A Novel Strategy for the Construction of Functionalized 1,5‐ Benzodiazepines via a Tandem Conjugated Addition/Cyclization Process

Abstract

A novel approach for the synthesis of functionalized 1,5-benzodiazepine is described. The protocol is triggered by a tandem conjugated addition/cyclization process from the readily available starting materials 1,2-phenylenediamine and ethyl propiolate. The products have secondary amino and ester groups, and a b-enamino ester, which can serve in further functionalizations to produce molecular diversity.

Late Transition Metal-Catalyzed Hydroamination and Hydroamidation

“…On the basis of this strategy, fused tricyclic benzo­[ b ]­[1,4]­diazepines can be accessed in good yields. For activated alkynes such as ethyl propiolate, the functionalized 1,5-benzodiazepine is formed even without catalyst, whereas nonactivated alkynes require the presence of a gold catalyst . In contrast, in the presence of a copper catalyst, ortho -phenylenediamines and terminal alkynes undergo another hydroamination cascade to form quinoxalines instead of 1,5-benzodiazepines …”

“…For activated alkynes such as ethyl propiolate, the functionalized 1,5-benzodiazepine is formed even without catalyst, whereas nonactivated alkynes require the presence of a gold catalyst. 804 In contrast, in the presence of a copper catalyst, ortho-phenylenediamines and terminal alkynes undergo another hydroamination cascade to form quinoxalines instead of 1,5-benzodiazepines. 805 Lei and Lu reported an intramolecular hydroamidation of ynamides followed by an intermolecular coupling with α,βunsaturated carbonyl compounds in the presence of a palladium catalyst to generate 1,3-oxazolidin-2-ones, imidazolidin-2-ones, or lactams (Scheme 277).…”