Catalyst-Free Accelerated Three-Component Synthesis of Betti Bases in Microdroplets

Due to their important roles in medicine and asymmetric metal catalysis, the formation of Betti bases has attracted wide interest in organic chemical community. Traditional multicomponent reaction methods for synthesizing Betti bases normally require long reaction times under harsh conditions (high temperature, microwave or ultrasonic irradiation, etc.) in the presence of various catalysts. In this study, we developed a mild, highly efficient and environmentally friendly method to synthesize Betti bases without the use of any catalysts in microdroplets. The Betti reaction was accelerated by 6.53x10(3) in microdroplets by comparing the measured rate constant in bulk. Fifteen Betti bases were synthesized by the microdroplet method using a variety of aldehydes, naphthols and amines with 68-98 % yields at a scaled-up amount of 1.9 g h(-1). Overall it is an attractive alternative to classic organic synthesis for the construction of Betti bases and derivatives.

Automated summary

The formation of Betti bases has attracted significant attention due to their important roles in medicine and asymmetric metal catalysis. In this study, a mild, efficient, and environmentally friendly method for synthesizing Betti bases without the use of any catalysts in microdroplets was developed. The microdroplet method accelerated the Betti reaction and achieved high yields compared to traditional methods.