Efficient Synthesis of 4H-3,1-Benzoxazine Derivatives via One-Pot Sequential Passerini-Azide/Palladium-Catalyzed Azide–Isocyanide Coupling/Cyclization Reaction

Abstract

A new, one-pot method for the synthesis of 4H-3,1-benzoxazine derivatives has been developed. The Passerini-azide reactions of 2-azidobenzaldehydes, trimethylsilyl azide, and isocyanides produced azide intermediate without separation, which then reacted with isocyanides to give 4H-3,1-benzoxazine derivatives via a tandem one-pot palladium-catalyzed azide–isocyanide coupling/cyclization reaction in moderate to good yields.

Nitrene-transfer from azides to isocyanides: Unveiling its versatility as a promising building block for the synthesis of bioactive heterocycles

“…presented their work on the synthesis of 4H-3,1-benzoxazine derivatives using a sequential one-pot, a three-component reaction catalyzed by Pd. 46 Initially, the passerine-azide adduct 15f was formed through a three-component reaction involving 2-azido-benzaldehydes 15a , trimethylsilyl azide 15c , and isocyanides 15b . Subsequently, the passerine-azide adduct 15f underwent a tandem palladium-catalyzed transformation to generate the carbodiimide intermediate 15h through an azide-isocyanide cross-coupling process.…”

Multicomponent cyclization with azides to synthesize N-heterocycles

“…Xiong et al developed a new, one-pot method for the synthesis of 4H-3,1-benzoxazine derivatives 81 (Scheme 34). 62 Initially, the P-3CR occurred among benzaldehyde, TMSN Organic & Biomolecular Chemistry Review tetrazole derivatives 94. 70 The utilization of sonication not only expedited the reaction rate but also facilitated the attainment of quantitative yields (Scheme 38).…”

Transition‐Metal‐Catalyzed Cross‐Coupling and Sequential Reactions of Azides with Isocyanides

“…[17] Xiong et al recently developed a one-pot sequential PasseriniÀ azide/Pd-catalyzed azideÀ isocyanide coupling/cyclization to efficiently synthesize 4H-3,1-benzoxazine derivatives. [33] The three-component PasseriniÀ azide reaction of 2-azidobenzaldehydes, TMSN 3 , and isocyanides initially afforded tetrazole intermediate 56 without isolation. Afterward, it underwent a Pd-catalyzed azideÀ isocyanide coupling and subsequent intramolecular nucleophilic cyclization to produce the target product 58 (Scheme 23).…”

“…Xiong et al. recently developed a one‐pot sequential Passerini−azide/Pd‐catalyzed azide−isocyanide coupling/cyclization to efficiently synthesize 4 H ‐3,1‐benzoxazine derivatives [33] . The three‐component Passerini−azide reaction of 2‐azidobenzaldehydes, TMSN 3 , and isocyanides initially afforded tetrazole intermediate 56 without isolation.…”