Nitrenes carbonyl, insertion reactions

N-benzylaniline with phosgene, and then with sodium azide to produce carbonyl azide 52. On heating, nitrogen is evolved and a separable mixture of nitrene insertion product 53 and the desired ketoindazole 54 results. The latter reaction appears to be a Curtius-type rearrangement to produce an N-isocyanate (54a), which then cyclizes. Alkylation of the enol of 54... 

The quinoline-2-one was then converted into the required 1-methyl-(o-azidophenyl)-quinoline-2-one via known synthetic manipulations. Cyclization of this intermediate to the target Cryptotackieine was performed under microwave irradiation at 180 °C for 30 min, in the presence of trimethyl phosphine. It is noteworthy that the same aza-Wittig reaction, when carried out under classical heating for 24 h, furnished inferior yields. The quinolin-2-one intermediate, when heated at 150 °C in o-xylene under conventional heating conditions, underwent a nitrene insertion at the C-4 position of the pyridinone ring. Subsequent Red-AI reduction of the carbonyl group furnished the Cryptosanguinolentine. 

Aromatic nitrenes are as selective in their insertion reactions as carbonyl nitrenes. In phenyl nitrene the insertion yields into primary, secondary and tertiary C—H bonds are in the approximate ratios 1 10 100 . Aromatic nitrenes insert into aromatic G—H bonds about as efficiently as into secondary G—H bonds of aliphatic hydrocarbons photolysis and thermolysis of 2-azidobiphenyI produces... 

The la type classification also applies to a group of reactions attributable to nitrene or related (nitrenoid) intermediates. Although not as prominent as carbonyl condensation reactions, these reactions are especially useful for carbazole synthesis. These are formally insertion reactions but mechanistic scrutiny frequently reveals that the reactions are more complicated than a one step insertion process (Scheme 29). 

A very reactive nitrogen atom is required to convert benzenes or naphthalenes into pyridines, and there are a number of such reactions which involve nitrenes or nitrenoid species. A number of substituted benzenes have been treated with sulfonyl diazide or carbonyl diazide and moderate yields of pyridines recorded (27CB1717). Thus p-xylene gives 2,5-dimethylpyridine there is no indication of the fate of the carbon atom which is lost. More controlled reaction is possible in intramolecular insertions. The examples in which o-nitrotoluene is converted into a derivative (759) of 2-acetylpyridine, and where 2,3-diazidonaphthalenes give 3-cyanoisoquinolines (760) are quoted in a review (81 AHC(28)231>. 

The synthesis of metal-coordinated 1-azirines and the reactions of azirines induced by metals have opened a new area in the chemistry of this small ring heterocycle. Many of the reactions encountered bear resemblance to previously discussed thermally and photo-chemically induced reactions of 1-azirines. The reaction of a series of diiron enneacarbonyls in benzene results in coupling and insertion to give diimine complexes and ureadiiron complexes as well as pyrroles and ketones (76CC191). A mechanism for the formation of these products which involves initial 1,3-bond cleavage and generation of a nitrene-iron carbonyl complex as an intermediate was proposed. 

Nitrene can be generated by Pd-catalyzed deoxygenation of organic nitro compounds with CO. Carbonylation of nitroenamine 226, derived from 2-nitroaniline and a-substituted aldehyde, was carried out using Pd(dba)2 and dppb. A mixture of 1,2-dihydroquinoxaline 227 and 3,4-dihydroquinoxaline 228 was obtained via sequential reactions of carbon monoxide insertion, heterocyclization, and A-alkylation followed by dealkylation [115]. 

It could be that even in this reaction the anions promote the formation of a doubly-bridged nitrene (A), which then undergoes aromatic C-H insertion or, after carbonylation, affords compound 5 (Scheme 5). (See, however, the discussion on the effect of the chloride anion on the reactivity of Ru3(CO)i2 reported in the previous section.)... 

Nitrenes, like carbenes, are immensely reactive and electrophilic, and the same Wolff-style migration (insertion into an adjacent C—C bond) takes place in which the substituent R migrates from carbon to the electron-deficient nitrogen atom of the nitrene. The product is an isocyanate. Isocyanates are unstable to hydrolysis attack by water on the carbonyl group gives a carbamlc acid, which decomposes to an amine. Alternatively, reaction with an alcohol gives a carbamate. If the alcohol is BnOH, the product is a Cbz-protected amine. 

In general high pressure and temperature are required for these reactions to occur. However there are significant examples of reactions catalysed at atmospheric pressure, in part icular for the synthesis of isocyanates (4.2.5.). In the majority of cases the most important steps of these reactions are supposed to be the deoxygenation of the nitro function by carbon monoxide iving a nitrene residue bound to the metal centre, followed by insertion of carbon monoxide into the metal-nitrene bond. This is a likely hyphotesis since nitrene complexes can be obtained by stoichiometric reactions of nitro compounds with metal carbonyls. Conversion of the imido metal complex to the observed... 

It is not clear why the ruthenium catalyst is not able to induce the heterocyclisation from the presumably intermediate nitrene complex (Scheme 6). The benzamides 32 could be formed via the insertion of an intermediate isocyanate in the aromatic C-H bond of the solvent. This reaction has some precedents, where benzanilides were obtained by reaction of PhNCO with benzene, or directly from nitrobenzene, carbon monoxide and benzene, catalysed by rhodium carbonyl clusters [56-58], However, the reluctance of Ru3(CO)i2 to catalyse the reduction of nitrobenzene to phenylisocyanate in solvents such as benzene [22, 23] does not support this hypothesis. 

The active nitrene intermediate should insert into a saturated C-H bond [8], excluding also that reaction 27 proceeds via the corresponding N-(2-aminobenzoyl)amidc. Nucleophilic nitrene complexes are known to react with the carbonyl group of aldehydes and ketones to yield the corresponding imines and a metal-oxo complex [91], However, the driving force of this reaction is the oxophilicity of early transition metals used in [91], whereas the catalyst used in this work are derivatives of the late-transition metals. Oxo derivatives of these metals in the low oxidation state are ver> rare. The mechanism followed by this reaction requires further investigation in order to be clarified. 

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