The asymmetric hydroformylation in the synthesis of pharmaceuticals
Article first published online: 21 SEP 2004
Copyright © 1991 Wiley-Liss, Inc.
Volume 3, Issue 4, pages 355–369, 1991
How to Cite
Botteghi, C., Paganelli, S., Schionato, A. and Marchetti, M. (1991), The asymmetric hydroformylation in the synthesis of pharmaceuticals. Chirality, 3: 355–369. doi: 10.1002/chir.530030422
- Issue published online: 21 SEP 2004
- Article first published online: 21 SEP 2004
- Manuscript Accepted: 14 MAY 1991
- Manuscript Received: 25 FEB 1991
- enantiomerically pure compounds;
- chiral drugs;
- enantioselective hydroformylation;
- enantioselective catalysts;
- biologically active compounds
The asymmetric hydroformylation reaction represents a potential powerful synthetic tool for the preparation of large number of different chiral products to be used as precursors of several organic compounds endowed with therapeutic activity. Essential and nonessential amino acids, 2-arylpropanoic acids, aryloxypropyl- and β-phenylpropylamines, modified β-phenylethylamines, pheniramines, and other classes of pharmaceuticals are available through enantioselective oxo-reaction of appropriate functionalized olefins; this process is catalyzed by rhodium or platinum complexes with chiral ligands, mainly chelating phosphines, and sometimes affords very high enantiomeric excesses. Furthermore, the application of many simple optically active aldehydes arising from asymmetric hydroformylation as chiral building blocks for the synthesis of complex pharmacologically active molecules such as antibiotics, peptides, antitumor macrocycle compounds, and prostaglandins is conveniently emphasized. The possibility of a future application of this asymmetric process for the production of many synthons to obtain other valuable pharmaceuticals is widely discussed too.