Base or nucleophile? DFT finally elucidates the origin of the selectivity between the competitive reactions triggered by MeLi or LDA on propanal.

The competition between basicity and nucleophilicity of two standard organolithium reagents was studied using DFT. Comparing the reactivity of solvated (MeLi)2 and (LDA)2 toward propanal finally explains why methyllithium adds onto the carbonyl while LDA deprotonates the α-position, in accord with experiment and Ireland's deprotonation TS.

A DFT theoretical analysis of aldehyde condensation pathways onto methyllithium, lithium dimethylamide, and their aggregates

A DFT analysis of the condensation of monomeric methyllithium and lithium dimethylamide (LMA), as well as their homo and hetero dimers, on formaldehyde and acetaldehyde is reported. A stable complex, exhibiting a directional interaction between a lone pair of the oxygen on the aldehyde and a lithium, is first found. At this stage, the aldehyde carbonyl and the Li-X (X = C or N) bonds lie in the same plane. To proceed, the condensation reaction has to go through a transition state that mainly consists of a rotation of the aldehyde plane, placing it perpendicular to the C-C or C-N forming bond. The reaction then leads, in a strongly exothermic final step, to the addition product that is a lithium alcoholate or alpha-amino alcoholate, associating into an hetero-aggregate with the remaining moiety of the initial dimer. From the relative heights of the activation barriers, it appears that, for the heterodimer MeLi-LMA, the formation of the C-N bond should be kinetically favored over the C-C one, while the lithium ethylate resulting from the C-C binding is the thermodynamic product. A decomposition of the activation energy barriers has been carried out in order to determine the physicochemical forces responsible for the variation of the condensation activation barriers with the structure of the final species formed. The results obtained are discussed in relation with corresponding experimental data.

Theoretical Investigations of the Influence of Pressure on the Selectivity of the Michael Addition of Diphenylmethaneamine to Stereogenic Crotonates.

SIBFA (sum of interactions between fragments ab initio computed) molecular mechanics systematics has been modified to take into account the effect of pressure on intra- and intermolecular energies. The van der Waals radii are related to the pressure, using Bridgman results on the variation of crystal volume, on one hand, and the relation between the volume of an atom and its van der Waals radius on the other. This procedure produces a decrease of the volume of the systems considered. The modified systematics is used for the study of the conformation at 1 atm and 15 kbar of two stereogenic crotonates and of the complexes formed by these two molecules with the diphenylmethaneamine and the three solvent molecules present in the experiment. The results obtained show that in the case of NMECC 1a the diastereoselectivity induced by high pressure and by the presence of methanol proceeds from an important stabilization of the pro-R reactive complex in which the crotonate has a stacked-transoid conformation. This stabilization is mainly due to intermolecular interactions. In the case of the second crotonate considered, NMCC 1b, our results indicate that pressure induces a stabilization of the pro-R and pro-S complexes having the axial conformation for which the reaction exhibits little diastereoselectivity in qualitative agreement with experimental data. This study tends to show that it is possible to account theoretically for the influence of pressure on molecular conformation and/or complex structure, using a molecular mechanics method that is able to take into account the variation of volumes of the different entities present in the system studied.