SYNTHESIS AND FURTHER REACTIVITY OF FUNCTIONALIZED LACTAM-DERIVED ENOL TRIFLATES

Pyrrolidinone- and piperidinone-derived enol triflates 2 were prepared in high yield (60-97%) from the corresponding lactams 1 using KHMDS a nd N-(5-chloro-2-pyridyl)triflimide. A structure-stability study on th e less stable pyrrolidinone-derived triflates revealed that an N-tosyl group is essential, and an cr-ethoxy substituent enhances thermal sta bility. Substituents at the 3- and 4- position are tolerated. Substitu tion of the triflate moiety by a wide variety of functional groups was achieved under mild conditions via metal-mediated reactions. Although cuprate couplings proceeded in only moderate yields, several palladiu m-catalyzed reactions gave good yields of interesting molecules for fu rther synthetic operations (for example, Stille coupling with vinylsta nnanes, cross-coupling with arylzincs, and carbonylation processes). P reparation of the first enantiopure lactam-derived enol triflate 15 (f rom (S)-pyroglutamic acid) is described. Enamide hydrogenation of deri vative 17 allowed the synthesis of a proline analogue 18 in excellent yield and diastereoselectivity (86% de).