C-H bond, amination

In 1982, Breslow and coworkers reported the first example of iron-catalyzed nitrene C-H bond insertion [29]. They used [Fe(TTP)] as catalyst and PhINTs as nitrene precursor to achieve C-H bond amination of cyclohexane. However, the product yield was low (around 10%). Subsequently, the same authors found that iminoio-dane 7 derived from 2,5-diisopropylbenzenesuIfonamide underwent intramolecular C-H amination efficiently with [Fe(TPP)Cl] as catalyst at room temperature, giving the insertion product in 77% yield (Scheme 29) [85]. 

Iron phthalocyanine is an efficient catalyst for intermolecular amination of saturated C-H bonds. With 1 mol% iron phthalocyanine and 1.5 equiv. PhlNTs, amination of benzylic, tertiary, and ally lie C-H bond have been achieved in good yields (Scheme 31). With cyclohexene as substrate, the allylic C-H bond amination product was obtained in 75% yield, and the aziridination product was found in minor amount (17% yield) [79]. 

The fact that complex 38 does not react further - that is, it does not oxidatively add the N—H bond - is due to the comparatively low electron density present on the Ir center. However, in the presence of more electron-rich phosphines an adduct similar to 38 may be observed in situ by NMR (see Section 6.5.3 see also below), but then readily activates N—H or C—H bonds. Amine coordination to an electron-rich Ir(I) center further augments its electron density and thus its propensity to oxidative addition reactions. Not only accessible N—H bonds are therefore readily activated but also C—H bonds [32] (cf. cyclo-metallations in Equation 6.14 and Scheme 6.10 below). This latter activation is a possible side reaction and mode of catalyst deactivation in OHA reactions that follow the CMM mechanism. Phosphine-free cationic Ir(I)-amine complexes were also shown to be quite reactive towards C—H bonds [30aj. The stable Ir-ammonia complex 39, which was isolated and structurally characterized by Hartwig and coworkers (Figure 6.7) [33], is accessible either by thermally induced reductive elimination of the corresponding Ir(III)-amido-hydrido precursor or by an acid-base reaction between the 14-electron Ir(I) intermediate 53 and ammonia (see Scheme 6.9). 

A C—C bond is weaker and breaks more easily and more often than a C—H bond. Amines A and B both lose a CH, (m = 15) 59- 15 = 44. 

Suzuki-Miyaura Coupling Followed by Oxidative C-H Bond Amination or Amidation (Pd[0]/Pd[II])... 

C-H Amination. A number of amine-based starting materials will react with PhI(OAc)2 and a transition metal catalyst to promote selective C-H bond amination. Intramolecular oxidation of substrates such as carbamates, ureas, sulfamates, sulfonamides, and sulfamides affords the corresponding heterocycles in high yields and, in many cases, with excellent diastereocontrol (eqs 60 and 61). Insertion into optically active 3° C-H centers is reported to be stereospecific (eq 62). Chiral Ru, Mn, and Rh catalysts have all been utilized for asymmetric C-H amination, though product enantiomeric induction is variable. Many of the heterocyclic structures furnished from these reactions function as versatile precursors to 1,2- and 1,3-amine derivatives. 

Nitrenes are the nitrogenous isoelectronic analogs of carbenes. In the context of developing new protocols for asymmetric functionalization of C—H bonds, amination via metal nitrenoids species is direct and significantly important. In the past decade, remarkable progress has been made in this area. This section provides an overview of these developments. The reactions will be presented according to the type of the metal involved in these transformations. 

Scheme 1.35 Rh -catalyzed asymmetric C—H bond amination reactions reported by Hashimoto.

In 2006, Davies and co-workers demonstrated dirhodium tetracarboxylate, Rh2(S-TCPTAD)4 as an efficient catalyst to enable the intermolecular and intramolecular (not shown here) C—H bond amination reactions, respectively. Utilizing this catalyst, the aminated product 98 was obtained in excellent... 

In 2010, by employing asymmetric C—H bond amination reactions developed by Du Bois, Kang and Lee reported a highly efficient and enantioselee-tive synthesis of (S)-dapoxetine, which is a potent selective serotonin reuptake... 

Scheme 1.40 Rh-catalyzed intermolecular C-H bond amination reactions reported by Davies.

Scheme 1.45 Intermolecular C—H bond amination of complex molecules reported by Dauban.

In 2011, Katsuki and co-workers achieved a highly enantioselective intramolecular C—H bond amination with azide compounds as the nitrene precursors for the first time. They synthesized a series of Ir-salen complexes by a modular route. A survey of these catalysts revealed that the cyclization of 2-ethylbenzenesulfonyl azides 137 proceeded smoothly only at the ben-zylic positions in high levels of enantioselectivity. Surprisingly, when acyclic substrates having a homobenzylic methylene carbon atom such as 139 were employed, six-membered sultams 141 were produced (Scheme 1.53). It was inferred that the control of regio-, diastereo- and enantioselection largely depends on whether the substrate can adopt a conformation that permits... 

