Synthesis of Fused and Linked Bicyclic Nitrogen Heterocycles by Palladium-Catalyzed Domino Cyclization of Propargyl Bromides

• Published in: Chemistry : a European journal Vol. 16; no. 28; pp. 8410 - 8418
• Main Authors: Okano, Akinori, Tsukamoto, Koji, Kosaka, Shohei, Maeda, Hatsuo, Oishi, Shinya, Tanaka, Tetsuaki, Fujii, Nobutaka, Ohno, Hiroaki
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 26-07-2010; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Bromides; Carbon; Catalysis; Catalysts; Chemistry; Construction; Cyclization; Derivatives; domino reactions; Functional groups; heterocycles; Molecular Structure; Nitrogen - chemistry; palladium; Palladium - chemistry; Pargyline - analogs & derivatives; Pargyline - chemistry; propargylic compounds; Synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201000653

The palladium(0)‐catalyzed direct construction of bicyclic heterocycles is described. Treatment of propargyl bromides that have nucleophilic functional groups connected by two or three carbon atoms with catalytic [Pd(PPh3)4] affords bis‐cyclization products in good yields. The desired bicyclic heterocycles can be obtained selectively when using substrates with appropriate nucleophilic groups. We also describe the reaction of a 2‐alkynylazetidine derivative with a catalytic amount of [Pd(PPh3)4] under base‐free conditions, which affords the same fused heterocycles as the corresponding propargyl bromides.
Palladium‐catalyzed bis‐cyclization: Propargyl bromides that have nucleophilic functional groups, such as 5‐bromohept‐3‐yne‐1,7‐diamine derivatives, react with [Pd(PPh3)4] and NaH/MeOH to selectively give fused nitrogen heterocycles that can be readily converted into the fused pyrroles in good yields (see scheme). The reaction of a 2‐alkynylazetidine derivative with a catalytic amount of [Pd(PPh3)4] proceeds under base‐free conditions to give the same fused heterocycle.