Catalytic Asymmetric Synthesis of [2,3]‐Fused Indoline Heterocycles through Inverse‐Electron‐Demand Aza‐Diels–Alder Reaction of Indoles with Azoalkenes

Abstract

An unprecedented catalytic asymmetric inverse-electron-demand aza-Diels-Alder reaction of indoles with in situ formed azoalkenes is reported. A diverse set of [2,3]-fused indoline heterocycles were achieved in generally good yields (up to 97 %) with high regioselectivity and diastereoselectivity (>20:1 d.r.), and with excellent enantioselectivity (up to 99 % ee).

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…1,2‐Diaza‐1,3‐dienes, which can be readily generated in situ from α‐ halogeno hydrazones 290 under the action of a base, appeared useful intermediates for the synthesis of various five‐ or six‐membered nitrogen‐containing heterocycles [274] . Wang and co‐authors [275] were the first to carry out a catalytic asymmetric IED aza‐DAR of these labile electron‐deficient species with electron‐rich alkenes. They reported an efficient asymmetric synthesis of highly functionalized [2,3]‐fused indoline‐tetrahydropyridazine heterocycles 292 bearing contiguous quaternary and tertiary stereogenic centers from α‐ halogeno hydrazones 290 and N ‐substituted indoles 291 (Scheme 109).…”

Syntheses of Heterocycle-2,3-Fused Indoline and Azaindoline ­Derivatives

“…In this regard, [4+2]-cycloaddition has been the most frequently applied method for synthesizing six-membered-ring-fused indolines. Wang and co-workers reported a copper-catalyzed [4+2]-cycloaddition of indoles with chlorinated hydrazones, 9 and the Ji group reported a metal-free dearomatization of indoles with -bromo hydrazones. 10 Palacios and co-workers reported a [4+2]-cycloaddition between indoles and nitrosoalkenes, 11 and the Larionov group reported the first example of a copper-catalyzed asymmetric [4+2]-cycloaddition of nitrosoalkenes.…”

Catalytic Asymmetric Inverse‐Electron‐Demand Hetero‐Diels−Alder Reactions

“…In the possible mechanism, the 1,2‐diaza‐1,3‐diene was activated by the Cu(I) complex via the bidentate coordination. Then, the activated 1,2‐diaza‐1,3‐diene reacted with indoles through C2,C3‐annulation to generate the [2,3]‐fused indoline heterocycles …”