Synthesis of quinolines via Rh(III)-catalyzed oxidative annulation of pyridines

Selective synthesis of quinolines has been achieved via oxidative annulation of functionalized pyridines with two alkyne molecules under Rh(III)-catalyzed cascade C-H activation of pyridines using Cu(OAc)(2) as an oxidant. The selectivity of this reaction is oxidant-dependent, particularly on the anion of the oxidant.     

Solvent-free synthesis of functionalized pyridine derivatives using Wells-Dawson heteropolyacid as catalyst

Wells-Dawson heteropolyacids (H₆P₂W₁₈O₆₂·24H₂O) were used as catalysts in the Hantzsch-like multicomponent condensation reaction with 3-formylchromones as aldehyde component, a β-ketoester and ammonium acetate, under solvent-free conditions at 80 °C. Although the desired products were obtained, functionalized pyridines were the main reaction product and became the alternative route to dihydropyridine ring formation. Based on the proposed mechanisms for the formation of each of the obtained products, the multicomponent reaction was modified to afford only the functionalized pyridines (60-99%). Our procedure represents a clean alternative for the synthesis of several highly functionalized pyridines.     

A practical, one-pot synthesis of sulfonylated pyridines

A concise and efficient one-pot synthesis of functionalized sulfonylated pyridines via an S(N)Ar reaction of readily available pyridines and sodium sulfinate salts in the presence of tetrabutylammonium chloride is presented.     

Regioselective functionalization of trisubstituted pyridines using a bromine-magnesium exchange

A tosyloxy substituent in position 2 allows a highly regioselective Br/Mg exchange reaction on 3,5-dibromopyridine derivatives using iso-PrMgCl.LiCl. The resulting functionalized pyridylmagnesium reagents react with various electrophiles in position 3. Acylated pyridines of this type can be readily converted into pyrazolo [3,4-b] pyridines.     

Partial reduction of electron-deficient pyridines

The partial reduction of electron-deficient pyridines is described herein. Mono- and disubstituted pyridines can be transformed into functionalized dihydropyridines using either Birch reduction conditions or sodium/naphthalene in THF. The compounds formed by these high-yielding reductive alkylation protocols have potential as synthetic intermediates, and we have shown that bicyclo compounds containing 6,5, 6,6, and 6,7 ring systems can be prepared in one step via a base-promoted cylization.     

Convenient synthesis of 4-amino-7-(dialkylamino)pyrido[2,3-d]pyrimidines from polysubstituted pyridines

A convenient synthesis of 4-amino-7-(dialkylamino)pyrido[2,3-d]pyrimidines via cyclization of functionalized pyridines is reported. The preparation of the starting pyridines from 3-amino-3-(dialkylaraino)propene-nitriles and ethoxymethylenemalononitrile is described.     

Facile synthesis of benzo[4,5]furo[3,2-c]pyridines via palladium-catalyzed intramolecular Heck reaction

The heating of 4-chloropyridine with 2-bromophenol in either neat or DME as solvent gives rise to 2-bromophenoxy pyridines, which were treated with Pd(OAc)₂ and various ligands to afford functionalized benzo[4,5]furo[3,2-c]pyridines.     

Catalytic coupling of C-H and C-I bonds using pyridine as a directing group

A method for the palladium-catalyzed arylation of pyridines and pyrazoles has been developed. Both aliphatic and aromatic C-H bonds may be functionalized using this method. A bromo substituent is tolerated on the aryl iodide coupling component. [reaction: see text]     

Polyfunctional pyridines from nitroacetamidine and β-diketones. A useful synthesis of substituted imidazo [4,5-b] pyridines and related compounds

Nitroacetamidine undergoes a useful cyclocondensation with β-diketones to produce substituted 2-amino-3-nitropyridines. Use of an acylpyruvate generates hitherto unreported 2-amino-3-nitropyridine-4-carboxylates. These may be converted easily to functionalized imidazo[4,5-b]pyridines and oxazolo-[5,4-b]pyridines.     

Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols

The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.     

Synthesis of quinoline and benzo[b]thiophene derivatives by ring annelation of pyridines and thiophenes

Selected ortho-disubstituted pyridines and thiopenes react with Michael acceptors to give functionalized quinolines or benzo[b]thiopenes, respectively.     

A novel synthesis of 2,5-di-substituted pyridine derivatives by the ring opening and closing cascade (ROCC) mechanism

A new regioselective method for the synthesis of 2-aryl-5-benzoylpyridine derivatives has been developed. The reaction proceeds via ring opening and closing cascade mechanism (ROCC) of isoxazole to synthesize various functionalized pyridine derivatives. This is the first report for the preparation of 2,5-di-substituted pyridines using Fe/NH₄Cl as a reducing reagent.     

