The palladium‐catalyzed Heck reaction is a well‐known, Nobel Prize winning transformation for producing alkenes. Unlike the alkenyl and aryl variants of the Heck reaction, the alkyl‐Heck reaction is ...still underdeveloped owing to the competitive side reactions of alkyl–palladium species. Herein, we describe the development of a deaminative alkyl‐Heck‐type reaction that proceeds through C−N bond activation by visible‐light photoredox catalysis. A variety of aliphatic primary amines were found to be efficient starting materials for this new process, affording the corresponding alkene products in good yields under mild reaction conditions. Moreover, this strategy was successfully applied to deaminative carbonylative alkyl‐Heck‐type reactions.
Single‐electron process: A deaminative alkyl‐Heck‐type reaction and its carbonylative variant proceed through photocatalytic C−N bond activation. This process represents a significant complement to the classic palladium‐catalyzed Heck reaction, and features easily available starting materials, good reaction efficiency, and mild reaction conditions. Tppy=2,4,6‐triphenylpyridine.
Catalytic asymmetric cycloadditions via transition-metal-containing dipolar intermediates are a powerful tool for synthesizing chiral heterocycles. However, within the field of palladium catalysis, ...compared with the well-developed normal electron-demand cycloadditions with electrophilic dipolarophiles, a general strategy for inverse electron-demand ones with nucleophilic dipolarophiles remains elusive, due to the inherent linear selectivity in the key palladium-catalyzed intermolecular allylations. Herein, based on the switched regioselectivity of iridium-catalyzed allylations, we achieved two asymmetric 4+2 cycloadditions of vinyl aminoalcohols with aldehydes and β,γ-unsaturated ketones through synergetic iridium and amine catalysis. The activation of vinyl aminoalcohols by iridium catalysts and carbonyls by amine catalysts provide a foundation for the subsequent asymmetric 4+2 cycloadditions of the resulting iridium-containing 1,4-dipoles and (di)enamine dipolarophiles. The former provides a straightforward route to a diverse set of enantio-enriched hydroquinolines bearing chiral quaternary stereocenters, and the later represent an enantio- and diastereodivergent synthesis of chiral hydroquinolines.
Porphyry and skarn deposits in the middle Yangtze Valley within the Northern Yangtze Craton have a combined tungsten resource of ~3milliontonnes (Mt) and represent one of the most important tungsten ...regions in the world. The Dahutang porphyry tungsten deposit, with reserves of >1Mt, is one of the largest deposits. Uranium–Pb analyses for the ore-related granitoids yield ages of 147.4±0.58Ma–148.3±1.9Ma for porphyritic biotite granite, 144.7±0.47Ma–146.1±0.64Ma for fine-grained granite, and 143.0±0.76Ma–143.1±1.2Ma for granite porphyry, a progressive youngling of ages that is consistent with field observations. Geochemical data show that the three types of granite are characterized by enrichments in Rb, Pb, and U, and depletion in Ba, Nb, P, and Ti, with ASI molar Al2O3/(CaO+Na2O+K2O)>1.1 that is characteristic of a peraluminous melt. The P2O5 contents of the granites are 0.13–0.37% and have a positive correlation with SiO2, and they are thus S-type intrusions. They exhibit initial 87Sr/86Sr of 0.721 to 0.731 and εNd(t) of −5.06 to −7.99 for porphyritic biotite granite, 0.7196 to 0.7289 and −6.29 to −6.74 for fine-grained granite, and 0.7153 to 0.7365 and −5.09 to −7.64 for granite porphyry. Chondrite-normalized rare earth element (REE) patterns for the granites are characterized by enrichment in the light REE and a strong negative Eu anomaly, indicating that they were derived from the Proterozoic pelitic and psammitic basement strata and experienced strong fractional crystallization of plagioclase. Our ca. 150–140Ma age for the Dahutang S-type magmatism and W mineralization is identical to that of the I-type magmatism related to Cu–Au–Mo–Fe-bearing porphyry and skarn deposits along the middle to lower Yangtze River Valley. We propose that the latest Jurassic to earliest Cretaceous granitoids and ores formed during a tearing of the subducting Izanagi slab, which caused the upwelling of asthenosphere and resulting mantle–crust interaction. The S-type granitoids and related W ore systems resulted from the re-melting of the Proterozoic crust, whereas the I-type granitic rocks and related ores are attributed to the partial melting of the subducted slab.
