Copper‐Catalyzed Electrophilic Etherification of Arylboronic Esters with Isoxazolidines

Abstract

A copper-catalyzed electrophilic etherification of arylboronic esters is reported. Isoxazolidines are utilized as easily available and stable [RO] + surrogates to give 1,3amino aryl ethers. The O-selective arylation of isoxazolidines takes place without causing competitive N-arylation. In contrast to previously reported anionic conditions, our copper-catalyzed conditions are mild enough to achieve high functional group tolerance. Preliminary mechanistic studies and DFT calculations support that the reaction proceeds via a transmetalation/oxidative addition pathway, followed by a Lewis acid-promoted reductive elimination to induce the crucial O-selectivity. Aromatic ethers are important functional groups in a wide range of molecules with numerous applications such as biologically active compounds and pharmaceuticals. [1] Transition metal-catalyzed formation of carbonÀ oxygen bonds have been extensively studied as one of the promising methods to generate aromatic ethers. To date, most coupling reactions that construct carbonÀ oxygen bonds utilize nucleophilic oxygen atoms and electrophilic carbon centers as seen in the Ullman-Goldberg coupling [2] and the Buchwald-Hartwig coupling. [3] Oxidative Chan-Evans-Lam coupling [4] using boronic acids is another promising approach. However, few examples of electrophilic etherification have been reported in spite of its potential utility.

Copper-Catalyzed Electrophilic Enamidation Using Dioxazolones through Hydrozirconation of Alkynes

“…On the basis of the mechanism of our previous report on the copper-catalyzed electrophilic amidation of aryl trifluoroborates, , we propose a plausible catalytic cycle for the electrophilic enamidation (Scheme ). After hydrozirconation of alkyne 4 , transmetalation of vinyl zirconium intermediate 12 with a copper salt provides a more reactive vinyl copper species I , which could undergo oxidative addition to dioxazolone 16 .…”