Chirality transfer through [3,3]-sigmatropic rearrangements is one of the most reliable approaches for accessing enantiopure multifunctional molecules. To maximize the potential utility of chirality transfer, we developed two types of novel sequential sigmatropic rearrangements of allylic diols: 1) the sequential Claisen/Claisen rearrangement (Scheme 2), and 2) the sequential Claisen/Overman rearrangement (Table 1, Scheme 3). While the former rearrangement gave two identical functional groups without protecting group manipulation of homoallylic diols, the latter rearrangement installed two different functional groups. Especially, the latter Claisen/Overman rearrangement was more challenging because it required the suppression of the second competitive Claisen rearrangement after the first rearrangement (12→9). To overcome this inherent problem, the Claisen rearrangement via cyclic orthoamides was employed, furnishing the singly rearranged products 12, which underwent Overman rearrangement stereoselectively. To demonstrate the practical utility of the sequential sigmatropic rearrangements, we applied this methodology in the total synthesis of (-)-kainic acid (1, Scheme 5). A conspicuous feature of our approach is the use of chirality transfer in acyclic compounds made possible by taking advantage of the three secondary hydroxy groups embedded in D-arabinose (15). An S_N2' reaction (21→22) and the sequential Claisen/Overman rearrangements (23→24) could establish all of the chiral setereocenters (C2, C3, C4) in kainic acid (1). The resulting product 24 was successfully transformed to (-)-kainic acid (1).
