Influence of methoxy-and methyl-aromatic substituents on stereochemistry of the products in the acid-catalyzed cyclization of 2-(2-arylethyl)-1,3,3-trimethylcyclohexanols: stereocontrolled total synthesis of (±)-nimbidiol and (±)-nimbiol

Abstract

The distributions of the trans-and the cis-podocarpatrienes ( 5c-g ) and ( 6c-g) in the cyclialkylation reaction of the easily accessible cyclohexanols ( 4c-g) under a mild condition have been investigated. The cyclohexanol precursors having unactivated aromatic ring proceeds with high stereoselectivity leading to the respective trans-products, while the substrates with an electron donating methoxy or a methyl substituent with respect to the site of electrophilic attack result in the corresponding cis-and the trans-product mixtures. Consistent mechanisms for these stereochemical results have been advanced. Based on these results simple syntheses of the modified diterpenes (±)-nimbidiol (7) and (±)-nimbiolmethylether (18) have been realized.