- NOVEL METHODS FOR PREPARATION OF SUBSTITUTED PYRIDINES AND RELATED NOVEL COMPOUNDS
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The present invention relates to novel methods of preparation of substituted pyridines and the compounds produced therefrom. In particular, the present invention provides efficient methods for the construction of diversely substituted pyridines, with varying substitution patterns under simple and metal-free conditions with high atom- and pot-economy and excellent functional group tolerance, and which are useful for the synthesis of natural products.
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Paragraph 0195; 0196; 0197; 0224; 0225
(2020/04/10)
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- A simple, tandem approach to the construction of pyridine derivatives under metal-free conditions: A one-step synthesis of the monoterpene natural product, (-)-actinidine
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A simple and modular one-step synthesis of diversely substituted pyridines from readily available α,β-unsaturated carbonyl compounds and propargylic amines has been developed. The present protocol has a broad substrate scope and allows access to multi-substituted pyridines with select control of the substitution pattern under mild and metal-free conditions. The reaction involves imine formation followed by concomitant cyclization through an allenyl intermediate to afford pyridines in excellent yields, with water as the sole by-product. This mild strategy is also suitable for functionalization of natural products or other advanced intermediates having α,β-unsaturated carbonyl functionality. The utility of the present protocol was showcased with the synthesis of the monoterpene alkaloid, (-)-actinidine, an ant-associated iridoid.
- Uredi, Dilipkumar,Motati, Damoder Reddy,Blake Watkins
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supporting information
p. 3270 - 3273
(2019/03/30)
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- Facile Synthesis of Pyridines from Propargyl Amines: Concise Total Synthesis of Suaveoline Alkaloids
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A general and efficient protocol was developed for the synthesis of polysubstituted pyridines from propargyl amines and unsaturated carbonyl compounds through a tandem condensation/alkyne isomerization/6π 3-azatriene electrocyclization sequence. This process was found to be applicable to a wide range of readily available substrates (30 examples, up to 95 % yield) and could be readily performed on a preparative (20 g) scale. By taking advantage of this method for late-stage pyridine incorporation, we successfully completed the collective total synthesis of suveoline, norsuveoline, and macrophylline.
- Zhao, Zhiwen,Wei, Hongbo,Xiao, Ke,Cheng, Bin,Zhai, Hongbin,Li, Yun
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supporting information
p. 1148 - 1152
(2019/01/04)
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- Quick Access to Pyridines through 6π-3-Azatriene Electrocyclization: Concise Total Synthesis of Suaveoline Alkaloids
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Pyridine is a prevalent structural heterocyclic motifs in natural products, pharmaceuticals, and advanced materials. Several different methodologies have been developed for the synthesis of these kinds of molecules. However, a sustainable and efficient procedure for the synthesis of pyridines is still highly desirable. In this Synpacts article, we highlight our recent approach to the construction of highly substituted pyridines though a tandem condensation/alkyne isomerization/6π-3-azatriene electrocyclization sequence. The present protocol was used to synthesize a series of polysubstituted pyridines (30 examples) in moderate to good yields. The process also permitted the development of a concise strategy for collective total syntheses of suaveoline, norsuaveoline, and macrophylline.
- Li, Yun,Wei, Hongbo
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p. 1615 - 1620
(2019/08/26)
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- Pd(II)-Catalyzed C3-Selective Arylation of Pyridine with (Hetero)arenes
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Palladium catalyzed, nondirected C3-selective arylation of pyridines with arenes and heteroarenes in the presence of 1,10-phenanthroline as the ligand has been developed. The optimized conditions allow for a highly C3-selective arylation of pyridines, affording various 3,3′-bipyridines and 3-arylpyridines. (Chemical Equation Presented).
- Gao, Guo-Lin,Xia, Wujiong,Jain, Pankaj,Yu, Jin-Quan
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supporting information
p. 744 - 747
(2016/03/01)
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- Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy
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An efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide is reported. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields.
