Synthesis of bridged benzazocines and benzoxocines by a titanium-catalyzed double-reductive umpolung strategy
Plamen Bichovski1, Thomas M Haas, Daniel Kratzert
1Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104 Freiburg (Germany), Fax: (+49) 761-203-8715.
Abstract:
A sequence of two titanium(III)-catalyzed reductive umpolung reactions is reported that allows the rapid construction of benzazo- and benzoxozine building blocks. The first step is a reductive cross-coupling of quinolones or chromones with Michael acceptors. This reaction proceeds with complete syn-selectivity for the quinolone functionalization while the anti-diastereomers are obtained as the major products from chromones. With different reaction conditions, the stereochemical outcome can be altered to afford the syn-chromanone products as well. A subsequent reductive ketyl radical cyclization forges the tricyclic title compounds in good yields. A stereochemical model explaining the observed stereoselectivities is provided and the product configurations were unambiguously verified by X-ray analyses and 2D NMR spectroscopic experiments.
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