Transition-metal-free synthesis of aromatic amines via the reaction of benzynes with isocyanates

An unexpected reaction between benzynes and isocyanates to generate aromatic amines has been developed under transition-metal-free conditions. The in situ prepared anions formed through cleavage of the NC bond in isocyanates, reacted with aryne precursors to afford various aniline derivatives in moderate to excellent yield and tolerated various substituents on the o-silyl aryl triflate and the isocyanate.     

Sodium persulfate-promoted site-selective synthesis of mononitroarylamines under transition-metal-free conditions

A practical preparation of nitroarylamines from protected arylamines was herein disclosed. In this system, sodium nitrite acted as a nitration reagent in the presence of sodium persulfate without any transition-metal catalysts. This efficient site-selective protocol took place at room temperature for a short time through a free radical pathway.     

Transition-metal-free,atom-economical cascade synthesis of novel 2-sulfonated-benzo[f][1,7]naphthyridines and their cytotoxic activities

An efficient, transition-metal-free cascade synthetic method has been developed for new 2-aryl/heteroaryl sulfonated benzo[f][1,7]naphthyridines. It is tert-butyl hydroperoxide (TBHP) mediated highly regioselective sulfonylation?cyclization?aromatization process between N-(3-aryl/heteroarylprop-2-yn-1-yl)quinolin-3-amines and aryl/heteroaryl sulfonylhydrazides. This synthetic protocol offers one-step strategy for CS and CC bond formations with a broad range of functional group tolerance. It is a simple, mild, and atom-economical route for the synthesis of various valuable functionalized 1, 2-aryl/heteroaryl sulfonated benzo[f][1,7]naphthyridines in moderate yields. Since the core motif of 2-sulfonated benzo[f][1,7]naphthyridines are biologically and pharmaceutically important (TLR activity 7, 8 modulators). Additionally, the synthesized derivatives were evaluated for their in vitro cytotoxic activities against six human cancer cell lines including lung (NCIH23), colon (HCT15), gastric (NUCG-3), renal (ACHN), prostate (PC-3), and breast (MDA-MB-231) cell lines. These compounds displayed significant cytotoxic activities against all tested human cancer cell lines.     

Transition-metal-free sp3 C–H activation of 2-methylquinoline with terminal alkynes for synthesis of 3-(quinolin-2-yl)isoxazoles

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A direct route to isoflavan quinones. The synthesis of colutequinones A and B

The first syntheses of colutequinone A and colutequinone B were achieved. Radical generation via phenyliodoso diacetate was superior to radical generation via ammonium persulfate.     

Oxidative decarboxylation of arylacetic acids in water: One-pot transition-metal-free synthesis of aldehydes and ketones

One-pot transition-metal-free synthesis of aromatic aldehydes and ketones via oxidative decarboxylation of arylacetic acids in water is developed. Protocol relies on the direct decarboxylation of sp³-hybridized carbon in water without any over oxidation into carboxylic acids with minimal waste. Reaction mechanism is investigated and application of this protocol is demonstrated on a gram scale.     

Metal free coupling of heteroaryl N-tosylhydrazones and thiols: Efficient synthesis of sulfides

A metal free coupling of heteroaromatic N-tosylhydrazones with thiols is presented. A convenient synthetic route to synthesize heteroaryl N-tosylhydrazones is also showed. Valuable thioethers with pyrroles, pyridines, thieno[2,3-b]pyridines, imidazo[1,2-a]pyridines, and 6H-thieno[2,3-b]pyrroles derivatives were synthesized in good yields. This coupling reaction can be carried out in a one-pot fashion and scaled up to the gram scale by using heteroaryl aldehydes, without the need to isolate the N-tosylhydrazone.     

A new route to the versatile synthesis of thiopyrano[2,3-b:6,5-b′]diindoles via 2-(alkylthio)-indole-3-carbaldehydes

A versatile synthesis of symmetrically and unsymmetrically substituted thiopyrano[2,3-b:6,5-b′]diindoles has been developed by the condensation of 2-(alkylthio)-indole-3-carbaldehydes with indoline-2-thiones in the presence of catalytic amount of ethylenediamine diacetate (EDDA). The EDDA mediated condensation leads to a spontaneous cyclization followed by aromatization to form thiopyrano[2,3-b:6,5-b′]diindoles in quantitative yields.     

Heteroaromatic annulation studies on 10,11-dihydro-11-[bis(methylthio)methylene]dibenzoxepin-10-one: a facile access to novel dibenzoxepino[4,5]-fused heterocycles

10,11-Dihydro-11-[bis(methylthio)methylene]dibenzoxepin-10-one has been shown to be a useful three carbon synthon for the efficient regiospecific annulation of a variety of five- (pyrazoles, isoxazoles, thiophene, and γ-lactone) and six-membered (pyrimidines, pyridone and pyridines) heterocycles by cyclocondensation with heterobinucleophiles such as hydrazine, hydroxylamine, dimethylsulfonium methylide, guanidine, thiourea, cyanoacetamide, and substituted β-lithioaminoacrylonitrile.     

