Rh(II)-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides derived from N-tosylhydrazones and sulfides

In this paper, Rh₂(OAc)₄-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides derived from N-tosylhydrazones and sulfides is reported. A series of tosylhydrazones derived from aldehydes were successfully used for [2,3]-sigmatropic rearrangement by reaction with either allylic phenyl sulfides or propargyl phenyl sulfides. The reaction conditions were optimized and afforded the products in moderate to good yields. In addition, a novel and convenient approach for the synthesis of cyclobutenones and cyclopropanes has been developed through direct oxidation of the rearrangement products.     

Ruthenium–Porphyrin‐Catalyzed Diastereoselective Intramolecular Alkyl Carbene Insertion into C?H Bonds of Alkyl Diazomethanes Generated In Situ from N‐Tosylhydrazones

With a ruthenium–porphyrin catalyst, alkyl diazomethanes generated in situ from N‐tosylhydrazones efficiently underwent intramolecular C(sp³) H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99 % yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C H insertion of N‐tosylhydrazones can be viewed as reductive coupling between a CO bond and a C H bond to form a new C C bond, since N‐tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (±)‐pseudoheliotridane.     

Ruthenium–Porphyrin‐Catalyzed Diastereoselective Intramolecular Alkyl Carbene Insertion into CH Bonds of Alkyl Diazomethanes Generated In Situ from N‐Tosylhydrazones

With a ruthenium–porphyrin catalyst, alkyl diazomethanes generated in situ from N‐tosylhydrazones efficiently underwent intramolecular C(sp³)? H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99 % yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C? H insertion of N‐tosylhydrazones can be viewed as reductive coupling between a C?O bond and a C? H bond to form a new C? C bond, since N‐tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (±)‐pseudoheliotridane.     

A Novel Metal‐free Reductive Esterification of N‐Tosylhydrazones with Carboxylic Acids

A novel method for the synthesis of esters via reductive coupling of N‐tosylhydrazones with carboxylic acids under metal‐free conditions has been developed. Various functional groups were found to be tolerable under the reaction conditions to afford low to good yields.     

Oxidation of n-alkyl-n'-tosylhydrazines to hydroperoxides

N-Alky-N'-tosylhydrazines upon treatment with H₂O₂ and Na₂O₂ give with high yields the corresponding aliphatic hydroperoxides. A discussion on the possible reaction mechanism which involves the formation of an “ion pair” intermediate, is reported. The reaction of tosylhydrazones carried out under simular conditions to give dihydroperoxides and other compounds is also described.     

Pd–Carbene Migratory Insertion: Application to the Synthesis of Trifluoromethylated Alkenes and Dienes

Pd‐catalyzed cross‐coupling of halides with CF₃‐substituted diazo compounds or N‐tosylhydrazones has been explored for the synthesis of CF₃‐substituted alkenes and 1,3‐butadienes. Pd–carbene migratory insertion plays the key role in these transformations.     

Stereoselective Csp3–Csp2 Bond‐Forming Reactions by Transition‐Metal‐Free Reductive Coupling of Cyclic Tosylhydrazones with Boronic Acids

The reactions between alkenylboronic acids and tosylhydrazones derived from substituted cyclohexanones lead to the construction of disubstituted cyclohexanes with total regio‐ and stereoselectivity. In these transition‐metal‐free processes, a Csp³?Csp² and Csp³?H bond are formed on the same carbon atom. The stereoselective reaction is general for 2‐, 3‐, and 4‐substituted cyclohexanone tosylhydrazones, as well as for 2‐substituted cyclopentanones. However, no stereoselectivity is observed for acyclic derivatives. DFT computational modeling suggests that the stereoselectivity of the reaction is determined by the approach of the boronic acid to the diazocyclohexane on its most stable chair conformation through an equatorial trajectory.     

Rhodium(III)‐Catalyzed ortho Alkenylation of N‐Phenoxyacetamides with N‐Tosylhydrazones or Diazoesters through CH Activation

A coupling reaction of N‐phenoxyacetamides with N‐tosylhydrazones or diazoesters through Rh^III‐catalyzed C? H activation is reported. In this reaction, ortho‐alkenyl phenols were obtained in good yields and with excellent regio‐ and stereoselectivity. Rh–carbene migratory insertion is proposed as the key step in the reaction mechanism.     

