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A Ni-catalyzed cross-coupling reaction between aryl fluorides and dialkyl phosphonates [HP(O)(OR)

We report a visible-light-induced copper-catalyzed highly enantioselective umpolung allylic acylation reaction with acylsilanes as acyl anion equivalents. Triplet-quenching experiments and DFT calculations supported our reaction design, which is based on copper-to-acyl metal-to-ligand charge transfer (MLCT) photoexcitation that generates a charge-separated triplet state as a highly reactive intermediate. According to the calculations, the allylic phosphate substrate in the excited state undergoes novel molecular activation into an allylic radical weakly bound to the copper complex. The allyl radical fragment undergoes copper-mediated regio- and stereocontrolled coupling with the acyl group under the influence of the chiral N-heterocyclic carbene ligand.

A hollow-shaped caged triarylphosphine with three bulky triarylmethyl substituents at the positions meta to the P atom was synthesized. Its gold(I) complex was synthesized and characterized by NMR ...

Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). UMIN000027031 April 18, 2017

Compounds having cyclic molecular frameworks are highly regarded for their abundance and diverse utilities. In particular, medium-sized carbocycles and heterocycles exist in a broad spectrum of natural products, bioactive therapeutics, and medicinally significant synthetic molecules. Metal-mediated methods have been developed for the preparation of compounds containing a medium-sized ring (MSR) through cyclization of different classes of substrates and acyclic precursors. This review focuses on the methodologies for construction of MSRs via gold catalysis. Given the challenges in enabling the assembly of different ring sizes, we present here accounts on Au-mediated cyclization giving notable 7-membered and medium-sized (8-11-membered ring) structures. Emphasis on the pathway and mode of cyclization and the selection of precursors ranging from structurally biased compounds were outlined. Reactivity patterns and the choice of efficient Au catalysts for controlling reaction performance and selectivity in addition to mechanistic attributes are examined.

Hybridization of porous synthetic polymer and sophisticated ligand play important role in transition-metal catalysis for chemical transformations at laboratory and industrial level. A monolithic porous polymer, which is a single piece with continuous macropores, are desired for high permeability, fast mass transfer property, high stability, and easy modification. Herein, we first develop a monolithic porous polystyrene containing three-fold cross-linked PPh3 (M-PS-TPP) for transition-metal catalysis. The monolithic and macroporous structure of M-PS-TPP was fabricated via polymerization-induced phase separation using porogenic solvent. Moreover, the M-PS-TPP was synthesized using different feed ratios of divinylbenzene (DVB) for site-isolation and mono-P-ligating behavior of PPh3. 31P CP/MAS NMR analysis revealed that the different selectivity of M-PS-TPPs was obtained in formation of mono- P-ligation toward PdII. The macroporous properties and controlled mono-P-ligating behavior of M-PS-TPP facilitated a challenging Pdcatalyzed Suzuki-Miyaura cross-coupling reactions of chloroarenes.

Immobilized transition metals for continuous-flow catalyses are greatly in demand to achieve automation, scale-up, facile separation, regeneration, and energy-saving production with high level of sustainability and efficiency. Here, we report a tertiary phosphine immobilized on a macroporous monolith (M-PS-TPP) for the challenging Pd-catalyzed cross-coupling reaction of aryl chloride in a continuous-flow system. The monolithic and macroporous structure of M-PS-TPP was fabricated by bulk polymerization in the presence of a high internal phase emulsion (HIPE) template. Owing to the large pore size and high porosity, the M-PS-TPP showed high permeability against continuous flow of the mobile phase. The continuous-flow Suzuki-Miyaura cross-coupling reaction was realized by permeation of organic/aqueous media containing inorganic salt through a Pd-loaded monolith (M-PS-TPP-Pd) column without serious clogging. Controlling coordination chemistry and hydrodynamics of M-PS-TPP-Pd boosted highly active phosphine-metal complex formation and fast mass transfer of reactants. Indeed, the M-PS-TPP-Pd column showed surprisingly higher yields (similar to 93%) and turnover numbers (2704) under continuous-flow conditions than that under batch conditions (similar to 6%).

α-Aminoboronic acids, isostructural boron analogues of α-amino acids, have received much attention because of the important biomedical applications implicated for compounds containing this structur...

