Facially controlled C-methylation of oxolanyl and cyclopentyl acetate enolates: Application to the total synthesis of (+)-nephromopsinic acid

Article abstract of DOI:10.1002/ejoc.200400653

The stereoselectivity of the C-methylation of oxolanyl and cyclopentyl acetate enolates 5a-22a was investigated. The configuration of the C-methyl diastereomers was elucidated by a combination of crystal structure analysis, NMR spectroscopy and chemical correlations. Generally, the methylation proceeded re*-selectively, although with very different degrees of selectivity. The most important stereodirecting effect was a steric one exerted by the 5-phenethyl substituent, and this steric effect was strongly increased by the stereodirecting effect of a 3-OR group. Contrary to previous literature evidence, the endocyclic oxolanyl oxygen does not exert an effect. These findings were applied in a highly stereoselective synthesis of (+)-nephromopsinic acid (94). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.