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 eno l ether 14 (Scheme 11) and one carbon homologation of the diol 13 to g ive the key ethyl substituted cyclic ether 59 (Scheme 13). The lactone 49 was obtained by two efficient routes, namely a Claisen ring expans ion (Scheme 3) followed by alpha-hydroxylation (Scheme 6) and a Yamagu chi lactonization (Scheme 11). Elaboration of the (E)-pentenynyl side chain (Scheme 18) and introduction of bromine (Scheme 19) completed th e synthesis of (+)-laurencin 1.