Display omitted
•Petrogenesis of the granitoids within Dahutang tungsten deposit, South-Central China.•Zircon U-Pb ages for granitoids obtained range from 147.4±0.58 Ma to 143.0±0.76 Ma.•Petrochemical and Sr-Nd data indicate the granitoids are remelted from the crust.•Model for the petrogenesis and related mineraliztion of the deposit was proposed.
A copper‐catalyzed decarboxylative amination/hydroamination sequence of propargylic carbamates with various nucleophiles is described for the first time. It features an earth‐abundant metal catalyst, ...mild reaction conditions, and high efficiency. Further treatments of the resultant key intermediates using an acid or a base in one pot enable the controllable and divergent synthesis of two types of functionalized indoles. Moreover, experiments to demonstrate the synthetic potential of this methodology are performed.
Switch‐hitter: This work describes a copper‐catalyzed decarboxylative amination/hydroamination sequential reaction. The one‐pot treatment of an indoline intermediate with either an acid or a base enables the switchable synthesis of two types of functionalized indoles in generally high yields and with complete chemoselectivities (36 examples and up to 99 % yield).
A novel copper-catalyzed decarboxylative cyclization of ethynyl benzoxazinanones with P(O)H compounds has been developed. This protocol leads to a series of 2-phosphorylmethyl indoles with high ...efficiency and selectivity (up to 99% yield) through tandem C-P/C-N bond formation under mild conditions.
Medium-sized heterocycles are widespread among a spectrum of structurally intriguing and biologically significant natural products and synthetic pharmaceuticals. Metal-catalyzed high-order dipolar ...annulations resembling reactions of metal-containing reactive dipoles with dipolarophiles constitute a highly efficient and flexible strategy for constructing medium-sized heterocycles. Mechanistically, these annulation reactions usually proceeding through stepwise pathways are different from the classic high-order pericyclic reactions that follow the Woodward-Hoffman rules. More significantly, asymmetric high-order dipolar annulations using chiral organometallic catalysts have been proven successful for constructing chiral medium-sized heterocycles with high enantio- and diastereoselectivity. This review highlights the impressive advances in this area and is focused on the reactivity, scope, mechanisms and applications of high-order dipolar annulation reactions.
The advances on metal-catalysed high-order dipolar annulations were comprehensively summarized in this review. To further exploit the potential of this unique annulation strategy, a research outlook was also proposed.
Yanshanian (ca. 200–100 Ma) metallogeny of eastern Asia was dominantly controlled by oblique subduction and rollback of the Izanagi plate, and also, more locally in the north, by closure of the ...Mudanjiang Ocean basin and accretion of the Bureya-Jiamusi-Khanka block and the Sikhote-Alin terranes. Although exact distances are difficult to estimate due to Early Cretaceous crustal extension, ores related to Yanshanian subduction certainly developed for more than 1500 km landward from the active trench, such as exemplified by those deposits overprinting the Paleoproterozoic Trans-North China orogen. In the northern part of the Yanshanian orogen, and thus hosted within the eastern edge of the Central Asian orogenic belt, Endako-type porphyry Mo deposits related to subduction of the Mudanjiang slab formed throughout northeast China from 200 to 135 Ma. Extensional magmatism related to rollback of the slab led to widespread Au-Ag epithermal vein development and a scattering of small Cu-Au porphyry occurrences across the same area from 125 to 100 Ma. Sinistral strike-slip motion along the continental margin in adjacent Russia, caused by the NNW motion of the Izanagi plate, led to formation of 115–95 Ma post-collisional Cu-Au porphyries, Sn-W ores associated with reduced intrusions, and orogenic gold deposits in the central Sikhote-Alin region. In the North China block, whereas early Yanshanian ore formation was relatively limited, 130–120 Ma extension-related basement uplifts were associated with formation of two of China’s most important orogenic gold provinces on the Jiaodong Peninsula and in the East Qinling; in the latter, the entire period of late Yanshanian extension may be defined by widespread 148–107 Ma Mo-rich porphyry and skarn deposit formation. To the south along the Asian margin, the oblique NW-directed subduction of the Izanagi slab was responsible for the adakitic porphyry Cu deposit formation on the eastern side of the South China block at 175–155 Ma, which continued inland for as much as 500 km to the Cathaysia-Yangtze suture. The transition at 160–150 Ma to development of the Nanling W-Sn belt in the interior of Cathaysia roughly overlaps the time of tectonic switch to slab retreat, which gradually led to seaward migration of the extension-related magmatism forming the 145–133 Ma Sn ores and 110–100 Ma high to low sulfidation epithermal deposits along the Southeast Coast belt. A period of sinistral strike-slip along the southern end of the Tan-Lu fault system was possibly responsible for a tear in the Izanagi plate and consequential S-type magmatism forming W porphyry-skarn ores of the Jiangnan belt at 145–133 Ma and I-type magmatism leading to Fe-Cu-Au skarns at the northern edge of the Yangtze block. In summary, the early Yanshanian of eastern Asia was dominated by widespread subduction-related porphyry Mo formation in the north and localized porphyry Cu formation to the south, followed by late Yanshanian development of world-class Au, Mo, Sn, and W resources during subsequent slab retreat, continental-scale extension, and strike-slip events along continental margin transform faults.
