Palladium-Catalyzed α-Amino C-H Functionalization via Isomerization of α,ß-Unsaturated Carbonyls.

ABSTRACT

Palladium-catalyzed regioselective α-amino C-H functionalization via the isomerization of α,ß-unsaturated carbonyls including esters, ketones, and amides has been established, providing an easy access to a wide array of tricyclic 1,2,3,4-tetrahydro-b-carbolines, azepinoindoles, 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles, 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridines, 1,2,3,4-tetrahydropyrazino-[1,2-a]indoles, pyran-fused indoles, and tetrahydroisoquinolines in good to excellent yields. This transformation showed high regioselectivity, excellent functional group tolerance, and scalability. Moreover, this methodology was also employed as the key step for the total synthesis of desbromoarborescidines A, B, and C. Preliminary mechanistic studies revealed that the palladium catalyst not only formed [Pd-H] to promote the isomerization of α,ß-unsaturated carbonyls but also played a role as a Lewis acid for the final protonation/cyclization.