Azides reactions with alkenes

The Z-alkene ( ) was subjected to the same sequence (Scheme 4). The triflate ( ) was easily obtained, but in this case reaction with azide ion gave directly the diazoester (22). Molecular models show that the triazoline corresponding to (19) has severe steric interactions and is more accessible to deprotonation (cf. ref. 23). 

Reaction with alkenes 2, 1.6.6.1 Reaction with alkynes 2, 1.6.6.1 Reaction with arenes 2, 1.6.6.1 Reaction with azide 2, 1.5.2.1.2 Reaction with carbon at high temperatures 2. 

Reaction with Azide Anion and Azide-Containing Compounds. As initially reported in 1985, it is possible to add azides to alkenes using Mn(OAc)3. The reaction is thought to proceed by initial oxidation of the azide anion to an azide radical. An improved protocol to do the diazidation under milder conditions and in higher yields was reported (eq 19). ... 

Perhaps one of the most exciting developments in the chemistry of quinoxalines and phenazines in recent years originates from the American University of Beirut in Lebanon, where Haddadin and Issidorides first made the observation that benzofuroxans undergo reaction with a variety of alkenic substrates to produce quinoxaline di-AT-oxides in a one-pot reaction which has subsequently become known as the Beirut reaction . Many new reactions tend to fall by the wayside by virtue of the fact that they are experimentally complex or require starting materials which are inaccessible however, in this instance the experimental conditions are straightforward and the starting benzofuroxans are conveniently prepared by hypochlorite oxidation of the corresponding o-nitroanilines or by pyrolysis of o-nitrophenyl azides. 

When unacylated azides are used as nitrene precursors, the first reaction with an alkene is a cydoaddition, generating the corresponding 1,2,3-triazoline, which often eliminates N2 under the fierce reaction conditions to give an aziridine product (Scheme 4.9 ). 

DL-Valiolamine (205) was synthesized from the exo-alkene (247) derived from 51 with silver fluoride in pyridine. Compound 247 was treated with a peroxy acid, to give a single spiro epoxide (248, 89%) which was cleaved by way of anchimeric reaction in the presence of acetate ion to give, after acetylation, the tetraacetate 249. The bromo group was directly displaced with azide ion, the product was hydrogenated, and the amine acety-lated, to give the penta-A, 0-acetyl derivative (250,50%). On the other hand. 

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

The use of reductive alkylation conditions has been employed to access tricycles from the azide 353 <2002S242> (Equation 95). Hydroboration of the alkene double bond with dicyclohexylborane followed by reaction with the azide and subsequent elimination of nitrogen and cyclization gave the linear tricyclic diketopiperazine 354 and 355 as a mixture of diastereoisomers. 

Figure 17.9 A general Huisgen reaction involves the cycloaddition of an azide with an alkene or an azide with an alkyne. The products of these reactions are a triazoline ring or a triazole ring, respectively.

The radical carboazidation of alkenes has been achieved in water using triethylborane as initiator [118]. This efficient process is complete in one hour at room temperature in an open to air reaction vessel (Scheme 54, Eq. 54a). These new tin-free carboazidation conditions are environmentally friendly and allow to run reactions with an excess of either the alkene or the radical precursor. They are also suitable for simple radical azidation of alkyl iodides as well as for more complex cascade reactions involving annulation processes (Eq. 54b). In both reactions (Eq. 54a and 54b), an excess of triethylborane (3 equivalents) is required to obtain a good yield. This may be an indication that the chain process, more precisely the reaction between the phenylsul-fonyl radical and Et3B, is not efficient. 

Vogel and Delavier (26) reported a synthesis of the 6-azabicyclo[3.2.2]nonane skeleton 130 using an intramolecular azide-alkene cycloaddition strategy (Scheme 9.26). When refluxed in xylene, the azide 126 underwent an intramolecular 1,3-dipolar cycloaddition with the internal alkene. Nitrogen extrusion and subsequent rearrangement led to a mixmre of compounds 128, 129, and 130. Reactions of azides with the double bond of dienes were also used in various total syntheses of alkaloids, and will be discussed later in Section 9.2.2. 

Buchanan et al. (48) reported a new route to the synthesis of the chiral hydroxy-pyrrolidines 234 and 238 from D-erythrose (230) via an intramolecular cycloaddition of an azide with an alkene (Scheme 9.48). Wittig reaction of the acetonide 230 with (carbethoxyethylene)triphenylphosphorane gave the ( ) and (Z) alkenes 231 and 232. On conversion into the triflate followed by its reaction with KN3, the ( ) isomer 231 allowed the isolation of the triazoline 234 in 68% overall yield, which on treatment with sodium ethoxide afforded the diazo ester 235 in 86% yield. 

Schkeryantz and Pearson (59) reported a total synthesis of ( )-crinane (298) using an intramolecular azide-alkene cycloaddition (Scheme 9.59). The allylic acetate 294 was first subjected to an Ireland-Claisen rearrangement followed by reduction to give alcohol 295, which was then converted into the azide 296 using Mitsunobu conditions. Intramolecular cycloaddition of the azide 296 in refluxing toluene followed by extrusion of nitrogen gave the imine 297 in quantitative yield. On reduction with sodium cyanoborohydride and subsequent reaction with... 

In the case of electrophilic addition, the reactions of tricyclic dienes 1 with several electrophilic reagents have been investigated.1 7 Interestingly, some of these compounds undergo addition reactions with remarkable syn stereoselectivity. For example, the reaction of dimethyl tricy-clo[4.2.2.02,5]deca-3,9-diene-7,8-dicarboxylate with iodine azide solution, prepared in situ from an excess of sodium azide and iodine monochloride, in acetonitrile at — 5 C provided the. yyn-4-azido-3-iodo derivative 2 (Table 1) in 90% yield.1,2,4,6 The formation of the 5,>,n-4-azido-3-iodo derivative 2 is thought to be the first example of a syn addition of iodine azide to an alkene.1,2 The formation of the syn-product is best explained by the twist strain theory,8 according to which the syn transition structure A is favored over the an/7-coplanar transition structure B.1... 

Denson (Ref 9) on those a-azidoalkylidenimines which undergo cyclic isomerizations to tet-razoles and Boyer Canter (Ref 15) made a thorough survey of the available information on alkyl and aryl azides. Cirulis Straumanis (Ref 6) prepd a number of new azides of org bases bur none of these azides showed eiqjl props. Schaad (Ref 14) obtd a patent for the manuf of esters of hydrazoic acid based on the reaction of alkenes, cyclic olefins, ary 1-alkenes cycloalkylalkenes with HN3 in the presence of an acid catalyst... 

---