The direct and selective synthesis of phenols from aryl/heteroaryl halides KOH has been achieved through the use highly active monophosphine-based catalysts derived Pd2dba3 ligands L1 or L2 biphasic solvent system 1,4-dioxane/H2O. We have also demonstrated a one-pot method phenol formation/alkylation for preparation alkyl aryl ethers halides. In many instances, this protocol overcomes limitations in existing Pd-catalyzed coupling reactions aliphatic alcohols with Finally, we demonstrate that...

Objective To assess the safety and efficacy of secukinumab, a fully human monoclonal anti-interleukin-17A antibody, in patients with rheumatoid arthritis (RA). Methods Patients (n=237) inadequate response to methotrexate were randomly assigned receive monthly subcutaneous injections secukinumab 25 mg, 75 150 300 mg or placebo. The primary endpoint was American College Rheumatology 20% (ACR20) at week 16. Results Demographics baseline characteristics comparable across all treatment groups....

A good alternative: Highly reactive catalysts based on palladium and dialkylbiarylphosphino ligands provide unprecedented reactivity selectivity in CN bond-forming processes. The bulky monophosphine catalyst system Pd/1 was effective for the reaction of aryl/heteroaryl halides bearing primary amides 2-aminoheterocycles (see scheme; dba=dibenzylideneacetone, R=CONH2, NH2), thus showing that monodentate phosphines are viable alternatives to, sometimes superior chelating ligands.

We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our are in accord with previous report that suggests formation κ2-amidate complexes is deleterious to effectiveness catalyst for this transformation their can be prevented by use appropriate bidentate ligands. now provide data suggest certain ligands also prevent thereby generate more stable catalysts amination chlorides. Furthermore, computational studies shed light...

A wide range of aryl boronic 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s] were readily synthesized. Purifying by conventional silica gel chromatography is generally challenging; however, these introduced derivatives are easily purified on and isolated in excellent yields. We subjected the ArB(Epin) to Suzuki-Miyaura couplings, which provided higher yields desired biaryl products than those obtained using corresponding acids or pinacol esters.

Objective. To evaluate the longer-term safety and efficacy of secukinumab, a fully human monoclonal antiinterleukin-17A antibody, in patients with rheumatoid arthritis. Methods. In this 52-week, double-blind, placebo-controlled (up to Week 20) study ( NCT00928512 ), responding inadequately disease-modifying antirheumatic drugs (DMARD) or biologics were randomized receive monthly subcutaneous injections secukinumab (25, 75, 150, 300 mg), placebo. The results up 20 have been reported...

Benzo-fused nitrogen-containing heterocycles are abundant in biologically active compounds. One of the most important methods for preparing such is (3 + 2) cycloaddition reaction benzynes with 1,3-dipolar However, reactions unsymmetrically substituted generally show low selectivity and hence yield mixtures two regioisomers. In this paper, we describe synthesis both regioisomers multisubstituted benzo-fused azole derivatives as benzotriazoles, 1H-indazoles, benzo[d]isoxazoles through...

[reaction: see text] A selective and catalytic mono-N-alkylation method of both aromatic aliphatic amines using nitriles as an alkylating agent with Pd/C or Rh/C a catalyst is described. This particularly attractive to provide environmentally benign applicable alkylation without toxic corrosive agents such alkyl halides carbonyl compounds.

Two for the price of one: A method has been developed regiocontrolled synthesis multisubstituted biaryl derivatives. This protocol involves use tert-butyldimethylsilyl (TBDMS) group to direct regioselective Diels–Alder reaction a 3-TBDMS-benzyne with furan derivative and subsequent Hiyama cross-coupling TBDMS aryl iodides (see scheme).

Partial hydrogenation: Various mono- and disubstituted alkynes were partially hydrogenated to give cis-olefins with high selectivity using a 5 % Pd0–polyethyleneimine complex as catalyst without additives (see scheme). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2111/2008/z800535_s.pdf or from author. Please note: The publisher not responsible content functionality of any supporting supplied by authors. Any queries (other than...

