Mislow-Evans Rearrangement

In 1968, the German-born American chemist Kurt Mislow reported that when heating enantiomerically pure allylic sulfoxides, they underwent thermal racemization whilst enantiopure allylic sulfenates gave optically active sulfoxides. In 1971, David Evans and colleagues realized the synthetic potential of this technique in converting allylic sulfoxides to allylic alcohols via a sulfonate ester intermediate in the presence of a thiophile, usually a phosphite or other nucleotide. They also showed that it was applicable for a wide range of substrates. The first step of this transformation is a [2,3]-sigmatropic rearrangement of an allylic sulfoxide to a sulfenate ester, which became known as the Mislow-Evans rearrangement.

The second phase of the Evans reaction is the alkylation of the allylic alcohol via formation of an intermediate carbanion. Typically, the formation of the allylic carbanion is achieved through the use of a strong base such as n-butyl lithium or lithium diisopropylamide (LDA) at low temperatures. Alkylation of the allylic carbanion is also carried out at low temperatures in the presence of a variety of alkyl, allylic, and benzylic halides.

The reaction has general application in the preparation of trans-allylic alcohols and the total synthesis of the major urinary metabolite of the hormone Prostaglandin E2. Douglas Taber and colleagues utilized this to ensure the (E)-stereochemistry of the double bond.