Rhodium(III)‐Catalyzed ortho Alkenylation of N‐Phenoxyacetamides with N‐Tosylhydrazones or Diazoesters through C?H Activation

A coupling reaction of N‐phenoxyacetamides with N‐tosylhydrazones or diazoesters through Rh^III‐catalyzed C H activation is reported. In this reaction, ortho‐alkenyl phenols were obtained in good yields and with excellent regio‐ and stereoselectivity. Rh–carbene migratory insertion is proposed as the key step in the reaction mechanism.     

Mannich reactions of heterocycles with dimethyl(methylene) ammonium chloride: A high yield,one-step conversion of estazolam to adinazolam

The readily prepared ammonium salt, (CH₃)₂N⁺ = CH₂Cl^?, 4 , functionalized heterocycles differently, but in a predictable fashion, under neutral, basic or acidic conditions. Triazolo- and imidazobenzophenones 1b ′ and 5 , which primarily underwent intramolecular isomerization to indolols 2a ′ and 6a rather than intermolecular electrophilic substitution under conditions of the normal aqueous Mannich reaction, were converted with 4 to the desired benzophenone derivatives, 1c ′ and 7 , respectively, in moderate yields. The 1-unsubstituted triazolo- or imidazobenzodiazepines, 10a (estazolam) and 10b , were transformed to the corresponding 1-(dimethylamino)methyl derivatives, 11a (adinazolam) and 11b , in good to moderate yields (61% and 32%, respectively.) Under acidic reaction conditions, 1-methyl triazolobenzodiazepine, 10d (alprazolam), afforded 12e , the product of attack at C-4 of the triazolo[4,3-a][1,4]benzodiazepine ring system. Under strongly basic conditions in which the anion of 10d was generated prior to reaction with 4 , both 12e and its isomer, 15 , were formed. These results complement the report that 4 may be used to functionalize the 1-methyl position of triazolobenzodiazepines, and further demonstrate the versatility of reagent 4 in heterocyclic synthesis.     

Facile Synthesis of Biologically Active Peptides Using Phase Transfer Reagents as C-Terminal Protecting Group

Phase-transfer reagents (basic, neutral, and acidic) can temporarily protect carboxyl groups by salt formation of C-terminal free amino acids or peptides during peptide synthesis. The salts of amino acids or peptides behave as RNH₂ rather than RNH₃⁺. At least there is a sufficient concentration of the free amine to act as a nucleophile under the reaction conditions. Many biologically active small peptides have been synthesized by this procedure. No racemization was detected. Unusual amino acids such as β-alanine, and ε-aminohexanoic acid can be incorporated into peptides in high yields.     

Synthese und reduktive Cyclisierung eines Δ18-Dehydro-A/D-secocorrinkomplexes

A Δ¹⁸-dehydro-A/D-secocorrin complex has been synthesized and shown to cyclize smoothly to the corresponding corrin complex by electrochemical reduction in a protonating medium. The crucial step of the construction of the secocorrinoid substrate illustrates a novel variant of the Bamford-Stevens reaction.     

Rapid and facile synthesis of acyl azides from acyl halides using a polymer-supported azide ion under heterogeneous conditions

In this article a rapid and facile method for synthesis of acyl azide is described. The cross-linked poly(N-methyl-4-vinylpyridinium) azide ion, [P₄-VP]N₃ is prepared and used as an efficient polymeric reagent for synthesis of acyl azides from acyl halides at room temperature under heterogeneous conditions. Various benzoyl halides, with electron-withdrawing groups as well as electron-donating groups, were transformed into the corresponding benzoyl azides in high to excellent yields in short reaction times. The acyl azide products were characterized by FT-IR, and some of them were also characterized by ¹H-and/or ¹³C-NMR spectroscopy, and physical properties were compared to literature values of known compounds. The spent polymeric reagents can be regenerated and reused for several times without losing their activity. Relative to the reported methods, the present method has the advantages of operational simplicity, mild reaction conditions, fast reaction rates, simple reaction work-up and lower hazardous and potentially explosive nature. Also the present method is the first procedure for the synthesis of acyl azides from acyl halides by using a polymer-supported azide ion under heterogeneous conditions.     

