PyBox-La(OTf)3-Catalyzed Enantioselective Diels-Alder Cycloadditions of 2-Alkenoylpyridines with Cyclopentadiene.

The PyBox-La(OTf)3-catalyzed enantioselective Diels-Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.

Y(OTf)3-Salazin-Catalyzed Asymmetric Aldol Condensation.

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π-stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands.

N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution.

Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process.

Thiourea-Mediated Stereospecific Deoxygenation of Cyanoepoxides to Access Highly Diastereopure Alkenyl Nitriles.

A practical and efficient protocol for synthesis of >99% diastereopure Z- and E-alkenyl nitriles is developed, through tetramethylthiourea-mediated stereospecific deoxygenation of respective cis- and trans-cyanoepoxides in ethanol. The desired products are obtained in excellent yields.

Accessing para-Alkylphenols via Iridium-Catalyzed Site-Specific Deoxygenation of Alcohols.

An iridium-catalyzed and phenol-directed deoxygenation of benzylic alcohols comes as an alternative access to 4-alkylphenols, featuring low catalyst loading (S/C up to 20,000, TOF up to 12,400 h-1), high functionality compatibility, and excellent site-selectivity. The applications in late-stage modification of steroids and gram-scale total synthesis of a Gastrodia elata extract are highlighted. Mechanistically, the intermediacy of quinone methide controls the site-selectivity, and the formation of iridium hydride serves as the rate-limiting step.

Clinical efficacy and the influence of fibrinogen, homocysteine and prognosis in acute ischemic stroke patients treated with tirofiban plus TERVO stent thrombectomy.

To evaluate the clinical efficacy and the influence of fibrinogen, homocysteine and prognosis in acute ischemic stroke (AIS) treated with tirofiban plus TERVO stent thrombectomy. A retrospective study was conducted among 82 patients with AIS admitted to the Department of Neurology in Hengshui People's Hospital from December 2018 to December 2020 and they were evenly divided into control group and study group according to different methods. The control group received TERVO stent thrombectomy; the study group received tirofiban plus. The clinical efficacy, modified thrombolysis in cerebral infarction (mTICI) grade, serum levels of fibrinogen and homocysteine, National Institute of Health stroke scale (NIHSS), and activity of daily living (ADL) scores were compared. Significant higher clinical efficacy was observed in the study group vs. control group (all p<0.05). The study group witnessed lower percentage of 0~1 grade of mTICI blood flow in relative to the control group (all p<0.05). After treatment, significant reduction was observed in FIB and HCY in both groups, but the treatment in the study group resulted in a greater reduction (all p<0.05). After treatment, both groups reported a significant increase in NIHSS score and ADL score, with more increase in the study group (all p<0.05). The safety profiles were similar in the two groups with respect to the adverse reactions (p>0.05). Tirofiban plus TERVO stent thrombectomy could improve vascular recanalization rate, reduce fibrinogen and homocysteine levels and improve short-term prognosis in AIS patients.

Furan-2-yl Anions as γ-Oxo/Hydroxyl Acyl Anion Equivalents Enabled by Iridium-Catalyzed Chemoselective Reduction.

The last piece of the puzzle: Furan-2-yl anions are first demonstrated as robust γ-oxo and γ-hydroxyl acyl anion equivalents to convert aldehydes and ketones into trifunctionalized dihydroxyl ketones and hydroxyl diones through sequential nucleophilic addition, Achmatowicz rearrangement, and herein freshly established iridium-catalyzed highly selective transfer hydrogenation reduction.

Iridium-Catalyzed and pH-Dependent Reductions of Nitroalkenes to Ketones.

A highly chemoselective conversion of α,ß-disubstituted nitroalkenes to ketones is developed. An acid-compatible iridium catalyst serves as the key to the conversion. At a 2500 S/C ratio, nitroalkenes were readily converted to ketones in up to 72% isolated yields. A new mechanistic mode involving the reduction of nitroalkene to nitrosoalkene and N-alkenyl hydroxylamine is proposed. This conversion is ready to amplify to a gram-scale synthesis. The pH value plays an indispensable role in controlling the chemoselectivity.

Iridium-Catalyzed Stereoselective Transfer Hydrogenation of 1,5-Benzodiazepines.

