Synthesis of 2-iodoynamides and regioselective [2+2] cycloadditions with ketene

The first synthesis of 2-iodoynamides is described as well as the first [2+2] cycloadditions of ketene with iodo alkynes.National Institutes of Health (U.S.) (GM 28273)Boehringer Ingelheim PharmaceuticalsMerck Research Laboratorie

Lost in a sea of sameness : lack of differentiation dominates the telecommunications industry

Based on our analysis of the websites and Twitter feeds of the top 30 global players in the telecom sector , telecommunications companies are hell bent on telling their customers they are no different from their competitors. Everyone is selling similar solutions that claim to improve the customer ’s business by the identical processes of : transformation, acceleration, growth, integration, scalability, securit

A [4+4] annulation strategy for the synthesis of eight-membered carbocycles based on intramolecular cycloadditions of conjugated enynes

A [4+4] annulation strategy for the synthesis of eight-membered carbocycles is reported that proceeds via a cascade involving two pericyclic processes. In the first step, the [4+2] cycloaddition of a conjugated enyne with an electron-deficient cyclobutene generates a strained six-membered cyclic allene that isomerizes to the corresponding 1,3-cyclohexadiene. In the second step, this bicyclo[4.2.0]octa-2,4-diene intermediate undergoes thermal or acid-promoted 6-electron electrocyclic ring opening to furnish a 2,4,6-cyclooctatrienone. The latter transformation represents the first example of the promotion of 6-electron electrocyclic ring opening reactions by acid.National Institutes of Health (U.S.) (GM 28273)Pfizer Inc.National Science Foundation (U.S.). Graduate Research FellowshipAstraZeneca (Firm) (Graduate Fellowship)David A. Johnson Summer Graduate Fellowshi

Evaluating the thermal vinylcyclopropane rearrangement (VCPR) as a practical method for the synthesis of difluorinated cyclopentenes : experimental and computational studies of rearrangement stereospecificity

Vinyl cyclopropane rearrangement (VCPR) has been utilised to synthesise a difluorinated cyclopentene stereospecifically and under mild thermal conditions. Difluorocyclopropanation chemistry afforded ethyl 3-(1'(2'2'-difluoro-3'-phenyl)cyclopropyl) propenoate as all four stereoisomers (18a, 18b, 22a, 22b) (all racemic). Trans-E isomer (18a), prepared in 70% yield over three steps, underwent near quantitative VCPR to difluorocyclopentene 23 (99%). Rearrangements were followed by 19F NMR (100-180 °C). While cis/trans cyclopropane stereoisomerisation was facile, favouring trans-isomers by a modest margin, no E/Z alkene isomerisation was observed even at higher temperatures. Neither cis nor trans Z-alkenoates underwent VCPR, even up to much higher temperatures (180 oC). Cis-cyclopropanes underwent [3,3]-rearrangement to afford benzocycloheptadiene species. The reaction stereospecificity was explored using electronic structure calculations and UB3LYP/6-31G* methodology allowed the energy barriers for cyclopropane stereoisomerisation, diastereoisomeric VCPR and [3,3]-rearrangement to be ranked in agreement with experiment

Tricyclo­[3.3.1.03,7]nonane-3,7-diyl bis­(methane­sulfonate)

The crystal structure of the title compound, C11H18O6S2, was determined to investigate the effect of the eclipsed mesyl groups on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane [maximum deviation 0.01 Å], resulting in an eclipsing conformation of the C—O bonds. The C—C bond of the quaternary C atoms is 1.597 (3) Å is considerably longer than the other C—C bonds of the mol­ecule

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

A Common Carcinogen Benzo[a]pyrene Causes Neuronal Death in Mouse via Microglial Activation

BACKGROUND: Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels. CONCLUSIONS/SIGNIFICANCE: Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our study throws light on other health hazards that such pollutants may exert

Recent Progress in Steroid Synthesis Triggered by the Emergence of New Catalytic Methods

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154510/1/ejoc201901466_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154510/2/ejoc201901466.pd

New Syntheses and Ring Expansion Reactions of Cyclobutenimines

Two routes are reported for the synthesis of iminocyclobutenones having N-(het)aryl substitution: an addition/substitution sequence starting with cyclobutenediones and an aza-Wittig method. A new synthetic route to N-alkyl derivatives is also presented. This involves O-alkylation of 3-alkylamino-1,2-cyclobutenediones using Meerwein's reagent and subsequent deprotonation under non-hydrolytic conditions. Lithium organyls were found to add to the remaining carbonyl group. The resulting tertiary alcohols undergo ring enlargement on heating in xylene to give 4-aminophenols, 4-amino-1-naphthols, or cyclopenta-annulated quinolines from 4-vinyl, 4-aryl, and 4-alkynyl derivatives, respectively. © CSIRO 2010