The development of powerful new methods for the generation of carbon-carbon bonds has an impact on a wide array of disciplines that require the synthesis of organic compounds (e.g., biological chemistry, pharmaceutical chemistry, and biology). Transition metals can catalyze carbon-carbon bond-forming processes, such as cross-couplings of organic electrophiles and nucleophiles, that would otherwise be difficult or impossible to achieve. During the next grant period, this program will pursue a largely unexplored dimension of cross-coupling reactions-processes that employ alkyl electrophiles as substrates. Efforts will focus on the development of versatile catalysts, including chiral catalysts, for a wide range of powerful bond-forming processes. Such reactions have the potential to simultaneously generate a carbon-carbon bond and to define up to two new stereocenters. Mechanistic studies will play an important role in this project, since an improved understanding of metal-based reactivity could facilitate catalyst development. This research area offers an exciting opportunity to have a substantial impact on synthetic chemistry, as well as to enrich our understanding of once-unexpected chemical reactivity.

Public Health Relevance

In order to probe many biological questions and to develop new therapeutic compounds, there is a need to be able to synthesize organic molecules efficiently and to control the chirality (""""""""handedness"""""""") of the target compounds. This proposal is directed at addressing both of these challenges.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM062871-11
Application #
8207918
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2001-04-01
Project End
2012-05-31
Budget Start
2012-01-01
Budget End
2012-05-31
Support Year
11
Fiscal Year
2012
Total Cost
$118,727
Indirect Cost
$38,532
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
Ziegler, Daniel T; Fu, Gregory C (2016) Catalytic Enantioselective Carbon-Oxygen Bond Formation: Phosphine-Catalyzed Synthesis of Benzylic Ethers via the Oxidation of Benzylic C-H Bonds. J Am Chem Soc 138:12069-72
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

Showing the most recent 10 out of 33 publications