We are engaged in the systematic efforts to exploit new, efficient, and broadly useful palladium/norbornene (Pd/NBE) catalysis for site-specific arene mono- and di-functionalization. Our objective in the proposed funding period includes: first to develop new classes of vicinal di- functionalization, e.g. ortho amination, acylation, thiolation and annulation with epoxides by discovering new classes of electrophiles; and second to address the ?ortho effect? limitation (requirement of a pre-existing ortho substituent) by developing new NBE-type ligands. The proposed research is expected to vastly expand the toolbox for arene functionalization via site- specifically installing functional groups at unactivated positions, which in turn would streamline synthesis of complex biologically important molecules containing multi-substituted aromatic scaffolds.

Public Health Relevance

Poly-substituted arenes and heteroarenes are ubiquitous in pharmaceuticals and approved drugs; however, the efficiency of using conventional approaches to access these structural motifs remains to be improved. The outlined proposal aims to enable new efficient catalytic methods for direct preparation of poly-substituted arenes and heteroarenes from readily available feedstocks. Success of the proposed research would significantly expedite the synthesis of complex aromatic molecules, which, in turn, would ultimately accelerate drug discovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM124414-01A1
Application #
9513846
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2018-06-01
Project End
2022-04-30
Budget Start
2018-06-01
Budget End
2019-04-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637