Structural and electronic characteristics of thienyl(aryl)iodonium triflates

A general strategy toward the synthesis of aryliodonium triflate salts has been exploited to afford derivatives that incorporate thiophene and bithiophene components. Both mono- and bis(iodonium) salts have been realized, and a series of bithienyl(aryl)iodonium triflates with increasingly electron-withdrawing substituents on the aryl moiety have been synthesized. X-ray crystallographic analysis of four derivatives (4a, 4b, 6b, and 8c) demonstrates that the solid-state organization of these salts incorporates extensive networks of secondary bonding interactions between the cationic iodonium centers and the triflate counterions. UV-vis spectroscopic analysis shows that the electronic interactions between pendent aryl and heteroaryl groups across the iodonium center can be dictated by substitution. Furthermore, the energy of the HOMO-LUMO gap decreases substantially in weakly or noncoordinating solvents.     

Malononitrile as a carbonyl synthon: a one-pot preparation of heteroaryl amide via a SNAr-oxidation-displacement strategy

Malononitrile could be utilized as a synthon for the carbonyl moiety via a one-pot process that was initiated via base-mediated S_NAr substitution of a heteroaryl halide. Subsequent peracetic acid oxidation of the resultant anion delivered an electrophilic acyl nitrile in situ that readily reacted with added nucleophiles to afford heteroaryl carboxylic acid derivatives. The reaction of the sodium salt of malononitrile with a series of heteroaryl chlorides followed by the subsequent addition of an amine and peracetic acid provided the corresponding heteroaryl amides.     

Synthesis of novel cyclic α-amino acid derivatives via a one-pot sequential Petasis reaction/palladium catalysed process

A novel one pot Petasis reaction/palladium catalysed process is described involving 2-iodo/bromo benzylamine, ethyl glyoxalate and aryl/heteroaryl boronic acids. The in situ generated carbinolamine/imine undergoes the Petasis reaction to afford 2 which reacts with carbon monoxide or allene (1 atm) in the presence of Pd(0) to generate acyl palladium or π-allyl palladium species which are intercepted intramolecularly by the proximal secondary amine to afford isoindolone/4-methylene-3,4-dihydroisoquinoline α-amino acid derivatives in good yield.     

Copper‐Promoted Sandmeyer Difluoromethylthiolation of Aryl and Heteroaryl Diazonium Salts

An efficient copper‐promoted difluoromethylthiolation of aryl and heteroaryl diazonium salts is described. The reaction is conducted under mild reaction conditions and various functional groups were compatible. In addition, reactions of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a more practical one‐pot direct diazotization and difluoromethylthiolation protocol was developed, and it converts the aniline derivatives into difluoromethylthiolated arenes. The utility of the method is demonstrated by difluoromethylthiolation of a number of natural products and drug molecules.     

Dialkylaminoacetonitrile derivatives as amide synthons. A one-pot preparation of heteroaryl amides via a strategy of sequential SNAr substitution and oxidation

Dialkylamino acetonitrile derivatives were utilized as alternative to cyanohydrin synthons for preparation of the corresponding heteroaryl dialkyl amides via a strategy of sequential base-mediated coupling and oxidation. The most advantageous oxidant, NiO(2)-H(2)O, can readily oxidize 2-substituted aminoacetonitriles to the corresponding amides under both basic and neutral conditions by forming cyanohydrins in situ.     

Synthesis of substituted aryl amidines from aminoacetonitriles

Aryl aminoacetonitriles are oxidized by NiO₂-H₂O or MnO₂ in the presence of a wide range of NH₂-containing compounds to afford aryl amidines, presumably via iminium intermediates. A ‘one-pot’ procedure for the preparation of heteroaryl amidines from N-containing heteroaryl halides through a process comprising sequential S_NAr substitution and oxidation has also been developed.     

Cross-coupling of mesylated phenol derivatives with potassium ammonio- and amidomethyltrifluoroborates

A large array of aryl and heteroaryl mesylates have been successfully employed as electrophiles in a Csp(2)-Csp(3) Suzuki-Miyaura cross-coupling with potassium ammonio- and amidomethyltrifluoroborates to afford the corresponding products in high yields.     

A strategy for the synthesis of aryl alpha-ketoamides based upon the acylation of anions derived from cyanomethylamines followed by oxidative cleavage

[reaction: see text] Cyanomethylamines, prepared by alkylation of amines with chloroacetonitrile, were deprotonated using NaHDMS in THF, reacted with heteroaryl or substitutedphenyl esters, and then oxidized by adding Clorox(TM) to afford aryl alpha-ketoamides in a single operation in good overall yields.     

