Triazolines from alkyl azides

Stable triazolines are obtained from aryl azides and V-alkyl and N-aryl maleimides (Scheme 81 )307-309a the reaction succeeds with silyl azides310 and is utilized in the synthesis of polymers from bisazides and bismaleimides.311 312 Unlike maleimides, maleic anhydrides do not yield stable triazolines with trimethylsilyl azide the reaction products are oxazinediones (Section IV,A).310,313,314... 

Similarly to the reaction with diazomethane, [3 + 2] cycloaddition of alkyl azides to C70 affords three constitutionally isomeric adducts (87, 88, and ( )-89) 46.226,227 Thermal elimination of N2 from the fullerene-fused triazolines showed a preference for the formation of 6-5 open azahomofullerene structures (types 90 and ( )-91) as compared to the 6-6 closed aziridine isomers corresponding to 92 and 93 (Scheme 1.9).226,227... 

The dipolar cycloaddition of an alkyl azide with an alkene to form an aziridine has been exploited in the total synthesis of the alkaloid ( )-aspidospermidine <20050BC213>. Enone 353 was prepared in 11 steps from 3-ethoxycyclohexenone and coupled to 2-iodo nitrobenzene under Ullman cross-coupling conditions. The acetate group of 354 was hydrolyzed and the resulting alcohol converted to an azide using standard conditions in 75% overall yield. The cycloaddition of the azide with the enone was conducted in refluxing benzene for 3 days. The fused-ring aziridine 355 was the only product isolated. None of the initial dipolar cycloadduct triazoline was observed. The... 

Many of the cycloadducts formed from the dipoles in Table 15.3 are unstable, leading to other products. The reaction of alkyl azides with alkenes generates triazolines (15-54), which extrude nitrogen (N=N) upon heating or photolysis to give an aziridine. 

Five-membered rings have tilso been obtained from unsaturated alkyl azides. Heating of 5-azido-5-methyl-l-hexene (149) yielded a mixture of 2,5,5-trimethyl-1-pyrroline (151) and 2,2-dimethyl-1-aza-bicyclo[3,l,0]hexane (152) (total yield 70%, products ratio 2-2 1). This reaction however proceeds via the isolable triazoline 150 and no nitrene intermediates are involved... 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

Cyanogen azide reacts with olefins at 0-35° to afford alkyl-idene cyanamides and/or N-cyanoaziridines arising from decomposition of an intermediate unstable triazoline. 54 With norbomadiene the isolated product is N-cyano-3-azatricyclo-[3.2.1.0s-4-M<,]oct-6-ene (58) which is unstable and rearranges into N-cyano-2-azabicycIo[3.2.1]octa-3,6-diene (59).167... 

Spontaneous isomerization of triazolines to diazo compounds can lead to addition of the latter to a second molecule of olefin, especially in the case of acrylic derivatives, resulting in a A pyrazoline, which by proto tropic rearrangement, gives the A2-compound (Scheme 149). Pyrazolines have been observed in the reactions of alkyl,67 aryl,32,282 heterocyclic,283,453 and gly-cosyl288 azides. A A pyrazoline is reported from the addition of phenyl and tosyl azides to 3,3-dimethylcyclopropene in this case the diazoimine formed by a retro-1,3-addition of the primary cyclopropanotriazoline adduct reacts with another olefin molecule.82... 

The first synthesis of the parent compound of the benzo[4,5]thieno[2,3-c]pyrrole ring system 99 [27] and its derivatives was accomplished using the same synthetic sequence (Scheme 16). Starting with 2-mcthyl benzolb thiophcnc-3-carbaldehyde 100, an intermediate 101 was obtained. Treatment of bromo compound 101 with sodium azide in ethanol led to the stable triazoline 102.1,3-Dipolar cycloreversion of 102 was induced by a catalytic amount of p-TsOH to give the parent 27/-benzo [4,5]thieno[2,3-c]pyrrole 99. Alternatively, direct treatment of bromo compound 101 with excess ammonia furnished 99 in one step. Compound 99 was treated with Boc20 and DMAP to give the /V-Boc derivative 103. Reaction of 101 with alkyl- and arylamines, respectively, afforded the N-substituted benzo[4,5]thieno[2,3-c]pyrroles 105 via a retro-malonate addition from intermediate 104. 

Triazolines have also been easily obtained in the reactions of azides with unsaturated nitriles with ethylenesulphonic acid derivatives and with maleimides . Steric hindrance caused by additional substitution by alkyl or aryl groups lowers the yields and also influences the orientation. The reaction of phenyl azide with j3-nitrostyrene proceeded only at 130° and yielded only 20% of the expected 1,5-diphenyl-4-nitrotriazoline (229), together with 1,4-diphenyl triazole (230), resulting from addition in the opposite direction ". ... 

The addition of ozone (O3) to alkenes to give a primary ozonide (molozonide), which rearranges to an ozonide and eventually leads, on reduction, to carbonyl compounds (aldehydes and/or ketones), has already been mentioned and the reaction itself is shown in Scheme 6.11. However, it is important to recognize that this is only one example of a 4th- 2n electrocyclic addition and that orbital overlap for many sets of these reactions dictates their courses as well. Thus, to show the similarity of some of these dipolar 3 -f 2 addition reactions Equations 6.53-6.56 are provided. Although any alkene might be used as an example, (Z)-2-butene is used in each to emphasize that aU of them occur with retention of stereochemistry and, in the first (Equation 6.53), the reaction with ozone to form the primary ozonide (molozonide) is presented again (i.e., see Scheme 6.11). In a similar way, with a suitable azide, R-N3, readily prepared from an alkyl halide (Chapter 7), the same alkene forms a triazoline (Equation 6.54) and with nitrous oxide (N2O) the heterocycle (Chapter 13) cis -4,5-dimethyl-A -l,2,3-oxadiazoline (ds-4,5-dihydro-4,5-dimethyl-l,2,3-oxadiazole) (Equation 6.55). Finally, with a nitrile oxide, such as the oxide derived from ethanenitrile (acetonitrile [CH3ON]), the same alkene yields a different heterocycle, the dihydroisoxazole, 3,4,5-trimethyl-4,5-dihydroisoxazole (Equation 6.56). 

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