Kinetic Resolution of Alkylidene Norcamphors via a Ligand-Controlled Umpolung-Type 1,3-Dipolar Cycloaddition

• Published in: iScience Vol. 11; pp. 146 - 159
• Main Authors: Shen, Chong, Yang, Yuhong, Wei, Liang, Dong, Wu-Wei, Chung, Lung Wa, Wang, Chun-Jiang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.01.2019; Elsevier
• Subjects: Chemistry; Organic Chemistry; Organic Synthesis; Chemistry; Organic Synthesis; Organic Chemistry
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2018.12.010

Development of a general catalytic and highly efficient method utilizing readily available precursors for the regio- and stereoselective construction of bioactive natural-product-inspired spiro architectures remains a formidable challenge in chemical research. Transition metal-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides produces numerous N-heterocycles, but reaction control with the regioselectivity opposite to the conventional fashion has rarely been demonstrated. Herein, we report a unique ligand-controlled Cu(I)-catalyzed umpolung-type 1,3-dipolar cycloaddition of azomethine ylide to realize efficient kinetic resolution of racemic alkylidene norcamphors with the concomitant construction of previously inaccessible spiro N-heterocycles with high levels of regio- and stereoselectivity. The success of this methodology relies on the strategy of kinetic resolution, and the serendipitous discovery of a unique ligand-enabled regiospecific cycloaddition, which not only provides evidence for the existence of the minor zwitterionic resonance form in metallated azomethine ylide but also diversifies the existing chemistry of azomethine ylide-involved 1,3-dipolar cycloadditions with rare polarity inversion. [Display omitted] •Kinetic resolution of racemic alkylidene norcamphors•Spiro architectures incorporating norbornane and pyrrolidine scaffolds•Unique ligand-enabled umpolung-type 1,3-dipolar cycloaddition Chemistry; Organic Chemistry; Organic Synthesis