An efficient access to 2,3-diarylimidazo[1,2-a]pyridines via imidazo[1,2-a]pyridin-2-yl triflate through a Suzuki cross-coupling reaction-direct arylation sequence

An efficient method to prepare 2,3-diarylimidazo[1,2-a]pyridines is described. The procedure involves a Suzuki cross-coupling reaction followed by a direct arylation at position 3. Imidazo[1,2-a]pyridin-2-yl triflate was identified as a suitable coupling partner, permitting access to a variety of highly functionalized 2,3-diarylimidazo[1,2-a]pyridines.     

Synthesis of novel racemic 3,4-dihydroferroceno[c]pyridines via the Ritter reaction

A new approach for the synthesis of functionalized racemic 3,4-dihydroferroceno[c]pyridines via the Ritter reaction of 2-methyl-1-ferrocenylpropan-1-ol with nitriles in the presence of methansulfonic acid was developed. The scope and limitations of the reaction were evaluated. Selected racemic 3,4-dihydroferroceno[c]pyridines were successfully separated by preparative HPLC on a Chiralcel OD-H column. The absolute configuration of the enantiomers was determined by X-ray crystal structure analysis.     

Palladium‐Catalyzed Three‐Component Cascade Reaction: Facial Access to Densely Functionalized Indolizines

A palladium‐catalyzed three‐component cascade reaction of 2‐(2‐enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.     

Synthesis of 2,3-disubstituted pyrroles and pyridines from 3-halo-1-azaallylic anions.

A new synthesis of 2,3-disubstituted pyrroles and pyridines is described. The reaction of 3-halo-1-azaallylic carbanions, regiospecifically generated from alpha-halogenated ketimines, with omega-iodoazides led to the regiospecific formation of omega-azido-alpha-haloketimines. Treatment of these functionalized imines with tin(II) chloride afforded halogenated five- and six-membered cyclic imines, which were transformed under mild conditions into 2,3-disubstituted pyrroles and pyridines. The stereoselective reduction of 2,3-dialkyl-3-chloro-1-pyrrolines to afford cis-2,3-dialkyl-3-chloropyrrolidines is also reported.     

Ortho-metalation of pyridines by cationic yttrium methyl complexes

Selective C-H bond activation of pyridines by organometallic complexes is a reaction of synthetic importance for the synthesis of functionalized pyridines. By reacting the dicationic methyl complex of yttrium [YMe(thf)₆][BPh₄]₂ with substituted pyridines, both selectivity and kinetics have been studied. Electron donating properties of para-substituents of pyridines increase the rates of reaction. Hammett linear free energy relationship was found with ρ = –2.72. DFT calculations confirmed the two-step reaction consisting of ligand substitution followed by σ-bond metathesis. DFT calculations furthermore revealed for the C-H bond activation step an unusual transition state structure with a nearly linear methyl carbon-hydrogen-ortho-carbon arrangement.     

Stannous chloride mediated one pot synthesis of functionalized indole-3-yl pyridines using 3-cyanoacetylindoles and 3-formylchromones

An efficient one-pot synthesis of functionalized indole-3-yl pyridines by condensation of 3-formylchromones, cyanoacetylindoles and ammonium acetate has been achieved. A series of 17 new compounds were synthesized and all of them were characterized by FT-IR and NMR. The crystal structure of a typical compound was determined by X-ray diffraction. A variety of substrates can participate in the process resulting in high purity and good yields, making this methodology suitable for library synthesis in drug discovery.     

2-(Adamantan-1-yl)imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridines and Their Derivatives

A series of 1-adamantylimidazo[1,2-a]pyridines has been synthesized. The negative influence of electron-acceptor substituents in the pyridine ring on the alkylation of substituted 2-aminopyridines with bromomethyl (adamantan-1-yl) ketone has been demonstrated. Bromination of adamantylimidazo-[1,2-a]pyridines on boiling in liquid bromine or in the presence of a Lewis acid resulted in insertion of a bromine atom in the imidazole ring without affecting the adamantane nucleus. The compounds studied take part in the Ritter reaction despite the absence of an easily removed groups in the adamantane nucleus.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, 761–766, May, 2005.     

New Multicomponent Synthesis of Functionalized Nitriles and Esters of 6-Alkylsulfanyl-1,4-dihydronicotinic Acids

The multicomponent condensation of malononitrile, hydrogen sulfide, aryl or hetaryl aldehydes, 1,3-dicarbonyl compounds and alkylating reagents afforded functionalized nitriles and esters of 6-alkylsulfanyl-1,4-dihydronicotinic acids, their aromatic analogues and 1,4-dihydrothieno[2,3-b]pyridines.