Advances in the Synthesis of Imine‐Containing Azaarene Derivatives via Photoredox Catalysis

Abstract

Scheme 1. Classification of azaarenes and common strategies for ionic-type transformations using azaarenes as activating groups.

Catalytic Asymmetric Reductive Azaarylation of Olefins via Enantioselective Radical Coupling

“…Although aromaticity and the considerably weak electron-withdrawing ability of the azaarenes result in poor reactivity, a variety of photochemical transformations have been established, which could proceed under mild reaction conditions with high efficiency and good functional group tolerance. Moreover, the extension of these methods to the appealing asymmetric manifolds is achieving rapid advance. − For instance, by merging with chiral enamines or chiral hydrogen-bonding (H-bonding) catalysis, quite a few photocatalytic reactions of azaarene-containing substrates (e.g., bromides, alcohols, and olefins) have been deployed to building enantioenriched three-dimensional azaarene variants, wherein construction of stereocenters is via enantioselective protonation or enantioselective radical addition (Scheme A) . The dual catalyst system based on chiral H-bonding catalysis was also successfully leveraged to develop a series of asymmetric Minisci-type reactions of azaarenes, a direct functionalization approach via enantioselective radical addition (Scheme B) .…”

Catalytic Reductive Cross Coupling and Enantioselective Protonation of Olefins to Construct Remote Stereocenters for Azaarenes

“…Structurally diverse azaarenes exist widely in numerous natural products, pharmaceuticals, and agrochemicals as well as ligands and catalysts in catalysis. The prominent importance has inspired continuous pursuits for developing efficient catalytic synthetic protocols to access azaarene derivatives, especially in an enantioselective fashion. , Among them, exploiting the inherent electronic properties of azaarenes to directly trigger transformations has been appreciated as an expedient and practical strategy owing to the potential advantages of using simple and readily accessible feedstocks and avoiding tedious operations in the late-stage modifications of products. For instance, with respect to imine-containing azaarenes that feature an electron-withdrawing ability, a variety of catalytic asymmetric methods using 2-alkylazaarenes as pronucleophiles and 2-alkenylazaarenes as electrophiles have been established; ,− substantial enantioenriched azaarene derivatives bearing various α-, α,β-, β-, and γ-stereocenters were obtained.…”

“…Due to the weaker electron-withdrawing ability of azaarenes as compared to that of carbonyls, in recent years, photoredox catalysis has been extensively used in the synthesis of azaarene derivatives . In particular, the high reactivity of radicals has enabled various radical species to be successfully embedded on 2-alkyenylazaarenes via an addition–hydrogen atom transfer (HAT)/protonation process. ,,,, Furthermore, by merging extrinsic, chiral Brønsted acid catalysis, our group reported an efficient method to construct tertiary carbon stereocenters α to azaarenes through radical addition–enantioselective protonation of N -aryl glycines with α-branched 2-vinylazaarenes, in which prochiral anion intermediates were formed on the electrophilic olefins (Scheme B1).…”

Radical-based functionalization-oriented construction: rapid assembly of azaarene-substituted highly functionalized pyrroles

“…Accordingly, we envisaged exploring the viability of directly triggering transformations by exploiting the electron-deficient properties of these azaarenes and performing radical pathways, which have been verified to be a powerful functionalization tool for the synthesis of azaarene derivatives owing to the demonstrated considerable potential of using simple azaarene-containing feedstocks and their high reactivity. 5–7 To this end, we were intrigued in taking advantage of versatile radical addition to alkenylazaarenes 6 and using α-amino radicals as the reaction partners ( Scheme 1b ). In addition to having a robust ability to undergo addition to these inert alkenes, 7 α-amino radicals can be facilely generated from abundant α-amino acid derivatives 7 d ,8 through sustainable photoredox catalysis.…”