Tetrahydrobenzochromene Synthesis Enabled by a Deconjugative Alkylation/Tsuji–Saegusa–Ito Oxidation on Knoevenagel Adducts

Abstract

A modular and practical route to versatile cyano-1,3-dienes by a sequence involving deconjugative alkylation and "Tsuji-Saegusa-Ito oxidation" is reported. In this letter, the versatility of the products is also explored, including a route to benzochromene scaffolds common to many natural products.

Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides

“…As benzyl cyanide, an undesired side product potentially formed via the nucleophilic substitution of benzyl bromide with the cyanide ion, was not obtained, the three-component cyanoalkylation would be an inherently favorable process under toluene–solid KCN biphasic conditions. In addition, despite the well-known susceptibility of electron-deficient olefins represented by 1a to the deprotonation of their highly acidic γ-protons to generate vinylogous enolates that could also undergo alkylation, − such a two-component bond formation did not occur as an advantageous consequence of the biphasic reaction conditions. We next attempted the reaction with common chiral phase-transfer catalysts (3 mol %) under otherwise similar conditions to assess the feasibility of controlling both the relative and absolute stereochemistry.…”