Intramolecular cyclization reactions of carbonyl derivatives of hydroxysulfones

The gamma and delta-hydroxysulfone tert-butyl ester derivatives 2a-e are easily prepared from the corresponding hydroxysulfones by phase-transfer alkylation reactions. The sulfonyl carbanions of 2a-e are readily generated upon treatment with LHMDS in THF at -78degreesC and undergo intramolecular acylation reactions to give a variety of functionalized cyclic ethers 4a-e in good yields. The intramolecular aldol-type reaction of the sulfonyl carbanion of 6a is useful for the preparation of six-membered oxacyclic ring systems with high diastereo selective control and is best carried out under equilibrating conditions ((BuOK)-Bu-t in toluene), This study clearly shows that it is possible to generate an alpha-sulfonyl carbanion and effect its intramolecular cyclization even in the presence of other protons of comparable acidity elsewhere in the substrate. The scope, limitations and synthetic utility of this intramolecular cyclization strategy have been examined. (C) 2002 Elsevier Science Ltd. All rights reserved.