Facile Synthesis of Alkylidene Phthalides by Rhodium-Catalyzed Domino C-H Acylation/Annulation of Benzamides with Aliphatic Carboxylic Acids.

The Rh-catalyzed ortho-C(sp2 )-H functionalization of 8-aminoquinoline-derived benzamides with aliphatic acyl fluorides generated in situ from the corresponding acids has been developed. This reaction initiated with 8-aminoquinoline-directed ortho-C(sp2 )-H acylation, which was accompanied by subsequent intramolecular nucleophilic acyl substitution of amide group to produce alkylidene phthalides This approach exhibits high stereo-selectivity for Z-isomer products, and tolerates a variety of functional groups as well as aliphatic carboxylic acids with diverse structural scaffolds.

Oxidation of Enones for Regioselective [3+2] Cycloaddition through γ-Enone Radical Intermediates.

Herein, an oxidization reaction of enones with a CuII complex that leads to a new type of regioselective [3+2] cycloaddition is reported. Highly functionalized cyclopentenes and spirocyclic compounds are obtained in moderate-to-good yields. This cycloaddition reaction occurred through the formation of γ-enone radicals, providing a rarely explored reactivity pattern for enones.

Oxidation of Enones for Regioselective [3+2] Cycloaddition through γ-Enone Radical Intermediates.

Invited for the cover of this issue is the group of Min Zhang and Weiping Su at the Fujian Institute of Research on the Structure of Matter. Read the full text of the article at 10.1002/chem.201903551.

Cu-Catalyzed Sequential Dehydrogenation-Conjugate Addition for ß-Functionalization of Saturated Ketones: Scope and Mechanism.

The first copper-catalyzed direct ß-functionalization of saturated ketones is reported. This protocol enables diverse ketones to couple with a wide range of nitrogen, oxygen and carbon nucleophiles in generally good yields under operationally simple conditions. The detailed mechanistic studies including kinetic studies, KIE measurements, identification of reaction intermediates, EPR and UV-visible experiments were conducted, which reveal that this reaction proceeds via a novel radical-based dehydrogenation to enone and subsequent conjugate addition sequence.

Ultra-stable high-power mid-infrared optical parametric oscillator pumped by a super-fluorescent fiber source.

The longterm stability of the laser system is very important in many applications. In this letter, an ultra-stable, broadband, mid-infrared (MIR) optical parametric oscillator (OPO) pumped by a super-fluorescent fiber source is demonstrated. An idler MIR output power of 11.3 W with excellent beam quality was obtained and the corresponding pump-to-idler conversion slope efficiency was 15.9%. Furthermore, during 1h measurement at full power operation, the peak-to-peak fluctuation of idler output power was less than 1.9% and the corresponding standard deviation was less than 0.4% RMS, which was much better than that of a traditional single mode fiber laser pumped OPO system (10.9% for peak-to-peak fluctuation and 1.8% RMS for the standard deviation) in another experiment for comparison. To our knowledge, this is the first demonstration on a high-power, ultra-stable OPO system by using the modefree pump source, which offered an effective approach to achieve an ultra-stable MIR source and broadened the range of the super-fluorescent fiber source applications.

Recycling cellulases by pH-triggered adsorption-desorption during the enzymatic hydrolysis of lignocellulosic biomass.

Recycling of cellulases is an effective way to reduce the cost of enzymatic hydrolysis for the production of cellulosic ethanol. In this study, we examined the adsorption and desorption behaviors of cellulase at different pH values and temperatures. Furthermore, we developed a promising way to recover both free and bound cellulases by pH-triggered adsorption-desorption. The results show that acidic pH (e.g., pH 4.8) was found to favor adsorption, whereas alkaline pH (e.g., pH 10) and low temperature (4-37 °C) favored desorption. The adsorption of cellulases reached an equilibrium within 60 min at pH 4.8 and 25 °C, leading to approximately 50 % of the added cellulases bound to the substrate. By controlling the pH of eluent (citrate buffer, 25 °C), we were able to increase the desorption efficiency of bound cellulases from 15 % at pH 4.8 to 85 % at pH 10. To recover cellulases after enzymatic hydrolysis, we employed adsorption by fresh substrate and desorption at pH 10 to recover the free cellulases in supernatant and the bound cellulases in residue, respectively. The recycling performance (based on the glucose yield) of this simple strategy could reach near 80 %. Our results provided a simple, low-cost, and effective approach for cellulase recycling during the enzymatic hydrolysis of lignocellulosic biomass.

Causal Relationship Between Mood Swing and Gynecological Disorders: A Mendelian Randomization Study.

Background: Gynecological disorders are a wide range of health problems affecting the female reproductive system, which poses substantial health challenges worldwide. Increasing number of observational studies have associated mood instability to common female diseases, but the underlying causal relationship remains unclear. In this work, Mendelian randomization (MR) analysis was applied to explore the genetically predicted causal relationship of mood swings and several prevalent gynecological disorders. Methods: Instrumental variables (IVs) of mood swings were selected from UK Biobank (UKB), with 204,412 cases and 247,207 controls being incorporated. The genetic variants for female disorders were obtained from genome-wide association studies (GWASs) and FinnGen consortium. To avoid biases caused by racial difference, only European population was included here. Five strong analytical methodologies were used to increase the validity of the results, the most substantial of which was the inverse variance weighting (IVW) method. Pleiotropy, sensitivity, and heterogeneity were assessed to strengthen the findings. Results: We found mood swings was significantly positively associated with risk of endometrial cancer (OR= 2.60 [95% CI= 1.36, 4.95], P= 0.0037), cervical cancer (OR= 1.01[95% CI= 1.00,1.02], P= 0.0213) and endometriosis (OR= 2.58 [95% CI= 1.18, 5.60], P= 0.0170) by IVW method. However, there was no causal relationship between mood swing and ovarian cancer. No pleiotropy and heterogeneity existed and sensitivity tests were passed. Conclusion: This study reveals that mood swing may serve as a genetically predicted causal risk factor for endometrial cancer, cervical cancer, and endometriosis in the European population, while no such association was observed for ovarian cancer. These findings make up for observational research's inherent limitations and may improve patient outcomes in the field of gynecological health. However, the study's focus on European populations may limit the applicability of these results globally.

