C-H Bond Sulfonylation from Thianthrenium Salts and DABCO·(SO2)2: Synthesis of 2-Sulfonylindoles.

A three-component reaction of 1-(1H-indol-1-yl)isoquinolines or 1-(pyridin-2-yl)-1H-indoles, DABCO·(SO2)2, and thianthrenium salts under synergistic photoredox and palladium catalysis is accomplished. This direct C-H bond sulfonylation of indoles with the insertion of sulfur dioxide under mild conditions works efficiently, giving rise to a wide range of 2-sulfonated indoles in moderate to good yields under mild conditions. In this protocol, the generality of aryl/alkyl thianthrenium salts is demonstrated as well. A photoredox radical process combined with palladium catalysis is proposed.

Direct Transamidation of Thioamides with Amines via Acetophenone-Promoted Enamine Catalysis under Metal-Free Conditions.

Herein, we developed a highly selective, efficient, and simple method for direct transamidation of thioamides with amines, promoted by commercially available acetophenone under metal-/solvent-free conditions. The reaction tolerated a wide range of functional groups and substrates, including single- or double-thioamides, benzylamines, or alkyl/cycloalkyl-substituted aliphatic amines. The present protocol can be applied to gram-scale in good yields. In addition, the Pt-/Ni-complexes of double-transamidation products were obtained in good to excellent yields. The investigation of photophysical properties indicated that the fluorescence spectra of Pt-complexes showed an emission band centered at 550-750 nm and exhibited red fluorescence when irradiated by a UV lamp (365 nm).

Synthesis of 2,4-Dicyanoalkylated Benzoxazines through the Radical-Mediated Cascade Cyclization of Isocyanides with AIBN under Metal- and Additive-Free Conditions.

A general and novel method for the radical cascade cyclization of aryl isocyanides with AIBN has been described. This strategy provides straightforward access to various 2,4-dicyanoalkylated benzoxazines in moderate to good yields under metal- and additive-free conditions. The reaction can apply to a gram scale and tolerate diverse functional groups. 2,4-Dicyanoalkylated benzoxazine derivatives feature a large Stokes shift and intramolecular charge transfer properties.

Visible-light-induced three-component reactions of α-diazoesters, quinazolinones and cyclic ethers toward quinazoline-based hybrids.

An effective approach for the construction of 4-short-chain ether attached carbonyl group-substituted quinazolines was developed. Visible-light-induced three-component reactions of α-diazoesters, quinazolinones, and cyclic ethers, with a broad substrate scope and excellent functional group tolerance, under extremely mild conditions without the need for any additional additives and catalysts, selectively led to quinazoline-based hybrids in good to excellent yields. The synthesized hybrids, which are a conglomeration of a quinazoline, a short-chain ether, and a carbonyl group in one molecular skeleton, have potential for application in the development of new drugs or drug candidates.

Parametric cerebral blood flow and arterial transit time mapping using a 3D convolutional neural network.

PURPOSE: To reduce the total scan time of multiple postlabeling delay (multi-PLD) pseudo-continuous arterial spin labeling (pCASL) by developing a hierarchically structured 3D convolutional neural network (H-CNN) that estimates the arterial transit time (ATT) and cerebral blow flow (CBF) maps from the reduced number of PLDs as well as averages. METHODS: A total of 48 subjects (38 females and 10 males), aged 56-80 years, compromising a training group (n = 45) and a validation group (n = 3) underwent MRI including multi-PLD pCASL. We proposed an H-CNN to estimate the ATT and CBF maps using a reduced number of PLDs and a separately reduced number of averages. The proposed method was compared with a conventional nonlinear model fitting method using the mean absolute error (MAE). RESULTS: The H-CNN provided the MAEs of 32.69 ms for ATT and 3.32 mL/100 g/min for CBF estimations using a full data set that contains six PLDs and six averages in the 3 test subjects. The H-CNN also showed that the smaller number of PLDs can be used to estimate both ATT and CBF without significant discrepancy from the reference (MAEs of 231.45 ms for ATT and 9.80 mL/100 g/min for CBF using three of six PLDs). CONCLUSION: The proposed machine learning-based ATT and CBF mapping offers substantially reduced scan time of multi-PLD pCASL.

One-Pot Three-Component Synthesis of Phenanthrenes via Palladium-Catalyzed Catellani and Retro-Diels-Alder Reactions.

An efficient one-pot three-component palladium-catalyzed domino reaction of aryl iodide, 2-bromophenylboronic acid, and norbornadiene to produce phenanthrenes has been developed. Norbornadiene serves both as the activator of ortho-C-H bond and the source of ethylene via a retro-Diels-Alder reaction. The method features inexpensive and readily available substrates, a broad range of functional groups, and good yields.

Mn(III)-Mediated Radical Addition/Cyclization of Isocyanides with Aryl Boronic Acids/Diarylphosphine Oxides: Access to 11-Functionalized Dibenzodiazepines.