Potassium selenocyanate as an efficient selenium source in C-Se cross-coupling catalyzed by copper iodide in water

An efficient and conceptually new protocol for C-Se cross coupling of potassium selenocyanate with aryl halides via copper-catalyzed cascade reaction has been developed in water. Utilizing this protocol, a variety of aryl and heteroaryl halides were reacted with potassium selenocyanate to afford the corresponding diaryl selenides in moderate to good yields.     

Phosphomolybdic acid: a highly efficient solid acid catalyst for the synthesis of trans-4,5-disubstituted cyclopentenones

The furan-2-yl(phenyl)methanol undergoes smooth aza-Piancatelli rearrangement with aryl amines in the presence of 0.03 mol % phosphomolybdic acid in acetonitrile under reflux conditions to afford the corresponding trans-4,5-disubstituted cyclopentenone derivatives in good yields with high selectivity in short reaction time.     

Cinchona alkaloid-catalyzed asymmetric trifluoromethylation of alkynyl ketones with trimethylsilyl trifluoromethane

The first catalytic enantioselective trifluoromethylation of alkynyl ketones 1 with (trifluoromethyl)trimethylsilane is disclosed by an operationally simple procedure, based on the combination of ammonium bromide of bis-cinchona alkaloids with Me(4)NF to afford trifluoromethyl-substituted tertiary propargyl alcohols (up to 96% ee), which are the important chiral building blocks for pharmaceuticals. Biologically attractive aryl heteroaryl trifluoromethyl carbinols were also synthesized.     

Microwave-mediated synthesis of N-methyliminodiacetic acid (MIDA) boronates

A library of over 20, mainly aryl or heteroaryl, N-methyliminodiacetic acid (MIDA) boronates have been synthesised. A rapid microwave-mediated (MW) method (5–10 min) has been developed using polyethylene glycol 300 (PEG 300) as solvent. However, acetonitrile (MeCN) and dimethylformamide (DMF) were found to be alternative solvents, the latter especially for 2-substituted aryl boronic acids.     

Activation of Aryl and Heteroaryl Halides by an Iron(I) Complex Generated in the Reduction of [Fe(acac)3] by PhMgBr: Electron Transfer versus Oxidative Addition

The mechanism of the reactions of aryl/heteroaryl halides with aryl Grignard reagents catalyzed by [Fe^III(acac)₃] (acac=acetylacetonate) has been investigated. It is shown that in the presence of excess PhMgBr, [Fe^III(acac)₃] affords two reduced complexes: [PhFe^II(acac)(thf)_n] (n=1 or 2) (characterized by ¹H NMR and cyclic voltammetry) and [PhFe^I(acac)(thf)]^? (characterized by cyclic voltammetry, ¹H NMR, EPR and DFT). Whereas [PhFe^II(acac)(thf)_n] does not react with any of the investigated aryl or heteroaryl halides, the Fe^I complex [PhFe^I(acac)(thf)]^? reacts with ArX (Ar=Ph, 4‐tolyl; X=I, Br) through an inner‐sphere monoelectronic reduction (promoted by halogen bonding) to afford the corresponding arene ArH together with the Grignard homocoupling product PhPh. In contrast, [PhFe^I(acac)(thf)]^? reacts with a heteroaryl chloride (2‐chloropyridine) to afford the cross‐coupling product (2‐phenylpyridine) through an oxidative addition/reductive elimination sequence. The mechanism of the reaction of [PhFe^I(acac)(thf)]^? with the aryl and heteroaryl halides has been explored on the basis of DFT calculations.     

Room Temperature Copper(II)-Catalyzed Oxidative Cyclization of Enamides to 2,5-Disubstituted Oxazoles via Vinylic C-H Functionalization

A copper(II)-catalyzed oxidative cyclization of enamides to oxazoles via vinylic C-H bond functionalization at room temperature is described. Various 2,5-disubstituted oxazoles bearing aryl, vinyl, alkyl, and heteroaryl substituents could be synthesized in moderate to high yields. This reaction protocol is complementary to our previously reported iodine-mediated cyclization of enamides to afford 2,4,5-trisubstituted oxazoles.     

