We report here a catalytic method for the modular ring expansion of cyclic aliphatic alcohols. In this work, proton-coupled electron transfer activation of an allylic alcohol substrate affords an ...alkoxy radical intermediate that undergoes subsequent C–C bond cleavage to furnish an enone and a tethered alkyl radical. Recombination of this alkyl radical with the revealed olefin acceptor in turn produces a ring-expanded ketone product. The regioselectivity of this C–C bond-forming event can be reliably controlled via substituents on the olefin substrate, providing a means to convert a simple N-membered ring substrate to either n+1 or n+2 ring adducts in a selective fashion.
The directed activation of carbon-hydrogen bonds (C-H) is important in the development of synthetically useful reactions, owing to the proximity-induced reactivity and selectivity that is enabled by ...coordinating functional groups. Palladium-catalysed non-directed C-H activation could potentially enable further useful reactions, because it can reach more distant sites and be applied to substrates that do not contain appropriate directing groups; however, its development has faced substantial challenges associated with the lack of sufficiently active palladium catalysts. Currently used palladium catalysts are reactive only with electron-rich arenes, unless an excess of arene is used, which limits synthetic applications. Here we report a 2-pyridone ligand that binds to palladium and accelerates non-directed C-H functionalization with arene as the limiting reagent. This protocol is compatible with a broad range of aromatic substrates and we demonstrate direct functionalization of advanced synthetic intermediates, drug molecules and natural products that cannot be used in excessive quantities. We also developed C-H olefination and carboxylation protocols, demonstrating the applicability of our methodology to other transformations. The site selectivity in these transformations is governed by a combination of steric and electronic effects, with the pyridone ligand enhancing the influence of sterics on the selectivity, thus providing complementary selectivity to directed C-H functionalization.
High quality-factor (Q) optical resonators are a key component for ultra-narrow linewidth lasers, frequency stabilization, precision spectroscopy and quantum applications. Integration in a photonic ...waveguide platform is key to reducing cost, size, power and sensitivity to environmental disturbances. However, to date, the Q of all-waveguide resonators has been relegated to below 260 Million. Here, we report a Si
N
resonator with 422 Million intrinsic and 3.4 Billion absorption-limited Qs. The resonator has 453 kHz intrinsic, 906 kHz loaded, and 57 kHz absorption-limited linewidths and the corresponding 0.060 dB m
loss is the lowest reported to date for waveguides with deposited oxide upper cladding. These results are achieved through a careful reduction of scattering and absorption losses that we simulate, quantify and correlate to measurements. This advancement in waveguide resonator technology paves the way to all-waveguide Billion Q cavities for applications including nonlinear optics, atomic clocks, quantum photonics and high-capacity fiber communications.
An alcohol-directed, nickel-catalyzed three-component umpolung carboamination of unactivated alkenes with aryl/alkenylboronic esters and electrophilic aminating reagents is reported. This ...transformation is enabled by specifically tailored O-(2,6-dimethoxybenzoyl)hydroxylamine electrophiles that suppress competitive processes, including undesired β-hydride elimination and transesterification between the alcohol substrate and electrophile. The reaction delivers the desired 1,2-carboaminated products with generally high regio- and syn-diastereoselectivity and exhibits a broad scope of coupling partners and alkenes, including complex natural products. Various mechanistic experiments and analysis of the stereochemical outcome with a cyclic alkene substrate, as confirmed by X-ray crystallographic analysis, support alcohol-directed syn-insertion of an organonickel(I) species.
Easing oxygen into arenes
Although oxygen is all around us, it is often surprisingly difficult to use it for selective chemical oxidations, necessitating more expensive, wasteful alternatives. Li
et ...al.
report that careful ligand optimization produces palladium catalysts that can efficiently activate oxygen to hydroxylate a variety of aryl and heteroaromatic rings adjacent to a carboxylic acid substituent. The ligand binds to palladium through pyridine and pyridone components, and the authors posit that tautomerization between dative and anionic coordination modes plays a role in its effectiveness.
Science
, abg2362, this issue p.
1452
Ligand optimization enables palladium-catalyzed heteroarene hydroxylation adjacent to carboxylic acid substituents.
Hydroxylation of aryl carbon–hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from mono-anionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon–hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.
Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects thinking, memory, and behavior. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently identified ...common neurodegenerative disease that mimics the clinical symptoms of AD. The development of drugs to prevent or treat these neurodegenerative diseases has been slow, partly because the genes associated with these diseases are incompletely understood. A notable hindrance from data analysis perspective is that, usually, the clinical samples for patients and controls are highly imbalanced, thus rendering it challenging to apply most existing machine learning algorithms to directly analyze such datasets. Meeting this data analysis challenge is critical, as more specific disease-associated gene identification may enable new insights into underlying disease-driving mechanisms and help find biomarkers and, in turn, improve prospects for effective treatment strategies. In order to detect disease-associated genes based on imbalanced transcriptome-wide data, we proposed an integrated multiple random forests (IMRF) algorithm. IMRF is effective in differentiating putative genes associated with subjects having LATE and/or AD from controls based on transcriptome-wide data, thereby enabling effective discrimination between these samples. Various forms of validations, such as cross-domain verification of our method over other datasets, improved and competitive classification performance by using identified genes, effectiveness of testing data with a classifier that is completely independent from decision trees and random forests, and relationships with prior AD and LATE studies on the genes linked to neurodegeneration, all testify to the effectiveness of IMRF in identifying genes with altered expression in LATE and/or AD. We conclude that IMRF, as an effective feature selection algorithm for imbalanced data, is promising to facilitate the development of new gene biomarkers as well as targets for effective strategies of disease prevention and treatment.
Fast radio bursts are bright, unresolved, non-repeating, broadband, millisecond flashes, found primarily at high Galactic latitudes, with dispersion measures much larger than expected for a Galactic ...source. The inferred all-sky burst rate is comparable to the core-collapse supernova rate out to redshift 0.5. If the observed dispersion measures are assumed to be dominated by the intergalactic medium, the sources are at cosmological distances with redshifts of 0.2 to 1 (refs 10 and 11). These parameters are consistent with a wide range of source models. One fast burst revealed circular polarization of the radio emission, but no linear polarization was detected, and hence no Faraday rotation measure could be determined. Here we report the examination of archival data revealing Faraday rotation in the fast radio burst FRB 110523. Its radio flux and dispersion measure are consistent with values from previously reported bursts and, accounting for a Galactic contribution to the dispersion and using a model of intergalactic electron density, we place the source at a maximum redshift of 0.5. The burst has a much higher rotation measure than expected for this line of sight through the Milky Way and the intergalactic medium, indicating magnetization in the vicinity of the source itself or within a host galaxy. The pulse was scattered by two distinct plasma screens during propagation, which requires either a dense nebula associated with the source or a location within the central region of its host galaxy. The detection in this instance of magnetization and scattering that are both local to the source favours models involving young stellar populations such as magnetars over models involving the mergers of older neutron stars, which are more likely to be located in low-density regions of the host galaxy.
The selective C−H functionalization of aliphatic molecules remains a challenge in organic synthesis. While radical chain halogenation reactions provide efficient access to many halogenated molecules, ...the use of typical protocols for the selective halogenation of electron‐deficient and strained aliphatic molecules is rare. Herein, we report selective C−H chlorination and fluorination reactions promoted by an electron‐deficient manganese pentafluorophenyl porphyrin catalyst, Mn(TPFPP)Cl. This catalyst displays superior properties for the aliphatic halogenation of recalcitrant, electron‐deficient, and strained substrates with unique regio‐ and stereoselectivity. UV/Vis analysis during the course of the reaction indicated that an oxo‐MnV species is responsible for hydrogen‐atom ion. The observed stereoselectivity results from steric interactions between the bulky porphyrin ligand and the intermediate substrate radical in the halogen rebound step.
A deficiency that's a bonus: A highly electron‐deficient manganese porphyrin was found to effectively catalyze the radical halogenation of strained, electron‐deficient aliphatic substrates under mild conditions (see scheme). The bulkiness of the catalyst resulted in unique stereo‐ and regioselectivity.
A quinoline‐based ligand effectively promotes the palladium‐catalyzed borylation of C(sp3)H bonds. Primary β‐C(sp3)H bonds in carboxylic acid derivatives as well as secondary C(sp3)H bonds in a ...variety of carbocyclic rings, including cyclopropanes, cyclobutanes, cyclopentanes, cyclohexanes, and cycloheptanes, can thus be borylated. This directed borylation method complements existing iridium(I)‐ and rhodium(I)‐catalyzed CH borylation reactions in terms of scope and operational conditions.
A quinoline‐based ligand promotes the efficient palladium‐catalyzed borylation of primary β‐C(sp3)H bonds in carboxylic acid derivatives as well as secondary C(sp3)H bonds in a variety of carbocycles. This directed borylation method complements existing iridium(I)‐ and rhodium(I)‐catalyzed CH borylation reactions in terms of scope and reaction conditions.
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