Highly enantioselective electrophilic amination and michael addition of cyclic beta-ketoesters induced by lanthanides and (S,S)-ip-pybox: the mechanism.

High enantioselection is obtained in Michael additions of cyclic beta-ketoesters in the presence of lanthanium triflates and (S,S)-ip-pybox. Intermediates based on simultaneous coordination of the lanthanide to both (S,S)-ip-box and beta-ketoester (in keto and enolate forms) are detected by means of ESI mass spectrometry and NMR experiments, and a possible mechanism is proposed through theoretical calculations.

A QM/MM study of the asymmetric dihydroxylation of terminal aliphatic n-alkenes with OsO4.(DHQD)2PYDZ: enantioselectivity as a function of chain length.

The dihydroxylation of terminal aliphatic n-alkenes catalyzed by OsO4(DHQD)2PYDZ ((DHQD)2PYDZ=bis(dihydroquinidine)pyridazine) has been computationally studied by the hybrid QM/MM IMOMM(Becke3LYP:MM3) method. The cases of propene, 1-butene, 1-pentene, 1-hexene, 1-heptene, 1-octene, 1-nonene, and 1-decene have been considered. A systematic treatment for the large number of possible conformations of the longer chain alkenes has been defined and applied, leading to the selection of approximately 1700 conformations to be computed. The IMOMM calculations of the transition states formed between these conformations and the catalyst generate enantiomeric excesses that closely resemble the experimental data of related systems, specifically in the preference for the R isomer and in its dependence on the chain length of the substrate. The selectivity increases sharply with the elongation of the short-chain alkenes until a ceiling value is reached, with further elongations having little effect on the enantiomeric excess (ee). These results are rationalized through the partitioning of the total energy of selected conformers, a process that leads to the identification of the most relevant regions of the catalyst and the characterization of the interactions critical for selectivity.

Some critical issues in the application of quantum mechanics/molecular mechanics methods to the study of transition metal complexes.

The application of quantum mechanics/molecular mechanics (QM/MM) methods in transition metal chemistry is growing steadily. It becomes therefore appropriate to assess the importance of a number of technical issues associated to their implementation. This work presents the discussion of several of these issues, including the eventual need for conformational searches, the choice of the MM force field and the possibility of its tuning. The examples presented here prove that a proper handling of these technical aspects can lead to an improvement in the efficiency and quality of QM/MM calculations.