Acid Catalyzed Multicomponent Reaction to Access Functionalized N-Benzhydryl Amides: A Tandem Ritter Reaction

Acid catalyzed multicomponent reaction (MCR) for the synthesis of N-benzhydryl amide derivatives from aldehydes, N,N-disubstituted arylamines and nitriles is reported. The reaction is compatible with electronically differentiating aryl/heteroaryl aldehydes/acetals, different nucleophiles (cyclic and acyclic N,N-disubstituted arylamines,β-naphthols, 1,3 dicarbonyl, 1,3,5-trimethoxy benzene), alkyl nitriles, aryl/heteroaryl nitriles in catalytic TFA/TfOH through tandem Ritter reaction. The one-pot MCR with broad substrate scope generated a wide variety of sterically hindered N-substituted amides and is successfully applied for the synthesis of isoindolinone.     

Synthesis of internal alkynes via one-pot palladium-catalyzed and dehydrobromination reactions of 1,1-dibromo-1-alkenes

Tandem palladium-catalyzed cross-coupling of alkyl, alkenyl, alkynyl, aryl, and heteroaryl 2-substituted 1,1-dibromo-1-alkenes with aryl or heteroaryl boronic acids or borate esters and dehydrobromination of the intermediate coupled products afforded internal alkynes in moderate to good yields (up to 89%). The synthesis has been carried out in a one-pot process and in a two-step sequence according to the nature of the starting 1,1-dibromoalkenes. The reported protocol is compatible with the presence in the 1,1-dibromo-1-alkene molecule of additional reactive halogen–carbon bonds, thus allowing to build up more complex alkyne derivatives.     

Efficient construction of biaryls and macrocyclic cyclophanes via electron-transfer oxidation of Lipshutz cuprates

An efficient method for the homocoupling of aryl halides by electron-transfer oxidation of Lipshutz cuprates (Ar2Cu(CN)Li2) with organic electron acceptors is disclosed. Thus, various types of Lipshutz cuprates are prepared by successive treatment of aryl or heteroaryl bromides with tert-butyllithium and CuCN. The electron-transfer oxidation of Lipshutz cuprates with p-benzoquinones proceeds smoothly to afford the corresponding homocoupling products in moderate to good yields. Furthermore, it can be applied to the construction of either thiophene- or benzene-fused 10-membered ring cyclophanes. For the synthesis of 10-membered cyclophanes, the linear C-Cu-C structure of Lipshutz cuprates should be maintained in the dimetallacyclic intermediates, producing the large ring cyclophanes efficiently. The X-ray analysis of the cyclophanes reveals that the difference in the bridging atoms results in the different conformations of the macrocyclic rings. Thus, the silicon-bridged cyclophane 5a adopts a D2-symmetric structure with a twisted rhombic arrangement of four thiophene rings, whereas the methylene- and oxygen-bridged cyclophanes 5b and 5c possess C2h- and C2-symmetric structures with chair- and boatlike conformations, respectively. The 1H NMR spectrum of C2-symmetric 5c is temperature-dependent, and the activation energy (DeltaG) for the conformational change is 10.1 kcal/mol.     

5-Formyl-2-furylboronic acid as a versatile bifunctional reagent for the synthesis of pi-extended heteroarylfuran systems

5-Formyl-2-furylboronic acid reacts cleanly with a range of heteroaryl bromides under Suzuki-Miyaura cross-coupling conditions to produce 2-formyl-5-heteroarylfuran derivatives. Subsequent Wittig olefination reactions afford pi-conjugated alkene-pyridyl-furan derivatives.     

One-pot three component α-aminoalkylation of conjugated nitroalkenes and nitrodienes

Nitroethylenes possessing aryl, heteroaryl, and alkyl substituents at the β-position as well as δ-substituted nitrobutadienes undergo facile aminoalkylation at the α-position upon treatment with formaldehyde and a secondary amine in the presence of imidazole and trifluoroacetic acid to afford α-aminoalkylated nitroalkenes and nitrodienes in good to excellent yield and stereoselectivity.     

CuI/L (L=pyridine-functionalized 1,3-diketones) catalyzed C-N coupling reactions of aryl halides with NH-containing heterocycles

An efficient copper-catalyzed N-arylation and N-heteroarylation reactions of imidazole, pyrrole, indole, pyrazole, and perimidine with aryl or heteroaryl halides using pyridine-functionalized 1,3-diketone as ligands have been investigated. The ligands bearing pyridyl and 1,3-diketone moieties, which may form chelated Cu(I) species, are inexpensive and readily available. The combination of CuI and 1,3-di(pyridin-2-yl)propane-1,3-dione is very efficient for C-N coupling reactions to afford various N-arylated products in good to excellent yields.