1.3- Dipolar cycloadditions phenyl azide

Sustmann164 has also collected data for 1,3-dipolar cycloadditions. Phenyl azide (197) reacts fast with electron-poor and with electron-rich olefins, but slowly with a simple olefin. A plot of the rate constant against the energy of the... 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

The relative reaction rates of the 1,3-dipolar cycloaddition reaction of phenyl azide to dipolarophiles containing the C=C bond can be predicted by using the Jaguar V. 3.0 ab initio electronic package. Thermodynamic analysis of the 1,3-dipolar cycloaddition of organic azides with conjugated nitroalkenes at 273-398 K shows that temperature does not affect the course of these reactions in the vapour phase. Density-functional procedures have been used to explain the regioselectivity displayed by the 1,3-dipolar cycloaddition of azides with substituted ethylenes. A density-functional theory study of the 1,3-dipolar cycloaddition of thionitroso compounds with fulminic acid and simple azides indicates that the additions are not stereospeciflc. ... 

The kinetics of 1,3-dipolar cycloaddition of phenyl azide to nor-bornene in aqueous solutions was studied (Eq. 12.67).145 As shown in Table 12.1, when the reaction was performed in organic solvents, the reaction showed very small effects of the solvent, while in highly aqueous media, significant accelerations were observed. 

Benzocyclobutene, when generated by oxidation of its iron tricarbonyl complex, can function as the dipolarophile in 1,3-dipolar cycloaddition reactions with arylnitrile oxides (Scheme 113).177 Unfortunately the synthetic versatility of this type of process is limited because of the unreactivity of other 1,3-dipolar species such as phenyl azide, benzonitrile N-phenylimide, and a-(p-tolyl)benzylidenamine N-oxide.177... 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

Derivative 165 was treated with tosyl azide at room temperature for 48 h to give 167. Formation of this product was rationalized by a 1,3-dipolar cycloaddition with participation of the C=C bond in the pyrimidine ring in 165 to form a cycloadduct 166 at first, which underwent a [l,2]-methyl shift and a nitrogen elimination to yield 167. Stmcture elucidation of this product revealed the relative rzr-stereochemistry of the phenyl and methyl substituents. 

The thermal cycloaddition of azides to acetylenes is the most versatile route to 1,2,3-triazoles, because of the wide range of substituents that can be incorporated into the acetylene and azide components. The accepted mechanism for the reaction is a concerted 1,3-dipolar cycloaddition. The rates of addition of phenyl azide to several acetylenes have been measured the rates of formation of the aromatic triazoles are not appreciably different from the rates of cycloaddition to the corresponding olefins, indicating that the transition-state energy is not lowered significantly by the incipient generation of an aromatic system. 

Cycloaddition of p-methoxyphenyl azide to alkynic dipolarophiles at room temperature gives triazoles (697) and (698) (Equation (54)). A regiospecific addition is only observed in the case of Z = CH(OMe)2 <89H(29)967>. Phenyl azide and substituted benzyl azides undergo 1,3-dipolar cycloadditions with DM AD, phenylacetylene, and ethyl propiolate to afford 1-phenyl- and 1-benzyl-... 

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). 

Compound 156 (prepared by reaction of tetrabromocyclopropene and 2,5-dimethylfuran) underwent dipolar cycloaddition with phenyl azide to produce the fused triazole 157. The reaction was carried out in dichloromethane at room temperature over 2 days. This lower reaction temperature allowed for the isolation of the adduct 157, which was established by X-ray crystallographic analysis to be the product of ct>-selective addition. Heating triazole 157 in benzene at reflux for 2 h resulted in ring expansion producing a 1 1 mixture of compounds 158 and 159 (Scheme 16) <2004JOC570>. 

Phenyl azide is formed from phenyldiazonium chloride and sodium azide by way of two competing reactions (Figure 12.46). The reaction path to the right begins with a 1,3-dipolar cycloaddition. At low temperature, this cycloaddition affords phenylpentazole, which decays above 0°C via a 1,3-dipolar cycloreversion. This cycloreversion produces the 1,3-dipole phenyl azide as the desired product, and molecular nitrogen as a side product. 

FIGURE 18 Top Molecular structure of Rebek s capsule (59) for the acceleration of a 1,3-dipolar cycloaddition between phenylacetylene and phenyl azide. Bottom CAChe-minimized structure of the ternary complex. Symmetrically loaded capsules are also found in solution. (See Color Insert in the back of this book.)... 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

The influence of water as a solvent on the rate of dipolar cycloadditions has been reported [76]. Thus the rate of the 1,3-dipolar cycloaddition of 2,6-dichloroben-zonitrile N-oxide with 2,5-dimethyl-p-benzoquinone in an ethanol/water mixture (60 40) is 14-fold that in chloroform [76b]. Furthermore the use of aqueous solvent facilitates the workup procedure owing to the low solubility of the cycloadduct [76b]. In water-rich solutions, acceleration should be even more important. Thus in water containing 1 mol% of l-cyclohexyl-2-pyrrolidinone an unprecedented increase in the rate of the 1,3-dipolar cycloaddition of phenyl azide to norbornene by a factor of 53 (relative to hexane) is observed [77]. Likewise, the 1,3-dipolar cycloaddition of C,Ar-diphenylnitrone with methyl acrylate is considerably faster in water than in benzene [78]. Similarly, azomethine ylides generated from sarcosine and aqueous formaldehyde can be trapped by dipola-rophiles such as N-ethylmaleimide to provide pyrrolidines in excellent yields... 

Hessell ET, Jones WD (1992) Synthesis and structure of rhodium complexes containing a photolabile 72-carbodiimide ligand. 1,3-dipolar cycloaddition of phenyl azide to Tp Rh(CNR)2 (Tp = Hydrotris(3,5-dimethylpyrazolyl)borate). OrganometaUics 11 1496-1505... 

An unusual influence of water on the rate of 1,3-dipolar cydoadditions was first observed when 2,6-dichlorobenzonitrile N-oxide was allowed to react with 2,5-di-methyl-p-benzoquinone [50]. Likewise, bromonitrile oxide, generated in water at acidic pH, gave cycloadducts effidendy with water-soluble alkenes and alkynes [51]. In highly aqueous media remarkable accelerations for the cycloaddition of phenyl azide to norbomene were observed [52]. 

Phenyl azide reacts with alkenes to give 4,5-dihydro-1,2,3-triazoles (1,3-dipolar cycloaddition, see p 204), which are thermally or photochemically converted into aziridines through loss of nitrogen ... 

Reaction of phenyl azide and benzyl cyanide (in EtOH in the presence of EtONa at r.t.) surprisingly does not lead to the expected product of a 1,3-dipolar cycloaddition (A), but to 5-amino-l,4-diphenyl-l,2,3-triazole (B, 80%). Triazole B isomerizes readily on heating in pyridine solution to give 5-anilino-4-phenyl-1,2,3-triazole (C). 

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