Catalytic Asymmetric Synthesis of Chiral Propargylic Alcohols for the Intramolecular Pauson−Khand Cycloaddition

Abstract

Several methods for the catalytic asymmetric alkyne addition to aldehydes are used to prepare the propargylic alcohol-based chiral en-ynes. Protection of the propargylic alcohols with either an acetyl or a methyl group allows the resulting en-ynes to undergo the intramolecular Pauson-Khand reaction to form the corresponding optically active 5,5- and 5,6-fused bicyclic products with high diastereoselectivity and high enantiomeric purity. In the major product, the propargylic substituent and the bridgehead hydrogen are cis with respect to each other on the fused bicyclic rings. The enantiomeric purity of the propargylic alcohols generated from the asymmetric alkyne addition is maintained in the cycloaddition products. The allylic ethers of the chiral propargylic alcohols are prepared which can also undergo the highly diastereoselective Pauson-Khand cycloaddition with retention of the high enantiomeric purity. This study has shown that the size of the substituents at the propargylic position as well as on the alkyne is important for the diastereoselectivity with the greater bulkiness of the substituents giving higher diastereoselectivity.