Synthesis of 1-Substituted Cyclopropylamines via Formal Tertiary Csp3-H Amination of Cyclopropanes

A novel and facile approach to synthesis of 1-substituted cyclopropylamines via phosphine-catalyzed formal tertiary C-sp3-H amination of cyclopropanes was described. The indoles, pyrroles, imidazoles, uracils, 2-pyridone, pyrimidin-4(3H)-one, and phthalimide had been proven as good aminating partners. The present protocol features transition-metal-free, excellent regioselectivity, high-atom-economy, and mild reaction conditions and a broad range of substrates. The practicability of this protocol can also be demonstrated with late-stage modification of bioactive molecules, scaled up reaction, and divergent derivatization. Notably, the method has been used in the formal synthesis of the hormone-sensitive lipase (HSL) inhibitor. The mechanistic aspects were elucidated by both experimental and computational studies.

Automated summary

A new and facile method for the synthesis of 1-substituted cyclopropylamines via phosphine-catalyzed reaction was described. It shows good selectivity and efficiency, and practicality for late-stage modification, scaled-up reactions, and formal synthesis. Mechanistic aspects were elucidated through experimental and computational studies.