65. High Asymmetric Induction in Lewis Acid-Promoted Intramolecular Ene-Type Reactions: A diastereo- and enantioselective synthesis of (+)-α-allokainic acid. Preliminary Communication
    Oppolzer, W.; Robbiani, C.; Bättig, K.
    Helv. Chim. Acta 1980, 63, 2015-2018

The monocyclic amino diacid (+)-α-allokainic acid 1 has been prepared enantioselectively from the ester of cis-β-chloroacrylic acid and (−)-8-phenylmenthol by a series of four synthetic operations in over 15% yield. The crucial step is the intramolecular ‘ene-type’ reaction of the (Z)-diene 4 which on treatment with a mild Lewis acid undergoes a highly accelerated, dia- and enantiostereoselective cyclization to give the pyrrolidines 6 and 7 in a ratio of 95:5 (Scheme 3). Subsequent ester hydrolysis regenerates the auxiliary chiral alcohol. Similar cyclization of the (E)-diene 5 furnished a 15:85 mixture of 6 and 7 showing an efficient reversal of the optical induction by variation of the enoate geometry.

DOI : 10.1002/hlca.19800630729