Cause and effect: The first ortho-selective nucleophilic addition reaction of amines to 3-substituted benzynes has been achieved. Despite a large trimethylsilyl substituent, primary attack the C2 position 3-silylbenzynes produce 2-silylanilines (see scheme). This outcome is likely result from inductive electron-donating effect silyl group, which overrides its steric repulsion with approaching amines.

B+[4+2]: 3-Borylbenzynes undergo Diels–Alder reactions with substituted furans and pyrroles to give highly functionalized arylboronic acid derivatives either good or exclusive regioselectivities (see picture). The effect of the boryl group on regioselectivity arises from electronic rather than steric effects. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited typeset. They made available submitted by...

Benzynes were generated from o-(trimethylsilyl)phenols using nonafluorobutanesulfonyl fluoride (NfF) by a domino process, i.e., the nonaflation of phenolic hydroxyl group NfF followed attack produced ion on trimethylsilyl group. The benzyne immediately underwent various reactions to give polysubstituted benzenes.

We have devised a novel 1,3-benzdiyne equivalent, capable of quadruple functionalization by sequential benzyne generation and reaction with arynophiles. The key features this method include the chemoselective two triple bonds in single benzene ring under fluoride-mediated mild conditions, regiocontrol each substituent next to bond. This produced various benzo-fused heteroaromatic compounds via reactions arynophiles, such as furans, azides, diazo compounds. A validation is given convergent...

Efficient D 2 generation is crucial for synthesizing deuterated compounds. Our study shows that forms via the Grotthuss mechanism on Pd/C, where O and H* form an HD O* intermediate, involving proton–electron transfer from H to metal surface.

The first synthesis of aloin, a natural anthrone C-glycoside, was achieved via two sequential Diels–Alder (DA) reactions connecting 3-silyl-benzynes and 2-stannylfuran. silyl stannyl substituents contributed to the regioselectivity DA 9,10-ether cleavage adduct. subsequent conversion groups hydroxyl C10-glycosylation completed aloin.

A site- and stereoselective deuterium labelling method for carbohydrates has been developed using a Ru/C catalyst under continuous flow conditions. It demonstrated that enhancing the void fraction of...

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytichydrogenation conditions. For aromatic primary amines, corresponding secondary selectively obtained Pd/C-catalyzed hydrogenation Although use electron poor or bulky nitriles showed a lower reactivity toward reductive alkylation, addition NH4OAc enhanced give in good excellent yields. Under same reaction conditions, nitro compounds instead could directly transformed into...

Abstract Aims/introduction The aims of the present study were to investigate performance a novel sandwich enzyme‐linked immunosorbent assay ( ELISA ) for measuring glucagon (1–29) with monoclonal antibodies against both C‐ and N‐terminal regions (1–29), analyze differences in plasma levels responses oral glucose loading normal tolerance NGT subjects patients type 2 diabetes mellitus. Materials Methods cross‐reactivity proglucagon fragments using kit two types conventional radioimmunoassay...

Highly regioselective (3 + 2) cycloadditions of (trifluoromethanesulfonyloxy)benzynes [(triflyloxy)benzynes] with 1,3-dipoles followed by cross-coupling reactions provided multisubstituted benzo-fused heterocycles. The triflyloxy group at the 3-position benzynes, and even that remote 4-position, greatly affected regiocontrol cycloaddition. These groups also served to install other substituents their ipso-positions.

Abstract A heterogeneous palladium on carbon (Pd/C)‐catalyzed coupling between amines and aromatic halides including chlorides has been achieved using sodium tert ‐butoxide (NaO‐ t‐ Bu) 1,1′‐bis(diphenylphosphino)ferrocene (dppf) as a ligand in cyclopentyl methyl ether (CPME). The use of potassium (KO‐ place NaO‐ Bu brought about the benzyne‐mediated amination even without Pd/C dppf, giving mixture regioisomers when 4‐substituted bromobenzenes were employed substrate. combination Pd/C, could...

A new microwave applicator specifically designed for continuous flow synthesis has been developed and tested in the Fischer indole Diels–Alder reaction to afford products at a scale of 100 g h⁻¹.