Mechanistic nitrene formation

Several lines of inquiry have been explored to address key mechanistic issues in the rhodium-catalyzed C-H insertion of carbamates and sulfamates (Scheme 17.32) [99]. A pathway involving initial condensation between substrate 96 and PhI(OAc)2 to form iminoiodinane 97 was envisioned in the original design of this chemistry. Coordination of 97 to an axial site on the rhodium dimer would promote nitrene formation and the ensuing C-H insertion event Surprisingly, control experiments with PhI(OAc)2 and sulfamate 96 (or analogous carbamates) give no indication for a reaction between these two components. 

The hydrogenation of nitroacetophenones has been studied and considerable kinetic and mechanistic information obtained. Differences in reaction rate, bonding and selectivity have been observed. The formation of 1-indolinone from 2-NAP was unexpected and revealed the presence of a surface nitrene. This intermediate has not been postulated in nitroaromatic hydrogenation previously. Hydrogenation in the presence of deuterium revealed, as well as a kinetic isotope effect, that it is likely that... 

Nitrenium ions (or imidonium ions in the contemporaneous nomenclature) were described in a 1964 review of nitrene chemistry by Abramovitch and Davis. A later review by Lansbury in 1970 focused primarily on vinylidine nitrenium ions. Gassmann s ° 1970 review was particularly influential in that it described the application of detailed mechanistic methods to the question of the formation of nitrenium ions as discrete intermediates. McClelland" reviewed kinetic and lifetime properties of nitrenium ions, with a particular emphasis on those studied by laser flash photolysis (LFP). The role of singlet and triplet states in the reactions of nitrenium ions was reviewed in 1999. Photochemical routes to nitrenium ions were discussed in a 2000 review. Finally, a noteworthy review of arylnitrenium ion chemistry by Novak and Rajagopal " has recently appeared. 

Syntheses and photochemical behaviour of some azido-steroids have been described. Thermolytic and acid-catalysed reactions have also been studied and compared. Photolysis and thermolysis of azido-steroids led to alkyl migration products, endocyclic imines, and 1-2 hydrogen-transfer compounds, exocyclic imines giving ketones by hydrolysis. Pyrrolidine formation through a nitrene intermediate occurred only in the case of 6/3-azidopregnene. Mechanistic implications were fully discussed. 

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. ... 

While the majority of Rh-catalyzed C-H amination processes employ hyperva-lent iodine oxidants and sulfonamide derivatives, Lebel and coworkers have demonstrated that /V-tosyloxycarbamates will engage with catalytic Rh2(02CCPh3)4 and K2CC>3 to afford products of intramolecular C-H insertion (Fig. 22) [104, 5, 105]. Similar to Du Bois earlier work involving oxidative cyclization with 1 ° carbamates [94], the /V-tosyloxy derivatives display a strong bias for oxazolidinone formation. Selectivity trends and other mechanistic data support a reaction pathway involving a Rh-nitrene oxidant. Intermolecular amination of simple benzylic substrates... 

Dilution of toluene with the inert solvent methylene chloride was attempted in an effort to extend the singlet nitrene lifetime and enhance the yield of triplet nitrene [104]. Dilution, however, did not change the ratio of aryl C-H to benzyl C-H insertion products formed, instead the yield of all volatile products decreased at the expense of tar formation. Dilution with CH2C12 did not increase the yield of triplet nitrene derived products such as C6F5NH2 and decafluoroazobenzene, thus the yield of triplet phenyl nitrene is negligible (Table 7) in methylene chloride. The results can be understood with the aid of Scheme 10, which is identical to the mechanistic hypotheses written for parent phenyl azide (Scheme 7). 

