Chirality transfers through sequential sigmatropic rearrangements of allylic vicinal diols: Development and application to total synthesis of (-)-kainic acid

A detailed description is presented of two sequential sigmatropic rearrangements starting from enantiopure allylic vicinal diols. Starting from the same allylic diol, the sequential Claisen/Claisen rearrangement can install two identical functional groups in a one-pot reaction, whereas, the sequential Claisen/Overman rearrangement can introduce two different functional groups, both occurring without protecting group manipulation. Both sequential reactions proceeded with complete stereoselectivity, which was easily predictable by the judicious choice of two factors regarding the allylic diols: (1) the stereochemistry of the hydroxy groups and (2) the geometry of the olefin. To demonstrate this sequential rearrangement methodology, we accomplished the total synthesis of (-)-kainic acid, whose three contiguous stereocenters were completely established by three chirality transfer reactions (S _N2' and sequential Claisen/Overman reactions) of flexible acyclic intermediates derived from D-arabinose. A detailed investigation is described of two sequential sigmatropic rearrangements from allylic diols. Starting from the same allylic diol, either two identical functional groups (Claisen/Claisen) or two different functional groups (Claisen/Overman) were diastereoselectively installed. The reaction was successfully applied to the total synthesis of (-)-kainic acid.