Expanded Substrate Scope and Improved Reactivity of Ether-Forming Cross-Coupling Reactions of Organotrifluoroborates and Acetals

Abstract

Mixed acetals and organotrifluoroborates undergo BF3•OEt2 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 BF3•OEt2-promoted coupling reaction of mixed acetals and potassium alkynyl-, alkenyl-, aryl- and heteroaryltrifluoroborates to access substituted dialkyl ethers. This leaving group enables reaction to proceed rapidly under mild conditions (0 °C, 5–60 min) and permits reactions with electron-deficient potassium aryltrifluoroborates that were less reactive with other acetal substrates. A study of the reaction mechanism and characterization of key intermediates by NMR 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 as an activating ligand for the boron nucleophile is 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.

Metal-Free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

“…Initially, catalysts known to convert organotrifluoroborates to organodifluoroboranes were tested. Unfortunately Silica gel, 35 silicon tetrachloride, 36 and boron trifluoride 31,32 did not promote the formation of the desired ynone ( Table 1, entries 1-3). The use of chlorinated Lewis acid catalysts proved to be more successful.…”

Base‐Mediated O‐Arylation of Alcohols and Phenols by Triarylsulfonium Triflates

“…(3‐Phenoxyprop‐1‐yn‐1‐yl)benzene ( 3 q ) . Light yellow oil (34.8 mg, 84 %, Procedure B ), petroleum ether as eluent for column chromatography.…”

Practical and Highly Selective CH Functionalization of Structurally Diverse Ethers

“…The reaction proved general for a broad range of structurally and electronically varied potassium alkynyltrifluoroborates in high efficiency ( 3 a and 3 d – k ; Scheme ). The desired product was not detected when either the boronic acid 2 b or boronate ester 2 c was used, and might be ascribed to their reduced nucleophilicity compared with 2 a or the incompatibility towards the reaction conditions 2d. 9 Alkenyl trifluoroborate salts ( 2 l and 2 m ) are suitable coupling partners to deliver the desired vinyl THFs in good yields with olefin geometry highly conserved.…”