叶酸的平行催化波及其分析应用

在Britton-Robinson(pH 4.1)的缓冲溶液中叶酸于-0.56 V(vs.SCE)产生一还原波,该波能被氧化剂过硫酸钾催化形成平行催化波.催化波峰电位不变,峰电流增加10倍,二阶导数波波高与叶酸的浓度在5.0×10-9～3.5×10-7 mol/L范围内呈线性关系(r=0.999),检出限可达3.0×10-9mol/L.方法简便灵敏,运用该法测定了叶酸片剂中的叶酸.     

A concise synthetic strategy to alkynyl sulfides via transition-metal-free catalyzed C-S coupling of 1,1-dibromo-1-alkenes with thiophenols

A novel synthetic strategy to alkynyl sulfides via transition-metal-free catalyzed C-S coupling of 1,1-dibromo-1-alkenes with thiophenols has been developed. The new strategy which avoided the transition-metal toxicities is environmental friendly and very important for alkynyl sulfides synthesis.     

A simple and efficient approach for the synthesis of 2-aminated quinazoline derivatives via metal free oxidative annulation

A simple and efficient approach for the synthesis of 2-aminoquinazoline derivatives in moderate to good yields. This reaction employs mild reaction conditions, is metal-free and utilizes readily available starting materials making it a more viable reaction for scale up synthesis and ligand diversity. Notably, this methodology allows for the synthesis of 2-aminoquinazolines using a free amine or cyclic amine enabling structural diversity and good atom economy.     

α-Oxoketene dithioacetals mediated heteroaromatic annulation protocol for benzoheterocycles: an efficient regiocontrolled synthesis of highly substituted and annulated indazoles

An efficient regiocontrolled synthesis of highly substituted and annulated indazoles involving base induced addition-elimination of 1,3-diphenyl-5-cyanomethylpyrazole to a variety of acyclic and cyclic α-oxoketene, followed by acid assisted cycloaromatization of the resulting conjugate adducts has been reported.     

Halonium-initiated electrophilic cascades of 1-alkenoylcyclopropane carboxamides: efficient access to dihydrofuropyridinones and 3(2H)-furanones

Halonium-initiated cascade reaction of 1-alkenoylcyclopropane carboxamides was developed, which leads to the production of dihydrofuropyridinones and 3(2H)-furanones, respectively, depending on the property of substituents on the enone moiety.     

Decarboxylative difluoromethylation of aldehydes with PhSO2CF2COOK: A facile and efficient access to difluoromethylated carbinols

A novel decarboxylative difluoromethylation reaction of PhSO₂CF₂COOK with aldehydes under metal- and ligand-free conditions has been developed. The reaction is very mild and tolerates a wide range of aldehydes (both enolizable and non-enolizable aldehydes), providing a facile and efficient method for the synthesis of structurally diverse difluoromethylated carbinols in moderate to excellent yields.     

Hofmann rearrangement of primary carboxamides and cyclic imides using DCDMH and application to the synthesis of gabapentin and its potential peptide prodrugs

Two protocols for the efficient transformation of aromatic as well as aliphatic primary carboxamides to the corresponding carbamates and aromatic as well as aliphatic cyclic imides to the corresponding anthranilic acid derivatives & amino acid derivatives, respectively, are described. We also developed a novel methodology to the multigram scale synthesis of gabapentin and (S)-pregabalin. The gabapentin methyl carbamate was converted to novel potential peptide prodrugs of gabapentin.     

A simple one-pot synthesis of triflyl guanidines: access to highly substituted electron-poor guanidines

Unsymmetrical di- and trisubstituted triflyl guanidines are accessed through a simple, one-pot protocol from the corresponding isothiocyanate and amine. Furthermore, in the presence of base, trisubstituted triflyl guanidines are alkylated to obtain tetrasubstituted triflyl guanidines in high yields and complete regioselectivity.     

A new access to dihydrotropones through ring expansion of spirocyclohexadienones: synthesis and mechanism

In this paper we report the rearrangement of spirocyclohexadienones into dihydrotropones in basic conditions as a new method for the preparation of seven-membered ring ketones, which are key building blocks for the synthesis of tropoloalkaloids. DFT calculations and deuterium labeling studies support the mechanism we propose for this rearrangement, involving the ring opening of a spirocyclopropane intermediate followed by successive base-catalyzed 1,3-hydrogen shifts. The X-ray structure of the resulting dihydrotropone shows near-perfect planarity and the conjugation gain is likely to be the driving force of the reaction.     

Grignard additions to 2-uloses: synthesis of stereochemically pure tertiary alcohols

The addition of Grignard reagents to a number of 2-uloses has been investigated. Despite initial low diastereoselectivities it was found that tuning the ketone starting materials and studying solvent effects allowed formation of a single alcohol product.