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Several studies are conducted to explain the syntheses of 4,5-, 5,6-, and 6,7-indolyne precursors beginning from commercially available hydroxyindole derivatives. Thus formed precursors are hence shown to exhibit extremely high nucleophilic regioselectivity.

The density functional calculations are applied to study the regioselectivity and stereoselectivity aspects of the Diels-Alder/radical hydrodenitration reaction sequence leading to trans-fused ring systems. The stereoselectivity of radical hydrodenitration of the cis-Diels-Alder adduct are found to be related to the relative conformational stabilities of bicyclic radical intermediates.

Density functional theory calculations are used for examining the regioselectivities of many Diels-Alder reactions used en route to bisanthraquinone antibiotic BE-43472B. The effect of an aromatic conjugation group bonded to juglone is examined.

The density functional theory methods were used to study the mechanism of the asymmetric conjugate addition of alkenylboronates to enones catalyzed by binaphthols. The results obtained provide insight into the factors which affect the reactivities and stereoselectivities of various enones and alkenylboronates.

The GIAO [super 13]C NMR chemical shift calculation was used to show the possibility to distinguish between different diastereoisomers of a bifuranyl. The results obtained were found be sufficiently accurate to distinguish not only the pyran and furanyl isomers, but also between all the diastereoisomers forms such as natural product elatenyne with [2,2]]bifuranyl core.

The effects of the alkoxy protecting group present in the boron enolate on the level and sense of remote 1,5-stereoinduction are examined by using density functional theory calculations. The results have shown that the protecting groups lacking an aromatic group are used for giving high levels of 1,5-anti selectivity and also [beta]-methoxy groups have given rise to moderate levels of 1,5-anti selectivity.

The acetylacetone-benzaldimine Mannich reaction catalyzed by Mg(II) and Ca(II) salts of chiral phosphoric acids (CPA) has been investigated computationally by QM/MM methods. Enantioselectivity in this reaction is both larger than and in the opposite sense to that observed for the same reaction catalyzed by the protic CPA catalyst alone. We present a mechanistic model from which the characteristic differences between these metal and metal-free catalysts, which can coexist in the same reaction mixture, can be understood. Alkaline earth salts with chiral phosphate counterions are found to be more catalytically active than the protic form, and the Ca(II) and Mg(II) CPA salts react via different mechanisms, with a higher coordination number favored by calcium over magnesium. In the well-ordered chiral cavities around these metal centers, asymmetric induction arises from the steric interaction with the imine protecting group in the unfavorable pathway, with both substrates adopting well-defined conformations. These mechanistic models have allowed us to rationalize the stereochemical outcome across a range of bimolecular reactions promoted by divalent metal phosphates formed with different CPAs. [ABSTRACT FROM AUTHOR]

We describe the first theoretical study of a landmark example of chiral anion phase-transfer catalysis: the enantioselective ring-opening of meso-aziridinium and episulfonium cations promoted by asymmetric counteranion-directed catalysis (ACDC). The mechanism of ion-pairing, ring-opening, and catalyst deactivation have been studied in the condensed phase with both classical and quantum methods using explicitly and implicitly solvated models. We find that the stability of chiral ion-pairs, a prerequisite for asymmetric catalysis, is dominated by electrostatic interactions at long range and by CH⋯O interactions at short range. The decisive role of solvent upon ion-pair formation and of nonbonding interactions upon enantioselectivity are quantified by complementary computational approaches. The major enantiomer is favored by a smaller distortion of the substrate, demonstrated by a distortion/interaction analysis. Our computational results rationalize the stereoselectivity for several experimental results and demonstrate a combined classical/quantum approach to perform realistic modeling of chiral counterion catalysis in solution. [ABSTRACT FROM AUTHOR]

An ONIOM(QM/MM) study on the mechanism of the Michael addition to triple bonds catalyzed by chiral diiminophosphorane catalysts has been performed to understand the stereoselectivity of the product olefin. Our results are consistent with the experimental enantioselectivity, but more importantly, reveal that the Z vs E preference depends on the influence of the catalyst upon the geometry of the allenyl enolate formed in the addition step. These intermediates show an innate preference for a (Z)-configuration, although this can be suppressed by steric interactions due to a catalyst. This leads to two distinct mechanisms in which the kinetic basis for (E) or (Z)-stereoselectivity is determined by a different step. Bifunctional iminophosphorane catalysts are found to use steric interactions to override innate stereoelectronic effects of the allenyl enolate reactive intermediate. [ABSTRACT FROM AUTHOR]

