An advantageous synthesis of new indazolone and pyrazolone derivatives

The synthesis of new indazolone and pyrazolone derivatives starting from methyl anthranilate type substrates is presented. This general approach constitutes a novel and advantageous alternative for the synthesis of the target heterocycles, which implies the use of the environmentally friendly oxidizer PIFA. The synthetic design includes the oxidation of N-arylamides by the hypervalent iodine reagent to the corresponding N-acylnitrenium ions, which can be intramolecularly trapped by an amine moiety to furnish the title compounds by formation of a new N-N single bond.     

Regioselective Synthesis of N‐Heteroaromatic Trifluoromethoxy Compounds by Direct O−CF3 Bond Formation

The first one‐step method for the synthesis of ortho‐N‐heteroaromatic trifluoromethoxy derivatives by site‐specific O?CF₃ bond formation using hydroxylated N‐heterocycles and Togni's reagent is described. The approach enables the unprecedented syntheses of a wide range of six or five‐membered N‐heteroaromatic trifluoromethoxy compounds containing one or two heteroatoms from most commonly used hydroxylated N‐heterocycles. Notable advantages of this method include its simplicity and mild conditions, avoidance of the need for metals or toxic reagents, and compatibility with a variety of functional groups. Furthermore, this method is especially suitable for the larger scale application.     

Electrophilic (phenylsulfonyl)difluoromethylation of thiols with a hypervalent iodine(III)-CF2SO2Ph reagent

A hypervalent iodine(III)-CF₂SO₂Ph compound (3) has been successfully prepared with selective nucleophilic reaction using PhSO₂CF₂SiMe₃ reagent, and this previously unkown compound 3 was found to act as a new electrophilic (phenylsulfonyl)difluoromethylation reagent for a variety of S-nucleophiles under very mild reaction conditions.     

A versatile PIFA-mediated approach to structurally diverse pyrrolo(benzo)diazepines from linear alkynylamides

The addition of the hypervalent iodine reagent PIFA [phenyliodine(III) bis(trifluoroacetate)] to a series of properly substituted N-(3-aminopropyl)alkynylamides results in the efficient formation of a functionalized 5-aroyl-2-pyrrolidinone skeleton. By proper manipulations of the N(1)-substituents, through consecutive deprotection and/or reductive amination steps, a second cyclization process occurs yielding the target heterocycles. As it will be disclosed, the overall process is open to structural modifications that gives rise to a series of pyrrolo(benzo)diazepine derivatives.     

An efficient one-pot synthesis of β-enamino ketones from endo glucal via hypervalent iodine

β-Enamino ketones were successfully synthesized by reaction of endo glycals with primary or secondary amines in the presence of hypervalent iodine reagent in one pot. After the oxidation and protonation taking place on hypervalent iodine agent in acidic condition, endo glucals were effectively converted into the uncyclic β-alkoxyvinyl ketones. Further substitution of β-alkoxyvinyl ketones with primary or secondary amines provided the corresponding β-enamino ketone derivatives in 57-67% yields.     

Synthetic aspects of the oxidative amidation of phenols

The oxidative amidation of phenols effects the conversion of appropriately substituted phenols into 4-amidodienones (‘para-oxidative amidation’) or 2-amidodienones (‘ortho-oxidative amidation’) by the action of hypervalent iodine reagents. The reagent, (diacetoxyiodo)benzene (‘DIB’) is especially effective in these transformations. This paper focuses on techniques for the desymmetrization of the dienoes thus obtained, leading to the stereocontrolled creation of N-substituted spiro carbons. The methodology creates new opportunities in alkaloid synthesis, as apparent from a number of examples.     

Solvent‐Driven Iodine‐Mediated Oxidative Strategies for the Synthesis of Bis(imidazo[1,2‐a]pyridin‐3‐yl)sulfanes and Disulfanes

Two efficient iodine‐mediated strategies, which are economical and one‐pot, are described to access bis(imidazo[1,2‐a ]pyridin‐3‐yl)sulfanes and bis(imidazo[1,2‐a ]pyridin‐3‐yl)disulfanes in chloroform and acetic acid, respectively, by a direct oxidative homocoupling of imidazo‐heterocycles using inexpensive sodium sulfide as a sulfur source. These strategies are scalable, and an array of substrates delivered their corresponding stable sulfur‐bridged imidazo‐heterocycles in excellent yields.     

