Temporal separation of catalytic activities allows anti-Markovnikov reductive functionalization of terminal alkynes.

There is currently great interest in the development of multistep catalytic processes in which one or several catalysts act sequentially to rapidly build complex molecular structures. Many enzymes--often the inspiration for new synthetic transformations--are capable of processing a single substrate through a chain of discrete, mechanistically distinct catalytic steps. Here, we describe an approach to emulate the efficiency of these natural reaction cascades within a synthetic catalyst by the temporal separation of catalytic activities. In this approach, a single catalyst exhibits multiple catalytic activities sequentially, allowing for the efficient processing of a substrate through a cascade pathway. Application of this design strategy has led to the development of a method to effect the anti-Markovnikov (linear-selective) reductive functionalization of terminal alkynes. The strategy of temporal separation may facilitate the development of other efficient synthetic reaction cascades.