Gold catalysed regio- and chemoselective azo coupling of 1,2-and 1,4-diazoquinones with 1H-indoles

A synthetic method to prepare (E)-3-arylazoindoles efficiently that relies on the gold(i)-catalysed azo coupling of 1,2- and 1,4-diazoquinones with 1H-indoles under mild reaction conditions that did not require the exclusion of air or moisture is described. The suggested azo coupling mechanistic pathway delineates the first instance of a alpha-diazocarbonyl compound acting as a N-centred electrophile instead of undergoing decomposition of the dinitrogen functional group. Experimental studies based on a (1H-indol-3-yl)gold species that is proposed to be preferentially generated from the direct reaction of the group 11 metal complex and N-heterocycle over alpha-diazocarbonyl compound decomposition provides insight into this observed product regio- and chemoselectivity. The utility of the synthetic method was exemplified by the efficient preparation of one example at the 2 mmol scale at a catalyst loading of 1 mol %, assembly of two known (E)-diazene-based molecular photoswitches and late-stage functionalisation of two biologically relevant molecules.

Automated summary

This study presents a synthetic method for efficiently preparing (E)-3-arylazoindoles, which does not require the exclusion of air or moisture and can be conducted under mild reaction conditions. The suggested mechanistic pathway of the azo coupling reaction reveals the unique electrophilic behavior of α-diazocarbonyl compounds. Experimental studies provide insights into the preferential generation of a (1H-indol-3-yl)gold species and its impact on the regio- and chemoselectivity of the products. The utility of this synthetic method has been demonstrated in the synthesis of specific molecules, molecular switch assembly, and late-stage functionalization of biologically relevant molecules.