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 (−40 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 UV–vis spectroscopy; ESI–MS; 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]^−) 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]^− and [Cu^(II)(carb)_3]^− (carb = carbazolide), both of which have been identified under coupling conditions, are key intermediates, and [Cu^(II)(carb)_3]^− 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 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 Carbon–Carbon 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 C–N coupling with alkyl halides under mild conditions. In the present study, we establish that photoinduced, copper-catalyzed alkylation can also be applied to C–C 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 [Cu­(CN)₂]⁻ 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 tumor‐targeting deep‐blue nanoparticle‐based visible contrast agent is described, which, for the first time, offers in vivo tumor‐specific visible color staining. This technology thus enables color‐guided 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 surface‐conjugated 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 color‐guided 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