Rh-catalysed enantioselective [2+2+1] cycloaddition reactions using three different 2π-components

Abstract

Catalytic intermolecular [2+2+2] cycloaddition reactions of three 2π-components, such as alkynes and alkenes, are a valuable method to synthesize multi-substituted six-membered carbocycles in a single step with high atom economy. When one 2π-component reacts as a one-carbon unit, a five-membered carbocycle is accessible instead of a six-membered one. However, examples of catalytic intermolecular [2+2+1] cycloaddition reactions are scarce, and enantioselective or three different 2π-component versions remain elusive. Here we report the development of a Rh-catalysed enantioselective [2+2+1] cycloaddition reaction using three different 2π-components, cycloalkenes, acetylenecarboxylates and terminal alkynes, which can form a broad range of synthetically valuable chiral 3-methylenecyclopent-1-ene derivatives with excellent selectivity. Interestingly, the three-component cycloadducts are obtained in high selectivity, while all three 2π-components are mutually reactive. Experimental and theoretical mechanistic studies reveal that the reaction proceeds via the kinetically favoured vinylidene formation from a rhodacyclopentene and a terminal alkyne. Intermolecular [2+2+1] cycloaddition reactions are challenging owing to issues with chemoselectivity. Now a Rh-catalysed enantioselective [2+2+1] cycloaddition reaction using three different 2π-components is reported. The process can form a broad range of synthetically valuable chiral 3-methylenecyclopent-1-ene derivatives with excellent selectivity.