- Decarbonylative Pd-Catalyzed Suzuki Cross-Coupling for the Synthesis of Structurally Diverse Heterobiaryls
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Heteroaromatic biaryls are core scaffolds found in a plethora of pharmaceuticals; however, their direct synthesis by the Suzuki cross-coupling is limited to heteroaromatic halide starting materials. Here, we report a direct synthesis of diverse nitrogen-containing heteroaromatic biaryls by Pd-catalyzed decarbonylative Suzuki cross-coupling of widely available heterocyclic carboxylic acids with arylboronic acids. The practical and modular nature of this cross-coupling enabled the straightforward preparation of >45 heterobiaryl products using pyridines, pyrimidines, pyrazines, and quinolines in excellent yields. We anticipate that the modular nature of this protocol will find broad application in medicinal chemistry and drug discovery research.
- Blakemore, David C.,Cervantes-Reyes, Alejandro,Chinigo, Gary M.,Smith, Aaron C.,Szostak, Michal
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supporting information
p. 1678 - 1683
(2022/03/14)
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- Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines
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Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles.
- Dherange, Balu D.,Kelly, Patrick Q.,Levin, Mark D.,Liles, Jordan P.,Sigman, Matthew S.
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supporting information
p. 11337 - 11344
(2021/08/16)
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- N-heterocyclic carbene coordinated heterogeneous Pd nanoparticles as catalysts for suzuki-miyaura coupling
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Palladium nanoparticle (Pd NP) catalysts immobilized in a polymer with an N-heterocyclic carbene (NHC) moiety (PICBNHC-Pd) have been developed, wherein the NHC moiety plays dual roles as a crosslinker and a ligand to activate the Pd NPs. The presence of both Pd NPs and NHC was confirmed by STEM/EDS and SR-MAS NMR analyses, respectively. This PICB-NHC-Pd catalyst showed excellent activity in the Suzuki-Miyaura coupling reaction without leaching of Pd. Excellent results were obtained in gram-scale synthesis, and catalyst recovery/reuse experiments were completed without loss of catalyst activity.
- Min, Hyemin,Miyamura, Hiroyuki,Kobayashi, Shu
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supporting information
p. 837 - 839
(2016/07/16)
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- Synthesis of 3-Arylpyridines via Palladium/Copper-Catalyzed Annulation of Allylamine/1,3-Propanediamine and Aldehydes
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A novel and efficient method for the synthesis of 3-arylpyridines from allylamine/propanediamine and aldehydes by palladium/copper-catalyzed oxidative tandem cyclization has been developed. With this reaction, a series of desired 3-arylpyridines was synthesized in moderate yields via C-C/C-N bond formation and 6-endo/exo-trig cyclization.
- Yang, Xiaodong,Yang, Shenghua,Xiang, Likui,Pang, Xiaobo,Chen, Baohua,Huang, Guosheng,Yan, Rulong
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p. 3732 - 3736
(2016/01/25)
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- Palladium-catalyzed decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides
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Decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides is reported. Using a bimetallic system of Cu2O and Pd(PPh3)4, the scope of the reaction is demonstrated by the synthesis of 27 pyridine-containing biaryls in moderate to good yields.
- Chennamaneni, Lohitha Rao,William, Anthony D.,Johannes, Charles W.
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p. 1293 - 1296
(2015/03/04)
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- Very efficient and broad-in-scope palladium-catalyzed Hiyama cross-coupling. the role of water and copper(I) salts
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A very high-yielding Pd-catalyzed cross-coupling between aryl halides and aryl(trialkoxy)silanes is achieved in the presence of Cu(i) and a measured amount of water. This novel methodology is useful for the generation of a wide range of biaryls, particularly non-para substituted derivatives, which are usually less reported.
- Traficante, Carla I.,Mata, Ernesto G.,Delpiccolo, Carina M. L.
