Diastereoselective control of enolate alkylation in 2-acyl-2-alkyl-1,3-dithiane 1-oxides

Abstract

Stereochemical control of enolate alkylation in syn(5) and anti(4) acyl dithiane monosulphoxides has been investigated. The substrates were prepared in high yields from 2-substituted dithianes by acylation in two steps via the corresponding aldehydes followed by sulphoxidation. 2-Acyl-2-alkyl1,3-dithiane 1-oxides were readily deprotonated using a variety of bases. The enolates so generated reacted with methyl iodide and other alkylating agents to give diastereoisomeric mixtures of the alkylated products, the ratios observed being dependent upon the relative stereochemistry of the acyl dithiane oxide, the 2-alkyl substituent, and the base, solvent, and temperature used for the reaction. Diastereoselectivities sufficiently high that the minor isomer could not be detected by ¹H n.m.r. spectroscopy at 250 MHz have been observed in some cases (Tables 2 and 3), the most selective system being the anti 2-acyl-2-ethyl derivative (4c). The data obtained fall into clear patterns which may be rationalized by proposing chelated chair-form transition states involving interaction of both the enolate and sulphoxide oxygen atoms with the metal counter-ions.