A Ring Expansion Route to Benzofused N‐Heterocycles Through Aryne Insertion into 1,3‐Diaza‐heterocycles

Abstract

Arynes have been found to undergo formal σ‐bond insertion into a C(sp3)–N bond for the first time. This transformation is utilized in the ring expansion of 1,3‐diaza‐heterocycles to afford benzofused medium‐ring N‐heterocycles in a single step. This represents a novel route to biologically relevant 2,3,4,5‐tetrahydro‐1H‐benzo[e][1,4]diazepines, prepared directly from easily accessible imidazolidines. An example of the ring expansion of a 1,3‐diazetidine is also reported, which affords the corresponding 1,2,3,4‐tetrahydroquinazoline.

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors

“…Beside these previous achievements on aryne insertion into the C(sp 2 )−N bonds of ureas, amides, and imides, Jones et al recently accomplished a formal aryne insertion reaction into the C(sp 3 )−N bond of 1,3-diaza-heterocycles 7-12, which led to the construction of benzofused medium-ring N-heterocycles 7-13 (Scheme 94). 486 This transformation proceeds through a sequential N-arylation with aryne to generate zwitterion 7-14 that is in equilibrium with a ring-opened form 7-15 and an intramolecular cyclization to afford benzofused N-heterocycle 7-13.…”

Diverse Synthesis of Triarylselenonium Salts and o-(Alkoxy)aryl Aryl Selanes via Insertion of Benzyne into the Se═O Bond

“…As a highly active organic building block, benzyne has attracted extensive attention because of its uniqueness in concomitantly introducing two or more functional groups onto the same benzene ring . Along with the development of mild generation conditions in the past several decades, new modes of benzyne reactions were developed. − , Among those advances, insertion reactions, such as the insertion of benzyne into a C–C, N–C, OC, or NS bond, have emerged as a fruitful and useful subfield, ,, and they have been applied in the synthesis of natural products and bioactive molecules, as well. ,,,, For instance, Day and co-workers first discovered that benzyne could insert into the SO bond of dimethyl sulfoxide (DMSO), albeit with poor efficiency (Figure a) . In 2014, the group of Chen and Xiao reported an efficient insertion of benzyne into the SO bond by employing Kobayashi’s benzyne generation method (Figure b) .…”

Formation of Synthetically Versatile 2-Aminobenzophenones from Readily Accessed Acyl Hydrazides

“…Recognizing the potential of the protocol for the synthesis of functional 2-aminobenzophenones, we turned our attention to providing a tangible application of the protocol for the synthesis of a pharmaceutically relevant benzodiazepine (Scheme 3), as a representative example, especially as aryne chemistry is being increasingly employed to synthesize such systems. 45 Phenazepam is a member of a class of molecules that have found use in the treatment of various psychiatric and neurological disorders. 46 Furthermore, phenazepam can be employed as a precursor for the formation of more complex benzodiazepines such as cinazepam and 3-hydroxyphenazepam.…”