A method for elucidating the relative configuration of acyclic organic compounds was developed on the basis of carbon-proton spin-coupling constants ((2,3)J(C,H)) and interproton spin-coupling constants ((3)J(H,H)). This method is based on the theory that, in acyclic systems, the conformation of adjacent asymmetric centers is represented by staggered rotamers, and their relative stereochemistry can be determined using (2,3)J(C,H) and (3)J(H,H), because the combined use of these J values enables the identification of the predominant staggered rotamer(s) out of the six possible derived from threo and erythro configurations. Detailed conformational analysis for model compounds 1-4 revealed that this method is useful in most cases for assignment of the configuration of acyclic structures occurring in natural products, in which stereogenic methine carbons are often substituted with a methyl or a hydroxy (alkoxy) group. This J-based configuration analysis was applied to the stereochemical elucidation of carboxylic acid 5 derived from zooxanthellatoxin and proven to be a practical method even for natural products with complicated structures.

As the first step to understand the reaction mechanism and diastereoselectivity of sodium borohydride reduction of ketones, ab initio Car-Parrinello molecular dynamics simulation has been performed on a solution of NaBH4 in liquid methanol. According to pointwise thermodynamic integration involving constrained molecular dynamics simulations, it was strongly suggested that Na+ and BH4(-) are associated in the solvent forming contact ion pairs. Thus we propose a new transition state structure model that contains complexation of the carbonyl oxygen with sodium cation. Predicted diastereoselectivity of the reduction of some substituted cyclohexanones applying this novel transition state model is in good agreement with experimental data, showing its validity and effectiveness to investigate the diastereoselectivity of NaBH4 reduction of other ketones.

The “cis effect” is a phenomenon in which the cis isomer is more stable than the corresponding trans isomer or almost the same stability in some molecules with double bonds. In order to clarify the predominant factor of this cis effect in the 1,2-dihaloethenes (XHC=CHX; 1: X=F, 2: Cl, and 3: Br), the energetic amount of electron delocalizations and steric exchange repulsions were theoretically estimated using the natural bond orbital (NBO) theory at MP2/6-311++G(3df,3pd) level. Two delocalization mechanisms, periplanar hyperconjugations (synperiplanar and antiperiplanar effects) and halogen lone pair delocalizations into the C=C bond antibonding orbitals (LP effect), were found as the cis stabilizing forces, in which the total amount of LP effect was greater than those of periplanar effects, the dominant factor of the cis effect. Moreover, the origin of the cis preference of the LP effect was clearly elucidated with the application of orbital phase theory, i.e., the cyclic orbital interaction was continuous only in the cis isomers of 1–3. The total steric exchange repulsion between two isomers were all trans stabilizing and their energetic gains were 1.26, 16.48, and 23.22 kJ mol−1 for 1, 2, and 3, respectively. These steric forces obviously counteract against cis preferable delocalization mechanisms, especially in compounds with larger halogen atoms, but their amounts are apparently less than those of electron delocalizations (29.82, 40.00, and 34.46 kJ mol−1 for 1, 2, and 3, respectively). Therefore, electron delocalization, not exchange repulsion, has the largest responsibility for the relative energies of 1,2-dihaloethene systems. The importance of this work is the quantitative elucidation of the dominance of delocalization mechanisms over steric effects on the electronic and energetic view of a simple molecular structure.

A study of adamantanylidenes having a γ-substituent (R) was undertaken to gauge how inductive and steric effects of remotely positioned functional groups influence intra- and intermolecular product selectivity. 3H-Diazirines were thermolyzed or photolyzed to generate the corresponding carbenes. On rapid heating, the resulting carbenes isomerized to 2,4-didehydroadamantanes by intramolecular 1,3-CH insertions. When R was an electron donor (R(D)) mostly asymmetric 1-substituted derivatives were produced but when it was an electron acceptor (R(A)) the symmetric 7-substituted ones were formed. When solutions were exposed to UV-A light, intermolecular adducts from the carbenes and solvent predominated with lesser amounts of intramolecular product being formed. Valence isomerization of 3H-diazirines also afforded diazo compounds. In methanol, protonation of diazo compounds to give the corresponding 2-adamantyl cations exceeds their coupling. This diversion was controlled with fumaronitrile by trapping the diazo compounds. The adducts possessed mostly anti configurations with R = R(D) and syn arrangements with R = R(A). The connection between as- and anti-product formation and that of s- and syn-products was deemed to be the consequence of a rapid equilibrium between two distinct carbene conformations. This was qualified and quantified using ab initio calculations and NBO analyses.