Display omitted
•Early Yanshanian metallogeny was dominated by porphyry Mo in north eastern Asia.•Early Yanshanian metallogeny was dominated by porphyry Cu in south eastern Asia.•Late Yanshanian metallogeny was dominated by Au, Mo, Sn, and W resources.
Bis(3-indolyl)methanes are well-known natural products with a broad range of important biological functions including cancer cell growth inhibition and antimicrobial activity. Incorporation of a ...trifluoromethyl group is known to have a profound effect on the parent compound’s biological activities. Here, an efficient method for the synthesis of chiral trifluoromethylated bis(3-indolyl)methanes via a catalytic asymmetric Friedel–Crafts (F–C) alkylation reaction has been established. Both enantiomers of the catalysis products can be obtained by tuning the chiral substituents of the catalyst. With 5 mol % of the Ni(II)/(imidazoline–oxazoline) complex as the catalyst, the F–C reaction of indoles with β-CF3-β-(3-indolyl)nitroalkenes proceeded well to afford a series of chiral bis(3-indolyl)methanes bearing a trifluoromethylated all-carbon quaternary stereocenter in generally good yields with excellent enantioselectivities (up to 98% yield and 94% ee). Furthermore, by interchanging the indole moieties of the two reactants, indole vs β-CF3-β-(3-indolyl)nitroalkene in the F–C reaction, both enantiomers of a given trifluoromethylated bis(3-indolyl)methane were obtained with high enantioselectivities (89–94% ee) upon removal of the indole N-protecting group in the F–C products. The current work represents the first general catalytic enantioselective approach to the important class of trifluoromethylated bis(3-indolyl)methanes.
The clinical efficacy of the hospital preparation compound granules of Hedyotis diffusa (CGHD), which is composed of Hedyotis diffusa Willd, Smilax china L., Solanum lyratum Thunb., has accumulated a ...good reputation over the past decades. However, because it is a hospital preparation, few researchers have paid attention to it, resulting in a lack of systematic basic research studies. Thus, it is not clear whether there are safety concerns that restrict its clinical application, and toxicological evaluation of CGHD is needed.
The aim of this study was to evaluate the safety of CGHD by conducting acute toxicity and long-term toxicity experiments, with the objective of providing evidence for its clinical safety and a theoretical foundation for its clinical application.
KM mice were selected for the acute toxicity experiment and were administered water or CGHD-E 3 times within 24 h. The reactions of the animals to CGHD treatment were observed and recorded within 1 h after administration and then once a day for 14 consecutive days. SD rats were selected to conduct the long-term toxicity experiment. The drug-treated groups were administered different doses of CGHD-E, which were equivalent to 10 times, 20 times and 50 times the clinical dose in humans. The rats were administered the drug for 28 consecutive days. After 28 days, the animals were sacrificed, and routine blood tests, blood coagulation function analysis, liver and kidney function tests, and glycolipid metabolism related tests were conducted. The major organs of the rats were collected to calculate organ coefficients and perform hematoxylin-eosin (HE) staining.
In the CGHD-E acute toxicity experiment, the drug-treated groups did not show adverse reactions or poisoning symptoms, and the maximum tolerated dose of CGHD-E in mice was greater than 45.072 g/kg. In the long-term toxicity experiment, drug-treated rats generally exhibited a good condition, but continuous administration decreased on body weight and food intake, especially in male rats. Coagulation function alterations and the impact on the liver during long-term drug administration were also assessed, which should be emphasized in clinical applications. No significant toxic effects were observed according to routine blood tests or test of liver and kidney function, glucose and lipid metabolism, or ion metabolism.
The results of this study showed that CGHD was nontoxic or had low toxicity, providing not only a scientific basis for its clinical application, determining the appropriate clinical dose and monitoring clinical toxicity but also theoretical support for subsequent clinical drug trials.
PDF
