title: Expanded substrate scope and improved reactivity of ether-forming cross-coupling reactions of organotrifluoroborates and acetals.
abstract: Mixed acetals and organotrifluoroborates undergo BF(3)·OEt(2)-promoted cross-couplings to give dialkyl ethers under simple, mild conditions. A survey of reaction partners identified a hydroxamate leaving group that improves the regioselectivity and product yield in the BF(3)·OEt(2)-promoted coupling reaction of mixed acetals and potassium alkynyl-, alkenyl-, aryl- and heteroaryltrifluoroborates to access substituted dialkyl ethers. This leaving group enables the reaction to proceed rapidly under mild conditions (0 °C, 5-60 min) and permits reactions with electron-deficient potassium aryltrifluoroborates that are less reactive with other acetal substrates. A study of the reaction mechanism and characterization of key intermediates by NMR spectroscopy and X-ray crystallography identified a role for the hydroxamate moiety as a reversible leaving group that serves to stabilize the key oxocarbenium intermediate and the need for a slight excess of organodifluoroborane to serve as a catalyst. A secondary role for the boron nucleophile as an activating ligand was also considered. These studies provide the basis for a general class of reagents that lead to dialkyl ethers by a simple, predictable cross-coupling reaction.
authors.affiliation: Laboratorium für Organische Chemie, Department of Chemistry and Applied Biosciences, ETH-Zürich, Switzerland.
authors.forename: Cam-Van T
authors.initials: CV
authors.lastname: Vo
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Mitchell
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Bode
mesh_terms: D000080:Acetals / Q000737:chemistry*; D001881:Borates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004987:Ethers / Q000138:chemical synthesis* / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D008958:Models, Molecular
chemical_list: D000080:Acetals; D001881:Borates; D004987:Ethers; D005461:Fluorine