn” stereoisomer of 3,5-dimethyl-4-propargyl-1,6-heptadiene gives predominantly an enone containing both substituents in more hindered endo orientations; the “syn,anti” stereoisomer, upon reaction across the “syn” linkage similarly gives mostly endo product, but upon reaction across the “anti” portion of the molecule affords almost exclusively an enone in which the C6 methyl group possesses exo stereochemistry. 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 final products are examined in order to develop a reasonable predictive model.

Stereoselectivity favoring exo substituent orientation in the intramolecular Pauson-Khand reaction of 3-methyl-4-hydroxy-1,6-heptenynes to form bicyclo[3.3.0]octenones is affected by the relative stereochemistry at C3 and C4. Cycloaddition of one stereoisomer of 3,5-dimethyl-4-propargyl-1,6-heptadiene gives predominantly the bicyclo[3.3.0]octenone isomer containing both substituents in more hindered endo orientations. An explanation based upon the effect of conformational preferences prior to metallacycle formation is proposed.

Stereoselectivity favoring exo substituent orientation in the intramolecular Pauson-Khand reaction of 3-methyl-4-hydroxy-1,6-heptenynes to form bicyclo[3.3.0]octenones is affected by the relative stereochemistry at C3 and C4. Cycloaddition of one stereoisomer of 3,5-dimethyl-4-propargyl-1,6-heptadiene gives predominantly the bicyclo[3.3.0]octenone isomer containing both substituents in more hindered endo orientations. An explanation based upon the effect of conformational preferences prior to metallacycle formation is proposed.