Frontier Molecular Orbital Theory 1,3-dipolar cycloadditions

Frontier molecular orbital theory correctly rationalizes the regioselectivity of most 1,3-dipolar cycloadditions (73JA7287). When nitrile ylides are used as 1,3-dipoles, the dipole... 

An interpretation based on frontier molecular orbital theory of the regiochemistry of Diels Alder and 1,3-dipolar cycloaddition reactions of the triazepine 3 is available.343 2,4,6-Trimethyl-benzonitrile oxide, for example, yields initially the adduct 6.344... 

The rates of 1,3-dipolar cycloadditions of diazoalkanes to alkenes and alkynes have been determined electron-attracting substituents in the latter increase the rate, in accordance with frontier molecular orbital theory, which predicts that these reactions are controlled by the interaction of the highest occupied molecular orbital of the diazo-compound with the lowest unoccupied molecular orbital of the dipolarophile " the kinetics of the reactions of methyl diazoacetate or phenyl diazomethanesulphonate, on the other hand, give rise to U-shaped activity functions, which is also explained by the theory. Diazomethane or... 

The second-order rate constant of 1,3-dipolar cycloadditions of benzonitrile oxide (85) with various dipolarophiles A-E were determined in water and organic solvents. The greatest accelerating effect was observed in water for the cycloaddition of 85 with electron-rich dipolarophiles A and B and in -hexane for the cycloadditions with electron-poor dipolarophiles C-E (Table 5.6). The results were explained in terms of frontier molecular orbital theory and enforced hydrophobic interactions. 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and 1,3-dipolarophile approach, can be expected to influence the energy of the transition state—and therefore the reaction rate and the structure of the product. This is the essence of frontier molecular orbital (EMO) theory, several accounts of which have been published. 16.317 application of the FMO method to the pericyclic reactions of mesomeric betaines has met with considerable success. The following section describes how the reactivity, electroselectivity, and regioselectivity of these molecules have been rationalized. 

The molecular geometries and the frontier orbital energies of heterophospholes 28-31 were obtained from density functional theory (DFT) calculations at the B3LYP/6-311- -G, level. The 1,3-dipolar cycloaddition reactivity of these heterophospholes in reactions with diazo compounds was evaluated from frontier molecular orbital (FMO) theory. Among the different types of heterophospholes considered, the 2-acyl-l,2,3-diazaphosphole 28, 377-1,2,3,4-triazaphosphole 30, and 1,3,4-thiazaphosphole 31 were predicted to have the highest dipolarophilic reactivities. These conclusions are in qualitative agreement with available experimental results <2003JP0504>. 

In the beginning, Ken created a frontier molecular orbital (FMO) theory of regioselectivity in cycloadditions. In particular, his classic series of papers showed how FMO theory could be used to understand and predict the regioselectivity of 1,3-dipolar cycloadditions. Ken s generalizations about the shapes and energies of frontier molecular orbitals of alkenes, dienes, and 1,3-dipoles, are in common use today and they appear in many texts and research articles. 

Ess DH, Houk KN (2008) Theory of 1,3-dipolar cycloadditions distortion/interaction and frontier molecular orbital models. J Am Chem Soc 130(31) 10187-10198. doi 10.1021/ja800009z... 

Density functional theory (DFT) calculations at the B3LYP/6-31H-G"" level were carried out on the 1,3-dipolar cycloadditions of various heterophospholes, including 1,3-azaphosphole, with diazo compounds across the P=N bond <2003JP0504>. In most cases, the dominant frontier orbital interaction is between HOMO(diazo) with LUMO(heterophosphole) however, 1,3-azaphosphole has a HOMO of high energy and for it, HOMO(heterophosphole)-LUMO(diazo) is also important (HOMO = highest occupied molecular orbital LUMO = lowest unoccupied molecular orbital). 

Theoretical studies are also done to interpret the synthesis reactions and mechanism of reactions. The regioselectivity of 1,3-dipolar cycloaddition reaction between substituted trimethylstannyl-ethynes and nitrile oxides yielding isoxazoles, was interpreted by the application of frontier electron theory <93CPB478>. By the combination of experimental and molecular orbital (ab initio) studies, a multistep mechanism is proposed for unimolecular radical chemistry of isoxazoles in the gas phase <920MS(27)317>. 

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