C H amination reactions

Shortly after the discovery by He and coworkers, Diaz-Requejo and Perez et al. reported an intriguing silver-pyrazolylborate system that catalyzes the amination of aliphatic hydrocarbons.26 Earlier, they had developed a similar copper-pyrazolylbo-rate system that could also catalyze the C-H amination reaction. However, a different ligand was required with the silver catalyst system. 

Fig. 79 Cobalt porphyrin-catalyzed intermolecular C-H amination reactions...

Metal nitrene complexes were used in a number of C-H amination reactions (recent reviews [358, 359]). Copper ketiminate complexes react with azides to nitrene complexes, which were isolated [360]. (p-Ketiminate)copper(I) complex 262 (2.5 mol%) serves therefore as an efficient catalyst for the intermolecular C-H amination of alkylarenes, cycloalkanes, or benzaldehydes 260 using adamantyl azide 261 as the nitrogen source ig. 68) [361]. The corresponding adamantyl amines or amides 263 were isolated in 80-93% yield. Copper complex 262 forms initially a dinuclear bridged complex with 261. From this a copper nitrene complex is generated by elimination of nitrogen, which mediates the hydrogen abstraction from 260. 

A recent DFT study has shown that retention of configuration observed for the above reactions is in agreement with the insertion of singlet nitrene and a concerted product formation [150 is the transition state for the reaction shown in Equation (6.135)]. Du Bois and coworkers have performed detailed mechanistic investigations of the intramolecular sulfamate ester C-H amination reaction catalyzed by a dirhodium complex. Reactivity patterns, Hammett analysis, and kinetic isotope effect studies have provided support for the concerted, asynchronous transition structure 151. A similar conclusion was arrived at for an analogous intermolecular process. ... 

Recently, efficient rhodium-catalyzed intermolecular C—H amination reactions have been reported where a sulfonimidamide is used as the nitrene precursor [46]. The functionalizations of various C—H bonds proceed smoothly in this type of intermolecular amidation reaction (Equation 11.20) [47]. When chiral sulfonimida-mides are used, moderate to excellent diastereoselectivities can be achieved. 

Another intramolecular synthesis of carbazoles 270 employed amino biaryls 269 as the starting materials with 2-picolinic acid as a directing group to facilitate a net C—H amination reaction under copper catalysis in the presence of Mn02 and acetic acid. The directing group is removed spontaneously after the initial amination (140L2892). 

The isoelectronic [Ru -Ru ] complexes are relatively more accessible, and such complexes are proving to be useful for a range of chemical reactions. This article collects the chemistry at sites trans to the [Ru-Ru] single bond. The C-H activation, C-C bond formation, acceptorless alcohol dehydrogenation, cyclo-propanation, carbenoid C-H insertion, and C-H amination reactions are covered. Reactivity studies at axial sites on [Ru-Ru] multiply bonded systems are also included because of their direct relevance in catalytic chemistry. The purpose of this article is to highlight the recent progress on the axial-site chemistry on [Ru -Ru ] platforms with intent to infuse interests for further development. 

DESI Detecting intermediates (catalytic C-H amination reaction cycle) Perry eta/. [351]... 

In comparison, intermolecular reaction met high challenges due to both enthalpy and entropy reasons. In 2007, He and coworkers developed a disilver-based new catalyst 11 which showed high efficiency for intramolecular C-H amination reaction (Scheme 10) [32]. Such an intermolecular C-H amination/amidation ran at mild condition. The new catalyst set has successfully been applied to intermolecular amination reaction for the first time (Scheme 11). In the reaction, the catalyst was added in two portions in order to increase the yield. Under typical reaction condition, AgOTf (2 mol%) and ligand (2.4 mol%) were mixed in DCM in a tube for 20 min. Then the substrate (5.0 or 10.0 eqmv.), PhI=NNs (1.0 equiv.) and 4 A molecular sieves (2 g/mmol) were added under N2 atmosphere. The tube was sealed and heated to 50°C for 2 h before another AgOTf (2 mol%) and ligand (2.4 mol%) mixed in DCM were added. The reaction was carried out at 50°C... 

The chemoselectivity of the reaction favors insertion in the most electron-rich C—H bond available to produce an oxazolidinone (Eqs. (5.6) and (5.7)) [33, 49, 50). When a bicyclic system is formed, the C—H amination reaction leans toward the formation of the cis-isomer. The scope of the reaction is large and many examples of carbamates derived from primary and tertiary alcohols are known. The use of carbamates derived from secondary alcohols is, however, more limited to substrates having conformational bias and/or very reactive C—H bonds (benzylic and allyl-ic) [51, 52]. Otherwise the formation of the corresponding ketone is observed, probably via a hydride shift process, similar to what is observed in C—H bond insertion with metal carbene [53, 54). 

C—H amination reactions via oxidation with a hypervalent iodine reagent are also possible with sulfamates [44]. The formation of the 5-membered sulfamidate is only observed if no alternative cydization pathway is available (Eq. (5.10)). 

The development of in situ procedures to prepare iminoiodinanes from amine precursors and hypervalent iodine reagents has had a significant impact on the progress made towards C—H amination reactions. However, there are some drawbacks associated with the use of hypervalent iodine reagents, in particular, their cost... 

Trichloroethyl-N-tosyloxycarbamate has been designed by Lebel and Huard specifically to achieve intermolecular C—H amination reactions and leads to Troc-protected amines which are easy to cleave [76], The C—H amination of cyclic alkanes proceeds in good yields with 2 equiv of hydrocarbon substrate and 1 equiv of the amination reagent in the presence of 6 mol% of Rh2(tpa)4 (Eq. (5.25)). However, 5 equiv of alkane are usually required to achieve good yields with other substrates, such as aromatic compounds (Eq. (5.26)). In this case, the reaction is run without solvent. 

A few mechanistic studies have been performed by Lebel and Huard to establish the catalytic cycle of this C—H amination reactions [77]. It has been shown that the deprotonation of the N-tosyloxycarbamate does not occur in the absence of the transition metal complex. Furthermore, the nature of the leaving group does not affect the amination pathway. For instance, the regioselectivity (tertiary vs. secondary C—H bonds) for the amination of adamantane is conserved, independent of the nature of the sulfonyloxy group (Eq. (5.27)). 

In conclusion, the recent developments towards more practical reagents and catalysts to perform C—H amination reactions have provided a variety of new synthetic tools to prepare various nitrogen derivatives. Furthermore, a number of stereoselective methods have been recently disclosed. All this progress should promote the use of C—H amination reactions in total synthesis of natural products and biologically active compounds. 

In addition to the aziridination, this reagent also performs unprecedented C-H amination reactions of aliphatic hydrocarbons. Although the reaction requires large excess of the alkanes, the mild reaction conditions and high yields are impressive [42]. 

A strategy directed at exploiting another bimetallic framework with tethered carboxylate groups led to the isolation of an unusual dirhodium(ll) tetracarboxylate catalyst with calbc[4]arene (CLX), which was synthesized (Scheme 9.17) and used in C-H amination reactions [143] the structures of... 

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