Cine Substitution of N-Sulfonylindoles

Nucleophilic substitution at the 2-position of indoles bearing 3-position electron-withdrawing groups follows multiple pathways. Conventional nucleophilic aromatic substitution ensues when there is a 2-position leaving group, but in a cine substitution, the leaving group is on the adjacent nitrogen. Indoles bearing N-methoxy groups are excellent reactants for cine substitution, but are not very synthetically accessible. This study was predicated on finding a replacement in a sulfinate leaving group, which is well precedented in many organic transformations, and which enables easy preparation of the cine substitution reactants. With primary alkoxide nucleophiles, cine substitution proceeds well to generate 2-alkoxy-3-substituted indoles.