- Wei, Hongbo,Li, Yun,Xiao, Ke,Cheng, Bin,Wang, Huifei,Hu, Lin,Zhai, Hongbin
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supporting information
p. 5974 - 5977
(2016/01/09)
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- AMVN-initiated expedient synthesis of biaryls by the coupling reaction of unactivated arenes and heteroarenes with aryl iodides
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The role of radical initiators AMVN and AIBN has been studied in the potassium tert-butoxide mediated biaryl coupling reaction of aryl iodides with unactivated arenes. Radical initiator AMVN promoted carbon-carbon bond formation expeditiously from aryl iodide having various groups such as amino, methoxy, fluoro, methyl, and trifluoromethyl and arenes in the presence of potassium tert-butoxide (4 equiv.) at 110 °C in 2-5 h. Substituted arenes such as toluene, xylene, anisole, and fluorobenzene also proceeded to form biaryls under AMVN-initiated reaction conditions. Moreover naphthalene, pyridine, pyrimidine, and pyridazine also coupled with aryl iodides and produced biaryls in 41-82% yields. It seems that AMVN initiates the formation of the aryl radical, which enters the radical chain reaction. The generated aryl radical may combine with the arene leading to a biaryl radical, which upon protonation gives the biphenyl radical anion and tert-butanol. The biphenyl radical anion finally reacts with the aryl iodide generating the aryl radical and thus completes the radical chain reaction with concomitant release of biphenyl.
- Bhakuni, Bhagat Singh,Yadav, Abhimanyu,Kumar, Shailesh,Kumar, Sangit
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p. 827 - 836
(2014/02/14)
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- A Pd(II)-catalyzed ring-expansion reaction of cyclic 2-azidoalcohol derivatives: Synthesis of azaheterocycles
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(Chemical Equation Presented) A Pd(II)-catalyzed ring expansion-reaction of cyclic 2-azidoalcohol derivatives was found to proceed via an unprecedented C-C bond cleavage-C-N bond formation sequence, providing substituted azaheterocycles.
- Chiba, Shunsuke,Xu, Yan-Jun,Wang, Yi-Feng
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supporting information; experimental part
p. 12886 - 12887
(2009/12/06)
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- Novel CDK inhibition profiles of structurally varied 1-aza-9-oxafluorenes
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A series of 1-aza-9-oxafluorenes with functionally varied 3-substituents have been prepared from N-phenoxycarbonyl-4-phenyl-1,4-dihydropyridines and p-benzoquinone and biologically evaluated as inhibitors of various cyclin-dependant kinases. The absence o
- Voigt, Burkhardt,Meijer, Laurent,Lozach, Olivier,Sch?chtele, Christoph,Totzke, Frank,Hilgeroth, Andreas
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p. 823 - 825
(2007/10/03)
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- Synthesis of alkyl- and aryl-substituted pyridines from (α,β-unsaturated) imines or oximes and carbonyl compounds
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Reaction of a variety of (α,β-unsaturated) imines or oximes with aliphatic aldehydes or cyclic ketones in the presence of a secondary amine afforded alkyl-, and/or aryl-, and/or cycloalkyl-substituted pyridines. To explain their formation, a hetero Diels-Alder reaction has been postulated, in which an 1-aza-1,3-butadiene reacts with an in situ generated enamine.
- Vijn,Arts,Green,Castelijns
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p. 573 - 578
(2007/10/02)
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- Regioselective Addition ofd Copper-Zinc Aryl Organometallic Reagents to 3-substituted Pyridinium Salts
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A number of 3-substituted pyridinium salts are subjected to nucleophilic addition by copper-zinc aryl organometallic reagents.The adducts are oxidized subsequently to form the corresponding 4-arylpyridines.In all the cases 1,4-addition products are obtained predominantly.The regioselectivity can be rationalized according to the hard-soft acid-base principle.Calculations on both charge distributions and FMO coefficients indicate that these reactions may be classified on the basis of the type of soft acid-soft base reactions.The observed γ-attack complies very well with the orientation of the FMO coefficients as estimated by a semiempirical method.
