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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.

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]

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 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]

The stereochemistry of conformationally mobile five-membered rings is often hard to assign from NMR data, and [2,2′]bifuranyl systems are even more challenging. GIAO 13C NMR chemical shifts have been calculated for a series of [2,2′]bifuranyl and pyranopyran species, taking into account their conformational flexibility using weighted averages of the data for all low energy conformers. We show that calculation of 13C NMR chemical shifts using the geometries obtained using molecular mechanics greatly reduces the computational expense without a significant loss of accuracy, even in this demanding system. The results were sufficiently accurate to distinguish not only the pyran and furanyl isomers but also between all the diastereoisomeric forms. As a result of this validation, we predict the stereochemistry for the recently proposed revised structure of the natural product elatenyne, which contains a [2,2′]bifuranyl core. [ABSTRACT FROM AUTHOR]

The boron-mediated aldol reactions of certain types of β-alkoxy methyl ketone show remarkably high levels of stereoinduction with achiral aldehydes, leading preferentially to 1,5-anti related stereocenters. Given the low levels of asymmetric induction usually observed in acetate aldol reactions, this is of great synthetic utility and has been used successfully in the total synthesis of a number of polyketide natural products. We have investigated the effects of the alkoxy protecting group (OMe, OPMB, PMP acetal, tetrahydropyran, and OTBS) present in the boron enolate on the level and sense of remote 1,5- stereoinduction, using density functional theory calculations (B3LYP/6-31G**). Our predictions of diastereoselectivity from comparison of the competing aldol transition structures are in excellent qualitative and quantitative agreement with experimentally reported values. We conclude that the boron aldol reactions of unsubstituted boron enolates proceed via boat-shaped transition structures in which a stabilizing formyl hydrogen bond exists between the alkoxy oxygen and the aldehyde proton. It is this interaction that leads to preferential formation of the 1,5-anti adduct, by minimizing steric interactions between the β-alkyl group and one of the ligands on boron. In the case of silyl ethers, the preference for this internal hydrogen bond is not observed due to the size of the protecting group and the electron-poor oxygen atom that donates electron density into the adjacent silicon atom. We show that this stereochemical model is also applicable in rationalizing the 1,4-syn stereoselectivity of boron aldol reactions involving certain u-chiral methyl ketones. These detailed results may be summarized as a conformational diagram that can be used to predict the sense of stereoinduction. [ABSTRACT FROM AUTHOR]

Quantum chemical studies of C-ethylation of 1-methyl- and 1,4,4-trimethyl-tropane-derived enamines predict good (89:11 er, B3LYP) and high (98:2 er, B3LYP) levels, respectively, of asymmetric induction in the resulting α-alkylated aldehydes. The nonracemic tropanes were synthesized using Mannich cyclization strategies (Robinson-Schöpf and by way of a Davis-type N-sulfinyl amino bisketal, respectively), and ethylation of the derived enamines was found to support the predicted sense and magnitude of asymmetric induction (81:19 er and 95:5 er, respectively). A comparison of several computational methods highlights the robustness of predicted trends in enantioselectivity, enabling theory to guide synthesis.

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.

The stereochemistry of conformationally mobile five-membered rings is often hard to assign from NMR data, and [2,2']bifuranyl systems are even more challenging. GIAO (13)C NMR chemical shifts have been calculated for a series of [2,2']bifuranyl and pyranopyran species, taking into account their conformational flexibility using weighted averages of the data for all low energy conformers. We show that calculation of (13)C NMR chemical shifts using the geometries obtained using molecular mechanics greatly reduces the computational expense without a significant loss of accuracy, even in this demanding system. The results were sufficiently accurate to distinguish not only the pyran and furanyl isomers but also between all the diastereoisomeric forms. As a result of this validation, we predict the stereochemistry for the recently proposed revised structure of the natural product elatenyne, which contains a [2,2']bifuranyl core.