2,3-Disubstituted indoles from olefins and hydrazinesvia tandem hydroformylation–Fischer indole synthesis and skeletal rearrangement

Abstract

The tandem hydroformylation–Fischer indolisation protocol is used in the synthesis of 2,3-disubstituted indoles. After hydroformylation of selected olefins to form α-branched aldehydes in a one-pot procedure these are condensed with phenylhydrazine to give hydrazones. Upon acid-promoted [3,3]-sigmatropic rearrangement indolenine intermediates with quaternary centres in the 3-position are formed, which, after selective Wagner–Meerwein-type rearrangement of one of the substituents from the 3- to the 2-position, lead to 2,3-disubstituted indoles. Several olefins, bearing substituents with various functional groups, as well as cyclic olefinic systems are investigated.