Schiral hydroxy sulfoxides

The procedures used in the synthesis of non-racemic hydroxy sulfoxides are in some respects similar to those applied to the preparation of hydroxy sulfones, the difference being the location of a stereogenic centre on the sulfinyl sulfur atom. Thus, a cholesterol esterase (CE)-promoted kinetic resolution of alkyl aryl sulfoxides having pendant acetoxy group in the ortho position of the aryl ring 21 gave both the unreacted acetate and the corresponding hydroxyphenyl product 22 with moderate enantioselectivity (Equation 14).42 In turn, S-racemic w-hydroxyalkyl sulfoxides 23 and hydroxyalkylaryl sulfoxides 24, having the reacting primary hydroxy group very remote from the stereogenic centre (four bonds in 23 and six bonds in 24), were successfully resolved via enzymatic acetylation.43

An attempt at the enzymatic hydrolysis of racemic a-acetoxymethyl sulfoxides rac-25 gave the recovered esters in yields up to 40% and with ees up to 95%. The hydrolysis products, a-hydroxymethyl sulfoxides 26, underwent decomposition like in the case of analogous hydroxy sulfides (Equation 1) and hydroxy sulfones (Equation 8). A possible reverse reaction remained out of the question because of the inaccessibility of the corresponding sulfenic acids 27 (Equation 15).44

Some enzymes were found to exhibit high diastereoselectivity towards hydroxy sulfoxides. It was observed in the acetylation of the epimeric mixture of P-hydroxyalkyl sulfoxides 28 and 29, leading to the improvement of the diastere-omeric ratio,45a and in the acetylation of (R, R)-dihydroxythiolane 1-oxide 30, leading exclusively to cis-31 (Equation 16).33 Interestingly, single biotransformations of 1-phenylthio-2-propanone 32 by the fungus Helminthosporium sp. 4671 resulted in both sulfur oxidation to the sulfoxide and carbonyl reduction to the alcohol to give the hydroxy sulfoxide 33 with high diastereomeric excess (Equation 17).45b

Was this article helpful?

0 0

Post a comment