Strategies for the construction of morphinan alkaloid AB-rings: regioselective Friedel-Crafts-type cyclisations of gamma-aryl-beta-benzoylamido acids with asymmetrically substituted gamma-aryl rings

Journal article

The regioselectivity of the Friedel-Crafts-type cyclisation of a range of γ-aryl-β-benzoylamido acids, bearing oxy substituents at the C(3)- and C(4)-positions of the γ-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.

Authors: Davies, S; Goddard, E; Roberts, P; Russell, A; Smith, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Tetrahedron: Asymmetry
• Volume: 27
• Issue: 6
• Pages: 274-284
• Publication date: 2016-03-02
• Acceptance date: 2016-02-18
• DOI: 10.1016/j.tetasy.2016.02.010
• EISSN: 1362-511X
• ISSN: 0957-4166
• Keywords: SBTMR