Synthesis of medium ring ethers. 5. The synthesis of (+)-laurencin

The key steps involved in the enantioselective synthesis of (+)-laurencin (1), achieved in 27 stages from (R)-malic acid (20), involved methylenation of lactone (49), intramolecular hydrosilation of enol ether (14) and a carbon homologation of diol (13). This gave a key ethyl substituted cyclic ether (59). 49 was obtained through Claisen ring expansion, alpha-hydroxylation and Yamaguchi lactonization. The synthesis of 1 was completed with an elaboration of the (E)-pentenynyl side chain and introduction of bromine.