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Review
The 2×3 Toolbox of Organometallic Methods for Regiochemically Exhaustive Functionalization
Article first published online: 19 NOV 2004
DOI: 10.1002/anie.200300645
Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Schlosser, M. (2005), The 2×3 Toolbox of Organometallic Methods for Regiochemically Exhaustive Functionalization. Angew. Chem. Int. Ed., 44: 376–393. doi: 10.1002/anie.200300645
Publication History
- Issue published online: 29 DEC 2004
- Article first published online: 19 NOV 2004
- Manuscript Revised: 17 MAY 2004
- Manuscript Received: 22 DEC 2003
- Abstract
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Keywords:
- halogen–metal permutation;
- metalation;
- protecting groups;
- regioflexibility;
- synthesis planning
Abstract
This Review describes a concept aimed at rational and maximal structure proliferation. To this end, simple aromatic or heterocyclic starting materials, often bulk chemicals, are converted into all regionisomerically possible polar organometallic intermediates (mostly lithiated species), which then may be combined with any of the countless electrophiles to provide attractive new building blocks, particularly functionalized derivatives. The practical implementation relies on a set (“toolbox”) of sophisticated recipes developed by mechanistically guided modification of the two most prominent exchange methods used for the generation of polar organometallic compounds: hydrogen–metal and halogen–metal interconversion. These mutant methods (“old methods in a new outfit”) amplify the existing options for organic synthesis by ensuring maximum regioflexibility. At the same time they offer new insight into factors that govern organometallic reactivity and provide hints on how to alter or finetune this reactivity judiciously.