A Mn(III)-mediated radical addition/cyclization reaction of isocyanides with aryl boronic acids/diarylphosphine oxides has been developed. A series of 11-arylated/-phosphorylated dibenzodiazepines were efficiently constructed in moderate to excellent yields under mild reaction conditions via imidoyl radical process. The present protocol offers novel access to functionalized seven-membered N-heterocycles.

Transition metal-free regioselective direct acylation of quinazolines for the synthesis of acylquinazoline derivatives.

An efficient, mild method for direct regioselective acylation of quinazolines under metal-free conditions was developed with bis(trifluoroacetoxy)iodobenzene and trimethylsilyl azide at ambient temperature. The acylation reaction of quinazolines with aldehydes gave the corresponding acyl quinazolines in ethyl acetate with good to excellent yields and excellent functional group tolerance and site selectivity. In addition, the mechanism of the direct acylation of quinazolinone was investigated through HPLC-HRMS (high pressure liquid chromatography-high resolution mass spectrometry) and EPR (electron paramagnetic resonance) strategies.

One-pot synthesis of 11-sulfenyl dibenzodiazepines via tandem sulfenylation/cyclization of o-isocyanodiaryl amines and diaryl disulfides.

A one-pot sulfenylation/cyclization of o-isocyanodiaryl amines has been described for the preparation of 11-sulfenyl dibenzodiazepines. This AgI-catalyzed reaction covers an unexplored tandem process to give seven-membered N-heterocycles. This transformation shows a broad range of substrate scope, simple operation, and moderate to good yields under aerobic conditions. Diphenyl diselenide can also be produced in an acceptable yield.

DMF-Assisted Radical Cyclization of o-Isocyanodiaryl Ethers via 1,5-Aryl Migration: Construction of 2-Arylbenzoxazoles.

A novel DMF-assisted radical cyclization of o-isocyanodiaryl ethers via 1,5-aryl migration has been developed for the synthesis of a series of 2-arylbenzoxazoles by the FeCl3/TBHP/Et3N catalytic system in DMF. However, N,N-dimethylbenzo[d]thiazole-2-carboxamide and N,N-dimethylbenzo[d]selenazole-2-carboxamide were obtained from the corresponding substrate 2-isocyanophenyl p-methoxyphenyl thioether and 2-isocyanodiphenyl selenoether under the same conditions. A possible mechanism may involve aryl 1,5-migration and DMF-assisted radical cyclization of o-isocyanodiaryl ethers.

Tetrabutylammonium Chloride-Induced Cascade Radical Addition/Cyclization of O-Isocyanodiaryl Amines: A Novel Protocol for the Synthesis of 11-Trifluoromethylated Dibenzodiazepines.

A straightforward protocol for the synthesis of 11-trifluoromethylated dibenzodiazepines has been developed via TBAC-induced trifluoromethylation/cyclization of o-isocyanodiaryl amines using Togni's reagent as the trifluoromethyl source. This is the first report on the one-step construction of CF3-containing dibenzodiazepine drug skeletons. Additionally, a series of 11-trifluoromethylated dibenzodiazepines were afforded in moderate to excellent yields under transition-metal-free conditions.

Unexpected synthesis, delayed emission and solid-state acidochromism of novel 2,7-naphthyridine derivatives obtained from 2-(3,5-diaryl-4H-pyran-4-ylidene)malononitrile.

Two novel 2,7-naphthyridine derivatives are unexpectedly synthesized by the reaction of 2-(3,5-diaryl-4H-pyran-4-ylidene)malononitrile and benzylamine, and are achieved through different ring-closing mechanisms. These two derivatives with twisted molecular conformations display phosphorescence, thermally activated delayed fluorescence, and high contrast solid-state acidochromism due to special chemical structures.

Generation of Heteroaryl-Substituted Sulfonyl Compounds from Sulfur Dioxide via Remote Heteroaryl ipso-Migration.

The generation of heteroaryl-substituted sulfonyl compounds via a catalyst-, base-, and additive-free three-component reaction of heteroaryl-substituted tertiary alcohols, aryldiazonium tetrafluoroborates, and DABCO·(SO2)2 under mild conditions is developed. Various functional groups are tolerated well in this transformation, and a broad substrate scope is demonstrated. A preliminary mechanistic investigation shows that this reaction undergoes a radical process, including the insertion of sulfur dioxide, sulfonyl radical addition to unactivated alkene, and remote heteroaryl ipso-migration.

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives.

Great progress has been made in the tandem annulation of enynes in the past few years. This review only presents the corresponding reactions of 1,3-enyne structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles.

Evaluation of the diffusion MRI white matter tract integrity model using myelin histology and Monte-Carlo simulations.