The iridium-catalyzed transfer hydrogenation of alkenes using 1,4-dioxane as a hydrogen donor is described. The use of 1,2-bis-(dicyclohexylphosphino)ethane (DCyPE), featuring bulky and highly electron-donating properties, led to high catalytic activity. A polystyrene-cross-linking bisphosphine PS-DPPBz produced a reusable heterogeneous catalyst. These homogeneous and heterogeneous protocols achieved chemoselective transfer hydrogenation of alkenes over other potentially reducible functional groups such as carbonyl, nitro, cyano, and imino groups in the same molecule.

The hydroacylation of vinylarenes with acyl fluorides and hydrosilanes was enabled by a synergistic bimetallic Ni/Cu-catalytic system, giving access to the corresponding branched ketone products. The reaction takes place under mild conditions at 25-80 °C and tolerates base-sensitive functional groups such as methoxycarbonyl and acetoxy groups.

Herein, we describe a new catalytic approach to accessing aromatic amines from an abundant feedstock, namely phenols. The most reliable catalytic method for converting phenols to aromatic amines uses an activating group, such as a trifluoromethane sulfonyl group. However, this activating group is eliminated as a leaving group during the amination process, resulting in significant waste. Our nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including a formyl group, are compatible. A bisphosphine ligand immobilized on a polystyrene support (PS-DPPBz) is key to the success of this reaction, generating a catalytic species that is significantly more active than simple nonsupported variants.

Herein, we show the highly enantioselective borylation of unactivated methylene C(sp3)-H bonds in 2-alkylpyridines and 2-alkyl-1,3-azole derivatives using an iridium-BINOL-based chiral monophosphite catalyst system. Quantum chemical calculations using the artificial force induced reaction (AFIR) method suggested that a monophosphite-Ir-tris(boryl) complex generates a narrow chiral reaction pocket where the differentiation of the enantiotopic methylene C-H bonds is accomplished through an assembly of multiple noncovalent interactions.

A polystyrene-cross-linking tricyclohexylphosphine (PS-TCP) was synthesized through radical emulsion polymerization of 4-tert-butylstyrene as a monomer and tris(trans-4-styrylcyclohexyl)phosphine as a threefold cross-linker. The PS-TCP showed enhanced ligand performance compared to the corresponding polystyrene-triphenylphosphine hybrid PS-TPP and tricyclohexylphosphine in Pd-catalyzed Suzuki-Miyaura and Buchwald-Hartwig reactions of aryl chlorides.

Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition.In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air.A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups.Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031).UMIN000027031 DATE OF REGISTRATION: April 18, 2017.

Non-activated aryl fluorides reacted with potassium diorganophosphinites through a nucleophilic aromatic substitution (SN Ar) reaction. Remarkably, both electron-neutral and electron-rich aryl fluorides participated in the reaction with substantially stabilized anionic P nucleophiles to form the corresponding tertiary phosphine oxides. Quantum chemical calculations suggested a nucleophile-dependent mechanism that involves both concerted and stepwise SN Ar reaction pathways.

2,2'-Bipyridine ligands (dsbpys) with dumbbell-like shapes and differently substituted triarylmethyl groups at the C5 and C5' positions showed high ligand performance in the Ni-catalyzed cross-electrophile coupling and the Ni/photoredox-synergistically catalyzed decarboxylative coupling reactions. The superior ligand effects of dsbpys compared to the conventional bpy ligands were attributed to the monochelating nature of dsbpys.

The polystyrene-cross-linking bisphosphine ligand PS-DPPBz was effective for the Ir-catalyzed reversible acceptorless dehydrogenation/hydrogenation of N-heterocycles. Notably, this protocol is appl...

Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

Gastrointestinal decompression is generally applied to a non-strangulated acute small bowel obstruction (NSASBO). Although long tube (LT) placement and administration of Gastrografin through a nasogastric tube (NGT-G) have shown advantages over NGT alone in previous studies, no studies appear to have compared LT and NGT-G. In this multicenter, randomized controlled trial, patients with NSASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018 at 11 Japanese institutions. The primary endpoint was non-inferiority of NGT-G compared to LT for non-surgery rate, and the lower limit of the 95% confidence interval for the non-surgery rate (−15%) was set as the lower margin for inferiority of NGT-G compared to LT. In total, 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed in the present trial. The non-surgery rate was 87.4% in the LT group and 91.1% in the NGT-G group, with a 3.7% difference between NGT-G and LT (95.3%CI − 5.55 to 12.91; non-inferiority P = 0.00002923). On the other hand, the non-surgery rate with pure NGT-G alone (76.8%) that represents non-cross-over NGT-G without subsequent LT was significantly lower than that with LT (P = 0.039). Median procedure time was significantly shorter with NGT-G (1 min) than with LT (25 min; P

