Cobalt(iii)-catalysed annulation of indoles with phenylethynyl ether for the synthesis of the ABC ring system of ergot alkaloids

Abstract

A rational strategy has been developed to construct the ABC ring of ergot alkaloids, with this strategy involving the C4 alkenylation of indole followed by an annulation process triggered by β-carbon elimination. This innovative approach is notable as the first reported one-step synthesis of the ABC ring of an ergot alkaloid skeleton achieved through a C–H activation process. Moreover, a high-resolution mass spectrometry (HRMS) analysis identified a six-membered cobaltacycle intermediate, corroborating the suggested process. This one-step synthesis, through C–H activation, provides a streamlined and sustainable approach for forming ergot analogs, with broad substrate tolerance and efficient atom utilization, thus representing a valuable advancement in indole functionalization.