1.3- Dipolar cycloadditions relative rates

The approach precludes the usage of volatile organic solvents, is relatively much faster, efficient, and eco-friendly. Significant rate enhancements are reported in the 1,3-dipolar cycloaddition reactions including the use of covalently grafted dipolaro-philes on the ionic liquids [189]. 

Substituent effects on intramolecular dipolar cycloadditions can be illustrated by the gem-dicarboalkoxy effect (404). This effect (rel. rate >20) has been... 

The relative frontier molecular orbital (FMO) energies of the reagents are very important for the catalytic control of 1,3-dipolar cycloadditions. In order to control the stereochemical outcome of a reaction with a substoichiometric amount of a ligand-metal catalyst, it is desirable that a large rate acceleration is obtained in order to assure that the reaction only takes place in the sphere of the metal and the chiral ligand. The FMO considerations will be outlined in the following using nitrones as an example. 

The effects contributed by alkyl groups to the relative rate constants, kreh for the reaction of ozone with cis- and trans-1,2-disubstituted ethylenes are adequately described by Taft s equation = k °reX -f pSo-, where So- is the sum of Taft s polar substituent constants. The positive p values (3.75 for trans- and 2.60 for cis-l,2-disubstituted ethylenes) indicate that for these olefins the rate-determining step is a nucleophilic process. The results are interpreted by assuming that the electrophilic attack of ozone on the carbon-carbon double bond can result either in a 1,3-dipolar cycloaddition (in which case the over-all process appears to be electrophilic) or in the reversible formation of a complex (for which the ring closure to give the 1,2,3-trioxolane is the nucleophilic rate-determining step). 

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... 

Table 10.3. Representative Relative Rate Data for 1 -Dipolar Cycloadditions ...

Dipolarophiles which contain an electron-deficient substituent undergo smooth cycloaddition reactions with nitrile ylides. The relative reactivity of the nitrile ylide toward a series of dipolarophiles is determined primarily by the extent of stabilization afforded the transition state by interaction of the dipole highest-occupied (HO) and dipolarophile lowest-unoccupied (LU) orbitals. Substituents which lower the dipolarophile LU energy accelerate the 1,3-dipolar cycloaddition reaction. For example, fumaronitrile undergoes cycloaddition at a rate which is 189,000 times faster than methyl crotonate. Ordinary olefins react so sluggishly that their bimolecular rate constants cannot be measured. 

Sc(OTf) 3-catalyzed 1,3-dipolar cycloaddition reactions of phenyl aziridines with olefins such as cyclic enol ethers and allyltrimethylsilane also proceeded well [36]. Sc(OTf)3 could also be used as a catalyst for [3 + 2] cycloaddition of aziridines with various nitriles to give the corresponding imidizalines in good to excellent yields under solvent-free conditions (Scheme 12.20) [37]. Although a relatively large amount of Sc (OTf) 3 was used in this reaction, the fast reaction rate, mild conditions and experimental operational ease are the features of this system. 

Table 5.6 Relative rate constants for 1,3-dipolar cycloadditions of benzonitrile oxide (85) with dipolarophiles A-E in various reaction media...

Kinetic data regarding the 1,3-dipolar cycloaddition of phenyl azide with norbornene in various solvents to give triazoline 98 were reported by Engeberts (Table 5.8). A high reaction rate enhancement (a factor of 53 relative to n-hexane) was observed when the reaction was performed in water containing 1% of l-cyclohexyl-2-pyrrolidinone (NCP). 

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. ... 

In the case of one-step cycloaddition reactions involving an activated complex with a different dipolarity than the reactants, an increase in solvent polarity should enhance the reaction rate (c/ Fig. 5-6a). However, since two-step cycloadditions are consecutive reactions, the solvent effect depends on the relative size of AGf and AGf or of AGfi and AG cf. Fig. 5-6b). If the formation of the zwitterionic intermediate is irreversible, and AG > AG, then the first step is rate-determining in all solvents. Consequently, there is a rate acceleration with increasing solvent polarity. When AG < AG, this behaviour is reversed. If ever AG x AG, then only relatively... 

For the reaction of (122) with TCNE to form (123) the rate increase in going from carbon tetrachloride as solvent to acetonitrile is about 49(X), while for the reaction of (124) with (125) to produce (126) there is only about a factor of six increase in rate for reaction in acetonitrile relative to reaction in toluene there is no spectacular solvent effect. Does the latter reaction have a fundamentally different mechanism than is operative in [2 + 2] cycloadditions of enol ethers with TCNE Are the tetramethylene intermediates of quite different dipolar character ... 

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