Non-innocent electrophiles unlock exogenous base-free coupling reactions

Abstract

Numerous important transition metal-catalysed reactions rely on stoichiometric quantities of an exogenous base to enable catalytic turnover. Despite playing a fundamental role, the base poses major challenges, such as restricting the accessible chemical space or causing heterogeneous reaction mixtures. Here we introduce a unifying strategy that eliminates the need for an exogenous base through the use of non-innocent electrophiles (NIE), which are equipped with a masked base that is released in a controlled fashion during the reaction. The universal applicability of this concept was demonstrated by turning multiple, traditionally base-dependent, catalytic reactions into exogenous base-free homogeneous processes. Furthermore, the advantageous features of NIEs were demonstrated in multiple applications, such as in a micromole-scale fluorescence-based assay. This led to the discovery of a Ni-catalysed deoxygenation reaction of aryl carbamates using isopropanol as a benign reductant. In a broader context, this work provides a conceptual blueprint for the strategic utilization of NIEs in catalysis. Bases play a fundamental role in several iconic coupling reactions in organic chemistry but are simultaneously responsible for limitations, such as functional group tolerance. Now, a broadly applicable solution is presented that uses non-innocent electrophiles equipped with an encrypted base.