Synthesis of Indoles by a Combined Hydroformylation-Fischer Indolization Route

Significance

A one-pot, three-component reaction of olefins, phenyl hydrazine and carbon monoxide mediated by rhodium catalysts to yield 2,3-disubstituted indoles is described. The hydrofor­mylation of a variety of olefins leads to α-branched aldehydes, which are trapped by in situ phenyl hydrazine to form the corresponding hydrazones. Subsequent Fischer indolization under acidic conditions leads to intermediates which undergo Wagner-Meerwein rearrangement to furnish 2,3-disubstituted indoles. Migrations A and B are dictated by normal migratory aptitudes, e.g., PhCH₂ > Me; however, unsatisfactory regioselectivity is observed for styrene and functionalized olefins. The scope of the study was expanded to include cyclohexene, norbornene, indene and heterocyclic olefins.