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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM077635-06A1
Application #
8501892
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2007-06-05
Project End
2017-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
6
Fiscal Year
2013
Total Cost
$285,713
Indirect Cost
$95,713
Name
University of Houston
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
036837920
City
Houston
State
TX
Country
United States
Zip Code
77204
Roane, James; Daugulis, Olafs (2016) A General Method for Aminoquinoline-Directed, Copper-Catalyzed sp(2) C-H Bond Amination. J Am Chem Soc 138:4601-7
Mesgar, Milad; Daugulis, Olafs (2016) Silylaryl Halides Can Replace Triflates as Aryne Precursors. Org Lett 18:3910-3
Klimovica, Kristine; Kirschbaum, Kristin; Daugulis, Olafs (2016) Synthesis and Properties of ""Sandwich"" Diimine-Coinage Metal Ethylene Complexes. Organometallics 35:2938-2943
Nguyen, Tung Thanh; Grigorjeva, Liene; Daugulis, Olafs (2016) Cobalt-Catalyzed, Aminoquinoline-Directed Functionalization of Phosphinic Amide sp(2) C-H Bonds. ACS Catal 6:551-554
Daugulis, Olafs; Roane, James; Tran, Ly Dieu (2015) Bidentate, monoanionic auxiliary-directed functionalization of carbon-hydrogen bonds. Acc Chem Res 48:1053-64
Grigorjeva, Liene; Daugulis, Olafs (2015) Cobalt-promoted dimerization of aminoquinoline benzamides. Org Lett 17:1204-7
Truong, Thanh; Mesgar, Milad; Le, Ky Khac Anh et al. (2014) General method for functionalized polyaryl synthesis via aryne intermediates. J Am Chem Soc 136:8568-76
Grigorjeva, Liene; Daugulis, Olafs (2014) Cobalt-catalyzed, aminoquinoline-directed coupling of sp(2) C-H bonds with alkenes. Org Lett 16:4684-7
Grigorjeva, Liene; Daugulis, Olafs (2014) Cobalt-catalyzed direct carbonylation of aminoquinoline benzamides. Org Lett 16:4688-90
Grigorjeva, Liene; Daugulis, Olafs (2014) Cobalt-catalyzed, aminoquinoline-directed C(sp²)-H bond alkenylation by alkynes. Angew Chem Int Ed Engl 53:10209-12

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