Facially Controlled C ‐Methylation of Oxolanyl and Cyclopentyl Acetate Enolates: Application to the Total Synthesis of (+)‐Nephromopsinic Acid

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)