Synthesis of Naphthyridine and Azepine Backbones through Formal [4+3] and [4+2] Annulation via Cascade Ring‐Opening/Cyclization Reaction of 2H‐Azirines

Abstract

A zinc-mediated cascade ring-opening cyclization of 2H-azirines and enolized-o-alkenylquinoline carbaldehydes for the synthesis of naphthyridine and azepine skeletons has been disclosed. The regioselectivity of the reaction can be switched from a sevento a six-membered ring by shifting from two-to monosub-stituted 2H-azirine. This transformation involves the construction of two C=C and C=N double bonds. This report describes 2H-azirine-dependent cascade annulation in formal [4 + 3], and [4 + 2] cyclization reactions.

2H‐Azirines: Recent Progress in Synthesis and Applications

“…Balalaie and co‐workers [114] disclosed a switchable methodology for the synthesis of naphthyridine and azepine skeletons from 2H ‐azirines and enolized‐o‐alkenylquinoline carbaldehydes via a formal [4+3], and [4+2] cyclization reactions (Scheme 73). The selectivity could be controlled by switching the number of substituents on 2H ‐azirines, wherein monosubstituted 2H ‐azirine gives a six‐member ring other than a seven‐member ring towards two‐substituted 2H ‐azirine.…”

Recent Advances in the Synthesis of Fused‐Cyclic Quinolines

“…Balalaie et al could developed a novel pathway in order to construction of acridines. [174] This approach involves the reaction between monosubstituted 2H-azirines 269 and enolized-oalkynylquinoline carbaldehydes 268 to access acridine derivatives 270 (Scheme 85). Utilizing monosubstituted 2H-azirines for construction of acridines is one these advantages of this strategy.…”

“…A fascinating pathway for construction of azepinoquinoline was developed in Balalaie group [174] . This reaction proceed through a cascade ring‐opening cyclization of disubstituted 2 H ‐azirines 293 and enolized‐o‐alkynylquinoline carbaldehydes 268 and subsequently azepino[4,3‐ b ]quinolines form 294 (Scheme 93).…”

An Accesss to 4,5,6-Trisubstituted Pyrimidines from 2H-Azirines and α-Isocyanoacetates or α-Isocyanoacetamides Enabled by 1,3-Dipolar [3 + 2] Cycloaddition/Ring-Expanding/Oxidative Aromatization Process

“…2 H -Azirines, the smallest strained nitrogen-containing three-membered ring, represent a highly important class of compounds found in natural products and biological active compounds with significant biological and pharmacological properties . Also, due to their inherent reactivity, 2 H -azirines have been shown to be versatile reagents in organic transformation for the preparation of various azaheterocycles by a ring-opening reaction under certain conditions. , In the past decades, motivated by these inherent features of 2 H -azirines, a series of valuable azaheterocycles, such as indoles, pyrroles, pyridines, ] pyrazines, oxazoles, and imidazoles, have been explored by those outstanding organic chemists. Until now, 2 H -azirines have been employed to synthesize azaheterocycles with appropriate substrates under suitable reaction conditions.…”