Azide cyclizations, intramolecular

Azolo[l,8]naphthyridines. The reactions of the chloronaphthyridine 229 with o-phenylenediamine at 200 °C and with sodium azide in acetic acid give the fused-ring products 230 and 231, respectively (Scheme 54) <2003IJB192>. Amino acid-substituted naphthyridines can be cyclized to the fused imidazolones 232 upon treatment with phosphorus oxychloride and under microwave irradiation (Equation 62) <2002SC857>. Acylation of 2-hydrazino-naphthyridines followed by heating gives W-acyl compounds which are cyclized intramolecularly to the [l,2,4]tri-azolo[4,3- ][l,8]naphthyridines 233 (Scheme 55) <1996IJB106>. The same compounds may also be obtained from... 

A series of 5-aminoaryltetrazoles were obtained directly from the corresponding l-aryl-5-aminotetrazoles by a one-pot sequential ring-opening, azidation, and intramolecular cyclization. 5-Alkylamino-l-aryltetrazoles are formed by a similar mechanism from 1,4-disubstituted tetrazolium salts. The influence of the aryl substituents and reaction conditions on the regioselectivity of the intramolecular cyclization of the intermediate guanyl azides was revealed <2006S1307>. 

The reaction of sodium azide with 5-substituted 3-diethylamino-4-(4-methoxyphenyl)-isothiazole 1,1-dioxides afforded [l,2]thiazete 5,5-dioxides 56. It has been proposed that a nucleophilic addition of the azide ion to C-5 followed by ring closure gave a triazoline intermediate, which cyclized intramolecularly with concomitant nitrogen extrusion <02T5173>. 

Scrima M, Le Chevalier-Isaad A, Rovero P et al (2010) Cul-catalyzed azide-alkyne intramolecular i-to-(i + 4) side-chain-to-side-chain cyclization promotes the formation of helix-like secondary structures. Eur J Org Chem 2010 446-457... 

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. 

The formation of an azepine ring by means of an intramolecular azide cyclization has often provided the key step in the synthesis of clavicipitic acid (126) <84JOC23io> (Scheme 19). 

In our approach to the synthesis of amphorogynine C, we used the Claisen rearrangement product 10 as a starting material and an intramolecular olefin-azide cyclization as a key step. The retrosynthetic analysis is shown in Figure 14.9. The... 

Nucleoside N -oxides have proved useful in preventing intramolecular cyclizations during manipulation of the sugar moiety. A key step is the reductive removal of the oxide when needed. In the presence of Raney nickel, the oxide can be reduced selectively even when such easily reduced substituents as iodo are present. Azides, however, are reduced concomitantly with the oxide 105). 

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). 

An intramolecular version of an azide cycloaddition of 221 and 222 provided cyclopropylimines 224 and 225 via formation of triazoline 223 followed by extrusion of nitrogen with concomitant 1,2-hydrogen shift (Scheme 36) [58], The cyclization was found to be solvent dependent polar solvents such as DMF gave the best yields, whereas benzene gave several side products. 

Intramolecular nucleophilic additions by nitrogen functional groups onto pendant alkynes and allenes represent an important class of type la approaches to functionalized pyrroles. A platinum-catalyzed (PtCl4) cyclization of homopropargyl azides provided an entry to 2,5-disubstituted pyrroles and 4,5,6,7-tetrahydroindoles (fused pyrroles) <06OL5349>. 

Dipolar cycloaddition between azides and nitriles is also a well-established route to tetrazoles. If these two functional groups are closely located within one molecule, intramolecular cyclization can occur to yield fused tetrazoles. The present survey of the recent literature shows that this approach has also been successfully applied in some cases and led to the synthesis of novel ring systems belonging to this chapter. These results are depicted in Scheme 25. 

A ring-closure reaction to the bicyclic triazolopyridine system implying intramolecular 1,3-dipolar cycloaddition was published by Couty et al. <2004TL3725>. The reaction pathway started from an /V-propargylaruinoalcohol 398, which was treated first with thionyl chloride followed by sodium azide to give the intermediate 399, which underwent the desired cyclization to afford the final product 400. Although in other related cases (cf. Chapter 11.15 for tetrazolopyrazines) the yields were acceptable, this nitrogen positional derivative was obtained only in 20% yield. 

There has been little recent work on the stannaimines, R2Sn=NR. The compound [(Me3Si)2N]2SnNAr (Ar = 2,6-diisopropylphenyl) can be obtained as dark red crystals that are stable below —30 °C, and have an Sn=N bond length of 203.0(3) pm. Above —30 °C, cyclization slowly occurs by intramolecular addition of CH of an isopropyl group to the double bond. It reacts with 2,6-diethylphenyl azide to give the stannatetraazole (Equation (194)).592... 

In troponoid chemistry cine substitution occurs frequently. In many cases it can be explained by the intermediacy of dehydrotropolone species ( tro-polonyne ) as trapped, for example, by azides (Section II,A,3,h Scheme 34). An alternative mechanism may be a Michael-type addition followed by elimination. The intramolecular cyclizations depicted in Scheme 47 very likely proceed via Michael-type attack (73CRV293, p.351). 

In another approach, 2-(alkylamino)alcohol is employed as starting material for aziridine syntheses with the aid of dihalogenophosphoranes (70BCJ1185). Intramolecular transformation of 3-azidopropyloxirane 73 results in a simultaneous formation of a condensed aziridino[l,2-a]pyrrol-idine system (Scheme 39). The azide group is first transformed into imino-phosphorane 74, the nucleophilic N atom cleaves the oxirane to form betaine 75 [as in the Mitsunobu reaction (81S1)], and the phosphorus is shifted from N to O and then eliminated as phosphane oxide under simultaneous cyclization to bicyclic 76 (89JA7500). 

An intramolecular counterpart of this reaction is the cyclization (Scheme 17) of anions derived from vinyl azides the neutral azides fail to cyclize, presumably because the cyclic tautomer (the triazole) is not aromatic, whereas the anion is. 

Curtius degradation of the acyl azide and subsequent transesterification with tert-butanol and hydrolysis resulted in the A/-BOC amino acid 156. Compound 156 was readily cyclized with thionyl chloride, resulting in anhydride 157 diendo, R = H, Me diexo, R = H) in one step. In the cyclization step, acid chlorides were formed first and thereafter an intramolecular cyclization took place with loss of hydrogen chloride (93BSB227,93T1985). 

Sequential Mannich reaction of ester 210a or nitrile 210b, alkylation and displacement of quaternary ammonium salt affords azides 211. Further hydrogenation can be followed by intramolecular cyclization under basic conditions into pyrrolo-benzodiazepinone 212 (Scheme 44 (1994JHC1317, 1994S164)). 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

Other cycloadditions were reported. The intramolecular cycloaddition of alkenylnitrones was 2q>phed to the synthesis of piperidines <99TL1397, 99JCS(P1)185>. Cycloaddition of an alkenyl azide afforded piperidines after reduction of the bicyclo triazole <99T1043, 99EJOC1407>. Similar to the cyclization of the diazo imide 2 in section 6.1.2.1, isomiinchnone intermediates can rearrange to functionalized piperidines <99JOCS56>. 

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