Recent progress in the electrochemistry of hypervalent iodine compounds

Hypervalent iodine compounds constitute a well-established and broadly used reagent family in organic synthesis. As they are usually either used in stoichiometric quantities or generated in situ from an aryl iodide precursor using a terminal oxidant, the associated waste and separation problems pose major challenges en route to sustainable and scalable processes. In this regard, the use of inexpensive electric current as a traceless oxidant for the in-situ generation of hypervalent iodine has emerged as a promising alternative. This review summarizes the advances over the past 2 years, including improved electrolysis protocols, new synthetic applications, and concepts for enhancing the sustainability of the reactions.     

Synthesis of aggregation pheromone components of cerambycid species through α-hydroxylation of alkylketones

The synthesis of 3-hydroxy-2-hexanone and 2,3-hexanediol, two components of the aggregation pheromone of several cerambycid species, is disclosed in here. Starting from 2-hexanone, through an α-hydroxylation using (diacetoxyiodo)benzene, 3-hydroxy-2-hexanone is obtained in good yield. Further reduction of this compound, gives 2,3-hexanediol in excellent yield. A study of the α-hydroxylation reaction of several alkylketones using an hypervalent iodine reagent is also disclosed in here. The synthesis of optically active compounds (R)- and (S)-3-hydroxy-2-hexanone was achieved starting from 2-hexanone with nitrosobenzene and l- and d-proline respectively, in several reaction media.     

Merging Copper(I) Photoredox Catalysis and Iodine(III) Chemistry for the Oxy-monofluoromethylation of Alkenes

A simple process for the oxy-monofluoromethylation of alkenes is described. In combination with visible-light copper(I) photoredox catalysis, an easily accessible iodine(III) reagent containing monofluoroacetoxy ligands serves as a powerful source of a monofluoromethyl (CH₂F) radical, enabling the step economical synthesis of γ-fluoro-acetates from a broad range of olefinic substrates under mild conditions. Applications to late-stage diversification of alkenes derived from complex molecules, amino acids and the synthesis of fluoromethylated heterocycles are also demonstrated.     

Reaction of (diacetoxyiodo)benzene with excess of trifluoromethanesulfonic acid. A convenient route to para-phenylene type hypervalent iodine oligomers

Reaction of (diacetoxyiodo)benzene [PhI(OAc)₂] in trifluoromethanesulfonic acid (TfOH) resulted in oligomerization of PhI(OAc)₂. Quenching with NaBr gave the bromide salts of hypervalent iodine oligomers that were determined by thermolysis with KI to be a para phenylene type of oligomers. Neutralization of the reaction mixture of PhI(OAc)₂ and TfOH with aqueous NaHCO₃ yielded the triflate salts of iodine oligomers. Furthermore, quenching the reaction mixture with aromatic substrates afforded arylated iodine oligomers. These iodine oligomers were found to be 3-4 of the number average degree of polymerization (P_n) by GC analysis of the thermolysis products and ¹H NMR analysis. The major products, trimer and tetramer, were synthesized independently.     

Oxidative rearrangement of alkenes using in situ generated hypervalent iodine(III)

A novel protocol for the oxidative rearrangement of alkenes using in situ generated hypervalent iodine(III) was developed. This approach uses inexpensive, readily available, and stable chemicals (PhI, mCPBA, and TsOH) giving rearrangement products in yields comparable to those obtained using the more expensive commercially available [hydroxy(tosyloxy)iodo]benzene [HTIB or Koser’s reagent]. Additionally, an alternative protocol for the synthesis of 1-methyl-2-tetralone through the one-step epoxidation/rearrangement of 4-methyl-1,2-dihydronaphthalene using mCPBA and TsOH was developed.     

Towards new camptothecins. Part 3: Synthesis of 5-methoxycarbonyl camptothecin

The synthesis of two camptothecin analogs substituted by a carbonyl function on position 5 of cycle C was realized. New conditions were studied to obtain the E-lactone ring of these heterocycles. These compounds were obtained from the reaction of Bredereck's reagent with indolizines derived from pyroglutamic acid. This yielded dimethylaminovinyl groups whose oxidation by NaIO₄ yielded ketones. The indolizinones obtained were reacted in Friedlander condition, to give the scaffold of the desired camptothecins.     

