Abstract
An overview of new concepts, new algorithms, and new computational
protocols directed at synthetic chemists interested in generating
chiral catalysts is presented in this report. A new mapping tool
called stereocartography is described, which allows one to locate
the most stereoinducing region around a proposed catalyst. Extant
QSAR methods including Comparative Molecular Field Analysis (CoMFA)
and a new technique called QM-QSAR are tools for modeling stereoinduction
and for making predictions about whether a proposed chiral catalyst
will be effective or not. Database mining with the intention of
locating unbiased, unique ligand motifs for use in catalysis is
described. Functionality mapping of transition states is introduced
with the idea of locating where around that transition structure,
functional groups assist or interfere with a given reaction coordinate.
Functionality mapping in combination with database mining is shown
to be an effective way to generate new catalysts for asymmetric
induction. Beyond these new tools, more advanced treatments of chirality
are investigated - the relationship between the chirality
content of a catalyst and its ability to induce asymmetry is discussed
along with the concept of distorting a ligand to make it more or
less chiral.
1 Introduction
1.1 Background
1.2 Computational Chemistry
2 New Concepts in Asymmetric Synthesis
2.1 Stereocartography
2.2 Comparative Molecular Field Analysis (CoMFA)
2.3 QM-QSAR
2.4 Database Mining
2.5 Functionality Mapping
2.6 Functionality Mapping + Database Mining
2.7 Chirality Content and Stereoinduction
2.8 Chirality Content and Ligand Distortion
3 Future Prospects
Key words
asymmetric synthesis - chirality - computational
chemistry - chiral catalysts
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Email: david@chem.ch.huji.ac.il.
