Enantioselective total synthesis of (-)-triptolide, (-)-triptonide, (+)- triptophenolide, and (+)-triptoquinonide

Abstract

The first enantioselective total synthesis of (-)-triptolide (1), (-)- triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc) 3, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)Triptophenolide methyl ether (5) was then prepared in >99% enantiomeric excess (>99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral β-keto esters 17 (without an α-substituent) and 17a (with an α-chloro substituent).