Copper(I)‐Catalyzed Alkylation of Polyfluoroarenes through Direct C?H Bond Functionalization

The copper(I)‐catalyzed alkylation of electron‐deficient polyfluoroarenes with N‐tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp²) C(sp³) bonds with polyfluoroarenes through direct C H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.     

Copper(I)‐Catalyzed Alkylation of Polyfluoroarenes through Direct CH Bond Functionalization

The copper(I)‐catalyzed alkylation of electron‐deficient polyfluoroarenes with N‐tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp²)? C(sp³) bonds with polyfluoroarenes through direct C? H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.     

Generation of 10-Diazolongibornane from Longifolene and Synthesis of Neolongifolene-the Elusive Progenitor of Isolongifolene

Neolongifolene 2, the elusive progenitor of isolongifolene 3, has been synthesised from longifolene in five steps. The strategy consists in generating the crucial longibornyl-10-cation 11 under basic conditions (via 10-diazolongibornane 9 in a protic Bamford-Stevens reaction), which then expels a proton after prior rearrangement, thus affording the target olefin 2; on exposure to any acid, 2 readily collapses into isolongifolene 3.     

Removal of cobalt from liquid radioactive waste by in situ electrochemical synthesis of ferrite

This study combined electrochemical synthesis with traditional ferrite method to remove Co²⁺ from simulated liquid radioactive waste (LRW). The experiment investigated the effects of various reaction conditions including current density, reaction time for electrosynthesis, reaction temperature, initial pH value and boric acid concentration as well as the type of power supply by measuring the concentration of Co²⁺ in the effluent, explored the reaction mechanism by measuring particles using XRD. The results showed that it was feasible to remove Co²⁺ from simulated LRW by electrochemical synthesis of ferrite. The best removal efficiency of 99.99% (the concentration of Co²⁺ in the effluent was 0.447 μg/L) was achieved under the optimal reaction conditions, the sediment was mainly composed of the mixture of CoFe₂O₄ and Fe₃O₄.     

Stereoselektive totalsynthese von (±)-torreyol

Enones of formulae Ia-d undergo cyclization to give stereoselectively the enol esters IIa-d, respectively, IIa-d are suitable synthones for some sesquiterpene syntheses .— In this paper the synthesis of torreyol (1) is described by an all step stereocontrolled reaction sequence: cyclization educt 10 (Ic) was prepared by alkylation of 8 with 5 and enol ether cleavage of 9. The reaction sequence 11a (IIc)→14a 15 → 18 (ester hydrolysis, formation of the tert. alcohol, degradation of the isopropenyl group) followed by oxidation resulted in the formation of ketone 19 whose relative configuration was determined by the 2D J-resolved 400 MHz ¹H NMR spectrum. After methylation at C-8 (22→23) the tosylhydrazone 25 underwent Bamford-Stevens reaction to yield (±)-1.     

Kinetics and mechanism of the defluorination of 8-fluoropurine nucleosides in basic and acidic media

For investigating the stability of C(8)-fluorine bond in 8-fluoropurine nucleosides some protected 8-fluoroguanosine, 8-fluoroinosine and 8-fluoroadenosine derivatives were prepared by direct fluorination of acetyl-protected purine nucleosides with elemental fluorine in solvents such as chloroform, acetonitrile and nitromethane. Fluorination reactions conducted in chloroform medium gave better yields of 8-fluoropurines. The fluorination yields were slightly lower when acetonitrile or nitromethane was used as solvent, but the product purification was found to be much easier. When the synthesized, protected fluoronucleosides were subjected to standard basic (NH₃ in methanol or 2-propanol) and acidic (HCl in methanol) deprotection conditions relevant to nucleoside chemistry, an efficient defluorination reaction took place. The kinetics of these defluorination reactions were conveniently followed, under pseudo-first-order reaction conditions, using ¹⁹F NMR spectroscopy. ¹H NMR, LC-MS and mass spectroscopy identified the products of the kinetic reaction mixtures. The defluorination reaction rate constants (k_obs) in basic media depended upon the electron density at C(8) while the k_obs data in acidic medium were determined by the pK_a of N⁷. An addition-elimination based mechanism (S_NAr) has been proposed for the defluorination reactions of these 8-fluoropurine nucleosides.