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p. 26796 - 26800
(2015/03/30)
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- Cross-coupling study of iodo/chloropyridines and 2-chloroquinoline with atom-economic triarylbismuth reagents under Pd-catalysis
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This study describes the palladium-catalyzed couplings of iodopyridines, chloropyridines, and chloroquinoline with atom-economic BiAr3 reagents in sub-stoichiometric loadings. Mono-arylations of iodo and chloropyridines produced arylpyridines i
- Rao, Maddali L.N.,Dhanorkar, Ritesh J.
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p. 338 - 349
(2015/03/04)
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- Rapid microwave-assisted sol-gel preparation of Pd-substituted LnFeO 3 (Ln = Y, La): Phase formation and catalytic activity
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We present a rapid microwave-assisted sol-gel approach to Pd-substituted LnFeO3 (Ln = Y, La) for applications in C-C coupling reactions. These materials could be prepared in household microwave ovens in less than 15 minutes of reaction time with the final materials displaying well-defined structure and morphology. Phase evolution was studied using time-dependent microwave heatings and then compared with the results obtained from thermogravimetric analyses. Materials were confirmed to be phase pure by laboratory and synchrotron X-ray diffraction. Substituted Pd is ionic as shown by the binding energy shift from X-ray photoelectron spectroscopy. The short heating periods required for phase purity allow these materials less time for sintering as compared to conventional solid state preparation methods, making relatively high surface areas achievable. These materials have been successfully used as catalyst precursor materials for C-C coupling reactions in which the active species is Pd0. Pd-substituted LnFeO3 (Ln = Y, La) provides Pd0 in solution which can be complexed by the ligand SPhos, allowing for aryl chloride coupling.
- Misch, Lauren M.,Birkel, Alexander,Figg, C. Adrian,Fors, Brett P.,Hawker, Craig J.,Stucky, Galen D.,Seshadri, Ram
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supporting information
p. 2079 - 2087
(2014/01/17)
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- Triarylbismuthanes as threefold aryl-transfer reagents in regioselective cross-coupling reactions with bromopyridines and quinolines
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Cross-coupling studies using bromopyridines and bromoquinolines with triarylbismuths as threefold coupling reagents in substoichiometric amounts under Pd-catalysed conditions are disclosed. The reactivity was high with both mono- and dibromopyridyl substrates, and mono- and bis-couplings were carried out regioselectively. A library of monoaryl and diaryl pyridines was formed in high yields. A one-pot strategy provided a simple and straightforward synthesis of both symmetrical and unsymmetrical diarylpyridines. Arylations of 2-bromo- and 3-bromoquinolines were achieved with triarylbismuth reagents. This study demonstrates that triarylbismuths may be used as threefold arylating reagents for the synthesis of aryl pyridines and quinolines through couplings with bromopyridines and bromoquinolines under Pd-catalysed conditions. Copyright
- Rao, Maddali L.N.,Dhanorkar, Ritesh J.
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supporting information
p. 5214 - 5228
(2014/10/15)
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- Direct arylation of pyridines without the use of a transition metal catalyst
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A method for achieving the direct arylation of pyridines with phenylhydrazine hydrochloride was developed in this study. This new reaction proceeds readily at room temperature without the use of any transition metal catalysts. This method allows rapid access to various arylated heterocycles that are more difficult to access through traditional methods.
- Li, Yahui,Liu, Wei,Kuang, Chunxiang
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supporting information
p. 7124 - 7127
(2014/07/07)
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- Synthesis of heteroaryl compounds through cross-coupling reaction of aryl bromides or benzyl halides with thienyl and pyridyl aluminum reagents
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An efficient method for synthesis of useful biaryl building blocks containing 2-thienyl, 3-thienyl, 2-pyridyl, and 3-pyridyl moieties was provided through cross-coupling reactions of aryl bromides or benzyl halides with heteroaryl aluminum reagents in the presence of Pd(OAc)2 and (o-tolyl)3P. The coupling reaction also worked efficiently with heteroaryl bromides affording series of heterobiaryl compounds. The reaction of phenylbromide with in situ prepared 3-pyridyl aluminum was demonstrated to afford the product 8a in high yield. Additionally, the catalytic system was also suited well for the coupling reaction of benzyl halides with pyridyl aluminum reagents to afford series of pyridyl-arylmethane.
