SYNTHESIS, SEPARATION AND ABSOLUTE-CONFIGURATION ASSIGNMENT TO ENANTIOMERS OF 1,3-BENZODITHIOLE 1-OXIDE AND 2-ALKYL-1,3-BENZODITHIOLE 1-OXIDES

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 (6cis-1R,2S, 6trans-1R,2R), 2-ethyl (7cis-1R,2S, 7trans-1R,2R) and 2-isopropyl (8cis-1R,2S, 8trans-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 (9cis-1R,2R,2'S, 9cis-1S,2R,2'S, 9trans-1S,2S,2'S 9trans-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 9trans-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.