The primary goal of the proposed research is to develop new and useful transformations using carbon-hydrogen bond activation reactions. While extensive synthetic methodology has been developed based on oxidative addition reactions of C-X bonds (X=halogen, heteroatom), catalytic C-C bond forming reactions arising from C-H bond activation are less common despite the wider availability, price, and environmental advantages of the starting hydrocarbons compared to functionalized compounds. The reactions arising from C-H bond activation will complement the current methods for C-C bond formation and will have a substantial impact on synthetic methodology. In this project, palladium-catalyzed arylation, alkylation, vinylation, and alkynylation of unactivated sp3 C-H bonds will be explored in context of synthesis of biologically relevant unnatural amino acid derivatives. Furthermore, we will explore palladium-catalyzed fluorination of unactivated sp3 C-H bonds. Additionally, we have obtained preliminary results showing that auxiliaries developed for the palladium-catalyzed C-H bond functionalization are effective for copper-catalyzed sp2 C-H bond arylation, sulfenylation, and amination. We have a substantial amount of preliminary data showing that proposed chemistry is viable and may lead to useful methodology.
The specific aims of the research are as follows: 1. New auxiliary and reaction development for sp3 C-H bond conversion to C-C bonds, 2. Fluorination of unactivated sp3 C-H bonds, 3. Auxiliary assisted, copper-catalyzed C-H bond functionalization.

Public Health Relevance

The primary goal of the proposed research is to develop new and useful transformations using carbon-hydrogen bond activation reactions. We propose new transformations that will lead to more efficient pathways for making pharmaceutical intermediates. These more efficient methods may lead to lower-cost production of medications. Additionally, improved synthetic methods may allow production of complicated drug structures that currently would be too expensive.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Houston
Schools of Arts and Sciences
United States
Zip Code
Nguyen, Tung Thanh; Grigorjeva, Liene; Daugulis, Olafs (2018) Cobalt-Catalyzed Coupling of Benzoic Acid C-H Bonds with Alkynes, Styrenes, and 1,3-Dienes. Angew Chem Int Ed Engl 57:1688-1691
Kwak, Se Hun; Gulia, Nurbey; Daugulis, Olafs (2018) Synthesis of Unsymmetrical 2,6-Diarylanilines by Palladium-Catalyzed C-H Bond Functionalization Methodology. J Org Chem 83:5844-5850
Mesgar, Milad; Nguyen-Le, Justin; Daugulis, Olafs (2018) New Hindered Amide Base for Aryne Insertion into Si-P, Si-S, Si-N, and C-C Bonds. J Am Chem Soc :
Nguyen, Tung Thanh; Daugulis, Olafs (2017) Palladium-catalyzed, aminoquinoline-directed arylation of phosphonamidate and phosphinic amide sp3 C-H bonds. Chem Commun (Camb) 53:4609-4611
Mesgar, Milad; Daugulis, Olafs (2017) Synthesis of 1,2-Bis(trifluoromethylthio)arenes via Aryne Intermediates. Org Lett 19:4247-4250
Gulia, Nurbey; Daugulis, Olafs (2017) Palladium-Catalyzed Pyrazole-Directed sp3 C-H Bond Arylation for the Synthesis of ?-Phenethylamines. Angew Chem Int Ed Engl 56:3630-3634
Nguyen, Tung Thanh; Grigorjeva, Liene; Daugulis, Olafs (2017) Aminoquinoline-directed, cobalt-catalyzed carbonylation of sulfonamide sp2 C-H bonds. Chem Commun (Camb) 53:5136-5138
Kocen, Andrew L; Brookhart, Maurice; Daugulis, Olafs (2017) Palladium-catalysed alkene chain-running isomerization. Chem Commun (Camb) 53:10010-10013
Nguyen, Tung Thanh; Grigorjeva, Liene; Daugulis, Olafs (2016) Cobalt-Catalyzed, Aminoquinoline-Directed Functionalization of Phosphinic Amide sp2 C-H Bonds. ACS Catal 6:551-554
Klimovica, Kristine; Kirschbaum, Kristin; Daugulis, Olafs (2016) Synthesis and Properties of ""Sandwich"" Diimine-Coinage Metal Ethylene Complexes. Organometallics 35:2938-2943

Showing the most recent 10 out of 48 publications