Abstract

This proposal outlines the development of new chemical methods for alkyl-alkyl cross- coupling reactions to form carbon-carbon bonds. The objectives of this project are to generate new strategies for stereospecific cross-coupling reactions, where the stereochemical information from the electrophilic reaction partner is translated to the newly formed stereogenic center of the product. These methods will be utilized in the synthesis of di- and triarylmethane analogs of anticancer agents. The development of these reactions will directly impact the development of new pharmaceutical agents by providing new methods for their preparation.

Public Health Relevance

The development of new chemical methods for organic synthesis is essential in the preparation of natural products and other bioactive molecules for preliminary biological studies, clinical trials, and production for market. Despite the advanced state of synthetic chemistry serious challenges remain. This proposal describes the development of new chemical reactions that will address one of these challenges, cross-coupling reactions that form tertiary stereogenic centers with control of absolute stereochemistry.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM100212-02
Application #
8523918
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2012-09-01
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$262,606
Indirect Cost
$74,431

  Institution

Name
University of California Irvine
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Hanna, Luke E; Harris, Michael R; Domon, Kenji et al. (2017) Nickel-Catalyzed Hydrogenolysis and Conjugate Addition of 2-(Hydroxymethyl)pyridines via Organozinc Intermediates. Org Lett 19:6304-6307
Zhang, Shuo-Qing; Taylor, Buck L H; Ji, Chong-Lei et al. (2017) Mechanism and Origins of Ligand-Controlled Stereoselectivity of Ni-Catalyzed Suzuki-Miyaura Coupling with Benzylic Esters: A Computational Study. J Am Chem Soc 139:12994-13005
Johnson, Aaron George; Tranquilli, Marissa M; Harris, Michael R et al. (2015) Selective synthesis of either enantiomer of an anti-breast cancer agent via a common enantioenriched intermediate. Tetrahedron Lett 56:3486-3488
Dawson, David D; Jarvo, Elizabeth R (2015) Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Benzylic Ethers with Isotopically-Labeled Grignard Reagents. Org Process Res Dev 19:1356-1359
Tollefson, Emily J; Hanna, Luke E; Jarvo, Elizabeth R (2015) Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers and esters. Acc Chem Res 48:2344-53
Harris, Michael R; Konev, Mikhail O; Jarvo, Elizabeth R (2014) Enantiospecific intramolecular Heck reactions of secondary benzylic ethers. J Am Chem Soc 136:7825-8
Yonova, Ivelina M; Johnson, A George; Osborne, Charlotte A et al. (2014) Stereospecific nickel-catalyzed cross-coupling reactions of alkyl Grignard reagents and identification of selective anti-breast-cancer agents. Angew Chem Int Ed Engl 53:2422-2427
Tollefson, Emily J; Dawson, David D; Osborne, Charlotte A et al. (2014) Stereospecific cross-coupling reactions of aryl-substituted tetrahydrofurans, tetrahydropyrans, and lactones. J Am Chem Soc 136:14951-8
Wisniewska, Hanna M; Swift, Elizabeth C; Jarvo, Elizabeth R (2013) Functional-group-tolerant, nickel-catalyzed cross-coupling reaction for enantioselective construction of tertiary methyl-bearing stereocenters. J Am Chem Soc 135:9083-90
Harris, Michael R; Hanna, Luke E; Greene, Margaret A et al. (2013) Retention or inversion in stereospecific nickel-catalyzed cross-coupling of benzylic carbamates with arylboronic esters: control of absolute stereochemistry with an achiral catalyst. J Am Chem Soc 135:3303-6

Showing the most recent 10 out of 11 publications