Ortho-C-H amination

In addition to the perfluoroalkylation of arenes Pd(dba)2 competently facilities the ortho-C-H amination of A-aryl benzamides with electrophilic 0-benzoyl hydroxylamines. Pd(dba)2 showed equal reactivity to other precatalysts, such as Pd(OAc)2. Although mechanistically unclear, the addition of AgOAc signiflcantly improved conversion, while the addition of external phosphine ligands was detrimental. Finally, the 4-CF3(C6p4) directing group was optimal because acidic N-H bonds are essential for this transformation (eq 36). ... 

A Ru(II)-catalyzed ortho C-H amination of arenes with thiophenes and other heteroqrcles at room temperature was achieved this year (130L5286). 

Type of reaction C-N bond formation Reaction conditions Acetone, room temperature Synthetic strategy Ru(ll)-catalyzed ortho-C-H amination Catalyst [Ru Cl2(p-cymeme)]2/K2C03... 

Keywords Substituted aryl/heteroaiyl benzamides, cyclic N-benzoyloxyamines, [Ru Cl2(p-cymeme)]2 complex as catalyst, potassium carbonate, argon atmosphere, acetone, room temperature, ortho-C-H amination, substimted aryl/heteroaryl amines... 

Glorius and co workers developed a Rh [III]-catalyzed ortho C-H amination using PivONH2 HOTf as nitrogen source [94]. Although the reaction only gave the... 

Similar to the ether substrates mentioned above, both cyclic and acyclic N-protected amines could be converted into their corresponding ortho-C—H bond functionalization products via the insertion of metal carbenoids derived from Rh catalysts and donor/acceptor diazo compounds. Thking Af-Boc-protected pyrrolidine 48 as an example (Scheme 1.15), Rh2(S -DOSP)4 catalyzed the decomposition of methyl phenyldiazoacetate la and converted the Af-Boc-pyrrolidine 48 into the corresponding C—H bond insertion product 49 in 72% yield, 94% ee, and 92% de. Furthermore, the C2-symmetric amine 50 could be formed in 78% yield and 97% ee under altered reaction conditions. Further investigation demonstrates that this intermolecular C—H bond insertion could also be applied in the kinetic resolution of 2-substituted pyrrolidine 51. The corresponding C—H bond insertion reaction proceeded smoothly, and subsequent treatment with TFA delivered the deprotected product 52 in high diastereo- and enantioselectivity (45% yield, 91% ee, >94% de). " ... 

The amide-directed palladium-catalyzed intermolecular C-H amination of arenes with the non-nitrene-based nitrogen source NFSi was selective at ortho position for para-substituted substrates, while selective at para-position for 2-OMe-substituted substrates (eq 66) 2-alkyl-substituted substrates failed to react. ... 

The reaction is postulated to proceed via an intramolecular migratory insertion of amine, followed by ortho-C-H bond activation and cyclization (Scheme 7.7). Notably, a catalytlcally active cationic ruthenium-acetyhde complex has been isolated and characterized in this case. 

The scope of the cobalt-catalyzed C-H amination was extended to phosphoryl azide derivatives (Scheme 10.20) [49]. Amination of the benzylic C-H bond of an alkyl group ortho to the phosphoryl azide is efficiently promoted by a cobalt(II) complex [Co(Pl)j with a D2 -symmetric tetraarylporphyrin ligand, which features proximal amide functionalities, thus affording a six-membered cyclic product. The amide functionalities of the catalyst appear to play critical roles in the amination reaction presumably by facihtating catalyst-substrate... 

All lation of Aromatic Amines and Pyridines. Commercially important aromatic amines are aniline [62-53-3] toluidine [26915-12-8], phenylenediamines [25265-76-3], and toluenediamines [25376-45-8] (see Amines, aromatic). The ortho alkylation of these aromatic amines with olefins, alcohols, and dienes to produce more valuable derivatives can be achieved with soHd acid catalysts. For instance, 5-/ f2 butyl-2,4-toluenediamine (C H gN2), which is used for performance polymer appHcations, is produced at 85% selectivity and 84% 2,4-toluenediamine [95-80-7] (2,4-4L)A)... 

Analogous alkoxy and aryloxyrhenium complexes do not show the same reactivity. However, Brown and Mayer discovered soon thereafter that a different rhenium complex could mediate C—O bond formation.68 Photolysis of the Re(V) complex 13 led to C—H activation and formation of a phenyl rhenium oxo, 14. Yields were improved from 30-40% to 90% upon addition of pyridine to the photolysis mixture. The role of pyridine was unclear, because other tertiary amines provided no such improvement in yield. Substituted benzenes showed a preference for para activation over meta fluorobenzene also gave a significant amount of ortho activation. 

A copper(ii) oxide-catalyzed regioselective synthesis of 1-alkyl- and l-aryl-l//-indazoles from ortho-hzXogcnztcA alkanoylphenones, benzophenones, and arylcarboxylic acids with hydrazines in the presence of potassium carbonate has been developed <20070L525>. A palladium-catalyzed C-H activation/intramolecular amination reaction sequence provided a new route to 3-aryl/alkylindazoles <20070L2931>. 

Unlike most of the other oxidative reactions developed in our group, the I(III)-mediated amination did not require the arene reagent to be used as a solvent. Near 1 1 ratios of the N-H and the C-H substrate could be used. Unfortunately, the metal-free amination provided intractable mixmres of products with monosubstituted and nonsymmetric arene substrates (Scheme 9). This problem was exemplified by the amination of toluene, which produced three regiomers in a 10 6 5 (ortho/meta/para) ratio. We demonstrated the application of the metal-free amination reaction with 18 substrates, but all nonsymmetric arenes produced complex mixtures of aminated products. " ... 

The L -iodane PhI(OAc)2 has been used extensively, most notably by Sanford, to oxygenate the C-H bonds of arenes and even alkanes in the presence of palladium catalysts." Interestingly, this reaction was likely mediated by a binuclear complex featuring two Pd(III) atoms joined by a palladium-palladium (Pd-Pd) bond however, this complex can disproportionate into a Pd(IV)-Pd(II) complex without a formal Pd-Pd bond, and this intricate interplay is often controlled by the presence and nature of hypervalent iodine oxidants." We discovered that this reaction manifold could be extended to include the amination of arene substrates heating 2-phenylindole 51 in the presence of the -iodane 49 and palladium acetate provided the ortho-aminated product 52 in a 19% yield however, switching the metal from palladium acetate... 

In 2013, Arnold and co-workers revisited the possibility of engineering an enzyme eatalyst for this useful transformation. Combining ortho-substituted benzenesulfonyl azides 142 with engineered P450 enzymes which include a reduced Fe center resulted in an efficient intramolecular benzylic C—H bond amination reaction. The desired aminated products 143 were produced in 73% ee with a total turnover number (TTN) of 383. In addition, expression of the eatalyst in E. coli makes the reaction proceed smoothly on a 50 mg scale with high ee value (Seheme 1.54). 

To overcome the ring closure of intermediate 10 giving rise to by-product 8 that was particularly encountered with secondary alkyl halides. Tautens and coworkers [22] developed conditions that favor the oxidative addition of alkyl hahdes. The methodology was widely applied to the intramolecular (Scheme 19.12) and intermolecular ortho alkylation of aromatic C-H bonds with secondary alkyl iodides and bromides [23]. Depending on the terminating reactions employed (the Heck reaction, direct arylation of heterocycles, and the Buchwald-Hartwig amination), a variety of valuable heterocydes were efficiently prepared. It should be pointed out that the reaction of enantioenriched substrates occurred with... 

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