Synthesis of bridged benzazocines and benzoxocines by a titanium-catalyzed double-reductive umpolung strategy.

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.