A 25-year-old man, with a retroperitoneal bulky mass invading the posterior pancreas head, was referred to investigate and treat his rapidly advancing disease. An endoscopic ultrasonography guided-fine needle aspiration biopsy (EUS-FNAB), performed the next day, and followed by immunostaining for human chorionic gonadotropin (hCG), led to a histological diagnosis of choriocarcinoma. An elevated level of serum hCG also supported the diagnosis. Systemic chemotherapy by etoposide and cisplatin was initiated within a week, with precautions taken to avoid tumour lysis syndrome and choriocarcinoma syndrome. EUS-FNAB enabled a prompt diagnosis and suitable treatment for choriocarcinoma and was considered as an effective diagnostic tool for rare tumours with rapid progression.

BACKGROUND AND AIM Most polyps detected during colonoscopies are diminutive or small, and they rarely have advanced histology. Real-time prediction of advanced histology would help clinicians to assess the need for pathological evaluation. Here, we investigated endoscopic predictors of advanced histology in diminutive and small polyps. METHODS Consecutive patients with adenomatous polyps (

Triarylmethylium-o,o-dimers adopt a twisted geometry so that two diarylmethyliums are stacked in a slipped manner. Thus, chiral auxiliaries on the aryl groups induce a preference in the axial chirality of the central biphenyl unit. Strong circular dichroism is attained through exciton coupling, which can be used for additional spectral output in their electrochromic behavior. Diastereoselectivity based on π–π stacking exhibits unique solvent effects, thus endowing multifunctional response properties.

The palladium-catalyzed asymmetric side-chain C(α)-allylation of 2-alkylpyridines, without using an external base, was developed. The high linear selectivities and enantioselectivities were achieved using new chiral diamidophosphite monodentate ligands. Given that the reaction conditions do not require an external base, this catalyst system enabled chemoselective C(α)-allylation of 2-alkylpyridines containing α-carbonyl C-H bonds, which are more acidic than α-pyridyl C-H bonds.

A borate-containing caged triarylphosphine L-X (X = Na or NBu4), featuring a 9-phospha-10-boratriptycene framework, was synthesized and characterized by NMR spectroscopy and X-ray diffraction analysis. The NMR coupling constant of the corresponding phosphine selenide indicated a higher electron-donating property of the borate-phosphine L compared to that of the 9-phospha-10-silatriptycene derivative (Ph-TRIP). The coordination property of L-X to [PdCl(η3-allyl)]2 was dependent on the countercation, giving a neutral Pd complex [PdCl(η3-allyl)(L-NBu4)] from L-NBu4 in CH2Cl2 or a zwitterionic Pd complex [Pd(η3-allyl)(MeCN)(L)] from L-Na in MeCN/CH2Cl2. Utility of L-X as a ligand for metal catalysis was demonstrated in the Pd-catalyzed Suzuki–Miyaura cross-coupling of aryl chlorides.

Trialkylphosphine organocatalysis has enabled the regioselective anti-carboboration of alkynoates with 9-BBN-based 1,1-diborylalkanes to produce secondary allylboranes with β-alkoxycarbonyl and γ-boryl substituents. The utility of the densely functionalized allylboranes was demonstrated by the highly diastereoselective allylation of N-(trimethylsilyl)aldimines to produce homoallylamines containing tertiary allylborane and acrylate moieties.

Cationic gold(I) complexes with hollow-shaped triethynylphosphine ligands efficiently catalyzed intramolecular [2+2] cycloaddition of 1,9-enynes to afford cyclobutene-fused eight-membered carbocycles that were difficult to synthesize by other catalytic systems. Various 1,9-enynes with carbon linkers with or without a fused ring underwent efficient [2+2] cycloaddition with 5 mol% of the Au catalyst bearing the triarylmethyl-end-capped triethynylphosphine in CH2Cl2 at rt in the presence of MS 4A as an additive. More challenging 1,9-enyne substrates with fully saturated acyclic carbon linkers underwent eight-membered ring formation at 60 °C in ClCH2CH2Cl in the absence of MS 4A, forming monocyclic 1,3-dienes as major products.

