) Palladium-catalyzed coupling reactions serve as extremely useful tools for the synthesis of biologically active compounds. We propose to develop more powerful catalysts for these reactions, focusing primarily on complexes that employ bulky, electron-rich P(t-Bu)3 as a ligand. For an array of important carbon-carbon bond-forming processes (e.g., Suzuki, Heck, Stille, and Negishi couplings), we intend to develop: general methods for coupling organic chlorides; versatile catalysts for coupling organic bromides, iodides, and triflates under mild conditions (e.g., at room temperature) and general methods for coupling organic phosphates and tosylates. Although our primary objective is to provide practical catalysts that will be widely applied by synthetic chemists both in basic research and in pharmaceutical/chemical development, we will also pursue mechanistic studies directed at furnishing an improved understanding of the origin of the unusual reactivity of Pd/P(t-Bu)3 in these coupling processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062871-03
Application #
6636607
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2001-04-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
3
Fiscal Year
2003
Total Cost
$279,511
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Wang, Zhaobin; Yin, Haolin; Fu, Gregory C (2018) Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins. Nature 563:379-383
Wang, Zhaobin; Bachman, Shoshana; Dudnik, Alexander S et al. (2018) Nickel-Catalyzed Enantioconvergent Borylation of Racemic Secondary Benzylic Electrophiles. Angew Chem Int Ed Engl 57:14529-14532
Choi, Junwon; Fu, Gregory C (2017) Transition metal-catalyzed alkyl-alkyl bond formation: Another dimension in cross-coupling chemistry. Science 356:
Mu, Xin; Shibata, Yu; Makida, Yusuke et al. (2017) Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling. Angew Chem Int Ed Engl 56:5821-5824
Kalek, Marcin; Fu, Gregory C (2017) Caution in the Use of Nonlinear Effects as a Mechanistic Tool for Catalytic Enantioconvergent Reactions: Intrinsic Negative Nonlinear Effects in the Absence of Higher-Order Species. J Am Chem Soc 139:4225-4229
Fu, Gregory C (2017) Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes. ACS Cent Sci 3:692-700
Schmidt, Jens; Choi, Junwon; Liu, Albert Tianxiang et al. (2016) A general, modular method for the catalytic asymmetric synthesis of alkylboronate esters. Science 354:1265-1269
Zuo, Zhiwei; Cong, Huan; Li, Wei et al. (2016) Enantioselective Decarboxylative Arylation of ?-Amino Acids via the Merger of Photoredox and Nickel Catalysis. J Am Chem Soc 138:1832-5
Chu, Crystal K; Liang, Yufan; Fu, Gregory C (2016) Silicon-Carbon Bond Formation via Nickel-Catalyzed Cross-Coupling of Silicon Nucleophiles with Unactivated Secondary and Tertiary Alkyl Electrophiles. J Am Chem Soc 138:6404-7
Liang, Yufan; Fu, Gregory C (2015) Nickel-Catalyzed Alkyl-Alkyl Cross-Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds having a Perfluoroalkyl Substituent. Angew Chem Int Ed Engl 54:9047-51

Showing the most recent 10 out of 71 publications