- Chen, Xu,Zhou, Lingmin,Li, Yimei,Xie, Tao,Zhou, Shuangliu
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p. 230 - 239
(2014/01/17)
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- Palladium-catalyzed Suzuki-Miyaura coupling of aryl sulfamates with arylboronic acids
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Readily available NHC-Pd(ii)-Mp complexes 2 showed efficient catalytic activity toward the Suzuki-Miyaura coupling of aryl sulfamates with arylboronic acids or potassium phenyltrifluoroborate, giving the expected coupling products in good to high yields.
- Wang, Zhan-Yong,Ma, Qin-Na,Li, Ren-Hao,Shao, Li-Xiong
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p. 7899 - 7906
(2013/11/19)
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- Pd-catalyzed C3-selective arylation of pyridines with phenyl tosylates
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We have discovered that phenyl tosylates can be used to arylate pyridines at the C3-position using a Pd(OAc)2-1,10-phenanthroline catalyst system. We also discovered that the reaction of 4-methylpyridine with naphthyl tosylates occurred on the methyl group instead of at the C3-position. The Royal Society of Chemistry 2013.
- Dai, Fenglin,Gui, Qingwen,Liu, Jidan,Yang, Zhiyong,Chen, Xiang,Guo, Ruqing,Tan, Ze
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supporting information
p. 4634 - 4636
(2013/06/05)
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- Facile synthesis of 3-arylpyridine derivatives by palladacycle-catalyzed Stille cross-coupling reaction
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The Stille cross-coupling reaction of a variety of aryl halides (X=Cl, Br, I) with 3-alkylstannylpyridines highly catalyzed by cyclopalladated ferrocenylimine has been developed. This reaction allows formation of arylpyridine derivatives in moderate to excellent yields. Functional groups on aryl halides, such as amino, hydroxyl, keto, and aldehyde are tolerated and the reactions with arylbenzoxale substrates also proceed well.
- Ma, Gaizhi,Leng, Yuting,Wu, Yusheng,Wu, Yangjie
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p. 902 - 909
(2013/07/25)
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- Metal-free arylation of benzene and pyridine promoted by amino-linked nitrogen heterocyclic carbenes
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An amino-linked nitrogen heterocyclic carbene (amino-NHC), 1-tBu, has been shown to mediate carbon-carbon coupling through the direct C-H functionalization of benzene and pyridine in the absence of a metal catalyst. Using EPR, the first spectroscopic evidence corroborating the single electron transfer mechanism for the metal-free carbon-carbon coupling manifold, as reported by others, is introduced.
- Chen, Wen-Ching,Hsu, Yu-Chen,Shih, Wei-Chun,Lee, Ching-Yu,Chuang, Wen-Han,Tsai, Yi-Fang,Chen, Peter Ping-Yu,Ong, Tiow-Gan
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supporting information; experimental part
p. 6702 - 6704
(2012/07/14)
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- Palladium-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with aryl and heteroaryl chlorides
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An efficient, palladium-catalyzed Hiyama cross-coupling reaction of aryltrifluorosilanes with aryl chlorides has been developed. A wide variety of functionalized biaryl derivatives were isolated in good to excellent yields. The scope of this reaction has also been extended to heteroaryl chlorides, affording the corresponding heterobiaryl compounds in high yields.
- Molander, Gary A.,Iannazzo, Laura
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p. 9182 - 9187
(2011/12/16)
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- Suzuki-Miyaura cross-coupling of aryl carbamates and sulfamates: Experimental and computational studies
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The first Suzuki-Miyaura cross-coupling reactions of the synthetically versatile aryl O-carbamate and O-sulfamate groups are described. The transformations utilize the inexpensive, bench-stable catalyst NiCl 2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups are tolerated, in addition to those that possess ortho substituents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative addition with carbamates or sulfamates occurs via a five-centered transition state, resulting in the exclusive cleavage of the aryl C-O bond. Water is found to stabilize the Ni-carbamate catalyst resting state, which thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest.
