Davies, Stephen G.Goddard, Euan C.Roberts, Paul M.Russell, Angela J.Smith, Andrew D.Thomson, James E.Withey, Jonathan M.2017-01-122022-05-282022-05-282016Davies, S. G., Goddard, E. C., Roberts, P. M., Russell, A. J., Smith, A. D., Thomson, J. E., & Withey, J. M. (2016). Strategies for the construction of morphinan alkaloid AB‐rings: regioselective Friedel‐Crafts‐type cyclisations of γ‐aryl‐β‐benzoylamido acids with asymmetrically substituted γ‐aryl rings. Tetrahedron: Asymmetry, 27(6), 274‐284. doi:10.1016/j.tetasy.2016.02.010https://hdl.handle.net/20.500.14078/671The regioselectivity of the Friedel-Crafts-type cyclisation of a range of -aryl--benzoylamido acids, bearing oxy substituents at the C(3)- and C(4)-positions of the -aryl ring, has been investigated. In all of the cases examined (with 3,4-dimethoxy, 3,4-methylenedioxy and 3-hydroxy-4-methoxy substituents) the Lewis acid promoted cyclisation proceeds with exclusive regioselectivity for attack at the C(6)-position rather than at the C(2)-position, and furnishes the corresponding, N- and O-protected 3-amino-6,7-dihydroxy-1-tetralone derivatives. This inherent regioselectivity can be overturned by the regioselective introduction of chlorine as a blocking group for the C(6)-position; subsequent Lewis acid promoted cyclisation then proceeds with exclusive regioselectivity for attack at the C(2)-position to deliver the corresponding N- and O-protected 3- amino-5-chloro-7,8-dihydroxy-1-tetralone derivative. These complementary cyclisation protocols represent useful methods for the preparation of these benzo-fused carbocyclic ring systems, which are the functionalised AB-rings of a range of morphinan alkaloids.935.75 KBPDFenAll Rights ReservedArticle Post-Printhttps://doi.org/10.1016/j.tetasy.2016.02.010