Cycloaddition with alkyl azides

The [2+3] cycloaddition of methylidene borane 36 with alkyl azides furnishes the intermediate triazaboroles 37a, which further undergoes silicon migration from carbon to nitrogen resulting in the formation of 37b. The driving force for the reaction is the stabilization of the ring system due to aromatization (6rt electrons) (Scheme 4) <2004ZFA508>. 

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... 

Irradiation of the pyrazoline mixture 12, 13, and ( )-14 yielded methanofullerenes 15 and 16 (7 1) with a closed transannular 6 - 6 bond besides minor amounts of a third constitutional isomer (17), whereas thermolysis of the same mixture gave 17 and inherently chiral ( )-18 (4 l),both constituting core-modified fullerenes [76] (Scheme l).With open transannular 6-5 bonds , the functionalized regions of 17 and ( )-18 resemble methanoannulene sub-structures. [3 + 2]Cycloaddition of alkyl azides to C70 affords triazolines which are isolable when the temperature does not exceed ca. 50 °C. Similar to the reaction with diazomethane, three constitutionally isomeric adducts were observed [77,113], and the regioisomer of type 19 [113] with the substituent of the heterocycle located above the apex of C70, predominated over its regioisomer of type 20 in two in-... 

Mock et al. reported that 1.3-dipolar cycloaddition of alkynes with alkyl azides, both substituted with a terminal amine group, yielding triazoles, is catalyzed by CB[6] m aqueous acid solutions.The reaction proceeds with... 

By virtue of the propargyl substituent of 369, efficient and predictable site-specific alkylation of nucleic acids with the possibility of bioconjugation via Huisgen [2-I-3] cycloaddition can occur. Thus, DNA lesion of 372 could afford triazole 374 following reaction with alkyl azides 373 (Scheme 77). 

It is tempting to think that allylic cations would behave similarly to other stabilized cations in their reactions with alkyl azides. " In practice what happens is invariably an initial formal [3+3] cycloaddition of azide to the allylic cation, which is followed by a migration event (typically of hydride) or trapping by a nucleophile. Pearson and coworkers found that when sulfonylindole 27 was treated with SnCk at -78 °C, followed by basic workup, triazoline adducts 28 were obtained as mixture of chloride epimers (Scheme 7.24). When A -alkyl indoles (e.g. 29) were subjected to Lewis acidic conditions, tri-azines such as 30 were obtained as the sole products. In the former case involving an iV-sulfonyl indole, a [3+2] cycloaddition pathway explains the product, whereas the iV-alkyl indoles examined underwent [3+3] cycloaddition. 

In the field of dihydrotriazoles, some results were previously published by Quasi et al. on the photoextrusion of nitrogen out of dihydrotriazole as well as dihydrotetrazole derivatives. Their dihydrotriazole synthesis was based on Trost s and Pearson s 1,3-dipolar cycloaddition from the lithium enolate of methylisobutyrate with alkyl azides at a lower temperature (-78°C). °... 

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. 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

Weinreb and co-workers (16) reported a high-pressure-induced 1,3-dipolar cycloaddition of alkyl and phenyl azides with electron-deficient alkenes at ambient temperature. As a representative example, phenyl azide underwent cycloaddition with methyl crotonate (69) at 12 kbar to give the triazoline 70 (43%) and the p-amino diazoester 71 (53%). The high-pressure conditions resulted in high yield and a shorter reaction time (Scheme 9.16). 

Sha et al. (45) reported an intramolecular cycloaddition of an alkyl azide with an enone in an approach to a cephalotaxine analogue (Scheme 9.45). Treatment of the bromide 205 with NaN3 in refluxing methanol enabled the isolation of compounds 213 and 214 in 24 and 63% yields, respectively. The azide intermediate 206 underwent 1,3-dipolar cycloaddition to produce the unstable triazoline 207. On thermolysis of 207 coupled with rearrangement and extrusion of nitrogen, compounds 213 and 214 were formed. The lactam 214 was subsequently converted to the tert-butoxycarbonyl (t-Boc)-protected sprrocyclic amine 215. The exocyclic double bond in compound 215 was cleaved by ozonolysis to give the spirocyclic ketone 216, which was used for the synthesis of the cephalotaxine analogue 217. 

The 1,3-dipolar cycloaddition of azidoalkylphosphonates to enamines afforded A2-1,2,3-triazoles which are further converted to the 1,2,3-triazoles [95H(40)543] fused triazoles are similarly obtained when a cyclic enamine was employed. Fused 1,2,3-triazole (88), a xanthine oxidase inhibitor, was prepared by the reaction of an alkyl azide with cyanoacetamide with further elaboration of intermediate (87) by treatment with HMDS in xylene [95FES257]. The fused 4H-l,2,3-triazolo[l,5- ][l,4]benzodiazepin-6(5H)-one (90) was obtained from propargylamide (89) via an intermediate azide [95S647]. 

---