- Quasdorf, Kyle W.,Antoft-Finch, Aurora,Liu, Peng,Silberstein, Amanda L.,Komaromi, Anna,Blackburn, Tom,Ramgren, Stephen D.,Houk,Snieckus, Victor,Garg, Neil K.
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scheme or table
p. 6352 - 6363
(2011/06/19)
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- Efficient diphosphane-based catalyst for the palladium-catalyzed suzuki cross-coupling reaction of 3-pyridylboronic acids
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A highly active catalyst system derived from PdCl2 and 2,2',6,6'- tetramethoxy-4,4'-bis(diphenylphosphanyl)-3,3'-bi- pyridine (P-Phos) has been developed for the Suzuki cross- coupling reaction of pyridylboronic acid with a variety of aryl halides in good to excellent yields, even in the presence of hindered and functional groups. In addition, P-Phos also exhibited high activity in the palladium-catalyzed Suzuki reaction of 2,6-dimethoxypyridylboronic acid in excellent yields with a fast rate. The steric and electronic effects of the P- Phos-palladium complex to this cross-coupling reaction were also discussed.
- Fu, Xing-Li,Wu, Lei-Lei,Fu, Hai-Yan,Chen, Hua,Li, Rui-Xiang
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experimental part
p. 2051 - 2054
(2009/09/06)
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- N,N-diethyl O-carbamate: Directed metalation group and orthogonal Suzuki-Miyaura cross-coupling partner
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(Chemical Equation Presented) The first Suzuki-Miyaura cross-coupling of an aryl O-carbamate, a versatile and powerful directed metalation group (DMG) in directed ortho metalation (DoM) chemistry, is described using the inexpensive, bench-stable catalyst NiCl2(PCy3)2. Broad synthetic scope and good efficiency are demonstrated for aryl and heteroaryl O-carbamates. The role of water and hydrolysis equilibrium between free boronic acid and boroxine was established to be a crucial parameter for this transformation. When combined with DoM and traditional Pd-catalyzed Suzuki-Miyaura strategies, the methodology offers concise routes to uniquely substituted molecules, avoiding the need for protection/deprotection of the phenol and the use of strongly nucleophilic cross-coupling partners.
- Antoft-Finch, Aurora,Blackburn, Tom,Snieckus, Victor
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supporting information; experimental part
p. 17750 - 17752
(2010/03/25)
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- Vesicular monoamine transporter substrate/inhibitor activity of MPTP/MPP+ derivatives: A structure-activity study
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The active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), N-methyl-4-phenylpyridinium (MPP+), selectively destroys the dopaminergic neurons and induces the symptoms of Parkinson's disease. Inhibition of mitochondrial complex
- Wimalasena, D. Shyamali,Perera, Rohan P.,Heyen, Bruce J.,Balasooriya, Inoka S.,Wimalasena, Kandatege
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p. 760 - 768
(2008/09/19)
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- Highly efficient cyclopalladated ferrocenylimine catalyst for Suzuki cross-coupling reaction of 3-pyridylboronic pinacol ester with aryl halides
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The Suzuki cross-coupling reaction of 3-pyridylboronic pinacol ester with aryl iodides, bromides and chlorides was carried out in DMF/H2O (3/1, v/v) at 110 °C in the presence of cyclopalladated ferrocenylimine I and K2CO3 or CsCO3 (1.0 equiv.) without the protection of inert gas. By using this method the synthesis of 3-pyridyl biaryl compounds could be readily achieved.
