The Cyano Group as a Traceless Activation Group for the Intermolecular [3+2] Cycloaddition of Azomethine Ylides: A Five-Step Synthesis of (±)-Isoretronecanol

• Published in: Angewandte Chemie International Edition Vol. 54; no. 21; pp. 6306 - 6310
• Main Authors: Li, Jundong, Zhao, Huaibo, Jiang, Xunjin, Wang, Xiance, Hu, Haiming, Yu, Lei, Zhang, Yandong
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 18.05.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Activation; Arrays; Azo Compounds - chemical synthesis; Azo Compounds - chemistry; Biological Products - chemical synthesis; Biological Products - chemistry; Borohydrides; Chemistry; Chemistry, Multidisciplinary; Cyano groups; Cycloaddition; Cycloaddition Reaction; Physical Sciences; pyrrolidines; Pyrrolizidine Alkaloids - chemical synthesis; Pyrrolizidine Alkaloids - chemistry; reductive decyanation; Science & Technology; Sodium; Stereoisomerism; Strategy; Synthesis; Thiosemicarbazones - chemical synthesis; Thiosemicarbazones - chemistry; total synthesis; traceless activation; Transformations; ASYMMETRIC 1,3-DIPOLAR CYCLOADDITION; 2-AZAALLYL ANIONS; traceless activation; AMINE; DIBORANE; ELECTROORGANIC CHEMISTRY; SODIUM-BOROHYDRIDE; cycloaddition; pyrrolidines; TRANSMETALATION; reductive decyanation; GENERATION; total synthesis; CARBOXYLIC-ACIDS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201500961

The cyano group was used as a traceless activation group for the [3+2] cycloaddition of azomethine ylides in a two‐step process, thereby providing a highly effective approach to 5‐unsubstituted pyrrolidines. The transformation includes the silver acetate catalyzed intermolecular 1,3‐dipolar cycloaddition of α‐iminonitriles and an unprecedented sodium borohydride induced reductive decyanation reaction. A diverse array of substrates is amenable to this transformation. The methodology was further extended to a five‐step total synthesis of the pyrrolizidine natural product isoretronecanol. Without a trace…︁ A highly stereoselective cycloaddition strategy provided efficient access to a diverse array of 5‐unsubstituted pyrrolidines and enabled a five‐step total synthesis of isoretronecanol (see scheme). A novel role of sodium borohydride in reductive decyanation was observed.