Lewis acid mediated diastereoselective keto-ene cyclization on chiral perhydro-1,3-benzoxazines: synthesis of enantiopure cis-3,4-disubstituted 3-hydroxypyrrolidines

Chiral 2-acyl-3-allyl-perhydro-1,3-benzoxazines derived from (−)-8-aminomenthol were easily cyclized in the presence of Lewis acids at 0 °C. The diastereoselectivity of the cyclization was dependent on the nature of the Lewis acid. The cyclization compounds can be transformed into enantiopure cis-3,4-disubstituted 3-hydroxypyrrolidines by ring opening of the N,O-acetal moiety and subsequent elimination of the menthol appendage.