Aminations of C-H Bonds

Du Bois has extensively studied and developed the chemistry of carbamates that permit stereoselective C-H functionalization reactions via putative nitrenoid intermediates [22, 93, 101-106]. Thus, in the presence of diacetoxyiodobenzene, MgO, and 5 mol% Rli2(OAc)4, substrates such as 194 were converted into products that arise from C-H insertion (Equation 33) [102]. The amination was observed to proceed stereoselectively to give the corresponding product oxazolidinones (cf. 195) as single regio- and dia-stereomers. 

B Being at the right place at the right time, usually with my hands at least half open to latch on to the goodies that sail by on fortune s wind, has led to a fan-filled, variety-filled career in education and research.  

2 Roberts. J.D. (1990) The Right Place at the Right Time Profiles, Pathways, and Dreams Autobiographies of Eminent Chemists, ACS, Washington DC. 

13 a) Stork, G. and Gregson, M. (1969) Journal of the American Chemical Society, 91, 2373-2374 b) Stork, G. and Marx, M. (1969) Journal of the American Chemical Society, 91, 2371-2373 c) Stork, G. and Ficini, J. (1961) Journal of the American Chemical Society, 83, 4678-4678. 

16 Ponsford, R.J. and Southgate, R. (1979) Journal of the Chemical Society. Chemical Communications, 846-847. 

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The aziridination of olefins, which forms a three-membered nitrogen heterocycle, is one important nitrene transfer reaction. Aziridination shows an advantage over the more classic olefin hydroamination reaction in some syntheses because the three-membered ring that is formed can be further modified. More recently, intramolecular amidation and intermolecular amination of C-H bonds into new C-N bonds has been developed with various metal catalysts. When compared with conventional substitution or nucleophilic addition routes, the direct formation of C-N bonds from C-H bonds reduces the number of synthetic steps and improves overall efficiency.2 After early work on iron, manganese, and copper,6 Muller, Dauban, Dodd, Du Bois, and others developed different dirhodium carboxylate catalyst systems that catalyze C-N bond formation starting from nitrene precursors,7 while Che studied a ruthenium porphyrin catalyst system extensively.8 The rhodium and ruthenium systems are... 

Zhang and coworkers reported recently that (porphyrin)cobalt(II) complexes are suitable for intramolecular amination of C-H bonds. Initially, ort/io-substituted arylsulfonyl azides 333a were subjected to 2 mol% of Co(TPP) 326a. Benzosultams 334a were formed in 87-99% yield (Fig. 80) [370]. When substrates... 

The transition metal-catalysed amination of C-H bonds via reactive metal-imide intermediates (i.e., nitrenoids) remains a powerful taetie for C-N bond formation. In that context, the intramolecular C(ip )-H amination of biaryl azides as nitrenoid sources has been computationally explored regarding the nature of the transition metal that plays the catalytic role. Four common transition metals (Ir, Rh, Ru and Zn) have thus been considered, and while the calculations have revealed similar energy profiles regardless of the nature of the metal, catalytically active Ru speeies have nevertheless been shown to be the more efficient from a kinetic viewpoint. 

Roizen JL, Zalatan DN, Du Bois J. Selective intermolecular amination of C-H bonds at tertiary carbon centers. Angew Chem Int Ed. 2013 52 11343-11346. 

The reaction between the photoexcited carbonyl compound and an amine occurs with substantially greater facility than that with most other hydrogen donors. The rate constants for triplet quenching by amines show little dependence on the amine a-C-H bond strength. However, the ability of the amine to release an electron is important.- - This is in keeping with a mechanism of radical generation which involves initial electron (or charge) transfer from the amine to the photoexcited carbonyl compound. Loss of a proton from the resultant complex (exciplex) results in an a-aminoalkyl radical which initiates polymerization. The... 

Some 2-alkoxytetrahydropyrans show a reactivity toward oxidants which parallels the reactivity of polycyclic amines discussed above, and which is in line with the hypothesis that weakening of C-H bonds by hyperconjugation should also increase the rate of C-H bond cleavage. For instance, of the two epimeric pyrans sketched in Scheme 2.15 only that with an axial 2-H is oxidized by ozone [51]. The same selectivity has been observed in the oxidation of methyl a- and /3-glucopyranoside with ozone [52], and in homolytic C-H bond cleavage in cyclic ethers [53],... 

The chemoselectivity of the dioxirane oxyfunctionalization usually follows the reactivity sequence heteroatom (lone-pair electrons) oxidation > JT-bond epoxida-tion > C-H insertion, as expected of an electrophilic oxidant. Because of this chemoselectivity order, heteroatoms in a substrate will be selectively oxidized in the presence of C-H bonds and even C-C double bonds. In allylic alcohols, however, C-H oxidation of the allylic C-H bond to a,/ -unsaturated ketones may compete efficaciously with epoxidation, especially when steric factors hinder the dioxirane attack on the Jt bond. To circumvent the preferred heteroatom oxidation and thereby alter the chemoselectivity order in favor of the C-H insertion, tedious protection methodology must be used. For example, amines may be protected in the form of amides [46], ammonium salts [50], or BF3 complexes [51] however, much work must still be expended on the development of effective procedures which avoid the oxidation of heteroatoms and C-C multiple bonds. 

The best evidence for a CT process rather than direct hydrogen abstraction involves the values of kT s-butyl- and ferf-butylamine display much the same value 156> triethylamine and ferf-butyldimethylamine are equally reactive and some 50 times more so than primary amines 155>. Thus the rate constant for reaction is independent not only of the type of C—H bond a to the nitrogen but also of the presence or absence of a-hydrogens. Such evidence demands that abstraction of an a-hydrogen not be involved in the rate-determining quenching reaction. Moreover, the relative reactivity of amines (tertiary > secondary > primary) is proportional to the ease with which they are oxidized. 

This new disilver system was found to be more active in intramolecular amidation reactivity compared to the original [Ag2(t-Bu3tpy)2] catalyst, showing both increased yields and decreased temperature (from 82 to 50°C). More importantly, this system was able to catalyze the intermolecular amination reaction of both benzylic and inert aliphatic C—Hbonds.Asimilar copper system reported similar activity however, it was only able to aminate benzylic C—H bonds (Table I). In the silver case, it was found that substitutions on the 2 and 9 positions of the phenanthroline shut down the reactivity of the catalyst, suggesting the importance of keeping a disilver core structure. 

Oxidative Coupling of C-H Bonds Adjacent to the Nitrogen in Amines. 283... 

To date, some of the more interesting examples of N-atom transfer from Fe-based complexes involve the oxidative modification of C-H bonds that comprise the ligand framework (Fig. 14). Que and coworkers have shown that a tris-pyridyl Fe(II) complex will react in the presence of PhI=NTs to oxidize an arene C-H bond that is positioned proximally to the metal center [73]. Such sp2 amination... 

Compared with the tertiary amine system, there are few examples of oxidative activation of C—H bonds adjacent to an oxygen atom. DDQ was an effective oxidant for the oxidative activation of a-C—H bonds of ethers (Equation 11.7) [17]. 

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. 

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