Synthesis of Bridged Benzazocines and Benzoxocines by a Titanium‐Catalyzed Double‐Reductive Umpolung Strategy

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.

Direct conjugate alkylation of α,β-unsaturated carbonyls by TiIII-catalysed reductive umpolung of simple activated alkenes

“…With the 3-methylated quinolone 24a as substrate, acrylates could be employed efficiently in the reductive catalytic umpolung as well (entries [11][12][13][14][15]. Here, reasonable results were obtained with methyl, ethyl, and tert-butyl acrylate.…”

Electroreductive Intermolecular Coupling of Chromones with Benzophenones: Synthesis of 2‐Diarylmethylchromones and Tetrasubstituted Furans

“…Chromones 1a, [2f ] 1b, [7] 1c, [2f ] and isoflavones 1d, [7] 1e, [9] 1f, [9] 1g, [10] 1h, [11] were prepared by reported methods. Chromones 1a, [2f ] 1b, [7] 1c, [2f ] and isoflavones 1d, [7] 1e, [9] 1f, [9] 1g, [10] 1h, [11] were prepared by reported methods.…”

Metal‐Catalyzed β‐Functionalization of Michael Acceptors through Reductive Radical Addition Reactions

“…Themethod was further applied to the synthesis of functionalized quinolone and chromone derivatives,f or which acrylates could also be employed as coupling partners. [54]…”