SYNTHESIS OF MEDIUM RING ETHERS. 5. THE SYNTHESIS OF (+)-LAURENCIN

The enantioselective synthesis of (+)-laurencin 1 has been achieved in 27 steps from (R)-malic acid 20. The key steps involved methylenation of the lactone 49 followed by intramolecular hydrosilation of the enol ether 14 (Scheme 11) and one carbon homologation of the diol 13 to give the key ethyl substituted cyclic ether 59 (Scheme 13). The lactone 49 was obtained by two efficient routes, namely a Claisen ring expansion (Scheme 3) followed by α-hydroxylation (Scheme 6) and a Yamaguchi lactonization (Scheme 11). Elaboration of the (E)-pentenynyl side chain (Scheme 18) and introduction of bromine (Scheme 19) completed the synthesis of (+)-laurencin 1.