Catalytic Enantioselective Carbon–Oxygen Bond Formation: Phosphine-Catalyzed Synthesis of Benzylic Ethers via the Oxidation of Benzylic C–H Bonds

Benzylic alcohols and ethers are common subunits in bioactive molecules, as well as useful intermediates in organic chemistry. In this Communication, we describe a new approach to the enantioselective synthesis of benzylic ethers through the chiral phosphine-catalyzed coupling of two readily available partners, γ-aryl-substituted alkynoates and alcohols, under mild conditions. In this process, the alkynoate partner undergoes an internal redox reaction. Specifically, the benzylic position is oxidized with good enantioselectivity, and the alkyne is reduced to the alkene

Biphenyl-Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations To Form Functionalized Cyclopentenes

Because of the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. Introduced herein is a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes which bear a fully substituted stereocenter [either all-carbon or heteroatom-substituted (sulfur and phosphorus)]. Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four-carbon coupling partner is not the turnover-limiting step of the catalytic cycle

Direct Access to β-Fluorinated Aldehydes by Nitrite-Modified Wacker Oxidation

An aldehyde-selective Wacker-type oxidation of allylic fluorides proceeds with a nitrite catalyst. The method represents a direct route to prepare β-fluorinated aldehydes. Allylic fluorides bearing a variety of functional groups are transformed in high yield and very high regioselectivity. Additionally, the unpurified aldehyde products serve as versatile intermediates, thus enabling access to a diverse array of fluorinated building blocks. Preliminary mechanistic investigations suggest that inductive effects have a strong influence on the rate and regioselectivity of the oxidation

Frictional cooling of positively charged particles

One of the focuses of research and development towards the construction of a muon collider is muon beam preparation. Simulation of frictional cooling shows that it can achieve the desired emittance reduction to produce high-luminosity muon beams. We show that for positively charged particles, charge exchange interactions necessitate significant changes to schemes previously developed for negatively charged particles. We also demonstrate that foil-based schemes are not viable for positive particles.Comment: 15 pages, 6 figure

Strong Balmer lines in old stellar populations: No need for young ages in ellipticals?

Comparing models of Simple Stellar Populations (SSP) with observed line strengths generally provides a tool to break the age-metallicity degeneracy in elliptical galaxies. Due to the wide range of Balmer line strengths observed, ellipticals have been interpreted to exhibit an appreciable scatter in age. In this paper, we analyze Composite Stellar Population models with a simple mix of an old metal-rich and an old metal-poor component. We show that these models simultaneously produce strong Balmer lines and strong metallic lines without invoking a young population. The key to this result is that our models are based on SSPs that better match the steep increase of Hbeta in metal-poor globular clusters than models in the literature. Hence, the scatter of Hbeta observed in cluster and luminous field elliptical galaxies can be explained by a spread in the metallicity of old stellar populations. We check our model with respect to the so-called G-dwarf problem in ellipticals. For a galaxy subsample covering a large range in UV-V colors we demonstrate that the addition of an old metal-poor subcomponent does not invalidate other observational constraints like colors and the flux in the mid-UV.Comment: Accepted for publication in ApJ Main Journal, 9 pages, 5 figure

A Versatile Approach to Ullmann C−N Couplings at Room Temperature: New Families of Nucleophiles and Electrophiles for Photoinduced, Copper-Catalyzed Processes

The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C−N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C−N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease

The epochs of early-type galaxy formation as a function of environment

The aim of this paper is to set constraints of the epochs of early-type galaxy formation through the 'archaeology' of the stellar populations in local galaxies. Using our models of absorption line indices that account for variable abundance ratios, we derive the stellar population parameters of 124 early-type galaxies in high and low density environments. We find that all three parameters age, metallicity, and alpha/Fe ratio are correlated with velocity dispersion. We further find evidence for an influence of the environment on the stellar population properties. Massive early-type galaxies in low-density environments appear on average ~2 Gyrs younger and slightly more metal-rich than their counterparts in high density environments. No offsets in the alpha/Fe ratios, instead, are detected. We translate the derived ages and alpha/Fe ratios into star formation histories. We show that most star formation activity in early-type galaxies is expected to have happened between redshifts 3 and 5 in high density and between redshifts 1 and 2 in low density environments. We conclude that at least 50 per cent of the total stellar mass density must have already formed at z 1, in good agreement with observational estimates of the total stellar mass density as a function of redshift. Our results suggest that significant mass growth in the early-type galaxy population below z 1 must be restricted to less massive objects, and a significant increase of the stellar mass density between redshifts 1 and 2 should be present caused mainly by the field galaxy population. The results of this paper further imply vigorous star formation episodes in massive objects at z 2-5 and the presence of evolved ellipticals around z 1, both observationally identified as SCUBA galaxies and EROs.Comment: 20 pages, 10 figures, plus appendix, accepted by Ap

Direct Access to β-Fluorinated Aldehydes by Nitrite-Modified Wacker Oxidation

An aldehyde-selective Wacker-type oxidation of allylic fluorides proceeds with a nitrite catalyst. The method represents a direct route to prepare β-fluorinated aldehydes. Allylic fluorides bearing a variety of functional groups are transformed in high yield and very high regioselectivity. Additionally, the unpurified aldehyde products serve as versatile intermediates, thus enabling access to a diverse array of fluorinated building blocks. Preliminary mechanistic investigations suggest that inductive effects have a strong influence on the rate and regioselectivity of the oxidation