Nitrenes dienes

N-Aminobenzoxazolin-2-one (4), which was readily prepared by animation of benzoxazolin-2-one with hydroxylamine-O-sulfonic acid, is also a useful nitrene precursor (Scheme 2.2). Oxidation of 4 with lead(iv) acetate in the presence of a conjugated diene resulted in exclusive 1,2-addition of nitrene 5, to yield vinylazir-idine (6) in 71 % yield [6]. The formation of vinylaziridines through 1,2-additions of methoxycarbonylnitrene (2) or amino nitrene 5 contrasts with the claimed 1,4-ad-dition of nitrene itself to butadiene [7]. Since the reaction proceeded stereospecif-ically even at high dilution, the nitrene 5 appears to be generated in a resonance-stabilized singlet state, which is probably the ground state [8]. 

The dimerization appears to be a characteristic of triplet nitrenes, since it occurs on sensitization by such compounds as benzophe-none. When 2-azidobiphenyl is irradiated in Ihe presence of a triplet quencher (penta-I,3-diene to inhibit the formation o( an azocompound, the main product iscarbazole (5.36), which is formed by internal insertion into an aromatic C—H bond. Other nitrenes may also participate in intramolecular insertion, and this allows lactams to be formed from acyl azides (5.37). 

This nitrene-addition approach was used by Knight to synthesize vinyl aziridines from 1,3-dienes using PhI=NTs and a copper catalyst. The more electron-rich double bond is selectively transformed in most cases. When the electronic difference is negligible the regioselectivity is then determined by steric hindrance. A mixture of cis and tram isomers is usually obtained [95SL949],... 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

Benzofurazans show greater thermal stability but may be cleaved photochemically. Irradiation of benzofurazan in benzene and in methanol gives the azepine (26) and the urethane (27), respectively in the presence of triethyl phosphite (Z,Z)-l,4-dicyanobuta-1,3-diene is formed. The proposed mechanism (Scheme 3) involves nitrile oxide, oxazirene, acyl nitrene and isocyanate intermediates, and is supported by spectrophotometric studies (76HCA2727) and by trapping of the nitrile oxide as its isoxazole cycloadduct with DMAD (75JOC2880). 

With 1,3-dienes only 1,2-addition by nitrenes is observed. In the reaction of carbethoxynitrene with isoprene 43 in contrast to the singlet nitrene which does not discriminate between the disubstituted and the monosubstituted double bonds, the triplet nitrene prefers the methyl substituted double bond by a factor of 2 87). 

Symmetry Allowed Cycloaddition of SO to a diene Cheletropic Reactions involving 4 Electrons Addition of Carbenes or Nitrenes Reactions involving 6n Electrons Cycloaddition and Elimination Reactions involving 8ji Electroncs... 

In 2001, Rai and co-workers (114) reported a silver-mediated aziridination of olefins in THF with Chloramine-T. In their case, aprotic solvents gave better yields versus protic solvents. Then, in 2003, Komatsu and co-workers (115) used similar conditions and found no reaction in THF (solvent) while they detected 70% conversion in CH2CI2. Silver nitrate (AgNOs) was required stoichiometrically in this transformation. Komatsu proposed a nitrene-radical mechanism based on the fact that the reaction shut down in the presence of oxygen. They designed a model reaction using 1,6-dienes, and as they expected, bicyclic pyrrolidines were isolated as products instead of aziridines. The role of silver in this reaction is not clear and most likely a free nitrene radical is released with the precipitation of silver(I) chloride (Fig. 18). 

An important synthetic route to aziridines is the decomposition of organic azides to the correspondic nitrenes by loss of nitrogen. However, depending on the nature of both, the azide and the alkene and on the experimental conditions, the 1,3-cycloaddition of the azide group to the alkene double bond may occur to give a dihydro triazole, which can be converted in situ or after isolation to the aziridine. Furthermore, /3-functionalized amines are obtained from certain dihydro triazoles, or directly by reaction of azides with certain alkenes, and dihydropyrroles are obtained by reaction of azides with dienes, hence these topics will be treated separately (Section 7.2.9). 

The reaction of azides with 1,3-dienes affords vinyl aziridines (through nitrene or azide cycloaddition), which can be converted to dihydropyrroles. It is also possible that dihydropyrroles are directly produced from azidodienes. 

The addition of ethoxycarbonyl nitrene, generated by photolysis of ethoxycarbonyl azide or by a-elimination of 4-methylphenylsulfonyl carbamate, to conjugated dienes gave aziridines by 1,2-addition and dihydrooxazoles by rearrangement of the aziridines, generally with low overall yield18. 

The intramolecular reaction of alkyl nitrenes with a 1,3-diene is unsuitable for the preparation of fused bicyclic dihydropyrroles142. However, the intramolecular 1,3-dipolar cycloaddition reactions of the same substrates to give vinylaziridines, followed by rearrangement, can be utilized to achieve the desired target. 

Activated copper powder or copper(II) acetylacetonate were effective catalysts in the pyrolytic cyclization of 2-azido-3-(2,4-pentadienyl)-l,4-quinones to benzopyrolizines 17 by the presumed intermediacy of a copper(II)-nitrene species which adds to the diene by a radical pathway. Although the yields were generally low, complete regioselectivity and diastereoselectivity (simple and substrate induced) were observed152. 

The formation of type II aziridines can also be carried out via the formation of two bonds simultaneously. One of the most common is the formation of two C-N bonds (bonds c and e ) to generate the aziridine ring. This quite often takes the form of a nitrene or nitrene equivalent adding to an alkene. Another highly common route that forms two bonds simultaneously is the reaction of a monocyclic azirine with a difunctional molecule such as a diene or dipole to form bonds d and e . A significantly less common route is the formation of bonds c and b through the addition of carbene or carbene equivalent to a cyclic imine. 

Staurosporine and related molecules are under active investigation as potential anti-tumour agents. The synthesis illustrates several aspects of heterocyclic chemistry, including a 2-pyrone acting as a diene in an intramolecular Diels-Alder reaction, and the use of nitrene insertion for the formation of 5-membered nitrogen rings. 

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