Expanding the palette of phenanthridinium cations

5,6-Disubstituted phenanthridinium cations have a range of redox, fluorescence and biological properties. Some properties rely on phenanthridiniums intercalating into DNA, but the use of these cations as exomarkers for the reactive oxygen species (ROS), superoxide, and as inhibitors of acetylcholine esterase (AChE) do not require intercalation. A versatile modular synthesis of 5,6-disubstituted phenanthridiniums that introduces diversity by Suzuki–Miyaura coupling, imine formation and microwave-assisted cyclisation is presented. Computational modelling at the density functional theory (DFT) level reveals that the novel displacement of the aryl halide by an acyclic N-alkylimine proceeds by an SNAr mechanism rather than electrocyclisation. It is found that the displacement of halide is concerted and there is no stable Meisenheimer intermediate, provided the calculations consistently use a polarisable solvent model and a diffuse basis set

Copper-Catalyzed Regioselective Ortho C-H Cyanation of Vinylarenes

A copper-based catalytic technique for the regioselective ortho C-H cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of vinylarene derivatives. A copper-catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction.National Institutes of Health (U.S.) (GM46059

Tandem chemoselective Suzuki-Miyaura cross-coupling enabled by nucleophile speciation control

Control of boronic acid speciation is presented as a strategy to achieve nucleophile chemoselectivity in the Suzuki-Miyaura reaction. Combined with simultaneous control of oxidative addition and transmetallation, this enables chemoselective formation of two C-C bonds in a single operation, providing a method for the rapid preparation of highly functionalized carbogenic frameworks

Functionalization of Styrenes by Copper‐Catalyzed Borylation/ ortho‐Cyanation and Silver‐Catalyzed Annulation Processes

An efficient two‐step method for the assembly of indanone derivatives starting from a simple vinyl arene has been developed. The sequence first involves addition of bis(pinacolato)diboron (B2pin2) and N‐cyano‐N‐phenyl‐p‐methylbenzenesulfonamide (NCTS) to a broad range of styrenes by utilizing IMesCuCl as catalyst. This step simultaneously accomplishes hydroboration of the alkene and ortho cyanation of the benzene unit. The products thus obtained are further functionalized by a AgNO3/Selectfluor‐mediated coupling of the BPin and cyano functionalities to annulate a new five‐membered ring. This combined two‐step sequence provides a versatile method for the site‐selective derivatization of a broad range of vinyl arene substrates.A Cu and Ag sequence: The bis‐functionalization of styrenes is accomplished through a copper‐catalyzed process that enables hydroboration of the alkene and regioselective ortho cyanation of the arene. The resulting adducts are converted, by a radical cyclization process, into a cyclopentanone unit fused to the original aromatic ring. Together, these methods allow efficient cyclopentannulation of a broad range of styrene derivatives.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115938/1/anie_201507303_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115938/2/12683_ftp.pd

Synthesis of quaternary aryl phosphonium salts: photoredox-mediated phosphine arylation

We report a synthesis method for the construction of quaternary aryl phoshonium salts at ambient temperature. The regiospecific reaction invovles the coupling of phosphines with aryl radicals derived from diaryliodonium salts under photoredox conditions

Bone metastases from renal cell carcinoma: patient survival after surgical treatment

<p>Abstract</p> <p>Background</p> <p>Surgery is the primary treatment of skeletal metastases from renal cell carcinoma, because radiation and chemotherapy frequently are not effecting the survival. We therefore explored factors potentially affecting the survival of patients after surgical treatment.</p> <p>Methods</p> <p>We retrospectively reviewed 101 patients operatively treated for skeletal metastases of renal cell carcinoma between 1980 and 2005. Overall survival was calculated using the Kaplan-Meier method. The effects of different variables were evaluated using a log-rank test.</p> <p>Results</p> <p>27 patients had a solitary bone metastasis, 20 patients multiple bone metastases and 54 patients had concomitant visceral metastases. The overall survival was 58% at 1 year, 37% at 2 years and 12% at 5 years. Patients with solitary bone metastases had a better survival (p < 0.001) compared to patients with multiple metastases. Age younger than 65 years (p = 0.036), absence of pathologic fractures (p < 0.001) and tumor-free resection margins (p = 0.028) predicted higher survival. Gender, location of metastases, time between diagnosis of renal cell carcinoma and treatment of metastatic disease, incidence of local recurrence, radiation and chemotherapy did not influence survival.</p> <p>Conclusions</p> <p>The data suggest that patients with a solitary metastasis or a limited number of resectable metastases are candidates for wide resections. As radiation and chemotherapy are ineffective in most patients, surgery is a better option to achieve local tumor control and increase the survival.</p