An iridium-catalyzed highly stereoselective transfer hydrogenation of N-protected 2,4-disubstituted-1,5-benzodiazepines as well as dibenzo[1,5]oxa/thiazepines is realized in an aqueous solvent under acidic conditions, with formic acid as the hydride donor. Only trans-products are obtained in all the cases where diastereoselective issues are associated. The catalyst efficiency is highly dependent on the electronic and steric properties of the substrates. Topologically analyzing the angle of attack for hydride delivering revealed, stereoelectronically, that the steric interaction between the N-protecting group and the sterically large iridium hydride intermediate constitutes the main contributor to the excellent stereochemical control. Highly deuterated products can also be accessible with DCO2D as the deuteride donor. The observed primary kinetic isotope effect (kH/kD = 4.24) suggests that the formation of iridium hydride through ß-hydride elimination should be the rate-determining step (with C-H bond cleavage). The potential use of the chirally modified iridium catalysts in a chemical resolution of racemic 1,5-benzodiazepines is also conceptually demonstrated.

Correction: Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates.

Correction for 'Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates' by Ziyang Dong et al., Chem. Commun., 2022, 58, 7980-7983, https://doi.org/10.1039/D2CC02882D.

Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates.

1,2,3-Thiadiazoles serve as masked S-electrophilic thia-1,3-dipoles. Under rhodium/racemic BINAP catalysis, they undergo denitrogenative (3 + 2) umpolung transannulations with aryl isothiocyanates with inverse regioselectivity and excellent stereoselectivity, yielding N-aryl 3H-1,2-dithiol-(Z)-3-imines in a redox-neutral, step-efficient, and functionality-tolerant manner. An intramolecular S-S bond is impressively forged.

Catalytic Diastereospecific and Enantioselective (3 + 2) Transannulations of 1,2,3-Thiadiazoles with Strained Norbornene Derivatives.

With the adoption of a ring-strain-release strategy, iridium-catalyzed transannulations with norbornene derivatives are achieved in a diastereospecific and enantioselective manner. The first asymmetric transannulations of 1,2,3-thiadiazoles are reported.

Iridium-catalyzed highly stereoselective deoxygenation of tertiary cycloalkanols: stereoelectronic insights and synthetic applications.

Excellent and unique diastereoselectivity is observed in the iridium-catalyzed deoxygenation of tertiary cyclohexanols and cyclopentanols. The substituent effect on the diastereoselectivity and detailed control models are analyzed case by case, using tertiary monocyclic and polycyclic cyclohexanols, bicyclic bridged cycloalkanols, and cyclopentanols as the model substrates. The selectivity is decided by the steric environment of the carbocation intermediates and is independent of the catalyst loading. Stereoelectronically, the iridium hydride approaches the carbocation in directions perpendicular to the carbocation plane. The sterically large iridium hydride delivers its hydride in the sterically least hindered direction to the carbocation. The deoxygenation has found important applications in the stereospecific arylations of sterically complex compounds. Our deoxygenation is stereochemically very different from the coupling reactions and can be used to specifically synthesize stereoisomers that are not available via cross-couplings.

Efficacy of nifedipine tablets plus aspirin in patients with gestational hypertension and the effect on coagulation function and hemorheology.

OBJECTIVE: This study aimed to investigate the clinical efficacy of Nifedipine tablets plus Aspirin for hypertensive disorder complicating pregnancy and the effect on coagulation function and hemorheology. METHODS: A retrospective analysis of the clinical data from 108 patients with gestational hypertension hospitalized between March 2016 and March 2017 was carried out. These patients were randomly assigned into a research group and a control group, with 54 patients in each group. Patients were treated with Aspirin in the control group, and the combination of Nifedipine tablets and Aspirin in the research group so as to compare the clinical efficacy and the effect on coagulation function and hemorheology after therapy. Albumin, total protein, 24-hour urinary protein and mean arterial pressure (MAP) were observed and compared between the two groups. RESULTS: The overall effective rate of treatment in the research group was significantly higher than that in the control group (P < 0.05). The prothrombin time (PT) and fibrinogen (FIB) levels were markedly superior to those before therapy in the research group (P < 0.001), and the PT and FIB after treatment were remarkably better in the research group than in the control group (P < 0.001). The levels of plasma viscosity (PV), low-shear whole blood viscosity (LBV), and high-shear whole blood viscosity (HBV) after therapy were markedly reduced than before therapy in the two groups (P < 0.05), and the levels of PV, LBV, and HBV after therapy were significantly lower in the research group than those in the control group (P < 0.05). Adverse reactions after therapy were reported at a significantly lower incidence in the research group than the control group (P < 0.05). Adverse pregnancy outcomes were reported at a significantly lower incidence in the research group than in the control group (P < 0.05). The research group significantly outperformed the control group on Albumin, total protein, 24-hour urinary protein and mean arterial pressure (P < 0.05). CONCLUSION: Nifedipine tablets plus Aspirin for patients with gestational hypertension can effectively improve coagulation function and hemorheological parameters, with high safety.

