Palladium-Catalyzed Asymmetric Synthesis of Methylidene Cyclobutanes via Enantioselective Intramolecular Heck-Type
Haoting Yu1, Bing Xu1,2, Junliang Zhang1,3,4
1Department of Chemistry, State Key Laboratory of Green Chemical Synthesis and Conversion, Fudan University, Shanghai, P. R. China.
Abstract:
Cyclobutanes as well as 2-substituted alkylidene cyclobutanes (ADCBs) are important skeletons in pharmaceuticals and versatile precursors in organic synthesis. However, enantioselective synthesis of ADCBs remains an underexplored area of research due to the high ring strain and competing side reactions. Herein, we report a Pd-catalyzed asymmetric intramolecular Heck-type reaction that provides a series of 1-methylidene-2-arylcyclobutanes in moderate to good yields with excellent enantioselectivity and chemoselectivity. This method features broad substrate scope and demonstrates potential utility for constructing the core skeletons of bioactive molecules. Mechanistic studies indicate that the rate-determining step of this reaction depends on the electron density of the aryl bromide moiety. Dmdba plays an important role in improving the chemoselectivity.
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