Regioselective, Transition Metal-Free C–O Coupling Reactions Involving Aryne Intermediates

Abstract

A new transition-metal-free synthetic method for C-O coupling between various aryl halides and alkoxides is described. This type of transformation is typically accomplished using palladium catalysts containing a specialized phosphine ligand. The reactions reported here can be performed under mild, ambient conditions using certain potassium alkoxides and a range of aryl halides, with iodide and bromide derivatives giving the best results. A likely mechanistic pathway involves the in situ generation of an aryne intermediate, and directing groups on the aryl ring inductively control regioselectivity.

Competing Pathways in O‐Arylations with Diaryliodonium Salts: Mechanistic Insights

“…Aryne intermediates are known to react with nucleophiles with poor regioselectivity in the absence of strong directing groups, [13] and aryne formation was hence hypothesized to explain the observedr egioisomericm ixture of 2.T his was supportedb yatrapping experimentw ithe xcessf uran, giving Diels-Alder adduct 6a together with diaryl ether 2b as a single regioisomer (Scheme 3b). Furthermore, the ortho-iodo products 5 were no longer formed.…”

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

“…[6] Conversely,the seminal discovery and ensuing mechanistic investigation of aryne reactivity was found to occur by ortho-C À Hd eprotonation of an aryl halide at low temperature (À33 8 8C) followed by halide elimination. [9] Herein, we describe the discovery and development of an approach that offers recourse to difunctionalized aryne precursors and provides high and predictable selectivity in the formation of aryne intermediates by CÀHdeprotonation. [8] Ar ecent example of this strategy at ambient temperature further exemplifies the challenge of substrates having multiple leaving groups wherein polysubstitution and competing S N Ar reactivity were observed.…”

“…[8] Ar ecent example of this strategy at ambient temperature further exemplifies the challenge of substrates having multiple leaving groups wherein polysubstitution and competing S N Ar reactivity were observed. [9] Herein, we describe the discovery and development of an approach that offers recourse to difunctionalized aryne precursors and provides high and predictable selectivity in the formation of aryne intermediates by CÀHdeprotonation. In this work, unsymmetrical aryl(mesityl)iodonium salts engage an amide base at mild temperature and the transient aryne intermediate is trapped in cycloaddition and nucleophilic addition reactions (Scheme 2a).…”

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

“…Despite the inherent efficiency of this strategy over contemporary methods, application to highly functionalized substrates has also been limited in practice because of challenges in both regioselective deprotonation at C−H bonds and chemoselective elimination of a single leaving group when multiple potential groups are present . A recent example of this strategy at ambient temperature further exemplifies the challenge of substrates having multiple leaving groups wherein polysubstitution and competing S N Ar reactivity were observed …”