Synthesis, separation and absolute configuration assignment to enantiomers of 1,3-benzodithiole 1-oxide and 2-alkyl-1,3-benzodithiole 1-oxides

Abstract

1,3-Benzodithiole 1-oxide, 5, has been resolved into enantiomers using chiral stationary phase high performance liquid chromatography. Alkylation of an excess (25%) of the late eluting (+)-(1R) enantiomer of the sulfoxide 5 under basic conditions yielded both cis and trans isomers of 2-methyl (6_cis-1R,2S′,6_trans-1R,2R), 2-ethyl (7_cis-1R,2S′, 7_trans-1R,2R) and 2-isopropyl (8_cis-1R,2S′, 8_trans-1R,2R)-benzodithiole 1-oxide (25% e.e.) and allowed a stereochemical correlation of absolute configuration between the sulfoxides 5–8.

Treatment of racemic 1,3-benzodithiole 1-oxide (5_1S/5_1R) with potassium bis(trimethylsilyl)amide and (S)-(+)-1-iodo-2-methylbutane yielded four diastereoisomers of 2-(2′-methylbutyl)-1,3-benzodithiole 1-oxide (9_{cis-1R,2S,2′S′}, 9_{cis-1S,2R,2′S′}, 9_{trans-1S,2S,2′S}, 9_{trans-1R,2R,2′S}) which were separated by chiral stationary phase HPLC (CSP-HPLC). The most strongly retained diastereoisomer was analysed by X-ray crystallography and was assigned the (1S:2S:2′S) absolute configuration. Further alkylation of 9_{trans-1S,2S,2′S} under similar conditions yielded 2-(2′S-methylbutyl)-2-(2″S-methylbutyl)-1,3·benzodithiole 1-oxide 10 of (1S,2′S,2″S) configuration exclusively. The same stereoisomer of the sulfoxide 10 was also obtained by dialkylation of the early eluting (–)-enantiomer of 1,3-benzodithiole 1-oxide (5_1S) using (+)-1-iodo-2-methylbutane, thus enabling the unequivocal establishment of the absolute configurations of the enantiomers of 1,3-benzodithiole 1-oxides listed in Table 1. A comparison of circular dichroism (CD) spectra for sulfoxides 5–9 indicates that this method may also be used to correlate absolute configurations of 2-alkyl substituted 1,3-benzodithiole 1-oxides.