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.
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.
|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|
|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|
|Swift, Elizabeth C; Jarvo, Elizabeth R (2013) Asymmetric transition metal-catalyzed cross-coupling reactions for the construction of tertiary stereocenters. Tetrahedron 69:5799-5817|
|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|