- Shiao, Min-Jen,Chia, Win-Long,Shing, Tai-Li,Chow, Tahsin J.
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p. 2101 - 2121
(2007/10/02)
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- PYRIDINE SYNTHESIS VIA ANODIC OXIDATION OF 1-ACYLDIHYDROPYRIDINES
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The preparation of several substituted pyridines via anodic oxidation of 1-acyldihydropyridines is reported
- Comins, Daniel L.,Killpack, Michael O.
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p. 2025 - 2028
(2007/10/02)
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- Regioselective Addition of Grignard Reagents to 1-Acylpyridinium Salts. A Convenient Method for the Synthesis of 4-Alkyl(aryl)pyridines
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The addition of Grignard reagents to 1-acylpyridinium salts afforded 1-acyl-2-alkyl(aryl)-1,2-dihydropyridines and 1-acyl-4-alkyl(aryl)-1,4-dihydropyridines.The regioselectivity of this reaction, 1,2- vs. 1,4-addition, was examined and found to be dependent upon the structures of the Grignard reagent and the 1-acyl group.Pyridine, 2-picoline, and 3-picoline were studied, and in most cases, significant amounts of 1,4-addition occurred.When a catalytic amount of cuprous iodide was present, nearly exclusive 1,4-addition resulted.The crude 1,4-dihydropyridines were aromatized by heating with sulfur to provide 4-substituted pyridines and picolines in good yield and high isomeric purity.
- Comins, Daniel L.,Abdullah, Abdul H.
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p. 4315 - 4319
(2007/10/02)
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- Synthesis of 4-Substituted Thiosemicarbazones of 3-Methyl-4-phenylpyridine-2-carboxaldehyde as Antitumor Agents
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A convenient synthesis of 3-methyl-4-phenylpyridine-2-carboxaldehyde (4) is described.Reaction of 4 with 4-substituted thiosemicarbazides (6) gives thiosemicarbazones (7) some of which (7b, 7g, 7i and 7j) exhibit significant antitumor activity in animals.Thiosemicarbazides (6e - 6j) have been prepared from the corresponding isothiocyanates (5) (which result from sodium chlorite oxidation of the addition products of CS2 and the appropriate amine) and hydrazine.Isomerisation of 1,3-dimethyl-4-phenyl-1,2,3,6-tetrahydropyridine (Δ4-isomer) to 1,2,5,6-tetrahydro analog (Δ3-isomer, 1) has been effected with refluxing conc.HCl.
- Rahman, M. F.
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p. 828 - 830
(2007/10/02)
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- Synthetic Applications of N-N Linked Heterocycles. Part 7. The Preparation of 4-Alkyl- and 4-Aryl-pyridines by Regiospecific Attack of Grignard Reagents γ to Quaternary Nitrogen in N-(2,6-Dimethyl-4-oxopyridin-1-yl)pyridinium Salts
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N-(2,6-Dimethyl-4-oxopyridin-1-yl)pyridinium salts (4), new reagents for the regiospecific synthesis of 4-substituted pyridines, give moderate to high yields of 4-alkyl- and 4-aryl-pyridines (8) - (10) on reaction with Grignard reagents.The scope and limitations on the reaction, which proceeds via 1,4-dihydro-intermediates (5) - (7), are explored.No 2-substituted pyridines were detected.Some reactions with organolithium compounds are also described.
- Katritzky, Alan R.,Beltrami, Hector,Sammes, Michael P.
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p. 2480 - 2484
(2007/10/02)
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- TRANSFORMATIONS IN THE PYRIDINE SERIES. A SIMPLE PREPARATION OF 3-METHYL-4-PHENYLPYRIDINE AND CORRESPONDING 2-CARBOXAMIDES
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A simple 3-step synthesis of 3-methyl-4-phenylpyridine (2), a key intermediate in the synthesis of several diverse types of potential pharmaceutical agents is reported.Conversion of this pyridine derivative, which is easily prepared on a large scale, to a
- Harrison, Ernest A.,Rice, Kenner C.
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p. 813 - 816
(2007/10/02)
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