9 research outputs found
In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis
Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidineâ5âcarbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ highâresolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively
A Combined Experimental and Theoretical Study on the Stereodynamics of Monoaza[5]helicenes: Solvent-Induced Increase of the Enantiomerization Barrier in 1-Aza-[5]helicene
Helicenes and heterohelicenes are attractive compounds with great potential in materials sciences to be used in optoelectronics as ligand backbones in enantioselective catalysis and as chiral sensors. The properties of these materials are related to the stereodynamics of these helical chiral compounds. However, little is known about features controlling stereodynamics in helicenes; in particular, for heterohelicenes the position of the heteroatom could be relevant in this respect. Herein the complete stereodynamic characterization of monoaza[5]helicenes is shown by enantioselective dynamic HPLC and DFT calculations. At variance with previous theoretical calculations, 1-aza[5]helicene shows a surprisingly high enantiomerization barrier, which is triggered by specific solvent interactions
Toward structure-based predictive tools for the selection of chiral stationary phases for the chromatographic separation of enantiomers
International audienceChirBase, a database for the chromatographic separation of enantiomers containing more than 200,000 records compiled from the literature, was used to develop quantitative structure activity models for the prediction of which chiral stationary phase will work for the separation of a given molecule. Constructuion of QSAR models for the enantioseparation of nineteen chiral stationary phases was attempted using only analyte structural information, leading to the producton of self-consistent models in four cases. These models were tested by predicting which in-house racemic compounds would and would not be resolved on the different columns. Some degree of success was observed, but the sparseness of data within ChirBase, which contains enantioseparations for only a subset of molecules on a subset of columns under a variety of conditions may limit the creation of effective models. Augmented data sets gleaned from automated chromatographic method development systems deployed in academic and industrial research laboratories or the use of models that take other factors such as solvent composition, temperature, etc. into account could potentially be useful for the development of more robust models
A Combined Experimental and Theoretical Study on the Stereodynamics of Monoaza[5]helicenes: SolventâInduced Increase of the Enantiomerization Barrier in 1âAzaâ[5]helicene
Helicenes and heterohelicenes are attractive compounds with great potential in materials sciences to be used in optoelectronics as ligand backbones in enantioselective catalysis and as chiral sensors. The properties of these materials are related to the stereodynamics of these helical chiral compounds. However, little is known about features controlling stereodynamics in helicenes; in particular, for heterohelicenes the position of the heteroatom could be relevant in this respect. Herein the complete stereodynamic characterization of monoaza[5]helicenes is shown by enantioselective dynamic HPLC and DFT calculations. At variance with previous theoretical calculations, 1-aza[5]helicene shows a surprisingly high enantiomerization barrier, which is triggered by specific solvent interactions
An Asymmetric, Catalytic (4 + 3) Cycloaddition Reaction of Cyclopentenyl Oxyallylic Cations
Treatment of 2-tosyloxycyclopentanone
with substituted furans in
the presence of a chiral amino alcohol catalyst and K<sub>2</sub>HPO<sub>4</sub> results in the formation of (4 + 3) cycloaddition products
with enantioselectivities that exceed 90% in certain cases
Development of a Thiophosphorylation Process for the Synthesis of 2â˛F-Thio-Adenosine Monophosphate
The
process development for 2â˛F-thio-adenosine monophosphate,
an intermediate for MK-1454, an immunooncology therapeutic, is described.
Kinetic profiling, nuclear magnetic resonance monitoring, investigation
of product decomposition pathways, and crystallization control identified
important parameters for an efficient thiophosphorylation process.
Among those identified parameters are the use of pivaloyl as the protecting
group for the nucleoside starting material as well as the use of triethylphosphate
as a green reaction solvent, both of which are critical for allowing
a homogeneous reaction mixture and key to the success of the large-scale
reaction. These insights enabled an optimized thiophosphorylation
process, which delivered 2â˛F-thio-adenosine monophosphate in
77% overall yield at a 2.5 kg scale