Bond energy enabled amine distinguishing strategy: chemo-, regioselective 1,3-diamination of (trifluoromethyl)alkenes with different amines by two C(sp3)–F bond cleavages

Abstract

The methods to distinguish between amines are rarely investigated. In this article, a bond energy enabled amine distinguishing strategy is reported. With (trifluoromethyl)alkenes as linchpins, a chemo-, regioselective three-component defluorinative 1,3-diamination reaction with two different amine nucleophiles was achieved. Remarkably, the different bond energies of the two sequentially cleaved C(sp³)–F bonds efficiently distinguishes the two different amines via their different priorities involved in these two different steps. Thus, this ipso-defluorinative amination-triggered 1,3-diamination transformation affords various monofluoroalkenylated acyclic 1,3-diamines in high yields with excellent Z/E selectivity. This protocol is successfully applied in the late-stage functionalization of drug derivatives from Celebrex and Sulthiame. A sequential ipso-/γ-selective defluorinative amination pathway is involved via two C(sp³)–F bond cleavages in a CF₃ group.