Photocatalytic Enantioselective Radical Cascade Multicomponent Minisci Reaction of β-Carbolines Using Diazo Compounds as Radical Precursors.

Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of β-carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of β-carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo-/enantio-selective control, and good functional group tolerance, allowing access to a variety of valuable chiral β-carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions.

Nickel-Catalyzed Asymmetric Decarboxyarylation with NHP Esters of α-Amino Acid to Chiral Benzylamines.

A nickel-catalyzed asymmetric decarboxyarylation of NHP esters via reductive cross-coupling has been established. Utilizing the NHP of amino acid esters as radical precursors furnishes a new protocol in which structurally diverse chiral benzylamines could be accessible. This method has demonstrated excellent catalytic efficiency, high enantioselective control, mild conditions, and good functional group tolerance, thus enabling the late-stage modification of bioactive molecules and pharmaceuticals.

Visible-Light Photoredox-Catalyzed Three-Component Reaction of Carbazoles with Alkenes and -(Difluoromethyl)sulfonium Salt: A Practical Approach to Access Difluoroalkyl-Functionalized Carbazoles.

A mild and elegant multicomponent protocol for construction of CFH-containing carbazoles was accomplished by visible-light photoredox catalysis with formation of two new C-C bonds in a single step to deliver a wide variety of structurally diverse difluoroalkylated carbazoles in moderate to good yields, featuring mild reaction conditions, synthetic simplicity, broad substrates, and good functional group tolerance.

Visible-light photoredox-catalyzed radical aryldifluoromethylation of -arylacrylamides with -(difluoromethyl)sulfonium salt.

A facile and highly efficient visible-light photoredox-catalyzed protocol for aryldifluoromethylation of acrylamides was developed using -(difluoromethyl)sulfonium salt as the difluoromethyl source. With this method, pharmaceutically interesting CFH-containing oxindoles were readily accessed from -arylacrylamides, and this method featured mild reaction conditions, a broad scope of substrates, good tolerance of functional groups, and good to excellent yields. Control experiments revealed that this protocol proceeded through a difluoromethylation/cyclization cascade process.

Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones.

CFH moiety has a significant potential utility in drug design and discovery, and the incorporation of CFH into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CFH-quinoxalin-2-ones.

A General and Efficient Solution to Monofluoroalkylation: Divergent Synthesis of Aliphatic Monofluorides with Modular Synthetic Scaffolds.

Monofluoroalkanes are important in many pharmaceuticals, agrochemicals and functional materials. However, the lack of easily available and transformable monofluoroalkylating reagents that facilitate a broad array of transformations has hampered the application of monofluoroalkylation. Herein, we report a general and efficient method of preparing diverse aliphatic monofluorides with monofluoroalkyl triflate as the synthetic scaffold.

Difluoromethyl Radical Triggered Tandem Reaction of -Allyl Amides to Difluoromethylated β-Amino Alcohols by Photoredox Catalysis.

An elegant tandem reaction process for transferring -allyl amide into CFH-β-amino alcohol is described. This approach proceeded smoothly under visible light irradiation in the presence of a 3 mol % Ir complex, exhibiting a broad substrate scope and functional group tolerance, and a variety of CFH-β-amino alcohols were readily accessed in good to excellent yields under mild conditions. The reliable mechanistic studies revealed that sequential difluoromethyl radical addition/carbocation trap/rearrangement is involved.

A multicenter survey of perioperative anxiety in China: Pre- and postoperative associations.

Objectives: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting.

Methods: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery.

Visible-Light-Driven Difluoromethylation of Isocyanides with -(Difluoromethyl)diarylsulfonium Salt: Access to a Wide Variety of Difluoromethylated Phenanthridines and Isoquinolines.

