meta C–H Arylation of Electron-Rich Arenes: Reversing the Conventional Site Selectivity

Abstract

Controlling site selectivity of C–H activation without using a directing group remains a significant challenge. While Pd­(II) catalysts modulated by a mutually repulsive pyridine-type ligand have been shown to favor the relatively electron-rich carbon centers of arenes, reversing the selectivity to favor palladation at the relatively electron-deficient positions has not been possible. Herein we report the first catalytic system that effectively performs meta C–H arylation of a variety of alkoxy aromatics including 2,3-dihydrobenzofuran and chromane with exclusive meta site selectivity, thus reversing the conventional site selectivity governed by native electronic effects. The identification of an effective ligand and modified norbornene (NBE-CO2Me), as well as taking advantage of the statistics, are essential for achieving the exclusive meta selectivity.

meta‐Selective C−H Arylation of Fluoroarenes and Simple Arenes

“…Based on our previous study,2 -pyridone-accelerated non-directed CÀH activation is highly controlled by the steric environment and thus always preferably occurs at C-5 of m-xylene and the subsequent norbornene relay to C-3 or C-4 will be impeded by steric effects of the methyl groups (See the Supporting Information for detailed explanation). [6,11,14] Notably, b-arylated naphthalene was afforded as the sole product in 42 % yield with naphthalene as the limiting reagent (3y). [13e] Siteselective arylation of 2,6-dimethylphenylboronic ester also Angewandte proceeded in moderate yields (3z).…”

β‐Selective C−H Arylation of Electron‐Deficient Thiophenes, Pyrroles, and Furans

“…It has been well documented that the C−H arylation of these arenes preferably proceed at the α ‐positions . To reverse this conventional site‐selectivity, a modified norbornene was introduced, which has been employed as a mediator by our group recently to realize a nondirected C−H activation on less electronically favored positions . With this design in mind, we selected thiophene‐2‐carboxylic acid methyl ester as the model substrate and began our study on ligand screening (Table ).…”

“…[2] To reverse this conventional site-selectivity, a modified norbornene was introduced, which has been employed as a mediator by our group recently to realize a nondirected CÀ H activation on less electronically favored positions. [10] With this design in mind, we selected thiophene-2-carboxylic acid methyl ester as the model substrate and began our study on ligand screening (Table 1). Electron-deficient quinoline-type ligands which demonstrated superior reactivity for nondirected CÀ H arylation of protected phenols yielded the desired β-arylation product as the sole regioisomer in less than 10 % yield.…”

Palladium/Norbornene‐Catalyzed Sequential ortho‐Acylation and ipso‐Alkenylation with Carboxylic Acid: Access to Polysubstituted Aryl Ketones

“…Since the pioneering work by Catellani, significant contributions have been made in this chemistry including the groups of Lautens, [10] Dong as well as others. [11] Contrast to well-studied terminating reagents for ispo-position couplings, functionalization at ortho-position was restricted to alkylation, [12] arylation, [13] amination, [14] acylation [15] and thiolation [16] (Scheme 1b).…”

“…In general, reactions in "non-polar" solvents performed much better than those in polar solvents (entries 7-10), and toluene was found to be the superior solvent. Varying the amount of DCC resulted in somewhat drop in the yields (entries [11][12][13], and the use of 4.5 equiv. of DCC show the best result.…”