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Facially Controlled C ‐Methylation of Oxolanyl and Cyclopentyl Acetate Enolates: Application to the Total Synthesis of (+)‐Nephromopsinic Acid
Author(s) -
Mulzer Johann,
Steffen Ulrich,
Martin Harry J.,
Zorn Ludwig
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400653
Subject(s) - chemistry , steric effects , stereoselectivity , methylation , diastereomer , substituent , selectivity , stereochemistry , total synthesis , methyl group , organic chemistry , catalysis , group (periodic table) , biochemistry , gene
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)