Consecutive Ring Expansion and Contraction for the Synthesis of 1‐Aryl Tetrahydroisoquinolines and Tetrahydrobenzazepines from Readily Available Heterocyclic Precursors

Abstract

Tetrahydroisoquinolines and tetrahydrobenzazepines were prepared by acid-promoted ring contraction of cyclic ureas,which were themselves formed by ring expansion of indolines and tetrahydroquinolines.The consequent overall one-carbon insertion reaction gives these 6-and 7-membered heterocyclic scaffolds in three steps from readily available precursors.O ther ring sizes may be formed by an alternative elimination reaction of bicyclic structures.S calability of the method was demonstrated by operating it in aflows ystem.

Metalloradical activation of carbonyl azides for enantioselective radical aziridination

“…26 As two examples, benzylamine and allylamine reacted readily with (R)-3p under the similar conditions to form aziridine-based chiral ureas 10p and 11p, respectively, in excellent yields without apparent racemization. Presumably due to the combined high nucleophilicity of the resulting secondary amines and good leaving ability of trichloroethyl group, the initial ring-opening products III of (R)-3p by the primary amines proceeded further to form intramolecular amide bonds in the presence of Lewis acids to generate imidazolidinones IV, which then underwent ring-contraction under Lewis acid catalysis 27 to yield the final products 10p and 11p. The N-deprotection and ring-opening reactions could proceed equally well with other chiral N-Troc-aziridines as exemplified by the stereospecific formations of N-H aziridine 4r and b-amino ether 5r from enantioenriched aziridine 3r (Scheme 3C).…”