6 research outputs found
Photoinduced, Copper-Catalyzed Alkylation of Amines: A Mechanistic Study of the Cross-Coupling of Carbazole with Alkyl Bromides
We have recently reported that a variety of couplings of nitrogen, sulfur, oxygen, and carbon nucleophiles with organic halides can be achieved under mild conditions (â40 to 30 °C) through the use of light and a copper catalyst. Insight into the various mechanisms by which these reactions proceed may enhance our understanding of chemical reactivity and facilitate the development of new methods. In this report, we apply an array of tools (EPR, NMR, transient absorption, and UVâvis spectroscopy; ESIâMS; X-ray crystallography; DFT calculations; reactivity, stereochemical, and product studies) to investigate the photoinduced, copper-catalyzed coupling of carbazole with alkyl bromides. Our observations are consistent with pathways wherein both an excited state of the copper(I) carbazolide complex ([Cu^I(carb)_2]^â) and an excited state of the nucleophile (Li(carb)) can serve as photoreductants of the alkyl bromide. The catalytically dominant pathway proceeds from the excited state of Li(carb), generating a carbazyl radical and an alkyl radical. The cross-coupling of these radicals is catalyzed by copper via an out-of-cage mechanism in which [Cu^I(carb)_2]^â and [Cu^(II)(carb)_3]^â (carb = carbazolide), both of which have been identified under coupling conditions, are key intermediates, and [Cu^(II)(carb)_3]^â serves as the persistent radical that is responsible for predominant cross-coupling. This study underscores the versatility of copper(II) complexes in engaging with radical intermediates that are generated by disparate pathways, en route to targeted bond constructions
Photoinduced Copper-Catalyzed Alkylation of Amines: A Mechanistic Study of the Cross-Coupling of Carbazole with Alkyl Bromides
Photoinduced, copper-âcatalyzed reactivity of unactivated aryl and alkyl halides and photophysical characterization of a Cu(I) bis(carbazolide) complex
In a 2012 result from the Peters and Fu groups published in Science, a luminescent Cu(PPh3)2(carbazolide) complex was able to perform C-N Ullmann coupling under unusually mild conditions with a 100W-mercury lamp. This study is to date the most substantial evidence toward a single electron transfer (SET) mechanism for Ullmann coupling. Since this result, there have been several joint publications from the Peters and Fu groups entailing ligandless, photo-induced, copper-catalyzed C-N coupling of carbazoles with alkyl halides, other nitrogen nucleophiles with more diverse halide electrophiles, alkylation of amides, as well as carbon-sulfur coupling under mild conditions. This work will describe new coupling reactions which have been obsd. with use of a similar photoinduced, copper-catalyzed methodol., identifying an SET step in the mechanism. It will also report photophys. characterization and data of a copper bis(carbazolide) intermediate in C-N Ullmann coupling
Photoinduced, Copper-Catalyzed CarbonâCarbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature
We have recently reported that, in
the presence of light and a
copper catalyst, nitrogen nucleophiles such as carbazoles and primary
amides undergo CâN coupling with alkyl halides under mild conditions.
In the present study, we establish that photoinduced, copper-catalyzed
alkylation can also be applied to CâC bond formation, specifically,
that the cyanation of unactivated secondary alkyl chlorides can be
achieved at room temperature to afford nitriles, an important class
of target molecules. Thus, in the presence of an inexpensive copper
catalyst (CuI; no ligand coadditive) and a readily available light
source (UVC compact fluorescent light bulb), a wide array of alkyl
halides undergo cyanation in good yield. Our initial mechanistic studies
are consistent with the hypothesis that an excited state of [CuÂ(CN)<sub>2</sub>]<sup>â</sup> may play a role, via single electron
transfer, in this process. This investigation provides a rare example
of a transition metal-catalyzed cyanation of an alkyl halide, as well
as the first illustrations of photoinduced, copper-catalyzed alkylation
with either a carbon nucleophile or a secondary alkyl chloride
Hydrogel Nanoparticles with Covalently Linked Coomassie Blue for Brain Tumor Delineation Visible to the Surgeon
Delineation of tumor margins is a critical and challenging objective during brain cancer surgery. A tumorâtargeting deepâblue nanoparticleâbased visible contrast agent is described, which, for the first time, offers in vivo tumorâspecific visible color staining. This technology thus enables colorâguided tumor resection in real time, with no need for extra equipment or special lighting conditions. The visual contrast agent consists of polyacrylamide nanoparticles covalently linked to Coomassie Blue molecules (for nonleachable blue color contrast), which are surfaceâconjugated with polyethylene glycol and F3 peptides for efficient in vivo circulation and tumor targeting, respectively. Hydrogel nanoparticles containing a high concentration of visible dye by covalent linkage, with PEGylated surface and conjugated tumor targeting moiety, enable visual delineation of brain tumors in vitro and in vivo. This technology enables colorâguided tumor resection in real time, with no need for extra equipment or special lighting conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90550/1/smll_201101607_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90550/2/884_ftp.pd