A computational rationale focused on donor—acceptor interactions J.
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 resonance 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. 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.Synthesis Towards Fulminic Acid and Its Derivatives in 1,3-Dipolar Cycloaddition Reactions _____ A thesis.
presented to. the faculty of the Department of Chemistry. In this second step of the experiment, the syn-benzaldehyde oxime produced undergoes hypochlorite oxidation to form the 1,3-dipolar benzonitrile oxide which then reacts with the dipolariphile styrene in a 1,3-dipolar cycloaddition reaction.
Approval of the thesis: CATALYTIC ASYMMETRIC ONE-POT SYNTHESIS OF PYRROLIDINES VIA 1,3-DIPOLAR CYCLOADDITION REACTION OF AZOMETHINE YLIDES submitted by SEYLAN AYAN in partial fulfillment of the requirements for the degree of Master of Science in Chemistry Department, Middle East Technical University by, Prof.
Mechanistic studies of 1,3-dipolar cycloadditions of bicyclic thioisomünchnones with alkenes. A computational rationale focused on donor–acceptor interactions diagrams etc. contained in this article in third party publications or in a thesis or dissertation provided that the correct acknowledgement is given with the reproduced material. In this second step of the experiment, the syn-benzaldehyde oxime produced undergoes hypochlorite oxidation to form the 1,3-dipolar benzonitrile oxide which then reacts with the dipolariphile styrene in a 1,3-dipolar cycloaddition reaction. 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.
Dr. Canan Özgen _____. 1,3-dipolar cycloaddition reaction. The addition of a 1,3-dipole to an alkene for the synthesis of biological active 1 five-membered heterocyclic rings is a very important. 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. 1. Introduction. Pioneered by Huisgen in the ’s 1, the 1,3-dipolar cycloaddition reaction between acetylenes and azides was brought back into focus by Sharpless and others 2 when they developed the concept of “click chemistry”.
This approach, based on the joining of smaller units mimics the approach used by nature to generate substances.