Activation of Remote meta‐C−H Bonds in Arenes with Tethered Alcohols: A Salicylonitrile Template

Abstract

Palladium-catalyzed activation of remote meta-C-H bonds in arenes containing tethered alcohols was achieved with high regioselectivity by using a nitrile template. Computational studies on the macrocyclic transition state of the regioselectivity-determining C-H activation steps revealed that both the C-N-Ag angles and gauche comformations of phenyl ether play an extremely important role in the meta selectivity.

Accessing Remote meta‐ and para‐C(sp2)−H Bonds with Covalently Attached Directing Groups

“…[31] phenethyl sulfonate (R = H) meta-olefination [32] aryl alcohol and acid (R = OMe) meta-olefination [33] aryl sulfonates (R = OMe) meta-silylation meta-germanylation [34] benzylsulfonyl esters phenylacetic acids meta-olefination [36] benzyl sulfonyl esters meta-olefination [41] benzyl sulfonates meta-cyanation meta-alkylation [43] [44] aryl sulfonates meta-cyanation meta-alkylation meta-alkenylation [43] [44] [44] phosphonate benzyl phosphonates meta-olefination meta-acetoxylation meta-hydroxylation [37] Angewandte Chemie Reviews…”

“…Thep otential of this procedure was demonstrated by sequential ortho-and meta-olefination of phenethylamine derivatives (31)(32)(33)(34)(35)(36). Finally,the directing group was removed under acid hydrolysis to afford meta-substituted phenylethylamine 37.…”

“…[33] With the help of as imilar 2-cyanophenol-derivatized template,t hey were able to achieve ah ighly regioselective meta-olefination of arange of aryl alcohols from adistal location of the directing group.I nt he presence of Pd(OAc) 2 as the catalyst, aw ide range of aryl alcohols,namely 3-phenylpropanols,2-phenoxyethanols,a nd 2-(phenylamino)ethanols,w ere succesfully olefinated at the meta-position with yields as high as 91 % (meta/others > 20:1; 86 a-g). [33] With the help of as imilar 2-cyanophenol-derivatized template,t hey were able to achieve ah ighly regioselective meta-olefination of arange of aryl alcohols from adistal location of the directing group.I nt he presence of Pd(OAc) 2 as the catalyst, aw ide range of aryl alcohols,namely 3-phenylpropanols,2-phenoxyethanols,a nd 2-(phenylamino)ethanols,w ere succesfully olefinated at the meta-position with yields as high as 91 % (meta/others > 20:1; 86 a-g).…”

Computational exploration of Pd‐catalyzed C–H bond activation reactions

“…In these two CMD models, the nitrile directing group of the template binds to one Pd or Ag, while the arene C–H bond is brought close to another Pd to undergo the acetate‐assisted C–H bond activation. The Pd–Ag heterodimeric model has also been applied to other systems …”

Mechanistic DFT Study on Rhodium(III)‐Catalyzed Double C−H Activation for Oxidative Annulations of 2‐Substituted Imidazoles and Alkynes

“…Numerous novel transformations have been developed with this strategy over recent decades, [1][2][3][4][5][6][7] and recently the activation of remote meta-CÀH bonds has been realized by elegant design of the DG in combination with as uitable metal catalyst. [8,9] In studies on the possible new roles of DGs, CÀHa ctivations with tracelessD Gs [10,11] ando xidizing DGs have been disclosed in recent years. [12,13] The latter concept has been found many applicationso fR h III catalysis.…”