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

Davies, Stephen
Goddard, Euan
Roberts, Paul
Russell, Angela
Smith, Andrew
Thomson, James
Withey, Jonathan
Faculty Advisor
Abstract (summary)
The 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.
Publication Information
Davies, 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.2016.02.010
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