Quantitative evaluation of brain myelination has drawn considerable attention. Conventional diffusion-based magnetic resonance imaging models, including diffusion tensor imaging and diffusion kurtosis imaging (DKI),1 have been used to infer the microstructure and its changes in neurological diseases. White matter tract integrity (WMTI) was proposed as a biophysical model to relate the DKI-derived metrics to the underlying microstructure. Although the model has been validated on ex vivo animal brains, it was not well evaluated with ex vivo human brains. In this study, histological samples (namely corpus callosum) from postmortem human brains have been investigated based on WMTI analyses on a clinical 3T scanner and comparisons with gold standard myelin staining in proteolipid protein and Luxol fast blue. In addition, Monte Carlo simulations were conducted to link changes from ex vivo to in vivo conditions based on the microscale parameters of water diffusivity and permeability. The results show that WMTI metrics, including axonal water fraction AWF, radial extra-axonal diffusivity De⊥, and intra-axonal diffusivity Dawere needed to characterize myelin content alterations. Thus, WMTI model metrics are shown to be promising candidates as sensitive biomarkers of demyelination.

Copper(II)-Catalyzed Domino Synthesis of 4-Benzenesulfonyl Isoxazoles from 2-Nitro-1,3-enynes, Amines, and Sodium Benzenesulfinate.

A simple and effective method for the synthesis of fully substituted 4-benzenesulfonyl isoxazoles through a copper(II)-catalyzed three-component reaction of 2-nitro-1,3-enynes, amines, and sodium benzenesulfinate is described. The reaction proceeds smoothly under mild conditions and provides the benzenesulfonyl isoxazoles with high chemoselectivity.

Three-Component Cascade Synthesis of Fully Substituted Trifluoromethyl Pyrroles via a Cu(II)/Rh(III)-Promoted Aza-Michael Addition/Trifluoromethylation Cyclization/Oxidation Reaction.

A three-component cascade reaction of 1,3-enynes, anilines, and Togni-II reagent has been developed to give fully substituted trifluoromethyl pyrroles with high regioselectivity under mild conditions. The transformation proceeds through a Cu(II)/Rh(III)-promoted cascade aza-Michael addition/trifluoromethylation cyclization/oxidation reaction, affording trifluoromethyl pyrrole derivatives as primary products.

Copper and manganese co-mediated cascade aza-Michael addition/cyclization and azidation of 1,3-enynes: regioselective synthesis of fully substituted azido pyrroles.

An efficient Cu and Mn co-mediated aerobic oxidative cyclization and azidation reaction of 1,3-enynes with amines and trimethylsilyl azide (TMSN3) for the synthesis of fully substituted azido pyrroles has been developed. The three-component reaction has the characteristics of high regioselectivity, wide substrate scope, and mild reaction conditions. A preliminary mechanism for this transformation is proposed.

Improved chemical exchange saturation transfer imaging with real-time frequency drift correction.

PURPOSE: To investigate the effects of frequency drift on chemical exchange saturation transfer (CEST) imaging at 3T, and to propose a new sequence for correcting artifacts attributed to B0 drift in real time. THEORY AND METHODS: A frequency-stabilized CEST (FS-CEST) imaging sequence was proposed by adding a frequency stabilization module to the conventional non-frequency-stabilized CEST (NFS-CEST) sequence, which consisted of a small tip angle radiofrequency excitation pulse and readout of three non-phase-encoded k-space lines. Experiments were performed on an egg white phantom and 26 human subjects on a heavy-duty clinical scanner, in order to compare the difference of FS-CEST and NFS-CEST sequences for generating the z-spectrum, magnetization transfer ratio asymmetry (MTRasym ) spectrum, and amide proton transfer weighted (APTw) image. RESULTS: The B0 drift in CEST imaging, if not corrected, would cause APTw images and MTRasym spectra from both the phantom and volunteers to be either significantly higher or lower than the true values, depending on the status of the scanner. The FS-CEST sequence generated substantially more stable MTRasym spectra and APTw images than the conventional NFS-CEST sequence. Quantitatively, the compartmental-average APTw signals (mean ± standard deviation) from frontal white matter regions of all 26 human subjects were -0.32% ± 2.32% for the NFS-CEST sequence and -0.14% ± 0.37% for the FS-CEST sequence. CONCLUSIONS: The proposed FS-CEST sequence provides an effective approach for B0 drift correction without additional scan time and should be adopted on heavy-duty MRI scanners.

Synthesis of Chiral ß-Fluoroalkyl ß-Amino Acid Derivatives via Palladium-Catalyzed Hydrogenation.

An enantioselective palladium-catalyzed hydrogenation of ß-fluoroalkyl ß-amino acrylic acid derivatives has been successfully developed, providing the corresponding chiral ß-fluoroalkyl ß-amino acid derivatives in good yields with excellent enantioselectivities. In addition, chiral γ-fluoroalkyl γ-amino alcohol could be synthesized by a simple reduction of the corresponding hydrogenated product. The mechanism of the reaction was explored by deuterium-labeling experiments.