Catalyst-Free Three-Component Petasis Reactions Accelerated in Microdroplets: Reaction Optimization and Senstive Detection by Mass Spectrometry

Due to their important roles in medicine, the product of the Petasis reaction has attracted extensive interest in pharmaceutical, medical and chemical communities. Traditional three-component Petasis methods normally use various catalysts under harsh conditions (high temperature, microwave, etc.) for long reaction times. In this study, we developed a green and highly efficient microdroplet method for accelerating the Petasis reaction, which obtain good yields without the need of any catalysts under mild reaction conditions. The Petasis reaction in microdroplets was suitable for a variety of salicylaldehydes, arylboronic acids and amines. The Petasis reaction in microdroplets was accelerated by approximately 4 orders of magnitude by comparing the measured rate constants in bulk. Further, a scaled-up amount of 0.8 g h⁻¹ was achieved for the Petasis reaction in microdroplets. This study supplies not only a high-efficiency and environment-friendly methodology to constructing aryl amines in organic community but also a useful derivatization strategy for highly sensitive mass spectrometric detection of arylboronic acids and aryl aldehydes.