Enantioselective heteroatom-directed C(sp3)–H borylation reactions of 2-aminopyridines and 2-alkylpyridines with Rh- and Ir catalytic systems using commercially available chiral monophosphine ligands, respectively, were developed. This methodology provides an innovative example of a homogeneous catalytic system for C(sp3)–H borylation, and allows the direct synthesis of optically active alkylboronates with a moderate level of enantioselectivity.

Because benzannulated and indole-fused medium-sized rings are found in many bioactive compounds, combining these fragments might lead to unexplored areas of biologically relevant and uncovered chemical space. Herein is shown that α-imino gold carbene chemistry can play an important role in solving the difficulty in the formation of medium-sized rings. Namely, phenylene-tethered azido-alkynes undergo arylative cyclization through the formation of a gold carbene intermediate to afford benzannulated indole-fused medium-sized tetracycles. The reactions allow a range of different aryl substitution patterns and efficient access to these otherwise difficult-to-obtain medium-sized rings. This study also demonstrates the feasibility of the semihollow-shaped C-dtbm ligand for the construction of a nine-membered ring.

Polystyrene-cross-linking triphenylphosphines having methyl groups as ortho substituents were synthesized. Coordination of the polymer-bound tri(o-tolyl)phosphine-type ligand toward a Pd(II) complex was investigated by 31P CP/MAS NMR spectroscopies. Effects of the ortho-methyl-substituent were evaluated in the Pd-catalyzed cross-coupling of aryl chlorides.

Prolinol-phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne-nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral β-lactams. A high level of enantiocontrol was achieved not only with aryl- or alkenylacetylenes but also with alkylacetylenes, which were important but unfavorable substrates in the previously reported protocols. Two-point hydrogen bonding between the chiral ligand and the nitrone oxyanion consisting of O-H⋅⋅⋅O and C(sp3 )-H⋅⋅⋅O hydrogen bonds is proposed.

A polystyrene-cross-linking bisphosphine PS-DPPBz was synthesized through radical emulsion copolymerization between 4-t-butylstyrene as a monomer and tetravinylated 1,2-bis(diphenylphosphino)benzene (DPPBz) as a 4-fold cross-linker. The location of the DPPBz bisphosphine moiety at the branching points of the cross-linked network organic polymer allowed controlled bisphosphine monochelation to transition metals under conditions where homogeneous ligands may form bischelated single metal complexes or multinuclear complexes. PS-DPPBz showed high ligand performance in first-row transition metal catalysis, enabling challenging molecular transformations that were not possible through the screening of existing homogeneous ligands. In the Ni-catalyzed amination of aryl chlorides with N-alkyl-substituted primary amines, the substrate scope has been expanded to include 2,6-disubstituted aryl chlorides and N-tertiary-alkyl-substituted primary amines. PS-DPPBz was effective for the Ni-catalyzed C–H/C–O coupling betwe...

A 61-year-old man who had undergone total nephrouretectomy eight months earlier for right ureteral carcinoma was referred for the investigation of elevated serum hepatobiliary enzymes. Computed tomography revealed a small mass invading the lower bile duct. Duodenoscopy revealed a central ulcerative tumor near the major papilla, and a biopsy histologically confirmed metastatic ureteral carcinoma. Endoscopic biliary stenting ameliorated the cholangitis, and gemcitabine-based chemotherapy was initiated. The patient was stable for a year until a duodenal stenosis developed and required duodenal stenting. Endoscopic procedures play important roles in the management of rare metastases to the duodenum.

A new class of triarylmethane-based phosphines (L1–L4) and their Pd(II) and Rh(I) complexes were synthesized and subsequently characterized by NMR spectroscopy and X-ray diffraction analysis. The reactions of these phosphines with [PdCl(π-allyl)]2 gave the square-planar Pd(II) complexes [PdCl(π-allyl)(L)] (L = L1–L4). The treatment of [PdCl(π-allyl)(L3)] and [PdCl(π-allyl)(L4)], which have CF3-substituted triarylmethane and 9-arylfluorene moieties, respectively, with LiOtBu afforded P,C(sp3)-chelated palladacycle complexes. Reversibility between a C(sp3)–M covalent bond and a C(sp3)–H···M interaction was experimentally demonstrated using [RhCl(nbd)]2 as a Rh(I) source. The triarylmethane-monophosphines L1–L4 were applied to the Pd-catalyzed 1,4-addition of arylboronic acids to enones.

