Carbon–hydrogen bond activation

In organic chemistry, carbon–hydrogen bond functionalization (C−H functionalization) is a type of organic reaction in which a carbon–hydrogen bond is cleaved and replaced with a C−X bond (where X is usually carbon, oxygen, or nitrogen). The term usually implies that a transition metal is involved in the C−H cleavage process. Reactions classified by the term typically involve the hydrocarbon first to react with a metal catalyst to create an organometallic complex in which the hydrocarbon is coordinated to the inner-sphere of a metal, either via an intermediate "alkane or arene complex" or as a transition state leading to a "M−C" intermediate. The intermediate of this first step (known as C−H activation and sometimes used interchangeably with C−H functionalization) can then undergo subsequent reactions to produce the functionalized product. Important to this definition is the requirement that during the C−H cleavage event, the hydrocarbyl species remains associated in the inner-sphere and under the influence of "M".

As an alternative definition, other authors use the term C−H functionalization to mean any organic transformation in which the net result is the transformation of a relatively inert C−H bond into a C−X bond (i.e., a functional group), irrespective of the reaction mechanism (or with an agnostic attitude towards it). In particular, this definition does not require a transition metal coordination to the hydrocarbon in the mechanism. This broader definition includes the narrower definition given above as a subset. However, this definition would also include iron-catalyzed alkane functionalization reaction that proceed through the oxygen rebound mechanism (e.g. cytochrome P450 enzymes and their synthetic analogues), in which a metal–carbon bond is not believed to be involved. Likewise, the ligand-based reactivity of many metal carbene species with hydrocarbons would also fall under this category, although some cases are mechanistically ambiguous. Some authors similarly define C−H activation broadly as the C−H cleaving step of any mechanism that results in functionalization of a hydrocarbon group (or any observable consequence of C−H bond cleavage, like H/D exchange). Still others maintain the original narrow definition of the term C−H activation, while using C−H functionalization in its broader sense.