Mechanistic overview[ edit ] Originally two proposed mechanisms describe the 1,3-dipolar cycloaddition:
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 Thesis on 1 3-dipolar cycloaddition 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.How to Cite. Aureggi, V. and Sedelmeier, G. (), 1,3-Dipolar Cycloaddition: Click Chemistry for the Synthesis of 5-Substituted Tetrazoles from Organoaluminum Azides and Nitriles.
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.
Dr. Canan Özgen _____. The 1,3-dipolar cycloaddition (1,3DC) reaction (Fig. ) can be more precisely defined as, the addition of 1,3-dipole to an alkene for the synthesis of five membered Dipolar Cycloaddition.
Synthesis Towards Fulminic Acid and Its Derivatives in 1,3-Dipolar Cycloaddition Reactions _____ A thesis. presented to. the faculty of the Department of Chemistry.