C-H bond insertion

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]. 

Under drastic thermal conditions, the iminosilane-LiF adduct 82 eliminates LiF and the iminosilane intermediate 83 rearranges intramolecularly by C-H bond insertion affording 2,2,4,4-tetra-/i /Z-butyl-l,3-diaza-2,4-disilabicy-clo[3.3.0]octane 84 in 87% yield (Equation 6) <1996JOM203>. 

The intramolecular addition of acylcarbene complexes to alkynes is a general method for the generation of electrophilic vinylcarbene complexes. These reactive intermediates can undergo inter- or intramolecular cyclopropanation reactions [1066 -1068], C-H bond insertions [1061,1068-1070], sulfonium and oxonium ylide formation [1071], carbonyl ylide formation [1067,1069,1071], carbene dimerization [1066], and other reactions characteristic of electrophilic carbene complexes. 

The formation of six-membered or larger rings by intramolecular C-H bond insertion normally requires the attacked position to be especially activated towards electrophilic attack [1157,1158]. Electron-rich arenes or heteroarenes [1159-1162] and donor-substituted methylene groups can react intramolecularly with electrophilic carbene complexes to yield six- or seven-membered rings. Representative examples are given in Table 4.8. 

Electrophilic carbene complexes can react with amines, alcohols or thiols to yield the products of a formal X-H bond insertion (X N, O, S). Unlike the insertion of carbene complexes into aliphatic C-H bonds, insertion into X-H bonds can proceed via intermediate formation of ylides (Figure 4.7). 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

Allylammonium ylides can undergo 2,3-sigmatropic rearrangement [1234]. With weakly nucleophilic amines, C-H bond insertion or hydride abstraction can compete efficiently with ammonium ylide formation. 

Intramolecular C-H bond insertion and ylide formation can compete with cyclopropanation. As shown in Figure 4.21, however, the chemoselectivity of the intermediate carbene complex can sometimes be controlled by the remaining metal-bound ligands [21,990,1075,1081,1223]. 

The presence of other hexane isomers and a typical hexane isomer distribution of 26% 2,3-dimethylbutane, 28% 2-methylpentane, 14% 3-methylpentane, 32% n-hexane, far from equilibrium, indicate that the 1-propyl cation (although significantly delocalized with protonated cyclopropane nature) is also involved in alkylation. It yields n-hexane and 2-methylpentane through primary or secondary C—H bond insertion, respectively (Scheme 5.3). 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

Deprotonation of the alkyne group of propargyl halides or sulfonates can also lead to elimination and formation of a vinylidene. Interestingly, these derivatives react with alcoholates, not yielding enol ethers via O-alkylation but undergoing C-H bond insertion instead (Scheme 5.52). 

Examples of carbene insertions into the carbon-silicon bond of SCBs have been known since 1967, when Seyferth studied the behavior of SCBs exposed to dichlorocarbene, which was generated by thermolytic activation of phenyl(bromodichloromethyl)mercury <1967JA1538>. The reaction produces a mixture of products arising from Si-C and C-H bond insertions, with the major products being the ring-expanded silacyclopentanes that result from Si-C bond insertions (Scheme 30). 

It was mentioned in Section 2.11.6.3.1 that the reaction of siletanes with thermolytically generated carbenes produces mixtures of products arising from competing Si-C and C-H bond insertions (Scheme 56) <1967JA1538,1971JA3709>. 

Stabilized carbenes derived from carbethoxy diazosulfones undergo selective C-H bond insertion to afford tetrahydrothiopyran 1,1-dioxides in moderate yield upon treatment with rhodium acetate <20070L61>. 

When an oxidative coupling or addition takes place in the presence of carbon monoxide, CO insertion occurs leading to ketones. The Ru3(CO)12-catalyzed reaction of alkenylpyridyl or Af-(2-pyridyl)enamines and ethene performed under an atmosphere of carbon monoxide leads to the selective formation of a,/3-unsaturated ketones [16] (Eq. 11). After activation of the vinyl C-H bond, insertion of both carbon monoxide and ethylene takes place to give 25. 