Conspectus: This Account describes the use of quantum-chemical calculations to elucidate mechanisms and develop catalysts to accomplish highly selective cyclization reactions. Chemistry is awash with cyclic molecules, and the creation of rings is central to organic synthesis. Cyclization reactions, the formation of rings by the reaction of two ends of a linear precursor, have been instrumental in the development of predictive models for chemical reactivity, from Baldwin's classification and rules for ring closure to the Woodward and Hoffmann rules based on the conservation of orbital symmetry and beyond. Ring formation provides a productive and fertile testing ground for the exploration of catalytic mechanisms and chemo-, regio-, diastereo-, and enantioselectivity using computational and experimental approaches. This Account is organized around case studies from our laboratory and illustrates the ways in which computations provide a deeper understanding of the mechanisms of catalysis in 5-endo cyclizations and how computational predictions can lead to the development of new catalysts for enhanced stereoselectivities in asymmetric cycloisomerizations. [ABSTRACT FROM AUTHOR]

We report a hybrid density functional theory--molecular mechanics study of the mechanism of the addition of nitroalkanes and phosphonates to benzaldehyde catalyzed by a chiral phosphacene catalyst developed by Ooi and co-workers. Our results are consistent with a reaction mechanism in which a catalyst molecule simultaneously interacts by hydrogen bonds with the nucleophile and the electrophile, transferring a proton to the aldehyde in concert with carbon--carbon bond formation. Despite the C2 symmetry of this class of organocatalyst, substrate recognition, and asymmetric induction in both reaction classes studied relies on interactions with nonequivalent N--H bonds that break symmetry. The origin of the stereo and diastereoselectivity is discussed in terms of steric effects and of the conformations adopted by the reactants, and the most favorable transition structure results from minimal geometric distortion energies. A rational model for predicting the major stereoisomer of reactions catalyzed by this chiral phosphacene, based on the qualitative assessment of steric interactions, is given. [ABSTRACT FROM AUTHOR]

The intramolecular Diels-Alder reactions of cycloalkenones and terminal dienes occur with high endo stereoselectivity, both thermally and under Lewis-acidic conditions. Through computations, we show that steric repulsion and tether conformation govern the selectivity of the reaction, and incorporation of either BF, or α-halogenation increases the rate of cycloaddition. With a longer tether, isomerization from a terminal diene to the more stable internal diene results in a more facile cycloaddition. [ABSTRACT FROM AUTHOR]

The Diels-Alder reactions of the cycloalkenes, cyclohexene through cyclopropene, with a series of dienes?1,3-dimethoxybutadiene, cyclopentadiene, 3,6-dimethyltetrazine, and 3,6-bis(trifluoromethyl)- tetrazine?were studied with quantum mechanical calculations and compared with experimental values when available. The reactivities of cycloalkenes as dienophiles were found by a distortion/interaction analysis to be distortion controlled. The energies required for cycloalkenes to be distorted into the Diels-Alder transition states increase as the ring size of cycloalkenes increases from cyclopropene to cyclohexene, resulting in an increase in activation barriers. The reactivities of the dienes are controlled by both distortion and interaction energies. In normal Diels-Alder reactions with cycloalkenes, the electron-rich 1,3-dimethoxybutadiene exhibits stronger interaction energies than cyclopentadiene, but the high distortion energies required for 1,3-dimethoxybutadiene to achieve transition-state geometries overtake the favorable interaction, resulting in higher activation barriers. In inverse-electrondemand Diels-Alder reactions of 3,6-dimethyltetrazine and 3,6-bis(trifluoromethyl)tetrazine, the reactivities are mainly controlled by interaction energies. [ABSTRACT FROM AUTHOR]

The site selectivities and stereoselectivities of C-H oxidations of substituted cyclohexanes and trans-decalins by dimethyldioxirane (DMDO) were investigated computationally with quantum mechanical density functional theory (DFT). The multiconfiguration CASPT2 method was employed on model systems to establish the preferred mechanism and transition state geometry. The reaction pathway involving a rebound step is established to account for the retention of stereochemistry. The oxidation of sclareolide with dioxirane reagents is reported, including the oxidation by the in situ generated tBu-TFDO, a new dioxirane that better discriminates between C-H bonds on the basis of steric effects. The release of 1,3-diaxial strain in the transition state contributes to the site selectivity and enhanced equatorial C-H bond reactivity for tertiary C-H bonds, a result of the lowering of distortion energy. In addition to this strain release factor, steric and inductive effects contribute to the rates of C-H oxidation by dioxiranes. [ABSTRACT FROM AUTHOR]