Highly Regio- and Stereoselective Dehydration of Allylic Alcohols to Conjugated Dienes via 1,4-syn-Elimination with H2 Evolution.

Abstract

Dehydration of alcohols is one of the most fundamental transformations in the organic chemistry class and one of the most widely used methods for producing alkenes in synthetic research. Numerous methods and reagents have been developed to control the regio- and stereoselectivity as well as the dehydration efficiency of normal alcohols. Despite these achievements, regio- and stereoselective and predictable dehydration of allylic alcohol has seldom been reported, except for limited substrates with a native preferred elimination position, as a result of the challenges that many potential dienes could be formed via 1,2- or 1,4-syn- or anti-elimination. Here, we report a tBuOK/potassium 2,2-difluoroacetate-mediated 1,4-syn-dehydration of allylic alcohol for the synthesis of regio- and stereodefined conjugated dienes via an in situ generated directing group strategy. This reaction exhibits a broad substrate scope and good functional group compatibility for primary-tertiary alcohols. The simple and scalable (up to 0.6 mol) procedure with readily available and inexpensive reagents makes it a practical method for conjugated diene synthesis. Mechanistic studies reveal that an acetate with tert-butoxide and allyloxide acetal moiety is formed as an intermediate, in which the acetate and the acetal act as the directing group for the base-promoted elimination. An unusual H2 evolution is also involved in the reaction.