Sustainable and Chemoselective Synthesis of α-Aminonitriles Using Lewis and Bronsted Acid-Functionalized Nanoconfined Spaces

alpha-Aminonitriles are significant components in the synthesis of biological compounds and complex drugs. Although efficient, procedures for synthesizing alpha-aminonitriles suffer from high loadings of expensive catalysts, long reaction times, energy-intensive conditions, and expensive, toxic solvents. Herein, we report the use of metal-organic framework Cr-MIL-101-SO3H as a catalyst for the facile synthesis of eight alpha-aminonitriles, five of which are reported as new molecules. We found that the presence of both open Cr3+ Lewis and -SO3H Bronsted acids in the MIL-101 pores is vital for the one-pot synthesis of alpha-aminonitriles. The catalytic reaction is conducted under solvent-free conditions at room temperature and a Cr-MIL-101-SO3H loading of 1% by the total mass, which is considered a sustainable synthetic pathway of alpha-aminonitriles. Additionally, we demonstrated for the first time that Cr-MIL-101-SO3H exhibits a high degree of catalytic chemoselectivity, differing substrates with sterically hindered and electronically withdrawn functional groups. Our study expands the existing family of alpha-aminonitriles and provides an intelligent strategy for the development of catalysts that can be used to synthesize functional alpha-aminonitriles with potential in therapeutics and health applications.

Automated summary

In this study, the metal-organic framework Cr-MIL-101-SO3H was used as a catalyst for the facile synthesis of eight alpha-aminonitriles, five of which are reported as new molecules. The catalytic reaction is conducted under solvent-free conditions at room temperature, with a low loading of the catalyst. Additionally, the catalyst exhibits a high degree of chemoselectivity and can be applied to substrates with sterically hindered and electronically withdrawn functional groups.