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Marchese AD, Durant AG, Lautens M. A Modular Approach for the Palladium-Catalyzed Synthesis of Bis-heterocyclic Spirocycles. Org Lett. 2021;24(1):95-99doi: 10.1021/acs.orglett.1c03682.
Marchese, A. D., Durant, A. G., & Lautens, M. (2022). A Modular Approach for the Palladium-Catalyzed Synthesis of Bis-heterocyclic Spirocycles. Organic letters, 24(1), 95-99. https://doi.org/10.1021/acs.orglett.1c03682
Marchese, Austin D, et al. "A Modular Approach for the Palladium-Catalyzed Synthesis of Bis-heterocyclic Spirocycles." Organic letters vol. 24,1 (2022): 95-99. doi: https://doi.org/10.1021/acs.orglett.1c03682
Marchese AD, Durant AG, Lautens M. A Modular Approach for the Palladium-Catalyzed Synthesis of Bis-heterocyclic Spirocycles. Org Lett. 2022 Jan 14;24(1):95-99. doi: 10.1021/acs.orglett.1c03682. Epub 2021 Dec 15. PMID: 34908419.
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Org Lett. 2022 Jan 14;24(1):95-99. doi: 10.1021/acs.orglett.1c03682. Epub 2021 Dec 15.

A Modular Approach for the Palladium-Catalyzed Synthesis of Bis-heterocyclic Spirocycles.

Organic letters

Austin D Marchese, Andrew G Durant, Mark Lautens

Affiliations

  1. Department of Chemistry, Davenport Chemical Laboratories, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.

PMID: 34908419 DOI: 10.1021/acs.orglett.1c03682

Abstract

A simple and modular approach toward bis-heterocyclic spirocycles using palladium catalysis is reported. The enclosed methodology leverages a Mizoroki-Heck-type reaction to generate a neopentylpalladium species. This species can undergo intramolecular C-H activation on a wide array of (hetero)aryl C-H bonds, generating a variety of [4.4] and [4.5] bis-heterocyclic spirocycles in up to 95% yield. A diverse range of bis-heterocyclic spirocycles were possible, with 24 examples and 18 different combinations of heterocycles were synthesized. Biologically relevant aza-heterocycles such as purine, pyrazole, (benz)imidazole, (aza)indole, and pyridine were readily incorporated into the spirocyclic core. The reaction was readily scalable to 1 mmol using a lower catalyst loading and number of base equivalents, and the product was purified without the use flash column chromatography.

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