Copper-Catalyzed Synthesis of Furan-Tethered Benzocyclobutenes via Carbene-Mediated 1,4-Sulfinate Migration-Annulation.

A copper-catalyzed intramolecular cascade reaction of conjugated enynones has been achieved via a pivotal 1,4-sulfinate migration step. This process leverages a cost-effective and ecofriendly copper salt as catalyst, enabling the efficient construction of five- and four-membered rings in a rapid, sequential manner, producing furan-tethered benzocyclobutenes in good to excellent yields under mild conditions. The reaction is characterized by 100% atom economy, outstanding efficiency, and excellent diastereoselectivity in the cases studied. The robustness of this method is evidenced by its compatibility with air exposure and the use of undistilled, commercially available solvents, further enhancing its practicality.

Fe-TiO2-x/TiO2 S-scheme homojunction for efficient photocatalytic CO2 reduction.

CO2-to-high value-added chemicals via a photocatalytic route is of interest but strangled by the low efficiency. Herein, a novel Fe-TiO2-x/TiO2 S-scheme homojunction was designed and constructed by using a facile surface modification approach whereby oxygen vacancy (OV) and Fe introducing on the TiO2 nanorod surface. The as-synthesized Fe-TiO2-x/TiO2 S-scheme homojunction exhibits positive properties on promoting photocatalytic CO2 reduction: i) the nanorod structure provides numerous active sites and a radical charge transfer path; ii) the doped Fe and OV not only synergistically enhance light utilization but also promote CO2 adsorption; iii) the Fe-TiO2-x/TiO2 S-scheme homojunction benefits photoexcited charge separation and retains stronger redox capacity. Thanks to those good characters, the Fe-TiO2-x/TiO2 homojunction exhibits superior CO2 reduction performances with optimized CO/CH4 generation rates of 122/22 µmol g-1h-1 which exceed those of pure TiO2 by more than 9.4/7.3 folds and most currently reported catalytic systems. This manuscript develops a facile and universal approach to synthesize well-defined homojunction and may inspire the construction of other more high-efficiency photocatalysts toward CO2 reduction and beyond.

Synthesis of 3-aminoquinolines from α-imino rhodium carbenes and 2-aminobenzaldehydes.

A facile and efficient synthetic method for 3-aminoquinolines has been reported. The straightforward process starts from easily available triazoles and 2-aminobenzaldehydes. Low catalyst loading and good functional group compatibility are the other two merits of this transformation. Easy decoration of the 3-aminoquinoline motifs enabled the convenient synthesis of bioactive molecules, demonstrating the potential of this protocol in organic synthesis.

Catalyst-Free Synthesis of Polycyclic Spiroindolines by Cascade Reaction of 3-(2-Isocyanoethyl)indoles with 1-Sulfonyl-1,2,3-triazoles.

A catalyst-free cascade reaction of 3-(2-isocyanoethyl)indoles and 1-sulfonyl-1,2,3-triazoles was realized. This dearomative spirocyclization provided an efficient protocol to synthesize a series of polycyclic indolines bearing spiro-α-carboline in moderate to high yields in one step under thermal reaction conditions.

Synthesis of Piperidin-4-one Derivatives via α-Imino Rhodium Carbene-Initiated 1,2-Aryl/Alkyl Migration and Annulation.

Valuable piperidin-4-one derivatives were synthesized in excellent yields via an α-imino carbene-initiated cascade reaction involving 1,2-aryl/alkyl migration and annulation. The excellent selectivity of alkyl migration was attributed to the neighboring group participation of 2-bromoethyl. Features such as high efficiency, excellent migrating selectivity, broad substrate scope, and convenient one-pot procedure qualified this protocol as an effective tool for piperidine derivative synthesis. The product could be transformed to a bioactive molecule easily. The migration-annulation reaction of α-imino carbene provided a powerful strategy for heterocycle construction.

Synthesis of dihydropyrroles from in situ-generated zwitterions via Rh2(adc)4/TBAI dual catalysis.

Triggered by formation of α-imino carbene, the regioselective synthesis of dihydropyrroles was achieved via a cascade 1,3-sulfinate migration/annulation. The sulfinate group was converted into sulfone during the group migration, and a stable anion bearing two electron-withdrawing groups was thus formed. The addition of a catalytic amount of iodide is believed to assist the cleavage of the C-O bond, and the formation of a more stable carbocation. Thermodynamic product dihydropyrroles were produced efficiently rather than kinetic product cyclopropanes. This dual catalysis system would afford chemists a new strategy to control the annulation selectivity of zwitterions bearing multiple reactive sites and may be employed in flexible and divergent synthesis of different ring systems.