New Short Synthesis of (5)‐2,3‐Dimethoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐iodobenzamide: Dopamine D2 Receptor

A new short and highly efficient synthesis of (5)‐2,3‐dimethoxy‐N[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐iodobenzamide (epidepride, 1) from 3‐methoxy‐salicylaldehyde (o‐vanillin, 2) and 3‐methoxysalicyclic acid (6) was achieved by employing a new iodination method with iodine monochloride and iodine nitrate under basic conditions.     

Facile Method for the Synthesis of Vicinal Azidoiodides by the Reaction of the NaN3–I2 System with Unsaturated Compounds

A facile and efficient method was developed for the synthesis of vicinal azidoiodides in 62–77% yields by the reaction of sodium azide and iodine with unsaturated compounds in methanol, aqueous methanol, or the water–methanol–tetrahydrofuran solvent system. The reaction in Et₂O or CHCl₃ produced only vicinal diiodides.     

Direct iodination of 3- and 4-nitropyrazoles with a reagent based on iodine monochloride and silver sulfate

The reagent obtained from iodine monochloride and silver sulfate in sulfuric acid easily iodinates I-methyl-3-nitropyrazole under mild conditions to give 4-iodo or 4,5-diiodo derivatives, 1-Methyl-4-nitropyrazole was also directly iodinated with this reagent for the first time. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1482–1484, August, 2000.     

Synthesis,Characterization, and Reactivity of a Hypervalent‐Iodine‐Based Nitrooxylating Reagent

Herein, the synthesis and characterization of a hypervalent‐iodine‐based reagent that enables a direct and selective nitrooxylation of enolizable C?H bonds to access a broad array of organic nitrate esters is reported. This compound is bench stable, easy‐to‐handle, and delivers the nitrooxy (‐ONO₂) group under mild reaction conditions. Activation of the reagent by Brønsted and Lewis acids was demonstrated in the synthesis of nitrooxylated β‐keto esters, 1,3‐diketones, and malonates, while its activity under photoredox catalysis was shown in the synthesis of nitrooxylated oxindoles. Detailed mechanistic studies including pulse radiolysis, Stern–Volmer quenching studies, and UV/Vis spectroelectrochemistry reveal a unique single‐electron‐transfer (SET)‐induced concerted mechanistic pathway not reliant upon generation of the nitrate radical.     

A Carbazole-Functionalized Porous Aromatic Framework for Enhancing Volatile Iodine Capture via Lewis Electron Pairing

Nitrogen-rich porous networks with additional polarity and basicity may serve as effective adsorbents for the Lewis electron pairing of iodine molecules. Herein a carbazole-functionalized porous aromatic framework (PAF) was synthesized through a Sonogashira–Hagihara cross-coupling polymerization of 1,3,5-triethynylbenzene and 2,7-dibromocarbazole building monomers. The resulting solid with a high nitrogen content incorporated the Lewis electron pairing effect into a π-conjugated nano-cavity, leading to an ultrahigh binding capability for iodine molecules. The iodine uptake per specific surface area was ~8 mg m⁻² which achieved the highest level among all reported I₂ adsorbents, surpassing that of the pure biphenyl-based PAF sample by ca. 30 times. Our study illustrated a new possibility for introducing electron-rich building units into the design and synthesis of porous adsorbents for effective capture and removal of volatile iodine from nuclear waste and leakage.     

Solvent directed electrophilic iodination and phenylselenenylation of activated alkyl aryl ketones

A mixture of molecular iodine and phenyliodine(III) bis(trifluoroacetate) (BTI) in CH₃CN (or CH₃OH) iodinates the aromatic ring of some activated alkyl aryl ketones. A different outcome results if PhSeSePh is used instead of I₂ in the presence of BTI. In CH₃CN the aromatic phenylselenenylation is still observed while in CH₃OH the formation of α-phenylseleno ketones occurs followed by the conversion of these intermediates into the corresponding α,α-dimethoxycarbonyl compounds, in moderate to good yields.     

A new crystal engineering approach for the synthesis of {[K.18-Crown-6]I3}n as a nanotube-Like and recyclable catalyst for the chemoselective silylation of alcohols

Reaction of 18-crown-6 with KI in ethanol solution followed by addition of iodine (I₂) afforded a unique triiodide salt with a nanotube-like structure ({[K.18-Crown-6]I₃}_n). It is shown that this reagent may be used for the chemoselective trimethylsilylation of alcohols. The synthesis of the crystalline reagent is a good example of crystal engineering. Reagent was recycled and reused.