Solid State Reactions.—There are three reports of kinetic and mechanistic studies on substitution in the solid state which may have some interest or relevance to cobalt(m) complex substitution mechanisms in solution. [Co(NH3)6](N3)3 decomposes to give cobalt nitride. The initial step, as in several solution mechanisms cited above, seems to be azide to cobalt electron transfer there is no evidence for nitrene intermediates. Decomposition of [Co(NH3)e]Cl3, which gives cobalt(ii) amongst the products, does not proceed via formation of [CoCl(NH3)5]Cl2, but for some nitrites, e.g. cis- and /ra j-[Coen2(NH3)2](N02)3, nitrite does enter the first co-ordination sphere of the cobalt in the course of reaction. Lastly, the mechanism of thermal and of photochemical decomposition of [Co(NH3)s(OH2)]X3 is said to be similar to the mechanism of reaction in solution, despite the ultimate formation of tetrahedral cobalt(ii) complexes in the solid state reactions. ... 

Tetrazoles tautomeric with azides and their (selective) photochemistry in matrix are a favorite topic of mechanistic investigation (see the chapter by Fausto in Vol. 39 of this series)." Recent reports concern tetrazolyl-1,2.4-triazoles, and a tetrazolylethanol." On the other hand, preliminary data about the photochemistry of the 2-azido analogue of 2 -deoxyuridine (that exists as the tetrazole tautomer) have been reported, showing the formation of the corresponding amine." Non nitrene paths can also be followed, as in the case of some phenyltetrazolethione that cleave forming an open-chain diradical that in turn loses a sulfur atom (Scheme 15). ... 

The results of the mechanistic study on the [Rh(CO)4] catalysed reactions are summarised in Scheme 18. The scheme includes the reduction of azoxybenzene to azobenzene, which has been independently shown to occur easily in the absence of nitrobenzene [190], The formation of azoxybenzene is explained by the trapping of free nitrosobenzene by the intermediate nitrene complex. Since nitrosobenzene may also react with [Rh(CO)4] and reenter the... 

The mechanisms and enantioselectivities of the Rh2L4 (L = formate, Al-methyl form-amide, S-nap)-catalysed intramolecular C-H aminations of 3-phenylpropylsulfamate ester have been studied with BPW91 DFT computations. The Rh2(II,II)-catalysed reactions start with the oxidation of the Rh2(n,n) dimer to a triplet mixed-valent Rh2(II,ni)-nitrene radical, which facilitates radical H-atom abstraction. However, a direct C-H bond insertion is postulated for the Rh2(HCOO)4-catalysed reaction. The Rh2(Al-methylformamide)4-catalysed reaction is a two-step process and so is the mechanism of the Rh2(5-nap)4 (41)-catalysed reaction of 3-phenylpropylsulfamate ester. The mechanistic proposal is supported by the calculated 94.2% ee which is in good agreement with the observed 92% ee ... 

The mechanistic dichotomy for conversion of ACC to ethylene seems clear from the large body of work presented above. Formation of N-heteroatom derivatives leads to the nitrene or nitrenium ion and results in a concerted mechanism, while electron transfer/free radical oxidants lead to a radical cation and result in a non concerted mechanism. Despite the significant evidence in favor of the radical pathway, reference to N-hydroxylation and nitrenium ion formation as a key step in ethylene biosynthesis has persisted, particularly in the plant physiology literature (2, 43-46). The sequence similarity of the EFE and several hydroxylase enzymes (vide supra) has only added fuel to this fire. However, consideration of the mechanisms for known hydroxylation processes makes the intermediacy of N-hydroxy-ACC very unlikely. 

The mechanistic nature of these nitrene insertion reactions remains unknown. A number of possible routes can be considered (Fig. 302), including (1) direct insertion, (2) initial formation of a metal-nitrene (imido) complex followed by insertion, (3) initial addition of nitrene fragment to sulfur (i.e., oxidation of sulfur) followed by an isomeric rearrangement. On the basis that copper(II) nitrene complexes are unknown (although they have been implicated in the copper-catalyzed aziridination process) this route is ruled out and literature precedent suggests that route (3) is most likely. 

From these studies, a general mechanistic scheme for the P4 N2-C3 interchange pathway is emerging. As shown in Scheme 15, photocleavage of the N1-N2 bond in 28 is suggested to result in the formation of a species I-l that was described as either a biradical or as a P-iminovinyl nitrene. The isomerization of terminal vinyl nitrenes to nitriles is a well-documented reaction. Accordingly, nitrene I-l would be... 

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