Sulfur-controlled and rhodium-catalyzed formal (3 + 3) transannulation of thioacyl carbenes with alk-2-enals and mechanistic insights.

A rhodium-catalyzed denitrogenative formal (3 + 3) transannulation of 1,2,3-thiadiazoles with alk-2-enals is achieved, producing 2,3-dihydrothiopyran-4-ones in moderate to excellent yields. An inverse KIE of 0.49 is obtained, suggesting the reversibility of the oxidative addition of thioacyl Rh(i) carbenes to alk-2-enals. The late-stage structural modifications of steroid compounds are realized. Moreover, our studies show that thioacyl carbenes have different reactivities to those of α-oxo and α-imino carbenes, and highlight the importance of heteroatoms in deciding the reactivities of heterovinyl carbenes.

Chiral Synthesis of McGeachin-Type Bisaminals.

Bridged [3.3.1]-bisaminal structures, namely 6,12-epiminodibenzo[b,f][1,5]diazocines, are herein named McGeachin-type bisaminals. The TsOH-catalyzed chiral synthesis of McGeachin-type bisaminals is first developed by condensation of two molecules of 2-(methylamino)benzaldehyde and one molecule of chiral amines. Two chiral diastereomers are generated simultaneously and are isolated by column chromatography in a total yield of up to 99%. The absolute structure of one stereoisomer was determined by X-ray crystallography.

Intramolecular Carbene C-H Insertion Reactions of 2-Diazo-2-sulfamoylacetamides.

The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo-N,N-dimethyl-2-(N,N-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its N-phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[c]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(N,N-dialkylsulfamoyl)acetamides; and (3) for 2-diazo-N-phenyl-2-(N-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the N-phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the N-aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group.

Fluorium-Initiated Dealkylative Cyanation of Thioethers to Thiocyanates.

Thioethers are converted to thiocyanates via fluorium-initiated dealkylative cyanation. Selectfluor is used as the oxidant, and trimethylsilyl cyanide is used as the cyanation reagent. The well-streamlined procedure is user-friendly, operationally simple, and step-economical. The current mechanistic studies show that the sulfur radical cation and cyano radical are both involved. They combine to deliver cyanosulfonium, an intermediate toward thiocyanate after dealkylation. Alternatively, a nucleophilic mechanism is also possible. Our dealkyaltive cyanation is also efficient in synthesizing thiocyanates with strongly electrophilic functionalities.

Rhodium-Catalyzed 1,1-Hydroacylation of Thioacyl Carbenes with Alkynyl Aldehydes and Subsequent Cyclization.

A rhodium-catalyzed 1,1-hydroacylation of thioacyl carbenes with alkynyl and alkenyl aldehydes and subsequent 6- endo-trig/dig cyclization are realized, giving structurally diverse 4 H-thiopyran-4-ones and 2,3-dihydro-4 H-thiopyran-4-ones in moderate to good yields. The oxidative addition of Rh(I) to aldehydes is proposed to be the turnover-limiting step. Manipulations of estrones demonstrate the applications of our formal (3 + 3) transannulations in the structural modifications of natural products.

Thermal conversion of primary alcohols to disulfides via xanthate intermediates: an extension to the Chugaev elimination.

Primary alcohols are converted into dialkyl disulfides via heating in situ generated O-alkyl S-difluoro(ethoxycarbonyl)methyl xanthates from ethyl bromodifluoroacetate and potassium xanthates, prepared from primary alcohols and carbon disulfide in the presence of KOH. The reaction mechanism is suggested as an alkyl C[1,3] shift followed by a radical mechanism. This extends to the Chugaev elimination which yields olefins. The current research provides easy access to dialkyl disulfides from commercially available primary alkanols.