Diene-iron tricarbonyl complexes undergo C—H bond insertion reac-... 

Figure 3 Thermal generation of a germylene followed by intramolecular C-H bond insertion...

With tetramethylsilane the only organic reaction product was the trimethylsilyl methyl mercaptan, (CHj)3SiCH2SH, as expected for a C—H bond insertion. Further evidence that the product arose from S( Z)) insertion was provided by the suppressing effect of CO2 on the reaction. A novel feature of this reaction is the large damping effect of (CH3)4Si on the CO rate, as shown by the product rate vs. substrate pressure plot in Figure 12. From simple stoichiometry the following relation should obtain for paraffinic insertion processes ... 

Carbene reactions are of virtually no synthetic importance for silicon-containing heterocycles, mostly because of the poor selectivity of the carbene insertion processes involved. Thus cyclization of carbene 475 may be effected via Caikyi Si, Caryi" Si and C—H bond insertions as well as via... 

Some ortho-substituted aromatic sulfonyl azides, like o-toluenesulfonyl azide (93), on thermolysis are converted into the corresponding sultams (94) (Scheme 60). The reaction probably involves intramolecular C—H bond insertion by the reactive o-toluenesulfonyl nitrene intermediate. The azide (N3- group also functions as a pseudohalide consequently,... 

Dihydrofurans. Alkylidenecarbene formation from a-alkoxyketones is followed by C-H bond insertion. 2,8-Dioxabicyclo[3.2.1]oct-6-enes can be made this way, although such compounds are unstable. 

Note that 2-dimethoxyphosphoryl-l,l-dimethylcyclopropane (3) can also be obtained by intramolecular C-H bond insertion of the carbene resulting from (/ert-butyl)(dimethoxyphos-phoryl)diazomethane. Compound 3 was obtained in 9% yield by the copper-catalyzed decomposition method, and in 21% using photolysis, while by [2-fl] cycloaddition, the yield was only 14%. - ... 

In contrast, reaction of the dichlorocarbene adduct to 9-mcthoxyphenanthrene with potassium tert-butoxide did not lead to the cycloproparene, but proceeded by dehydrochlorination to 1 -chloro-9-methoxy-laf/-cyclopropa[/]phenanthrene (16) as a reactive intermediate. This then rearranged to a vinylcarbene which, in turn, underwent intramolecular C —H bond insertion and aromatization to phenanthro[9,10-h]furan (17). ... 

The reaction of methane with the nitrosonium ion was investigated by Schreiner et al. at various levels of theory. They found that NO attacks preferentially on carbon instead of C-H bond insertion. A subsequent study for the reaction of ethane with NO again resulted in indication of direct attack on carbon rather than C-H or C-C bonds. ... 

Ab initio molecular orbital theory has been applied by Olah and coworkers to investigate the reactions of NO and the protonitrosonium ion HNO with methane. The reaction path was found to involve attack of NO on carbon instead of C-H bond insertion in accord with the studies of Schreiner et al. It was, however, pointed out that this is the consequence of the ambident electrophilic nature of NO and does not represent a general electrophilic reaction pathway for the reactions of methane. In fact, Schreiner and coworkers suggested that the electrophilic substitution of methane occurs by substitution of the nonbonded electron pair of methane instead of insertion of the electrophile into a C-H bond via 3c-2e bonding. Nonbonded electron pair formation in methane, however, can be considered only when methane would tend to flatten out (58) from its tetrahedral form, but this would be prohibitively energetic (>100 kcal mol ) and thus unlikely. 

Many organomagnesium derivatives (e.g., RMgX) undergo alkyl group exchange when treated with reactive alkanes through C-H bond insertion. Cyclopentadiene, indene, fluorene, and their derivatives are readily metallated in the absence of a diethyl ether solvenf [Eq. (6.99)] ... 

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