Nature has always been a source of inspiration for scientists. While most of research developments are centered on simulating nature, it would be worthwhile to challenge nature s ingenuity to mimic the synthetic reactions. To this end, catalytic C—H bond amination is an excellent platform for the development of a non-natural enzymatic reaction. Whereas enzymes are capable of inserting oxygen atoms into even inactivated C—H bonds, the sites into... 

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). 

Recently, Fasan and co-workers provided an alternative enzyme catalyst for this process. The optimal enzyme was found to be P450bm3FL 62, whieh afforded the products 143 with up to 390 TTN and 91% ee (Scheme 1.55). Meanwhile, this transformation is feasible on a preparative scale (30 mg, 42% yield). Soon after, Arnold and co-workers developed two engineered variants of P450bm3 that provide divergent regioselectivity for C—H bond amination... 

More recently, Dong s group developed a palladium-catalyzed synthesis of indoles from nitroalkenes [43]. This was the first report on transition metal-catalyzed transformation of conjugated nitroalkenes into indoles. Under mild reaction conditions (1 bar carbon monoxide, 110 °C), palladium catalyzes the reductive cyclization of nitroalkenes to form a putative nitrosoalkene intermediate, which then rearranges to provide 3-arylindoles in high yields (Table 9.5). Notably, this novel C-H bond amination takes advantage of carbon monoxide as an inexpensive stoichiometric reductant and produces carbon dioxide as the major byproduct. 

Scheme 12 Sp C-H bond amination using silver complex 8 as catalyst...

Chelate-assisted C-H bond aminations often require the presence of an oxidant in analogy to the previously discussed C-H oxygenations. Therefore, many protocols use a mixture of amine source and oxidant as reagents in order to achieve C-N bond formation. Intermolecular directed C-H aminations have been realized with this approach by Che and coworkers (Scheme 23.36). Remarkably, this methodology is capable of employing a variety of different directing groups as well as primary amides as amine sources [129]. 

Stoichiometric Aryl C-H Bond Amination Toward the goal of developing catalysts that can activate strong C-H bonds. Berry and coworkers have investigated diruthenium terminal nitrides supported by formamidinate ligands in a paddlewheel arrangement. Unlike mononuclear Ru nitrides, the RUj " "... 

Of note, thermolyzing solid samples of diruthenium azides, Ru2(p-ArNCHNAr)4(Nj) (where Ar = Ph and 3,5-Cl2(CgH3)), at 100 C also affords the C—H bond amination products [113, 115]. Differential scanning calorimetry (DSC) coupled to thermal gravimetric analysis indicated a two-step process, in which Nj is extruded in the first step. Despite the drastically different reaction... 

An effective process for generating tetrasubstituted amine derivatives is through the use of selective, intermolecular tertiary C-H bond amination using limiting amounts of 2,6-difluorophenyl sulfamate as source of nitrogen, [Rh2(esp)2] (esp = a,a,a, a -tetramethyl-l,3-benzenedipropionate) as the catalyst, PhMe2CC02H as additive and PhI(OAc)2 as the oxidant in i-PrOAc. The inclusion of both MgO and 5 A molecular sieves further improves catalyst TONs. Competition studies with substrates possessing disparate C-H bond types reveal variations in product selectivity, which derive solely from the choice of sulfamate ester. 

Iron(II) bromide catalyses the conversion of orf/to-substituted aryl azides into 2,3-disubstituted indoles via a tandem C-H bond amination [l,2]-shift reaction. The preference for the 1,2-shift is Me < 1° < 2° < Ph (Scheme 87). ... 

In 2005, Tsang et al. reported the new methodology for carbazole synthesis. The key feature of this methodology is the combination of a C—H bond functionalization and an intramolecular N-arylation (intramolecular C—H bond amination) starting from N-substituted-2-arylanilines. In the presence of a catalytic amount of... 

Optimization of the reaction condition expanded the scope of the substituent on nitrogen. Jordan-Hore et al. developed intramolecular C—H bond amination of N-alkyl-2-arylanilines 33 by using palladium(II) acetate as a catalyst and stoichiometric phenyliodosyl diacetate as an oxidant [20], Noteworthy is the fact that the reaction... 

Yamamoto and Matsubara reported the intramolecular C—H bond amination of N-unprotected 2-arylanilines 37 by using a platinum catalyst in hydrothermal water (250 °C, 4 MPa) (Scheme 23.15) [22], In this reaction system, water works as a... 

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