Asymmetric Synthesis of 5- and 6-Membered Lactones from Cyclic Substrates Bearing a C2-Chiral Auxiliary

Article abstract of DOI:10.1021/jo00003a038

Optically active lactones were synthesized by a novel asymmetric synthesis in which enantiotopic groups remote from a prochiral center were effectively discriminated.The cyclic diamide alcohols bearing a C₂-chiral auxiliary, (+)-<1,1'-binaphthyl>-2,2'-diamine (4), were designed and prepared such that the hydroxyl group should attack preferentially at one of the two carbonyl groups.By the catalytic action of trifluoroacetic acid, the substrates 6a,b and 19 were smoothly converted to the lactones 7a (71percent de), 7b (97percent de), and 20 (>99percent de), the configurations of whichwere determined to be R, S, and R, respectively.A naturally occurring pheromone, (R)-(+)-5-hexadecanolide (13), was synthesized optically pure from 7b.Transition-state models for the present asymmetric lactonization were constructed according to the stereoelectronic theory proposed by Deslongchamps.The stability of the models was assessed by MM2 calculation, and the direction of asymmetric induction thus calculated coincided with the experimental results.