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Synlett 2003(10): 1547-1565
DOI: 10.1055/s-2003-40849
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© Georg Thieme Verlag Stuttgart ˙ New York

Understanding Stereoinduction in Catalysis via Computer: New Tools for Asymmetric Synthesis

Kenny B. Lipkowitz*a, Marisa C. Kozlowskib
a Department of Chemistry, Ladd Hall 104, North Dakota State University, Fargo, North Dakota 58105-5516, USA
e-Mail: kenny.lipkowitz@ndsu.nodak.edu;
b Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA
e-Mail: marisa@sas.upenn.edu;
Further Information

Publication History

Received 5 May 2003
Publication Date:
24 July 2003 (online)

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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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For a complete description of this methodology see: Dixon, S. L.; Lauri, G.; Merz, K. M. Jr. in preparation.

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CAVEAT V2.2, Bartlett, P. A. U.; C. Berkeley.

73

Email: david@chem.ch.huji.ac.il.