Rh-Cataryzed Tandem Conjugate Addition-Mannich Cyclization Reaction: Straightforward Access to Fully Substituted Tetrahydroquinolines

摘要

Transition-metal-catalyzed tandem C-C bond formations are powerful methods for the synthesis of structurally complex molecules from relatively simple starting materials in a convergent way. Recently, several examples of Rh(I)-catalyzed tandem annulations with organoboron reagents have been demonstrated in which the tandem cyclization was triggered by conjugate addition to α,β-unsaturated carbonyl compounds or 1,2-addition across the alkynes. An organorhodium(I) intermediate generated via carborhodation onto the alkene or alkyne moiety added to the intramolecular carbonyl, cyano, alkyne, and alkene groups, providing five- or six-membered carbocycles via a sequential second carborhodation (routes A and B). Although several Rh(I)-catalyzed tandem reactions have been described, the process involving a imine group as a second electrophile has not yet been explored. Since both α,β-unsaturated carbonyl compounds and imines are good acceptors of organorhodium(I) species, we envisioned that electron-deficient alkenes bearing imine moiety placed at an appropriate position are interesting bifunctional substrates with regard to the possibility of a tandem cyclization reaction, which could afford N-heterocycles such as tetrahydroquinolines (route C). In parallel with our efforts to develop a catalytic system for heterocyclic synthesis,2 we were interested in developing a one-pot synthesis of N-heterocycles, tetrahydroquinolines, whereby a single catalytic system would invoke sequential C-C bond formations in an efficient manner.