Substituent effects on the rate of formation of azomethine ylides. A computational investigation.

The effect of substituents on the rate of conrotatory thermal cleavage of aziridine has been studied at the MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level and also using SCS-MP2 methodology. While the parent compound has a high free energy of activation (194.6 kJ mol(-1)), this value could be drastically lowered by substituent effects.

Torquoselectivity studies in the generation of azomethine ylides from substituted aziridines.

Aziridines are useful precursors to the azomethine ylide family of 1,3-dipoles whose cycloaddition chemistry has been extensively exploited in the synthesis of heterocyclic targets. The torquoselectivity of aziridines that lack a plane of symmetry was investigated as an essential component of the calculation of the overall relative reaction rates and in prediction of the stereochemistry of the 2,3-trans compounds in 1,3-dipolar cycloaddition chemistry. It has been found at the MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level that outward rotation is preferred for electronegative or anionic substituents while electropositive and cationic substituents favor inward rotation.

Is nucleophilic cleavage chemistry practical for 4-membered heterocycles?

A computational study at the MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level of the ammonolysis of halogen substituted azetidines, oxetanes and thietanes was performed in the gas phase and in the commonly used solvent, acetonitrile. Using the free energy of activation of a benchmark reaction for evaluation of synthetic viability, several haloazetidines and oxetanes that possessed the required reactivity were identified; however, no substituted thietane investigated herein was determined to be synthetically useful under the mild conditions selected for this study. In the case of the azetidines, the side reaction of displacement of halide ion was determined to be the preferred reaction course in acetonitrile; however, the amino product of the reactions of the 2-haloazetidines cleaved at an acceptable rate under mild conditions.

Dramatic effects of halogen substitution and solvent on the rates and mechanisms of nucleophilic substitution reactions of aziridines.

In a previous study we reported that fluorine substitution at the carbon positions of aziridine results in profound enhancements of the rate of reaction with ammonia, a typical nucleophile, in the gas phase. In this study the investigation is extended to include chloro- and bromoaziridines. Because syntheses are largely performed in the condensed phase, the present computational investigation [(MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level] was conducted with three typical solvents that cover a wide range of polarity: THF, CH3CN, and H2O.

The profound effect of fluorine substitution on the reactivity and regioselectivity of nucleophilic substitution reactions of strained heterocycles. A study of aziridine and its derivatives.

Unlike the synthetically exploited oxiranes and thiiranes, aziridines that lack electron-withdrawing substituents, such as acyl or sulfonyl functionalities at nitrogen, are rather unreactive. As expected, three-membered aziridine 6 was calculated to be significantly more reactive than azetidine 7 in nucleophilic cleavage by ammonia, a typical nucleophile. The reactivity of 7 was about the same as that of an acyclic model compound, 8, when release of ring strain in the transition state was taken into account.

A computational study to elucidate the extraordinary reactivity of three-membered heterocycles in nucleophilic substitution reactions.

The accelerated rates of small-membered heterocycles relative to acyclic analogues are typically rationalized solely in terms of relief of ring strain. The relative rates of attack of ammonia on oxirane, oxetane, thiirane, and thietane were determined computationally in the gas phase at the MP2(Full)/6-31+G(d) level with respect to the model acyclic compounds methoxyethane and thiomethylethane. Because the cyclic ether and thioether pairs have very similar strain energies, they should react at similar rates by the S(N)2 mechanism if the degree of strain energy release in the transition state is approximately equal.

Glycoside-clustering round calixarenes toward the development of multivalent ligands. Synthesis and conformational analysis of Calix[4]arene O- and C-glycoconjugates.

Bis- and tetra-O- and C-glycosyl calixarenes (calixsugars) have been prepared by tethering carbohydrate moieties to a tetrapropoxycalix[4]arene scaffold through alkyl chains. Two methodologies have been employed. One consisted of the stereoselective multiple glycosylation of upper rim calix[4]arene polyols leading to calix-O-glycosides; the other involved a multiple Wittig olefination of upper rim calix[4]arene-derived polyaldehydes by the use of sugar phosphoranes and reduction of the alkene double bonds affording calix-C-glycosides.

Computational and experimental studies of di- and tetrasubstituted calix[4]arenes.

Calixarenes are molecular bowls or baskets that have been demonstrated to serve as hosts for cations, anions, and neutral molecules. The central cavity and scaffolding of various functionalities on the upper and lower rims establishes this class of compounds as extremely important in supramolecular chemistry studies. In earlier studies, calixsugars (molecules that have sugar molecules appended to the upper rim of the calix) were prepared.