Nitrenes intramolecular cyclization

The intramolecular insertion of a sulphonyl nitrene into a side-chain methyl group to give 36 and 37 has already been mentioned, as has the intramolecular cyclization of ferrocenylsulphonyl azide to give the bridged ferrocene derivative (17). 

Extension of these studies to benzologues of tetrazolo[l,5- ]pyridine, that is, for tetrazolo[l,5- ]quinoline 21 and tetrazolo[5,l- ]isoquinoline 22, led to interesting results <2003JOC1470> as shown in Scheme 7. Both of these fused tetrazoles resulted in formation of a nitrene 23 and 24, respectively, which could be interconverted via formation of the fused cyclic carbodiimide derivative 25. Isoquinolylnitrene 24, furthermore, was found to undergo subsequent reactions ring opening afforded the vinylnitrene 26, which was transformed to o-cyanophe-nylacetonitrile 27 by a 1,2-H shift and to 4-cyanoindole 28 by an intramolecular cyclization in 40% and 25% yields, respectively. 

Indole synthesis.1 Indoles are formed by deoxygenation of o-nitrostyrenes with carbon monoxide catalyzed by Fe(CO)5 to give a nitrene, which undergoes intramolecular cyclization. Ru3(CO)12 and Rh6(CO)16 show comparable selectivity. Example ... 

A useful route to benzo derivatives (167) involves intramolecular cyclization of the nitrenes (166). Other methods which have been devised for the synthesis of type B systems are not versatile enough to justify generalization. 

The usual photoreaction of a vinyl azide is intramolecular cyclization to yield a 2H-azirine. Although this process is a well-established path to these compounds, the details of the mechanism by which the reaction occurs is unresolved. In some instances the formation of the azirine is thought not to involve the nitrene intermediate. However, other studies have shown that azirines and vinyl nitrenes are in thermal equilibrium and thus it seems likely that a vinylnitrene is the key intermediate in such reactions. 

When o-azidobenzoic acid and its potassium salt were photolysed in H2O, EtOH, THE, EtOH-H20 or THF-H2O, the major product was 2,1-benzisoxazo-lone, from intramolecular cyclization. Varying amounts of azepine products were observed, depending on the solvent. Intramolecular nitrene cyclization was also observed in the photolysis of the azido-functionalized cryptand (43), which afforded the benzopyrazole (44) after an aerobic workup. ... 

Oxidation of arylhydrazones proceeds with intramolecular cyclizations (eqs 37 and 38) and aziridines may be formed via nitrene additions (eq 39). ... 

Meth-Cohn and Suschitzky have developed optimum conditions for the intramolecular cyclization of a triplet nitrene by insertion into an adjacent C-H bond. The cyclization of 84 is best carried out thermally at the highest convenient temperature. 

Recently, very fast intramolecular cyclization of singlet nitrene was observed upon photolysis of ort/ o-nitrophenyl azide (76). It is well known,that pyrolysis and photolysis of 76 leads cleanly to benzofuroxan (77). According to the results of recent computational stud) and early experiments, the pyrolysis of 76 produces 77 by a concerted one-step mechanism. However, photolysis of 76 produces 77 through a stepwise mechanism. Formation of singlet nitrene 78 from excited 76 was detected to occur with a time constant 500fs. The lifetime of nitrene 78 is very short - 8.3ps, and corresponds to ring-closure reaction rate constant 1.2 x 10" s. ... 

The rapid development of C-H functionalization has helped in accomplishing the synthesis of a variety of complex heterocycles from simple precursors. Recendy, Ramana and co-worker demonstrated a simple one-pot procedure for the Cu(I)-catalyzed SNAr reaction of o-bromochalcones 1 with sodium azide followed by intramolecular cyclization through nitrene C-H insertion to provide 2-aroylindole derivatives 2 [56] (Scheme 7.1) on the basis of their previous work [57]. Furthermore, this methodology is also applicable with the 2 -bromocinnamates giving the indole-2-carboxylates. 

Moody and Rahimtoola reported a short synthesis of staurosporinone (293) without the use of protecting groups at the indole or the lactam nitrogen (761,762). This route involves an intramolecular Diels-Alder reaction of the pyrano[4,3- 7]indol-3-one 1325 and a subsequent cyclization by nitrene insertion. The pyrano[4,3-l7]indol-3-one 1325 was obtained in four steps from ethyl indol-2-yl... 

Alkene epoxidation 35 Diazo cyclization 22 Intramolecular C-H insertion by nitrene 8,153... 

Oxidation of the 1-aminoquinazolinones (44) with lead tetraacetate culminated in the intramolecular addition of the resulting N-nitrene intermediate to the triple bond to give the pyrrolo[2, l-b]quinazoline (45) [85CC544 86JCS(P1)1215]. The pyrrole ring of 47 was also formed by cyclization of 2-methyl-3-phenacylquinazolin-4-one (46) with dilute aqueous alkali followed by fusion (86T4481). 

Exposure of the (cycloalkenyl)methyl carbamates 304 to iodosylbenzene in the presence or absence of Rh2(OAc)4 gives the tricyclic aziridines 305 (Scheme 88) (02OL2137). Reactions of 305 with nucleophiles, facilitated with tosic acid or lithium perchlorate, proceed with cleavage of the C-N edge bond and afford the tf 7 z-spirooxazolidinones 306. Intramolecular aziridination of the indolyl carbamate 307 with DAIB, on the other hand, requires Rh(II)-catalysis and leads directly to the acetoxy-substituted YDi-spirooxazolidinone 308 (Scheme 88) (02OL2137). When iodosylbenzene is used instead of DAIB and alcohols are available in the reaction medium, alkoxy-substituted syn-spirooxazolidinones 309 are obtained. Whereas the conversion of 304 to 305 appears to proceed by direct cyclization of intermediate iminoiodanes, the production of 308 from 307 was attributed to the intervention of a rhodium nitrene, which collapses to 308 through zwitterionic intermediates (02OL2137). 

Some interesting intramolecular variants have been reported. For example, homoallylic alcohols (e.g. 139) can be treated with sulfamoyl chloride to form the corresponding sulfamates (140), which then engage in a direct intramolecular copper-catalyzed aziridination mediated by iodosylbenzene <02OL2481>. A carbamate tether is also effective in delivering the nitrene center to the olefin, as is the case with the cyclohexenyl derivative 142, which spontaneously cyclizes in the presence of iodosylbenzene <02OL2137>. The acetoxy-aminoquinazolinone 144 is converted to the lactone 145 via intramolecular aziridination upon treatment with lead tetraacetate and hexamethyldisilazane (HMDS) <02TL2083>. 

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