23 research outputs found
Synthesis and kinetic resolution of N-Boc-2-arylpiperidines
The chiral base n-BuLi/(-)-sparteine or n-BuLi/(+)-sparteine surrogate promotes kinetic resolution of N-Boc-2-arylpiperidines by asymmetric deprotonation. The enantioenriched starting material was recovered with yields 39-48% and ers up to 97:3. On lithiation then electrophilic quench, 2,2-disubstituted piperidines were obtained with excellent yields and enantioselectivities. © 2014 the Partner Organisations
Kinetic resolution of P-stereogenic phosphine boranes via deprotonation using s-butyllithium/(-)-sparteine
One-ligand catalytic asymmetric deprotonation of a phosphine borane: Synthesis of P-stereogenic bisphosphine ligands
Chiral Lithium N,P-amide Complexes. Synthesis, Applications and Structural Studies by NMR and DFT.
Enantiospecific synthesis reactions are of intense interest, owing to the increasing
request for enantiopure compounds in both research and industry. Lithium amides
containing a secondary chelating group are a class of powerful ligands for asymmetric
addition reactions. Based on earlier experiences with lithium N,O and N,S amides,
synthesis and properties of chiral lithium N,P amides and their use in asymmetric
addition are investigated in the present thesis.
Several chiral amines were synthesized with previously published methods, which were improved in different ways. A new synthetic route towards chiral aminophosphines via cyclic sulfamidates has been developed. The use of silica in the synthesis of sulfamidate and the chiral aminophosphine shortened the reaction time considerably, compared to previous methods. The reactions are fast, clean and highyielding. Furthermore, the synthesis could successfully be scaled up with no loss in yield or purity and gives a general and simple route to a wide variety of chiral N,P-ligands from cheap and readily available amino acids.
Solution studies using low temperature 6Li-NMR showed that the chiral lithium N,Pamides form various types of dimers depending on solvent and substituents in the
amino acid backbone. The Li-P interactions in these complexes proved much stronger
than expected, as indicated by the 6Li-31P coupling constant. A stability study on the
aminophosphines with 31P-NMR proved they are relatively air stable.
The newly synthesized lithium N,P amides were used as ligands in the asymmetric
1,2-addition of n-BuLi to benzaldehyde. The chiral N,P-ligands were found to induce
asymmetry to similar or better extent, compared to previously reported chiral N,Oand
N,S-ligands. Enantiomeric ratios up to 98:1 were obtained at –116 °C.
The experiments were complemented by quantum-chemical calculations employing
Density-Functional Theory and Molecular Mechanics (MM), in order to rationalize
the experimental findings. For the MM calculations, a tailored force field was
developed to allow a proper description of the Li-N interaction. Both the aggregation
and solvation of the ligand and the reaction mechanism were investigated. The
predicted solvation and aggregation states as well as the enantioselectivities were in
good accordance with experiment, provided that dispersion interaction was taken into
account in a proper way. It was found that Li-π and π-α-H interactions and solvation
within the complexes are the major contributions to the energy differences between the more stable (R)-transition state compared to its corresponding (S)-transition state
ESTIMATION OF THE ORDER OF A MOVING AVERAGE MODEL FROM AUTOREGRESSIVE AND WINDOW ESTIMATES OF THE INVERSE CORRELATION FUNCTION
Dynamics of the Lithium Amide/Alkyllithium Interactions: Mixed Dimers and Beyond
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