Amination of the Ortho C–H Bonds by the Cu(OAc)2-mediated Reaction of 2-Phenylpyridines with Anilines

Abstract

The reaction of 2-phenylpyridines with anilines in the presence of Cu(OAc)2 as a promoter results in selective mono-amination of the ortho C–H bonds in 2-phenylpyridines to give amine derivatives in high yields per the conversion. This is the rare example of the functionalization of C–H bonds to C–N bonds.

Copper‐Catalyzed Highly Regioselective Oxidative CH Bond Amidation of 2‐Arylpyridine Derivatives and 1‐Methylindoles

“…[4] Direct C À N bond formation based on Cu-mediated Ar À H functionalization was recently reported by Yu and coworkers, [5] employing 2-arylpyridines as the substrates and requiring a stoichiometric amount of CuA C H T U N G T R E N N U N G (OAc) 2 . Similar results were also found by Chatani et al [6] An improved Cu-catalyzed intramolecular version was later achieved by Buchwald and co-workers. [7] More recently, Cu-catalyzed direct aminations/amidations of aromatic C À H bonds, in the presence of a special ligand and a base were reported by Mori [8] and Schreiber.…”

Development of Divergent Synthetic Methods of Pyrimidobenzothiazine and Related Tricyclic Heterocycles

“…Reinaud and co-workers have reported a Cu-mediated ortho-hydroxylation reaction of benzamide 6 using a carboxyl group as a directing group (Scheme 2.3, eq 1) [24]. Yu et al (eq 2) [25] and Chatani et al (eq 3) [26] have independently reported Cu-mediated oxidative intermolecular C-H functionalization using a pyridine moiety as a directing group. The author designed an experiment for the oxidative introduction of heteroatoms by aromatic C-H functionalization with the assistance of an ortho-tetrahydropyrimidinyl group (eq 4).…”

“…In the presence of H 2 O (1.0 equiv), treatment of 2-phenyl-1,4,5,6-tetrahydropyrimidine (18a) with CuO, Cu(OH) 2 , Cu(OTf) 2 or Cu(tfa) 2 (1.0 equiv) in DMF at 130°C under an O 2 atmosphere led to the recovery of unchanged starting material and the desired C-H oxidation did not occur (entries 1-4). Using Cu(OAc) 2 , [25,26] however, led to the formation of the desired ortho-hydroxylated compound 19a (ca. 69 % yield) although the product yield of compound 19a was poorly reproducible because of its high basicity.…”

Direct Azole Amination: CH Functionalization as a New Approach to Biologically Important Heterocycles

“…The pioneering development of a simple copper-catalyzed CÀH amination was reported by Yu and co-workers, [5] using Cu(OAc) 2 /O 2 to effect the pyridine-directed functionalization of a C aryl À H bond with a variety of anionic nucleophiles, including halogens, cyanide, alcohols, and sulfonamides. However, selective amination at C2 of azoles does not rely on the presence of a directing group, but instead relies on the discovery of CÀH activation conditions that react preferentially at the electron-poor C2-position (as with the coppercatalyzed arylation developed by Daugulis et al [6] ).…”