Reductive Nitro-Mannich Route for the Synthesis of 1,2-Diamine Containing Indolines and Tetrahydroquinolines

A one-pot, 1,4-hydride addition nitro-Mannich reaction
between
a set of nitroalkenes 3 and a wide range of N-p-methoxyphenyl-protected aldimines, derived from
alkyl, aryl and heteroaryl aldehydes, followed by Zn/HCl reduction
leads to stereochemically defined 1,2-diamines. These underwent palladium-catalyzed
cyclization and depending upon the presence or not of the trifluoroacetamide
protecting group gave either tetrahydroquinolines 18 or
indolines 14 in high overall yield and diastereoselectivity
(19 examples each). In each case, the more nucleophilic pendant amine
cyclizes to give a benzofused saturated heterocyclic 5- or 6-membered
ring, with an additional vicinal amino stereocenter in each.