Stereospecific thio-claisen rearrangement of S-crotylic α-hydroxy ketene dithioacetals. Creation of three contiguous stereogenic centres.

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All four diastereoisomeric S-crotylic α-hydroxy ketene dithioacetals (ZE′, ZZ′, EE′ and EZ′) were prepared uniquivocally from S-methyl or S-crotyl (Z or E) β-hydroxy dithioesters by a tandem cis-deprotonation with LDA and S-alkylation. These dithioacetals underwent, in a refluxing cyclohexane solution, an easy thio-Claisen rearrangement into dithioesters, containing three contiguous chiral centres. The rearrangement is stereospecific. Furthermore each of the four system led to the formation of a different major diastereoisomer, thus making all of the four possible isomers (anti-anti, syn-syn, anti-syn and syn-anti) accessible. A relationship between the main component configuration and the starting dithioacetal geometry has been ruled out. The observed stereospecificity originates from two independent stereocontrols, an internal and an external one. The former is an aggreement with the classical internal control obtained with a [3.3] sigmatropic shift. The latter is a result of an asymmetric induction but surprisingly, is dependent on the S-crotylic double bond geometry. All the results were rationalised by transition state models and the configurations proven by chemical correlations: transformation into known esters and Swern oxidation.