Silver(I)‐ and Base‐Mediated formal [4+3] Cycloaddition of in Situ generated 1,2‐Diaza‐1,3‐dienes with C,N‐Cyclic Azomethine Imines: An Efficient Protocol for the Synthesis of Tetrazepine Derivatives

Abstract

A silver(I)‐ and base‐mediated formal [4+3] cycloaddition reaction of in situ generated 1,2‐diaza‐1,3‐dienes with in situ formed C,N‐cyclic azomethine imines has been developed. This protocol provided an efficient method for the synthesis of biologically important 1,2,4,5‐tetrazepine derivatives with a wild substrate scope and excellent functional group tolerance in moderate to excellent yields.magnified image

Recent Advances in Transition-Metal-Free (4+3)-Annulations

“…They generated an azoalkene 2.7d in situ using K 2 CO 3 from 2.7a as well as the azomethine ylide 2.7e in situ from 2.7b using AgOTf as a Lewis acid catalyst in a one-step procedure. 20 The scope was found to be broad, and generally gave moderate to excellent yields for all substrates, regardless of substitution on 2.7a. The terminal alkyne was not tested in this reaction and only the phenyl substituent was used in that position.…”

“…Most recently, and in analogy to the work by Chen and Xiao, 19 Hou and Gong 20 synthesized the sulfonylated analogues 2.7c of the tetrazepine derivates (Scheme 2.7). They generated an azoalkene 2.7d in situ using K 2 CO 3 from 2.7a as well as the azomethine ylide 2.7e in situ from 2.7b using AgOTf as a Lewis acid catalyst in a one-step procedure.…”

“…Scheme 2 20. Base-controlled divergent synthesis of 5-cyanobenzoxepines and benzofuro[2,3-b]pyridines from 2-bromophenylacetonitriles and ynones…”

[5+2] Cyclization of N,N′‐Cyclic Azomethine Imines with 1,3,5‐Triazines: An Efficient Protocol for the Synthesis of Tetrazepine Derivatives

“…Recently, Darehkordi et al reported the synthesis of trifuoromethylated 1,2,4,6‐tetrazepines by intramolecular crosscoupling of C(sp 2 )−H and N−H bonds using I 2 /KI as the catalyst (Scheme 1b) [3] . Afterwards, a silver(I)‐ and base‐mediated formal [4+3] cycloaddition reaction of in situ generated 1,2‐diaza‐1,3‐ dienes with in situ formed azomethine imines to afford tetrazepine derivatives has been developed by Hou and co‐workers (Scheme 1c) [4] . Nevertheless, the development of simple and efficient methodologies on rapidly assembling tetrazepine derivatives is highly desirable.…”

A [4+3] Cycloaddition Reaction of Aza-ortho-quinone Methides with C,N-Cyclic Azomethine Imines for Synthesis of 1,2,4-Triazepines

“…17 Among those azomethine imines, we identified C,N-cyclic azomethine imines as useful building blocks for further [3+2], 18 [3+3], 19 [3+4], 20 or [3+2+3] 21 cycloadditions. On the basis of [4+3] cycloadditions involving aza-orthoquinone methides and our previous work on cycloaddition reactions, 22 we surmised that aza-ortho-quinone methides and C,N-cyclic azomethine imines might undergo a novel [4+3] annulation for the synthesis of seven-membered heterocyclic compounds to give 1,2,4-triazepines (Scheme 2d). To our delight, under the optimized reaction conditions, 1,2,4-triazepine derivatives, the [4+3] cycloaddition products, were obtained in satisfactory yields.…”