UNIVERSITY OF ARIZONA, TUCSON, ARIZONA UNIVERSITY OF ARIZONA, DEPT OF CHEMISTRY
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Michael P. Doyle
B.S. 1964, College of Saint Thomas
Ph.D. 1968, Iowa State University

office OC 328
email mdoyle@u.arizona.edu
phone (520) 626-4815
fax (520) 626-7960

Highly Enantioselective Transition Metal Catalysts for Organic Syntheses

Our research program is focused on the design and development of transition metal catalysts capable of high selectivity in organic chemical transformations that extend from intermolecular reactions to macrocyclizations. Focus is placed on pharmaceutical applications.

We have developed chiral catalysts that are effective for a broad range of metal carbene and Lewis acid catalyzed transformations. None are as general in their applications as dirhodium(II) compounds that possess four chiral carboxamidate ligands. Optical yields at or greater than 95% have been achieved in intramolecular cyclopropanation reactions with allyl diazoacetates and diazoacetamides, in alkyne cyclopropenation reactions, and in gamma-lactone production from carbon-hydrogen insertion reactions of diazoacetate esters, including those of lignan lactones, deoxysugar derivatives, and other pharmaceutically active compounds. Diastereoselectivity, regioselectivity, and chemoselectivity are high, and enantiomer differentiation is achieved with exceptional ease.

Catalyst turnover is high, especially in scale-up, and when immobilized on polymer supports, the recoverable dirhodium(II) catalyst retains its effectiveness in eight or more sequential transformations. The basis for the high level of enantiocontrol that has been achieved with the use of these dirhodium(II) carboxamidates is attributed to the organization of the four chiral amide ligands around the dirhodium nucleus and stabilization of the intermediate metal carbene.

Previously regarded as selective only for the formation of five- and six-membered ring ketones and lactones in intramolecular reactions, transformations of diazocarbonyl compounds catalyzed by select rhodium(II) and copper(I) compounds have been broadly extended to the production of ten- to twenty-membered rings with high chemoselectivity, as well as enantio- and regiocontrol. Enantiocontrol is also high with these catalysts in hetero-Diels-Alder reactions where record low catalyst loadings are required (<0.01 mol % catalyst). Extension to other reactions is underway.


SELECTED PUBLICATIONS

M. P. Doyle, I. M. Phillips, and W. Hu, "A New Class of Chiral Lewis Acid Catalysts for Highly Enantioselective Hetero-Diels-Alder Reactions: Exceptionally High Turnover Numbers from Dirhodium(II) Carboxamidates," J. Am. Chem. Soc., 123, 5366-5367 (2001).

M. P. Doyle, W. Hu, and D. J. Timmons, "Highly Stereoselective Syntheses of Five- and Seven-Membered Ring Heterocycles from Ylides Generated by Catalytic Reactions of Styryldiazoacetates with Aldehydes and Imines," Org. Lett., 3, 3741-3744 (2001).

M. P. Doyle, W. Hu, and M. V. Valenzuela, "Total Synthesis of (S)-(+)-Imperanene. Effective use of Regio- and Enantioselective Intramolecular Carbon-Hydrogen Insertion Reactions Catalyzed by Chiral Dirhodium(II) Carboxamidates," J. Org. Chem., 67, 2954-2959 (2002).

W. Hu, D. J. Timmons, and M. P. Doyle, "In Search of High Stereocontrol for the Construction of cis-Disubstituted Cyclopropane Compounds. Total Synthesis of a Cyclopropane-Configured Urea-PETT Analog That is a HIV-1 Reverse Transcriptase Inhibitor," Org. Lett., 4, 901-904 (2002).

M. P. Doyle, D. J. Timmons, J. S. Tumonis, H.-M. Gau, and E. C. Blossey, "Preparation and Catalytic Properties of Immobilized Chiral Dirhodium(II) Carboxamidates," Organometallics, 21, 1747-1749 (2002).

M. P. Doyle, "Asymmetric Cyclopropanation and C-H Insertion," in Catalytic Asymmetric Synthesis, Second Edition, I. Ojima, Ed., John Wiley & Sons, Inc., New York, 2000, Chapter 5.


UNIVERSITY OF ARIZONA CHEMISTRY HOMEPAGE SITE CONTACT
chemweb@arizona.edu
LAST MODIFIED
date: Tue, 05 Nov 2002 18:21:46 GMT
time: Tue, 05 Nov 2002 18:21:46 GMT