Efficient and selective preparation of organic molecules is critical for the synthesis of therapeutics. Many of the most proficient known processes depend on the availability of catalysts. One of the advantages of organometallic catalysis is the ability to tune the activity and selectivity through modification of the ligands around the metal center. Recently, major advances have been reported thanks to the use of electron-rich phosphines and cyclic diaminocarbenes. We have uncovered several novel families of stable carbenes, such as the cyclic (alkyl)(amino)carbenes and the diaminocyclopropenylidenes, which behave as even more electron-donating ligands. They have already allowed for improving known palladium and ruthenium catalyzed processes, and even for promoting new metal catalyzed reactions. The full catalytic potential of complexes bearing these carbene ligands will be investigated. In order to obtain even more robust and efficient transition-metal catalysts, novel types of carbon- based ligands, which surpass the electron donating properties imposed by any other ligands, will be prepared. Special attention will be drawn on families of ligands for which it will be possible to precisely tune the steric and electronic parameters. There is a high demand for technology to produce therapeutics in a pure enantiomeric form, thus optically active versions of our new ligands will be prepared. The studies will be focused on catalytic processes for which real difficulties remain, and on chemical transformations, which have not yet been achieved, but are of critical importance for building the skeleton of complex molecules. Cascade reactions that involves several reactants, yet a single catalyst, and which lead to biologically relevant heterocycles and to important synthons will be developed. To accelerate the widespread implementation of our ligands, we have already formalized a collaboration with Robert Grubbs at Caltech, and we are looking forward to further partnerships. The ultimate goal of this research effort is to find truly practical catalysts, and catalytic reactions, which will find applications in both industry and academia for the selective synthesis of biologically important compounds. )

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM068825-08
Application #
8299498
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2005-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
8
Fiscal Year
2012
Total Cost
$386,574
Indirect Cost
$96,235
Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Martin, Caleb D; Soleilhavoup, Michele; Bertrand, Guy (2013) Carbene-Stabilized Main Group Radicals and Radical Ions. Chem Sci 4:3020-3030
Back, Olivier; Henry-Ellinger, Martin; Martin, Caleb D et al. (2013) 31P NMR chemical shifts of carbene-phosphinidene adducts as an indicator of the ?-accepting properties of carbenes. Angew Chem Int Ed Engl 52:2939-43
Ung, Gael; Bertrand, Guy (2013) *- and *-Hydride abstraction in Gold(I) alkyl complexes. Angew Chem Int Ed Engl 52:11388-91
Ung, Gael; Soleilhavoup, Michele; Bertrand, Guy (2013) Gold(III)- versus gold(I)-induced cyclization: synthesis of six-membered mesoionic carbene and acyclic (aryl)(heteroaryl) carbene complexes. Angew Chem Int Ed Engl 52:758-61
Ruiz, David A; Ung, Gael; Melaimi, Mohand et al. (2013) Deprotonation of a borohydride: synthesis of a carbene-stabilized boryl anion. Angew Chem Int Ed Engl 52:7590-2
Mendoza-Espinosa, Daniel; Donnadieu, Bruno; Bertrand, Guy (2011) Facile preparation of homo- and hetero-dimetallic complexes with a 4-phosphino-substituted NHC ligand. Toward the design of multifunctional catalysts. Chem Asian J 6:1099-103
Dehope, Alan; Donnadieu, Bruno; Bertrand, Guy (2011) Grubbs and Hoveyda-Type Ruthenium Complexes Bearing a Cyclic Bent-Allene. J Organomet Chem 696:2899-2903
Mendoza-Espinosa, Daniel; Ung, Gael; Donnadieu, Bruno et al. (2011) Mesoionic thiazol-5-ylidenes as ligands for transition metal complexes. Chem Commun (Camb) 47:10614-6
Ung, Gael; Mendoza-Espinosa, Daniel; Bouffard, Jean et al. (2011) A stable acyclic ligand equivalent of an unstable 1,3-dithiol-5-ylidene. Angew Chem Int Ed Engl 50:4215-8
Martin, David; Soleilhavoup, Michele; Bertrand, Guy (2011) Stable singlet carbenes as mimics for transition metal centers. Chem Sci 2:389-399

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