Dehydrogenative synthesis of N-functionalized 2-aminophenols from cyclohexanones and amines: Molecular complexities via one-shot assembly.

Polyfunctionalized arenes are privileged structural motifs in both academic and industrial chemistry. Conventional methods for accessing this class of chemicals usually involve stepwise modification of phenyl rings, often necessitating expensive noble metal catalysts and suffering from low reactivity and selectivity when introducing multiple functionalities. We herein report dehydrogenative synthesis of N-functionalized 2-aminophenols from cyclohexanones and amines. The developed reaction system enables incorporating amino and hydroxyl groups into aromatic rings in a one-shot fashion, which simplifies polyfunctionalized 2-aminophenol synthesis by circumventing issues associated with traditional arene modifications. The wide substrate scope and excellent functional group tolerance are exemplified by late-stage modification of complex natural products and pharmaceuticals that are unattainable by existing methods. This dehydrogenative protocol benefits from using 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) as oxidant that offers interesting chemo- and regio-selective oxidation processes. More notably, the essential role of in situ generated water is disclosed, which protects aliphatic amine moieties from overoxidation via hydrogen bond-enabled interaction.

Rhodium(iii)-catalyzed indole synthesis at room temperature using the transient oxidizing directing group strategy.

Rh-catalyzed reactions of N-alkyl anilines with internal alkynes at room temperature have been developed using an in situ generated N-nitroso group as a transient oxidizing directing group. Due to mild reaction conditions, this method enabled synthesis of a broad range of N-alkyl indoles, including even two indole-based medicinal compounds. Our work disclosed the feasibility of the transient oxidizing directing group strategy in C-H functionalization reactions, which possesses the potential to enhance overall step-economy and impart new reactivity patterns to substrates.

Differentiation between enamines and tautomerizable imines in the oxidation reaction with TEMPO.

Enamine and imine represent two of the most common reaction intermediates in syntheses, and the imine intermediates containing α-hydrogen often exhibit the similar reactivity to enamines due to their rapid tautomerization to enamine tautomers. Herein, we report that the minor structural difference between the enamine and the enamine tautomer derived from imine tautomerization results in the different chemo- and regioselectivity in the reaction of cyclohexanones, amines and TEMPO: the reaction of primary amines furnishes the formal oxygen 1,2-migration product, α-amino-enones, while the reaction of secondary amines under similar conditions generates exclusively arylamines via consecutive dehydrogenation on the cyclohexyl rings. The 18O-labeling experiment for α-amino-enone formation revealed that TEMPO served as oxygen transfer reagent. Experimental and computational studies of reaction mechanisms revealed that the difference in chemo- and regioselectivity could be ascribed to the flexible imine-enamine tautomerization of the imine intermediate containing an α-hydrogen.

Dehydrogenative desaturation-relay via formation of multicenter-stabilized radical intermediates.

In organic molecules, the reactivity at the carbon atom next to the functional group is dramatically different from that at other carbon atoms. Herein, we report that a versatile copper-catalyzed method enables successive dehydrogenation or dehydrogenation of ketones, aldehydes, alcohols, α,ß-unsaturated diesters, and N-heterocycles to furnish stereodefined conjugated dienecarbonyls, polyenecarbonyls, and nitrogen-containing heteroarenes. On the basis of mechanistic studies, the copper-catalyzed successive dehydrogenation process proceeds via the initial α,ß-desaturation followed by further dehydrogenative desaturation of the resultant enone intermediate, demonstrating that the reactivity at α-carbon is transferred through carbon-carbon double bond or longer π-system to the carbon atoms at the positions γ, ε, and η to carbonyl groups. The dehydrogenative desaturation-relay is ascribed to the formation of an unusual radical intermediate stabilized by 5- or 7,- or 9-center π-systems. The discovery of successive dehydrogenation may open the door to functionalizations of the positions distant from functional groups in organic molecules.

Rh(III)-catalyzed amide-directed cross-dehydrogenative heteroarylation of pyridines.

A new catalytic methodology has been developed for the synthesis of heteroaryled pyridines via a rhodium(III)-catalyzed dehydrogenative cross-coupling reaction. This protocol features a good substrate scope with a broad range of functional group tolerance and high regioselectivity of the pyridyl C-H activation.

Rhodium(III)-catalyzed intermolecular N-chelator-directed aromatic C-H amidation with amides.

Rh(III)-catalyzed intermolecular direct aromatic C-H bond amidation with amides has been accomplished under mild reaction conditions. This protocol is applicable to a broad range of N-chelator-containing arenes amidated with aromatic and aliphatic sulfonamides. A possible mechanism is proposed according to the experimental results.