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.
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.
|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 direct carbonylation of aminoquinoline benzamides. Org Lett 16:4688-90|
|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, aminoquinoline-directed C(sp²)-H bond alkenylation by alkynes. Angew Chem Int Ed Engl 53:10209-12|
|Truong, Thanh; Klimovica, Kristine; Daugulis, Olafs (2013) Copper-catalyzed, directing group-assisted fluorination of arene and heteroarene C-H bonds. J Am Chem Soc 135:9342-5|
|Tran-Vu, Hung; Daugulis, Olafs (2013) Copper-Catalyzed Carboxylation of Aryl Iodides with Carbon Dioxide. ACS Catal 3:|
|Tran, Ly Dieu; Roane, James; Daugulis, Olafs (2013) Directed amination of non-acidic arene C-H bonds by a copper-silver catalytic system. Angew Chem Int Ed Engl 52:6043-6|
|Truong, Thanh; Daugulis, Olafs (2013) Divergent Reaction Pathways for Phenol Arylation by Arynes: Synthesis of Helicenes and 2-Arylphenols. Chem Sci 4:531-535|
|Nadres, Enrico T; Santos, Gerson Ivan Franco; Shabashov, Dmitry et al. (2013) Scope and limitations of auxiliary-assisted, palladium-catalyzed arylation and alkylation of sp2 and sp3 C-H bonds. J Org Chem 78:9689-714|
|Nadres, Enrico T; Daugulis, Olafs (2012) Heterocycle synthesis via direct C-H/N-H coupling. J Am Chem Soc 134:7-10|
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