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Iridium-Catalyzed Asymmetric Hydrogenation of Carbocation Precursors via Wagner–Meerwein Rearrangement
Stockholm University, Faculty of Science, Department of Chemistry.ORCID iD: 0000-0002-9998-6767
Stockholm University, Faculty of Science, Department of Chemistry.ORCID iD: 0000-0001-7947-3860
Stockholm University, Faculty of Science, Department of Chemistry.ORCID iD: 0000-0002-1383-8246
Number of Authors: 42026 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 148, no 19, p. 19781-19788Article in journal (Refereed) Published
Abstract [en]

Carbocation rearrangement is a powerful tool for converting a simple precursor into a complex molecular scaffold. However, controlling the stereoselectivity of a reaction that involves carbocation rearrangement is challenging and remains elusive. In this study, we demonstrate a novel iridium-catalyzed Wagner–Meerwein rearrangement and asymmetric hydrogenation of carbocation precursors (1-(aryl)-1-(1-methylcyclobutyl/cyclopentyl) ethan-1-ol) for the synthesis of various optically active gem-dimethyl cycloalkanes. Hence, enantiopure gem-dimethyl-containing compounds are important motifs found in many natural products, and some are FDA-approved drugs. Our methodology starts with an iridium-catalyzed formal deoxygenation of tertiary alcohols to generate a tertiary carbocation that triggers the Wagner–Meerwein rearrangement via the ring expansion and alkyl migration cascade to furnish a stable tertiary-benzyl carbocation. Sequential olefination and in situ asymmetric hydrogenation provide access to various gem-dimethyl chiral cycloalkanes in excellent yield (> 99%) and enantioselectivity (ee up to > 99%). Otherwise, establishing a high yield and enantioselectivity in a saturated cyclic hydrocarbon next to a sterically hindered gem-dimethyl group would not be possible by conventional methods.

Place, publisher, year, edition, pages
2026. Vol. 148, no 19, p. 19781-19788
National Category
Materials Chemistry
Identifiers
URN: urn:nbn:se:su:diva-256158DOI: 10.1021/jacs.6c01858PubMedID: 42085341Scopus ID: 2-s2.0-105039296884OAI: oai:DiVA.org:su-256158DiVA, id: diva2:2066093
Available from: 2026-06-04 Created: 2026-06-04 Last updated: 2026-06-04Bibliographically approved

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