Synthesis of Azepane Derivatives via Formal 1,3-Migration of Hydroxy and Acyloxy Groups and Selective Annulation.

Formal 1,3-migration of hydroxy and acyloxy groups initiated by α-imino rhodium carbene was achieved, and the following selective annulations of the corresponding zwitterions could efficiently afford azepane derivatives. Benefiting from a time-saving procedure as well as a good functional group tolerance, this unique migration-annulation protocol could provide an efficient tool for synthesizing seven-membered N-heterocycles. The plausible mechanism is discussed.

Synthesis of α-Amino Cyclobutanones via Formal 1,3-Hydroxy Migration Triggered by Formation of α-Imino Rhodium Carbene.

Formal intramolecular 1,3-OH migration of α-imino carbene was achieved producing a unique zwitterion, and the subsequent selective annulation afforded α-amino cyclobutanone. Features such as readily available substrates, mild reaction conditions, a time-saving procedure, excellent functional group compatibility, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of strained cyclic compounds. Density functional theory calculations were in good agreement with experimental observations, and a plausible mechanism is presented.

Access to tetrahydrocarbazoles and pyrrolo[3,4-b]carbazoles through sequential reactions of triazoles and indoles.

Tetrahydrocarbazoles and pyrrolo[3,4-b]carbazoles could be synthesized conveniently through sequential reactions of ester-tethered 1-sulfonyl-1,2,3-triazoles and indoles. The reaction conditions were mild and the procedures were quite simple. Moreover, the key intermediate α,ß-unsaturated imine acted as a [2C] synthon in the [4 + 2] cycloaddition reaction, and the imino group could be used as a nucleophile to construct the fourth ring.

Synthesis of benzothiazonine by rhodium-catalyzed denitrogenative transannulation of 1-sulfonyl-1,2,3-triazole and thiochromone.

A facile synthesis of multi-functionalized benzothiazonine was achieved by the rhodium-catalyzed denitrogenative annulation of 1-sulfonyl-1,2,3-triazole and thiochromone. In view of the excellent atom economy, broad substrate scope and easy availability of starting materials, the protocol provided an efficient strategy for the construction of medium N,S-heterocycles.

Synthesis of Cyclopropanes via 1,3-Migration of Acyloxy Groups Triggered by Formation of α-Imino Rhodium Carbenes.

A novel and highly efficient synthetic approach to cyclopropanes was realized via 1,3-migration of acyloxy groups triggered by α-imino rhodium carbenes. Excellent chemoselectivity ensured broad compatibility of common functional groups. Merits such as readily available substrates, mild reaction conditions, and time-saving processes qualified this transformation as an attractive alternative strategy to synthesize multifunctionalized cyclopropanes. Primary investigations and discussion on the mechanism are presented.

From Oxygen to Sulfur and Back: Difluoro -H-phosphinothioates as a Turning Point in the Preparation of Difluorinated Phosphinates: Application to the Synthesis of Modified Dinucleotides.

A simple, two-step procedure to convert α,α-difluorinated H-phosphinic acids into the corresponding H-phosphinothioates is described. The usefulness of these species is demonstrated by their transformation into difluorinated phosphinothioyl radicals and their addition onto alkenes. Additionally, sequential treatment of H-phosphinothioates by a strong base and a primary alkyl iodide constitutes an alternate route to the formation of the C-P bond. Both methods efficiently deliver difluorinated phosphinothioates. Similar reactions carried out with the fully oxygenated counterparts clearly indicate the superiority of the sulfur-based species and emphasize the crucial role played by sulfur in the construction of the second C-P bond. Oxidation easily transforms the thereby obtained phosphinothioates into the corresponding phosphinates. The whole strategy is applied to the stereoselective preparation of dinucleotide analogues featuring either a difluorophosphinothioyl or a difluorophosphinyl unit linking the two furanosyl rings.

Metal-free synthesis of imidazole by BF3·Et2O promoted denitrogenative transannulation of N-sulfonyl-1,2,3-triazole.

