Dearomatization Strategy and Palladium-Catalyzed Domino Reaction: Construction of Azepino[5,4,3-cd]indoles from 2-Alkynylanilines

Abstract

A facile approach to construct 3,4-fused tricyclic azepino[5,4,3-cd]indoles from 2-alkynyl anilines, isocyanides, and α,β-unsaturated acids is reported. This synthetic process involves a regioselective meta-functionalization of 2-alkynylanilines using a dearomatization strategy and a palladium(II)-catalyzed domino heterocyclization/Heck reaction.

Regio‐ and Chemoselective N‐1 Acylation of Indoles: Pd‐Catalyzed Domino Cyclization to Afford 1,2‐Fused Tricyclic Indole Scaffolds

“…Recently, Fan et al. reported the use of a Pd‐catalyzed domino reaction to construct 3,4‐fused tricyclic azepino[5,4,3 cd ]indoles;13 Lu et al. used a one‐pot Pd II ‐catalyzed reaction to construct cycloalkane‐fused indoles (Scheme a, b) 14.…”

Aniline Dearomatization and Silver‐Catalyzed [3+3] Dipolar Cycloaddition: Efficient Construction of Oxocino[4,3,2‐cd]indoles from 2‐Alkynylanilines and 2‐Alkynylbenzaldoximes

“…In connection with our recent research on the synthesis of 3,4‐difunctionalized benzofurans from 2‐alkynylphenols,10 we focused our attention on developing methods that directly convert 2‐alkynylanilines into 3,4‐fused indoles 11. For a medicinal chemistry project, we were interested in the synthesis of oxocino[4,3,2‐ cd ]indoles ( 3 ) because of their structural similarity to many natural products and potential biological activities 12…”

Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances

“…An interesting example of double cyclization initiated by intramolecular nucleophilic attack of a heteronucleophile on a triple bond coordinated to Pd(II) is proffered by the conversion of 2‐alkynylaniline derivatives into azepino[5,4,3‐ cd ]indoles (Scheme ) . The first cyclization step corresponds to a 5‐ endo ‐ dig annulation, with formation of the indole ring.…”

“…This is followed by a 7‐membered ring closure by intramolecular syn double bond insertion into the ensuing Ar–Pd bond and syn β‐H elimination to give the final product and Pd(0). The latter is finally reoxidized back to Pd(II) by the action of molecular oxygen (Scheme ) …”