Copper-Mediated Oxidative Transformation of N‑Allyl Enamine Carboxylates toward Synthesis of Azaheterocycles

• Published in: Journal of the American Chemical Society Vol. 136; no. 16; pp. 6011 - 6020
• Main Authors: Toh, Kah Kah, Biswas, Anup, Wang, Yi-Feng, Tan, Yun Yun, Chiba, Shunsuke
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.04.2014; Amer Chemical Soc
• Subjects: Alkenes - chemistry; Amines - chemistry; Carboxylic Acids - chemistry; Catalysis; Chemistry; Chemistry Techniques, Synthetic; Chemistry, Multidisciplinary; Copper - chemistry; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Oxidation-Reduction; Physical Sciences; Pyridines - chemistry; Science & Technology; Stereoisomerism; Substrate Specificity; CARBON BOND FORMATION; ALKYL RADICALS; CATALYZED SYNTHESIS; COPPER(I)-CATALYZED INTRAMOLECULAR ADDITION; RADICAL CYCLIZATION; CONSTRUCTION; EFFICIENT SYNTHESIS; CYCLOPROPANATION; POLYVALENT IODINE; DERIVATIVES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja500382c

A method for synthesis of 3-azabicyclo[3.1.0]­hex-2-enes has been developed by intramolecular cyclopropanation of readily available N-allyl enamine carboxylates. Two complementary reaction conditions, CuBr-mediated aerobic and CuBr2-catalyzed-PhIO2-mediated systems effectively induced stepwise cyclopropanation via carbocupration of alkenes. Oxidative cyclopropane ring-opening of 5-substituted 3-azabicyclo[3.1.0]­hex-2-enes was also developed for synthesis of highly substituted pyridines. In addition, diastereoselective reduction of 3-azabicyclo[3.1.0]­hex-2-enes to 3-azabicyclo[3.1.0]­hexanes was achieved using NaBH3CN in the presence of acetic acid.