Synthesis and Further Reactivity of Functionalized Lactam-Derived Enol Triflates

• Published in: Journal of organic chemistry 1997-11, Vol.62 (23), p.8131-8140
• Main Authors: Luker, Tim, Hiemstra, Henk, Speckamp, W. Nico
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo971192s

Pyrrolidinone- and piperidinone-derived enol triflates 2 were prepared in high yield (60−97%) from the corresponding lactams 1 using KHMDS and N-(5-chloro-2-pyridyl)triflimide. A structure−stability study on the less stable pyrrolidinone-derived triflates revealed that an N-tosyl group is essential, and an α-ethoxy substituent enhances thermal stability. Substituents at the 3- and 4-position are tolerated. Substitution 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 palladium-catalyzed reactions gave good yields of interesting molecules for further synthetic operations (for example, Stille coupling with vinylstannanes, cross-coupling with arylzincs, and carbonylation processes). Preparation of the first enantiopure lactam-derived enol triflate 15 (from (S)-pyroglutamic acid) is described. Enamide hydrogenation of derivative 17 allowed the synthesis of a proline analogue 18 in excellent yield and diastereoselectivity (86% de).