BF3·Et2O promoted metal-free denitrogenative transannulation of N-sulfonyl-1,2,3-triazole was reported. Rather than transition metals, BF3·Et2O was employed for the first time to promote the formation of α-diazoimines from N-sulfonyl-1,2,3-triazoles in nitriles, leading to the synthesis of various imidazoles. The protocol tolerates a broad range of functional groups and could also be applied to the late-stage modification of bioactive molecules, demonstrating the potential of this protocol in organic synthesis. A plausible mechanism was proposed.

Metal-Free Synthesis of (E)-Monofluoroenamine from 1-Sulfonyl-1,2,3-triazole and Et2O·BF3 via Stereospecific Fluorination of α-Diazoimine.

A general, stereospecific, and straightforward method for the rapid preparation of functionalized (E)-monofluoroenamines is reported. Rather than transition metals (Rh, Ni, Pd, Cu, Ag, etc.), Et2O·BF3 was employed to promote the formation of α-diazoimine through the Dimroth equilibrium of common 1-sulfonyl-1,2,3-triazole for the first time. An overall migration of fluoride from boron to the diazo-linked carbon of α-diazoimine was achieved. Derivations and late-stage modification of bioactive molecule were conducted. A plausible mechanism was also proposed.

[Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients. METHODS: The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed. RESULTS: Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 109/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048). CONCLUSION: Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 109/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.

Rhodium-catalyzed synthesis of 1,2-dihydropyridine by a tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole.

A tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole including formation of α-imino rhodium carbene, 1,2-migration of an acetoxy group and six electron electrocyclic ring closure was reported. The migration of the OAc group with excellent chemoselectivity was the crucial process, leading to the formation of 1,2-dihydropyridine specifically in up to 90% yield. Several transformations of the dihydropyridine product were also achieved illustrating the potential of the protocol in organic synthesis. Based on the observation of the intermediate, a plausible mechanism was proposed.

Metal-free synthesis of 2-aminonaphthalenes by intramolecular transannulation of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-triazoles.

A facile metal-free synthesis of naphthalenes by intramolecular transannulation of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-triazoles was realized. The in situ formed ketenimine was proposed as the key intermediate, and the desired 2-aminonaphthalenes were generated in up to 87% yield in refluxing 1,2-dichloroethane without any catalyst or additive.

Synthesis of Multifunctionalized 2-Carbonylpyrrole by Rhodium-Catalyzed Transannulation of 1-Sulfonyl-1,2,3-triazole with ß-Diketone.

A facile rhodium-catalyzed transannulation of 1-sulfonyl-1,2,3-triazoles with ß-diketones was realized, and a series of multisubstituted 2-carbonylpyrroles were synthesized efficiently (up to 94% yield). The protocol features several advantages, such as readily available materials, mild reaction conditions, a concise operating procedure, a broad reaction scope, and excellent regioselectivity when benzoylacetone derivatives were used.

Long-term outcomes of imatinib in patients with FIP1L1/ PDGFRA associated chronic eosinophilic leukemia: experience of a single center in China.

BACKGROUND: The FIP1L1/PDGFRA (F/P) fusion gene is the most common clonal genetic abnormality of chronic eosinophilic leukemia (CEL). Tyrosine kinase inhibitors (TKI), such as imatinib, have been demonstrated to be effective therapies for F/P mutated disease. The aim of this study was to analyze the treatment response and long term prognosis in patients with F/P mutated CEL. METHODS: The clinical features and treatment responses of 33 consecutive patients with F/P mutated CEL between August 2006 and October 2014 were analyzed. The 33 cases received imatinib therapy at an initial dose of 100 mg/day (30 patients) or 200 mg/day (3 patients); the maintenance dose depended on the response condition and patient willingness. Through the follow up, the molecular responses were regularly monitored. RESULTS: With a median follow up of 64 months, 94% of the 33 patients with F/P mutated CEL achieved a complete hematologic remission (CHR), and 97% achieved a complete molecular remission (CMR) after a median of 3 (1.5-12) months. Twenty-four cases received maintenance therapy, with a median CMR duration of 43 (5-88) months. Imatinib therapy was discontinued in 8 cases, including 4 cases who experienced relapse, and 4 patients who maintained CHR or CMR after discontinuing therapy with a median time of 47 (2-74) months. One case exhibited primary resistance with a PDGFRA T674I mutation. CONCLUSIONS: F/P mutated CEL has an excellent long-term prognosis following imatinib therapy. A 100 mg daily dose of imatinib is sufficient to induce remission, and a single 100 mg weekly dose maintains a durable remission. A subgroup of patients may maintain a durable remission after discontinuing therapy with a CMR.