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Regio‐ and Diastereoselective [3+2] Annulation of Aliphatic Aldimines with Alkenes by Scandium‐Catalyzed β‐C(sp<sup>3</sup>)−H Activation

Xuefeng Cong, Qingde Zhuo, Na Hao, Zhenbo Mo, Gu Zhan, Masayoshi Nishiura, Zhaomin Hou

2021Angewandte Chemie International Edition36 citationsDOI

Abstract

Abstract Here we report for the first time the regio‐ and diastereoselective [3+2] annulation of a wide range of aliphatic aldimines with alkenes via the activation of an unactivated β‐C(sp 3 )−H bond by half‐sandwich scandium catalysts. This protocol offers a straightforward and atom‐efficient route for the synthesis of a new family of multi‐substituted aminocyclopentane derivatives from easily accessible aliphatic aldimines and alkenes. The annulation of aldimines with styrenes exclusively afforded the 5‐aryl‐ trans ‐substituted 1‐aminocyclopentane derivatives with excellent diastereoselectivity through the 2,1‐insertion of a styrene unit. The annulation of aldimines with aliphatic alkenes selectively gave the 4‐alkyl‐ trans ‐substituted 1‐aminocyclopentane products in a 1,2‐insertion fashion. A catalytic amount of an appropriate amine such as adamantylamine (AdNH 2 ) or dibenzylamine (Bn 2 NH) showed significant effects on the catalyst activity and stereoselectivity.

Topics & Concepts

AldimineAnnulationChemistryCatalysisOrganic chemistryScandiumStereoselectivityMedicinal chemistryCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisSynthesis and Catalytic Reactions
Regio‐ and Diastereoselective [3+2] Annulation of Aliphatic Aldimines with Alkenes by Scandium‐Catalyzed β‐C(sp<sup>3</sup>)−H Activation | Litcius