Palladium-catalyzed stereoselective domino arylation-acylation: an entry to chiral tetrahydrofluorenone scaffolds Nina Kann 1 , Simon E. Lewis 2 , Petter Dunås 1 , Andrew J. Paterson 1 , Gabriele Kociok-K hn 2 , Martin Rahm 1 1 Chalmers University of Technology, Sweden, 2 University of Bath, UK Biocatalytic oxidation of benzoic acid [1] affords a highly functionalized chiral scaffold, which can be further diversified via palladium-catalyzed arylation. Depending on the substitution pattern of the aryl halide used, this reaction can proceed either via a Heck-type pathway, with concomitant 1,3-chirality transfer,[2] or via a domino arylation-cyclization.[3] The latter reaction gives access to tricyclic tetrahydrofluorenones with full regio- and stereoselectivity in a single step. Quantum chemical calculations were performed to explain the divergent behaviour of the two reactions. We envisage that this methodology can find applications in the synthesis of bioactive hydrofluorenones such as the cytotoxic kinamycins. References 1. Gibson, D. T.; Koch, J. R.; Kallio, R. E. Biochemistry 1968 , 7 , 2653−2662; (b) Lewis, S. E. In Asymmetric Dearomatization Reactions, You, L.-E., Ed. , Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, 2016, pp. 279-346. 2. Paterson, A. J.; Dunås, P.; Rahm, M.; Norrby, P.-O.; Kociok-K hn, G.; Lewis, S. E.; Kann, N. Org. Lett. 2020 , 22 , 2464–2469. 3. Dunås, P.; Paterson, A. J.; Kociok-K hn, G.;Rahm, R.; Lewis, S. E.; Kann, N. Chem. Commun. 2021 , 57 , 6518-6521.
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