A highly efficient approach of visible-light-driven radical difluoromethylation of isocyanides to access a wide variety of difluoromethylated phenanthridines and isoquinolines is herein described. Electrophilic -(difluoromethyl)diarylsulfonium salt proved to be a good difluoromethyl radical precursor under photoredox catalysis. A broad range of isocyanides were tolerated to furnish the corresponding difluoromethylated phenanthridines, isoquinolines, furo[3,2-]pyridine, and pyrido[3,4-]indole in moderate to excellent yields under mild conditions.

Difluoromethylation of Phenols and Thiophenols with the -(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study.

A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable -(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various ,-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO-, ArSH, ArOH, RSH.

Facile difluoromethylation of aliphatic alcohols with an S-(difluoro-methyl)sulfonium salt: reaction, scope and mechanistic study.

A facile and practical approach for the difluoromethylation of aliphatic alcohols with an S-(difluoromethyl)sulfonium salt was developed. A wide variety of alcohols with broad functional groups are compatible to furnish the corresponding alkyl difluoromethyl ethers in good to excellent yields under mild reaction conditions. Control experiments and DFT computational studies suggest that the difluoromethylation of alcohols mainly proceeds via a difluorocarbene pathway involving a five-membered transition state with the participation of water, whose crucial role in this reaction was also elucidated by control experiments.

Air- and Light-Stable S-(Difluoromethyl)sulfonium Salts: C-Selective Electrophilic Difluoromethylation of β-Ketoesters and Malonates.

Air- and light-stable electrophilic difluoromethylating reagents, S-(difluoromethyl)- S-phenyl- S-(2,4,6-trialkoxyphenyl) sulfonium salts were successfully developed, and the introduction of intramolecular hydrogen bonds plays a crucial role for the stabilities and reactivities of these reagents. C-selective difluoromethylation of a broad range of β-ketoesters and malonates proceeded smoothly under mild reaction conditions to give good to excellent yields with excellent C/O regioselectivities.

Remote anionic Fries rearrangement of sulfonates: regioselective synthesis of indole triflones.

An unusual NaH-mediated remote anionic 1,5-thia-Fries rearrangement reaction was developed. This method provides an efficient approach for the regioselective synthesis of not only 2-(2-hydroxyphenyl)-3-indole triflones but also related 3-sulfonylindoles.

Regioselective synthesis of heteroaryl triflones by LDA (lithium diisopropylamide)-mediated anionic thia-Fries rearrangement.

Novel heteroaryl triflones including oxindole, pyrazolone, pyridine, and quinoline derivatives have been regioselectively synthesized by LDA-mediated thia-Fries rearrangement for the first time. These reactions are also the first examples of the application of anionic thia-Fries rearrangement in heteroaromatic compounds.

Synthesis of indole and biindolyl triflones: trifluoromethanesulfonylation of indoles with Tf2O/TTBP (2,4,6-tri-tert-butylpyridine) system.

A convenient synthesis of indole triflones is reported. N-Alkyl, aryl and N-H indole triflones were obtained in 82-96% yields by the Tf(2)O/TTBP System. Biindolyl triflones were accessed in 51-81% yields for the first time by simple treatment of the resulting indole triflones with a base and without any use of organometallic chemistry.

[Patient-controlled analgesia with tramadol and tramadol/droperidol mixture after abdominal hysterectomy: a double-blinded, randomized controlled trial].

Objective: To compare the clinical efficacy and side effects of tramadol and the mixture of tramadol and droperidol for postoperative patient-controlled analgesia (PCA).

Methods: Sixty female patients, aged 18 - 65, scheduled for elective abdominal total hysterectomy with inhalational general anesthesia (induced with fentanyl and propofol, maintained with O(2)-N(2)O and enflurane or isoflurane supplemented by intermittent iv fentanyl and vercuronium for muscle relaxation) were allocated into 2 groups of 30 patients in a random and double blind manner: group 1 (20 mg tramadol) and group 2 (20 mg tramadol plus 0.1 mg droperidol), both with a lockout time of 10 minutes.