The carbon of diazomethane bears the largest HOMO orbital, while the terminal olefinic carbons of methyl acrylate and styrene bear the largest LUMO orbital. Hence, cycloaddition gives the substitution at the C-3 position regioselectively.
Mechanistic overview[ edit ] Originally two proposed mechanisms describe the 1,3-dipolar cycloaddition: Although, few examples exist of stepwise mechanism of the catalyst free 1,3-dipolar cycloaddition reactions for thiocarbonyl ylides,  and nitrile oxides  Pericyclic mechanism[ edit ] Huisgen investigated a series of cycloadditions between the 1,3-dipolar diazo compounds and various dipolarophilic alkenes.
Different substituents on the dipole do not exhibit a large effect on the cycloaddition rate, suggesting that the reaction does not involve a charge-separated intermediate.
Solvent polarity has little effect on the cycloaddition rate, in line with the pericyclic mechanism where polarity does not change much in going from the reactants to the transition state. Resonance structures can be drawn to delocalize both negative and positive charges onto any terminus of a 1,3-dipole see the scheme below.
A more accurate method to describe the electronic distribution on a 1,3-dipole is to assign the major Thesis on 1 3-dipolar cycloaddition contributor based on experimental or theoretical data, such as dipole moment measurements  or computations. Consequently, this ambivalence means that the ends of a 1,3-dipole can be treated as both nucleophilic and electrophilic at the same time.
The extent of nucleophilicity and electrophilicity at each end can be evaluated using the frontier molecular orbitalswhich can be obtained computationally. In general, the atom that carries the largest orbital coefficient in the HOMO acts as the nucleophile, whereas that in the LUMO acts as the electrophile.
The most nucleophilic atom is usually, but not always, the most electron-rich atom. Dipolarophile[ edit ] The most commonly used dipolarophiles are alkenes and alkynes. Heteroatom -containing dipolarophiles such as carbonyls and imines can also undergo 1,3-dipolar cycloaddition.
Other examples of dipolarophiles include fullerenes and nanotubeswhich can undergo 1,3-dipolar cycloaddition with azomethine ylide in the Prato reaction.
Solvent effects[ edit ] 1,3-dipolar cycloadditions experience very little solvent effect because both the reactants and the transition states are generally non-polar.
For example, the rate of reaction between phenyl diazomethane and ethyl acrylate or norbornene see scheme below changes only slightly upon varying solvents from cyclohexane to methanol. On the other hand, a close analog of this reaction, N-cyclohexenyl pyrrolidine 1,3-dipolar cycloaddition to dimethyl diazomalonate, is sped up only fold in DMSO relative to decalin.
Frontier molecular orbital theory[ edit ] 1,3-Dipolar cycloadditions are pericyclic reactions, which obey the Dewar-Zimmerman rules and the Woodward—Hoffmann rules. In the Dewar-Zimmerman treatment, the reaction proceeds through a 5-center, zero-node, 6-electron Huckel transition state for this particular molecular orbital diagram.
However, each orbital can be randomly assigned a sign to arrive at the same result. Such orbital overlap can be achieved in three ways: A dipole of this class is referred to as a HOMO-controlled dipole or a nucleophilic dipole, which includes azomethine ylidecarbonyl ylidenitrile ylideazomethine iminecarbonyl imine and diazoalkane.
These dipoles add to electrophilic alkenes readily. For example, the reactivity scale of diazomethane against a series of dipolarophiles is shown in the scheme below.
Diazomethane reacts with the electron-poor ethyl acrylate more than a million times faster than the electron rich butyl vinyl ether. This two-way interaction arises because the energy gap in either direction is similar. A dipole of this class is referred to as a HOMO-LUMO-controlled dipole or an ambiphilic dipole, which includes nitrile imidenitronecarbonyl oxidenitrile oxideand azide.
Any substituent on the dipolarophile would accelerate the reaction by lowering the energy gap between the two interacting orbitals; i.
For example, azides react with various electron-rich and electron-poor dipolarophile with similar reactivities see reactivity scale below. A dipole of this class is referred to as a LUMO-controlled dipole or an electrophilic dipole, which includes nitrous oxide and ozone.
For example, ozone reacts with the electron-rich 2-methylpropene abouttimes faster than the electron-poor tetrachloroethene see reactivity scale below. Reactivity[ edit ] Concerted processes such as the 1,3-cycloaddition require a highly ordered transition state high negative entropy of activation and only moderate enthalpy requirements.
Using competition reaction experiments, relative rates of addition for different cycloaddition reactions have been found to offer general findings on factors in reactivity. Conjugation, especially with aromatic groups, increases the rate of reaction by stabilization of the transition state.
During the transition, the two sigma bonds are being formed at different rates, which may generate partial charges in the transition state that can be stabilized by charge distribution into conjugated substituents.
More polarizable dipolarophiles are more reactive because diffuse electron clouds are better suited to initiate the flow of electrons. Dipolarophiles with high angular strain are more reactive due to increased energy of the ground state.
Increased steric hindrance in the transition state as a result of unhindered reactants dramatically lowers the reaction rate.
The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,leslutinsduphoenix.com ontology ID: RXNO A 1,3-DIPOLAR CYCLOADDITION APPROACH TO THE SYNTHESIS OF RESINIFERATOXIN. by. Jennifer A. Loyer-Drew. This thesis describes the development of two systems, each with a future THE MASKED ALDOL STRATEGY: 1,3-DIPOLAR CYCLOADDITION TO. Synthesis Towards Fulminic Acid and Its Derivatives in 1,3-Dipolar Cycloaddition Reactions _____ A thesis. presented to. the faculty of the Department of Chemistry.
Hetero-dipolarophiles add more slowly, if at all, compared to C,C-diapolarophiles due to a lower gain in sigma bond energy to offset the loss of a pi bond during the transition state. Isomerism of the dipolarophile affects reaction rate due to sterics.
Stereospecificity[ edit ] 1,3-dipolar cycloadditions usually result in retention of configuration with respect to both the 1,3-dipole and the dipolarophile. Such high degree of stereospecificity is a strong support for the concerted over the stepwise reaction mechanisms.
As mentioned before, many examples show that the reactions were stepwise, thus, presenting partial or no stereospecificity.A thesis submitted in conformity with the requirements for the degree of Master of Science () ii Phosgene-free synthesis of verdazyl radicals and enantioselective 1,3-dipolar cycloaddition reactions of azomethine imines generated in situ from verdazyl radicals Beom Youn Master of Science Graduate Department of Chemistry University of.
Utilizing a highly diastereoselective Rh(II)-catalyzed 1,3-dipolar cycloaddition of carbonyl ylides to various aldimines, syn-α-hydroxy-β-amino esters are formed in high yields and excellent diastereoselectivities.
The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles.
1,3-DIPOLAR CYCLOADDITION REACTIONS by LEO GAJSLER Thesis presented for the degree of DOCTOR OF PHILOSOPHY University of Edinburgh ABSTRACT A number of reactions between 1,3-dipoles and polydienes were studied, at varying molar ratios.
The. Synthesis Towards Fulminic Acid and Its Derivatives in 1,3-Dipolar Cycloaddition Reactions _____ A thesis. presented to. the faculty of the Department of Chemistry. Synthesis Towards Fulminic Acid and Its Derivatives in 1,3-Dipolar Cycloaddition Reactions _____ A thesis.
presented to. the faculty of the Department of Chemistry.