A Highly Efficient Strategy for One-Pot and Pseudo-Six-Component Synthesis of Hexahydroquinolines

Abstract

In this study, a homogeneous acid-catalyzed reaction of a series of benzaldehydes, benzylamines, and Meldrum's acid was presented, allowing the novel one-pot and multicomponent synthesis of hexahydroquinolines with high stereoselectivity. The current strategy has advantages including high regioselectivity, good efficiency, reasonable diversity, utilization of an inexpensive and safe catalyst, and easy purification of products by simple recrystallization. The current reaction utilizes 2 equiv of Meldrum's acid, 3 equiv of benzaldehyde derivatives, and one equiv of amine derivatives to yield (4'S,5'S,7'S)-1'-benzyl-2,2-dimethyl-4',5',7'-triphenyl-3',4',7',8'-tetrahydro-1'H-spiro[[1,3]dioxane-5,6'-quinoline]-2',4,6(5'H)-trione derivatives.

Scheme 1. Comparison between the Current Pseudo-Six-Component Strategy and Previously Reported Pseudo-Eight-Component Strategy

Scheme 2. Substrate Scope of One-Pot and Pseudo-Six-Component Synthesis of Hexahydroquinoline Derivatives (4)

Scheme 3. Proposed Reaction Mechanism for One-Pot and Pseudo-Six-Component Synthesis of Hexahydroquinoline (4a)

Scheme 4. Alternative Mechanism, Not Involving the Barbas Dienamine, for the Formation of Intermediate VIII

Figure 1

ORTEP diagram of 4a.