Addition, 1,3-dipolar, alkyl azides

In 1993, it was found that alkyl azides react with C o in a 1,3-dipolar cycloaddition manner [35]. The course of the reaction is closely analogous to the 1,3-di-polar addition of alkyl diazo compounds. Preliminary results on the reaction of Cso with organic azides were complicated. Treatment of Qo with SEM azide in refluxing chlorobenzene afforded two major products 3 and 4 (Fig. 2). While isN-i C spin-spin coupling experiments supported the structure for 4, the NMR spectrum of 3 contained a resonance at 160 ppm coupled to which was... 

In contrast to the difficulty in producing cyclobutadiene by the simple [2 + 2] cycloaddition of alkynes, the addition of 1,3-dipolar species across the carbon-carbon triple bond of alkynes is quite facile. Thus, in addition to the fourth example of Table 6.9 showing that alkyl azides can add across the triple bond, reactions such as that of ethyne (acetylene, H-C=C-H) with isocyanic acid (fulminic acid. 

Triazoks were synthesized from simple starting materials without the need for additional catalyst. Organic azides, generated in situ from alkyl halides and sodium azide, were reacted with acetylenes using the copper-catalyzed Huisgen 1,3-dipolar cydoaddition. 

Further examples of multifunctional isothiocyanates include aryl for-mamidinoyl-isothiocyanates RiNC(=NR )NCS, which may be isomerized into 3H-quinazoline-4-thiones and which undergo well-known amine addition and cycloaddition reactions associated with simpler isothiocyanates ° and sulphonyl isothiocyanates, for which 1,3-dipolar cycloaddition to alkyl azides has been demonstrated,thermolysis of the resulting thiatriazolines giving sulphonyl carbodi-imides ArS02N=O=NR. 

Reactions of salts of 1,2,3-triazole with electrophiles provide an easy access to 1,2,3-triazol-jV-yl derivatives although, usually mixtures of N-l and N-2 substituted triazoles are obtained that have to be separated (see Section 5.01.5). Another simple method for synthesis of such derivatives is addition of 1,2,3-triazole to carbon-carbon multiple bonds (Section 5.01.5). N-l Substituted 1,2,3-triazoles can be selectively prepared by 1,3-dipolar cycloaddition of acetylene or (trimethylsilyl)acetylene to alkyl or aryl azides (Section 5.01.9). 

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. 

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). 

Cycloadditions. Methyl and ethyl cyanoformate have been reported to undergo [4 + 2] cycloadditions, e.g. with cyclopentadienones and 2-alkyl-l-ethoxybuta-1,3-dienes to form pyridines (eq 21), and with cyclobutadienes to form Dewar pyridines (eq 22). Ethyl cyanoformate is also ein effeetive dipolarophile, undergoing 1,3-dipolar addition to azides (eq 23) and cyclic carbonyl ylides (eq 24). ... 

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