Nelson G. Rondan

Theoretical studies of stereoselective hydroborations

Abstract Asymmetric hydroborations of alkenes are outstanding examples of reactions which proceed with high acyclic stereoselection to give synthetically useful functionality. We have undertaken com- putational studies of these reactions as a part of our more general studies of stereoselective organic reactions. We wish to develop understanding of those factors which control stereoselectivity in known cases, and to develop both qualitative and quantitative methods to predict stereoselectivities of cases not yet investigated. Here, we detail our progress in understanding hydroborations, and in subsequent publications, we will report similar studies for other types of organic reactions, such as intermolecular and intramolecular cycloadditions, epoxidations, radical reactions, nucleophilic additions, and aldol condensations.

Theoretical studies of halocarbene cycloaddition selectivities : A new interpretation of negative activation energies and entropy control of selectivity

Abstract Ab initio RHF calculations with the 3–21G basis set have been carried out on cycloadditions of CF2 and CCl2 with ethylene. Although π-complex intermediates are predicted for both reactions at this level, MP2/3-21G calculations imply that there are no complexes in reactions of CCl2 or more reactive carbenes with ethylene or substituted alkenes. Nevertheless, negative activation energies can be observed, since ΔG reaches a maximum due to the increase in —TΔS for these bimolecular reactions. The apparent “entropy control” for reactive carbenes results from the rapid decrease in ΔH. As the reactivity of the alkene increases, the transition state shifts to an earlier point on the free energy surface, where —TΔS‡ is lower, but ΔH‡ is higher than for less reactive alkenes. Model potentials are developed for ΔH and —TΔS which reproduce experimental behavior, without the assumption of intermediates.

The relative rates of electron-rich and electron-deficient alkene cycloadditions to benzyne. Enhanced electrophilicity as a consequence of alkyne bending distortions.

Abstract Benzyne reacts more rapidly with electron-rich alkenes than electron-deficient alkenes, a result of the abnormally low energy LUMO of benzyne, which results from the acetylene bending enforced by the benzyne geometry.

Ab initio transition structures for 1,5-sigmatropic hydrogen shifts of 1,3-pentadiene and cyclopentadiene

Abstract 3-21G transition structures for 1,5-sigmatropic hydrogen shifts of 1,3-pentadiene and cyclopentadiene have been located. The CHC angles in the transition structures are 130° and 68°, respectively. The difference in calculated activation energies for the two reactions agrees with the experimental difference.

Stereoselectivities of benzonitrile oxide cycloadditions to cis disubstituted cyclopentenes and dihydrofurans

Abstract Benzonitrile oxide cycloadds preferentially anti to the substituents of cis -3,5-di-X-cyclopentenes, where X = OMe, OAc, OCOPh, Br, Cl, and OH. Higher stereoselectivities are found for cis -2,5-di-X-2,5-dihydrofurans. The origins of these selectivities, and contrasts with acyclic and cyclobutene analogs, are described.

Configuration and conformation of lithiated imines by DNMR studies and ab initio calculations

Abstract The N-isopropyl imine of lithioacetaldehyde, I, was found to exist as a 50 : 50 mixture of two isomers, as seen below 20°C by 1H and 13C NMR. Comparison of the population ratio and spectral characteristics of the isomers of this and related lithiated imines leads to the conclusion that they are rotamers all of which possess the syn configuration. This conclusion is supported by calculations of the barriers to interconversion.

On the mechanism of regioselectivity control by donor substituents on electrophilic alkenes: applications to quinone cycloadditionregioselectivity

Abstract Donor substitution on alkenes slightly increases the LUMO coefficient at the site of substitution. However, nucleophiles preferentially attack the unsubstituted terminus of the alkene due to direct repulsive interactions between the nucleophile and the substituent. Secondary orbital interactions make the terminus remote from the site of substitution the most electrophilic. LUMO coefficients, or equivalent spectroscopic measures, esr hyperfine coupling in the esr spectra of radical anions, are appropriate for prediction of reactivities of unsubstituted positions but not substituted ones.

The triplet ground state of di-tert-butylcarbene

Abstract STO-3G calculations indicate that the triplet state of di- tert -butylcarbene is on the order of 25 kcal/mol more stable than the singlet. Because of steric repulsions between the tert -butyl groups, the central CCC angles are 132.5° and 142° for the singlet and triplet, respectively. The normal alkyl group stabilization of the singlet is overridden by destabilization due to the seterically forced increase of the central angle.

Geometries and rotational barriers of alkylamides and lithium alkylamides.

The barriers to rotation of methylamide, ethylamide and the corresponding lithium amides have been computed at the ab initio 4-31G level. The barriers to rotation about the CN bond are higher for amides than for amines, but are lowered by coordination with Li+.

Transition structures for the reaction of difluorocarbene with propene

Abstract Two ab initio transition structures for the reaction of difluorocarbene with propene have been located with gradient techniques and the 3-21G basis set. The activation energy is 1.3 kcal/mol lower than for the reaction with ethylene. Two transition structures with the fluorines approaching syn or anti to the methyl group are identical in energy