Phosphine-Catalyzed Enantioselective [4 + 3] Annulation of Allenoates with C,N-Cyclic Azomethine Imines: Synthesis of Quinazoline-Based Tricyclic Heterocycles

Abstract

With the use of a commercially available chiral phosphine as the catalyst, the first catalytic enantioselective [4 + 3] annulation of allenoates with C,N-cyclic azomethine imines is developed. The reaction works efficiently under mild reaction conditions to afford seven-membered ring-fused quinazoline-based tricyclic heterocycles in high yields with good to excellent diastereo- and enantioselectivities.

Synthesis of N‐heterocycles via [4 + 3] cycloaddition of azomethine imine

“…The reaction of quinazoline‐based azomethine‐imine ( 50 ) with α‐benzyl allenoate ( 51 ) afforded quinazoline‐based tricyclic heterocycles ( 52 ) (Scheme 14). [ 15 ] The reaction proceeded via in situ generation of phosphonium (di)enolate zwitterions from allenoates ( 51 ). The reaction worked efficiently under mild condition to give high yield with excellent diastereoselectivity (33:1) and enantioselectivity (96% ee ).…”

Organophosphine-Catalyzed [4C+X] Annulations

“…In their following research, the enantioselective version of the phosphine-catalyzed [4+3] cycloaddition of α-substituted allenoates with C , N -cyclic azomethine imines was realized for the first time ( Scheme 25 ) [ 62 ]. The commercially available Kwon phosphine TP - 11 was identified as the optimal catalyst, mediating the asymmetric [4+3] cycloaddition to produce the seven-membered ring-fused quinazoline-based tricyclic heterocycles 80 in high to excellent yields with high to excellent enantioselectivities and mostly excellent diastereoselectivities.…”

“… Phosphine-catalyzed enantioselective [4+3] cycloadditions of α-substituted allenoates with azomethine imines [ 62 ]. …”

Catalyst‐Free Synthesis of Novel Dimeric Tetrahydroisoquinoline Derivatives through [2+2+2] Annulation

“…Catalytic cycloadditions of allenoates with activated imines have become a useful and efficient tool for the construction of various nitrogen‐containing heterocycles since the pioneering work of Lu's [3+2] cycloadditions of 2,3‐butadienoates with imines or alkenes have been reported . Plenty of elegant cycloadditions, such as [3+2], [4+2], [4+3] and domino annulations have been developed in recent years in this regard. The groups of Gladysz, Mariretti, Kwon, Lu, Shi, Guo, Kumar, Zhou and others have studied the [3+2] annulation of activated imine with allenoates allowing access to highly substituted five‐membered nitrogen‐heterocycles .…”