Nitrenes with alkanes

Photolysis of azidophosphodiesters 22 releases a nitrene that also inserts efficiently into the CH bonds of alkanes. When R H = 2,3-dimethylbutane is employed the yield of CH insertion adducts is almost 60%, with the remainder the amide 24. ... 

Assuming that singlet nitrene reacts with alkanes at near diffusion controlled rates allowed deduction of a rate constant of singlet-to-triplet nitrene intersystem crossing (ISC) of 2-8 X 10 s . This ISC rate is slower than in carbenes, but significantly faster than with arylnitrenes, which are discussed in a subsequent section. 

More importantly, this silver system catalyzes the intermolecular amination of hydrocarbons, as shown in Table 6.3. In addition to animating weaker benzylic C-H bonds, stronger aliphatic C-H bonds such as those in cyclohexane were also reactive. Although yields with more inert hydrocarbons were modest with the bathophenan-throline system, the discovery of the first silver-catalyzed intermolecular amination opens opportunities for further developments. This reaction favored tertiary cyclic sp3 C-H bonds over secondary cyclic sp3 C-H bonds, and showed limited success with simple linear alkanes. No conversion was observed with any aromatic C-H bonds. The compound NsNH2 was tested as the nitrene precursor with different oxidants. The use of PhI(OAc)2 as oxidant gave the expected amination product with a lower yield, while persulfate and peroxides showed no reactivity. 

Accordingly, cycloaddition reactions can be carried out in solvents such as alkanes, cycloalkanes and acetonitrile. The insertion reaction into the O-H-bond of alcohols is, in every case, faster than the cycloaddition reaction. Furthermore, 100% production of isocyanate was observed upon irradiation of benzoyl azide in dichloromethane solution, however, nitrenes that can be trapped by compounds with double bonds are also formed in this solvent [21]. 

The nitrogen source for the aziridination of alkenes, a nitrene or nitrenoid, can be generated in various ways (1) oxidation of a primary amine (2) base-induced -elimination of HX from an amine or amide with an electronegative atom X (X = halogen, O) attached to the NH group or by -elimination of metal halides from metal A-arenesulfonyl-A-haloamides (3) metal-catalyzed reaction of [A-(alkane/arenesulfonyl)imino]aryliodanes (4) thermolytic or photolytic decomposition of organyl azides and (5) thermally induced cycloreversion reactions . 

In the carbene insertions to alkane C-H bonds the same concept as for the olefin cyclopropanations is applied. In that work, the gold-catalyzed carbene transfer is now used for insertions into C-H bonds (equation 150), with a selectivity that is influenced by the electronic properties of the ligand and the counterion employed. The carbene and nitrene insertion is not limited to Csp H bonds, but N H (equation 151), O H (equation 152), and aryl Csp -H bonds react as well (equation 153). ... 

As shown in Scheme 17, C—H bonds are also prone to be activated by formal nitrene transfer from a metal center in a catalytic manner. Tp ML complexes have also induced this transformation, with both sp and sp C—H bonds. The first results were obtained employing Tp Cu(NCMe) as the catalyst for the functionalization of the C—H bonds of the alkyl substituents of arene substrates (Scheme 22). In addition to the benzylic sites, that can be considered as activated by the arene ring, the C—H bonds at the P-carbon in substrates such as ethylbenzene or cumene were also functionalized to a certain extent. The use of the silver-based Tp Ag catalyst afforded the functionalization of unactivated alkanes such as hexane or 2,3-dimethylbutane among others. These systems lack selectivity, a mixture of products derived from the insertion of the nitrene group into all available sites being obtained. It is worth noting that nitrene sources such as Phi = NTs, chloramine-T... 

Insertion of singlet nitrene 21 into the C-H bond of alkanes and into the 0-H bond of alcohols, addition of 21 to acetylenes, and reaction of 21 with benzene, followed by azepine formation, are all well docnmented. 

In the presence of a chiral catalyst such as rhodium(II) (5)-/V l,8-naphthanoyl-tert-leucinate dimer, Troc-amino indane was produced with 56% yield and 2.57 1 enantiomeric ratio. In contrast to other methods, no hypervalent iodine reagent (typically used stoichiometrically or in excess and forming iodobenzene as by-product) is required for oxidation of the amine component. However, a slight excess of the aromatic alkane component (5 equiv) must be used to achieve good conversions. The reactivity of rhodium nitrenes generated from 2,2,2-trichloroethyl-/V-tosyloxycarbamate with aliphatic alkanes is similar to the one observed with metal nitrenes obtained from the oxidation of sulfamate with hypervalent iodine reagent. Troc-protected amino cyclohexane and cyclooctane were obtained, respectively, in 73 and 62% yields when 2 equiv of alkanes was used, whereas yields up to 85% were observed with 5 equiv (eq 3). 

A review on the CH insertion reactions of carbenes and nitrenes with alkanes has appeared developing the current state of the art of this valuable synthetic method. ... 

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