P,P,P′,P′-Tetraethynylated bisphosphine and P-C-P pincer ligands with tris[3,5-di(tert-butyl)-4-methoxyphenyl]methyl end caps were synthesized. The bulky end cap groups of these ligands form a nano...

Background and Aims Post endoscopic submucosal dissection coagulation syndrome (PECS) occasionally occurs after colorectal endoscopic submucosal dissection (ESD), presenting with localized abdominal pain and inflammation. We conducted a randomized controlled trial (RCT) to assess the usefulness of endoscopic clipping closure to prevent PECS and delayed perforation (DP). Methods This is a multicenter, single-blind RCT. Prospectively enrolled patients undergoing colorectal ESD were randomly allocated to endoscopic clipping closure and nonclosure after ESD, stratifying by institution and tumor size. All participants underwent a computed tomography scan after ESD. PECS was defined as visual analog scale (VAS) ≥30 mm, an increase in VAS ≥20 mm from baseline, body temperature ≥37.5°C or white blood cells ≥10,000/μL after colorectal ESD. DP was defined as PECS accompanied by extraluminal air. The preplanned sample size was 320 patients, and the primary endpoint was the rate of PECS/DP. Results At the planned interim analysis, this trial was terminated by recommendation of the independent data and safety monitoring committee because conditional power with superiority was lower than the preplanned futility limit. Finally, 155 patients were analyzed. The rate of PECS/DP was 16% (95% confidence interval [CI], 8%-23%) in the nonclosure group and 24% (95% CI, 14%-34%) in the closure group (P = .184). All cases of DP were within minor criteria, and all PECS/DP patients were managed conservatively without surgical treatment. Simple periluminal air without PECS was observed in 16% (95% CI, 8%-23%) in the nonclosure group and 10% (95% CI, 3%-17%) in the closure group. Conclusion Endoscopic clipping closure could not reduce the high incidence of PECS/DP after colorectal ESD. (University Hospital Medical Network Clinical Trials Registry number: UMIN000027031.)

Herein, we show the highly enantioselective borylation of unactivated methylene C(sp

Background and aim Pancreatic cysts have been reported in cases with autoimmune pancreatitis (AIP) and are often treated by corticosteroid; however, their response to steroid has not been determined fully. We aimed to see the incidence and steroid response of pancreatic cysts and the features of cysts without proper response in cases with AIP. Methods Fifty-eight AIP cases were analyzed for the incidence and associated factors of pancreatic cystic lesions (≥ 10 mm). Of these, 47 cases, determined for steroid response, were retrospectively investigated for the factors associated with cyst change by corticosteroid therapy. Results At initial diagnosis, 17 pancreatic cystic lesions were recognized in 13 cases (22.4%) of AIP, with an average size of 30 mm (range: 11-130 mm), associated with higher incidence of elevated serum amylase (38.5% vs 11.1%, P = 0.02). Of these 13 cases, nine cases with 10 cystic lesions underwent steroid therapy in our hospital. All of seven unilocular cysts were dramatically shrunken or vanished in a few months; meanwhile, three cases with multilocular cysts showed scarcely any steroid response (P = 0.008). Of these three cases, two cases were revealed to accompany pancreatic ductal carcinoma, in contrast to null of seven unilocular cysts (P = 0.07). Conclusions Pancreatic cystic lesions are sometimes recognized in cases with AIP, and most unilocular cysts can be minimized by corticosteroids. However, clinicians must be alert for atypical pancreatic cysts, such as multilocular cysts or cysts without obvious steroid response.

The synthesis and characterization of a novel chiral phosphine–phosphoric acid ligand, (R)-3-diphenylphosphino-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate (2) and its rhodium(I) complexes are described. The single-crystal X-ray diffraction analysis of 2 showed the intermolecular hydrogen-bonding network of the phosphoric acid moiety. The reactions of 2 with [RhCl(cod)]2 in the presence of KOtBu or with [Rh(acac)(CO)2] (acac = acetylacetonate) gave P,O-chelating rhodium(I) complexes [Rh(2–H+)(cod)] 3 or [Rh(2–H+)(CO)]2 4, respectively. Their molecular structures were determined by single-crystal X-ray diffraction.