- Palladium-Catalyzed Direct Arylation of Alkylpyridine via Activated N-Methylpyridinium Salts
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An efficient Pd-catalyzed arylation of alkylpyridine based on the pyridinium activation strategy has been developed for synthesis of mixed aryl alkylpyridines. It was found that (1) the N-methyl group in the pyridinium salts acted as a transient activator and could be automatically departed after the reaction, (2) CuBr was an indispensable additive for achieving the C6-selective arylation, (3) the α-branched alkyl chain on the alkylpyridine greatly increased the yield of the product. Deuterium labelling experiment revealed that in the case of the α-branched alkylpyridine, the presence of CuBr completely inhibited the H/D exchange at the benzylic position and thus enabled the selective arylation at the C6 position. This protocol demonstrates a broad substrate scope, and with respect to both the aryl iodides and the α-branched alkylpyridine, the desired mixed aryl alkylpyridines were obtained in generally good to excellent yields.
- Chen, Xue,Li, Wen-Jing,Li, Shun,Tang, Juan,Du, Xi,Zheng, Xue-Li,Yuan, Mao-Lin,Fu, Hai-Yan,Li, Rui-Xiang,Chen, Hua
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p. 622 - 632
(2019/12/30)
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- The one-pot synthesis of pyridine derivatives from the corresponding 1,5-dicarbonyl compounds
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The optimization of the one-pot, acid-promoted synthesis of pyridine and alkylpyridine derivatives from simple alkyl-1,5-dicarbonyl derivatives and via the corresponding oxime intermediate is described. Of all the combinations of and solvents tested, the use of HCl in refluxing dioxane was found to result in the highest chemical yields. Twelve pyridines were prepared using this method.
- Mihara, Hiromichi,Miyakoshi, Takeru,Kikuchi, Yui,Konno, Hiroyuki
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p. 1375 - 1383
(2019/12/23)
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- Enantioselective Alkylation of 2-Alkylpyridines Controlled by Organolithium Aggregation
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Direct enantioselective α-alkylation of 2-alkylpyridines provides access to chiral pyridines via an operationally simple protocol that obviates the need for prefunctionalization or preactivation of the substrate. The alkylation is accomplished using chiral lithium amides as noncovalent stereodirecting auxiliaries. Crystallographic and solution NMR studies provide insight into the structure of well-defined chiral aggregates in which a lithium amide reagent directs asymmetric alkylation.
- Gladfelder, Joshua J.,Ghosh, Santanu,Podunavac, Ma?a,Cook, Andrew W.,Ma, Yun,Woltornist, Ryan A.,Keresztes, Ivan,Hayton, Trevor W.,Collum, David B.,Zakarian, Armen
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supporting information
p. 15024 - 15028
(2019/10/22)
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- Manganese-Catalyzed Kumada Cross-Coupling Reactions of Aliphatic Grignard Reagents with N-Heterocyclic Chlorides
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Herein we report the use of manganese(II) chloride for the catalytic generation of C(sp 2)-C(sp 3) bonds via Kumada cross-coupling. Rapid and selective formation of 2-alkylated N-heterocyclic complexes were observed in high yields with use of 3 mol% MnCl 2 THF 1.6 and under ambient reaction conditions (21 °C, 15 min to 20 h). Manganese-catalyzed cross-coupling is tolerant toward both electron-donating and electron-withdrawing functional groups in the 5-position of the pyridine ring, with the latter resulting in an increased reaction rate and a decrease in the amount of nucleophile required. The use of this biologically and environmentally benign metal salt as a catalyst for C-C bond formation highlights its potential as a catalyst for the late-stage functionalization of pharmaceutically active N-heterocyclic molecules (e.g., pyridine, pyrazine).
- Petel, Brittney E.,Purak, Merjema,Matson, Ellen M.
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supporting information
p. 1700 - 1706
(2018/07/13)
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- Photocatalyzed Site-Selective C(sp3)-H Functionalization of Alkylpyridines at Non-Benzylic Positions
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Tetrabutylammonium decatungstate (TBADT)-photocatalyzed C-H functionalization of alkylpyridines was investigated. Unlike alkylbenzene counterparts, alkylation of α-C-H bonds did not proceed for the reaction of 2- and 4-alkylpyridines and reluctantly proceeded for 3-alkylpyridines, which allow site-selective C(sp3)-H functionalization at nonbenzylic positions. The observed nonbenzylic site selectivities are rationalized by the polar inductive effects of pyridyl groups in the SH2 transition states. Consecutive γ-functionalization and α-bromofunctionalization were successfully carried out in selected cases.
- Fukuyama, Takahide,Nishikawa, Tomohiro,Yamada, Keiichi,Ravelli, Davide,Fagnoni, Maurizio,Ryu, Ilhyong
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supporting information
p. 6436 - 6439
(2017/12/08)
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- Developing Lithium Chemistry of 1,2-Dihydropyridines: From Kinetic Intermediates to Isolable Characterized Compounds
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Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine1-lithio-2-alkyl-1,2-dihydropyridines have been rarely isolated or characterized. This study develops their "isolated" chemistry. By a unique stoichiometric (that is1:1alkyllithium/pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert-butyl. Theoretical calculations probing the donor-free parent tert-butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)3 conformations. NMR spectroscopy studies (including DOSY spectra) and thermal volatility analysis compare new sec-butyl and iso-butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometryreaction of nBuLi/Me6TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine·Me6TREN and 2-n-butylpyridineimplying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine.
- Armstrong, David R.,Harris, Catriona M. M.,Kennedy, Alan R.,Liggat, John J.,McLellan, Ross,Mulvey, Robert E.,Urquhart, Matthew D. T.,Robertson, Stuart D.
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p. 14410 - 14420
(2015/10/05)
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- TRANSITION METAL-CATALYZED ALKYLATION OF C-H BONDS WITH ORGANOBORON REAGENTS
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One aspect of the present invention relates to methods for functionalization of 2-arylpyridine and arylpyrazoles with organoboron reagents in the presence of a transition metal catalyst to furnish alkylated arylpyridines and arylpyrazoles via regioselective functionalization of sp2 -hybridized C-H bonds at a position ortho to the point of attachment of the pyridine or pyrazole ring to the aromatic nucleus, hi other embodiments, the present invention provides for alkylation of sp3-hybridized C-H bonds in alkylpyridines.
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- Palladium-catalyzed alkylation of sp2 and sp3 C-H bonds with methylboroxine and alkylboronic acids: Two distinct C-H activation pathways
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Palladium-catalyzed alkylations of sp2 and sp3 C-H bonds with either methylboroxine or alkylboronic acids were developed. Ag2O or AgCO3 is used as a crucial oxidant and promoter for the transmetalation step. Ether, ester, alcohol, and alkene functional groups are tolerated. A new C-H activation pathway differing from the cyclometalation process is elucidated using methylboroxine as the coupling partner. Copyright
- Chen, Xiao,Goodhue, Charles E.,Yu, Jin-Quan
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p. 12634 - 12635
(2008/02/05)
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- Pharmaceutical compositions and methods of inhibiting gastric acid secretion
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Pharmaceutical compositions and methods of inhibiting gastric acid secretion by administering N-alkenyl and N-alkynyl thioamides.
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