- Zhang, Jinli,Zhao, Liang,Song, Maoping,Mak, Thomas C.W.,Wu, Yangjie
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p. 1301 - 1306
(2007/10/03)
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- An efficient Negishi cross-coupling reaction catalyzed by nickel(II) and diethyl phosphite
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A combination of diethyl phosphite-DMAP and Ni(II) salts forms a very effective catalytic system for the cross-coupling reactions of arylzinc halides with aryl, heteroaryl, and alkenyl bromides, chlorides, triflates, and nonaflates. The choice of solvent is quite important and the mixture of THF-N-ethylpyrrolidinone (NEP) (8:1) was found to be optimal. The reaction usually requires only 0.05 mol % of NiCl2 or Ni(acac)2 as catalyst and proceeds at room temperature within 1-48 h.
- Gavryushin, Andrei,Kofink, Christiane,Manolikakes, Georg,Knochel, Paul
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p. 7521 - 7533
(2007/10/03)
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- Pyridino-directed lithiation of anisylpyridines: New access to functional pyridylphenols
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The lithiation of nine anisylpyridines has been studied. While usual reagents did not react or gave addition products on pyridine ring, the BuLi-LiDMAE (LiDMAE=Me2N(CH2)2OLi) superbase induced exclusive pyridino directed metallation. The usefulness of this new reaction allowed the efficient preparation of a range of alpha functional pyridylphenols. A successful subsequent cyclisation of an appropriate isomer into corresponding benzofuropyridine was also performed.
- Parmentier, Micha?l,Gros, Philippe,Fort, Yves
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p. 3261 - 3269
(2007/10/03)
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- Directed ortho metalation methodology. The N,N-dialkyl aryl O-sulfamate as a new directed metalation group and cross-coupling partner for grignard reagents
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(Chemical Equation Presented) The ortho metalation (RLi/THF/-93°C) of 3 followed by quench with a variety of electrophiles constitutes a new general route to substituted aryl O-sulfamates 4a-k. The Kumada-Corriu cross-coupling of O-sulfamates 4e, 4n-s, and 6a with Grignard reagents gives biaryls 9a-m, and the use of 2-halo and boron derivatives 4h, 4i, and 4k for Suzuki-Miyaura cross-coupling and generation of benzynes leads to naphthols 7a and 7b. A relative metalation ranking of the OSONEt2 is reported.
- Macklin, Todd K.,Snieckus, Victor
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p. 2519 - 2522
(2007/10/03)
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- PHENYL SUBSTITUTED PIPERIDINE COMPOUNDS FOR USE AS PPAR ACTIVATORS
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PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.
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Page 102-103
(2008/06/13)
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- Pharmaceutical compositions for the treatment of disorders of the CNS and other disorders
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The present invention relates to a method of treating disorders of the central nervous system (CNS) and other disorders in a mammal, including a human, by administering to the mammal a CNS-penetrant α7 nicotinic receptor agonist. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier and a CNS-penetrant α7 nicotinic receptor agonist.
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- Pharmaceutical compositions for the treatment of CNS and other discorders
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The present invention relates to a method of treating disorders of the central nervous system (CNS) and other disorders in a mammal, including a human, by administering to the mammal a CNS-penetrant α7 nicotinic receptor agonist. It also relates to pharma
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- An Efficient Synthesis of the Novel Dopamine Autoreceptor Antagonist S-(-)-OSU6162, via Palladium Catalyzed Cross-Coupling Reaction.
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Optically active S-(-)-OSU6162 ((-)-1) has been synthesized in 4 steps with an overall yield of 48 percent.The four steps consists of palladium catalyzed cross-coupling, catalytic hydrogenation, classical resolution with tartaric acid and reductive amination.
- Sonesson, Clas,Lindborg, Jonas
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p. 9063 - 9066
(2007/10/02)
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- CHIRAL, POTENTIALLY IRREVERSIBLE LIGANDS FOR THE SIGMA RECEPTOR BASED ON THE STRUCTURE OF 3-(3-HYDROXYPHENYL)-N-PROPYLPIPERIDINE (3-PPP)
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(+)-3-PPP is an optically active, highly potent and selective ligand for sigma receptors.The resolved enantiomeric pairs of potential irreversible sigma ligands (5a,b) and (9a,b) were designed and synthesized based on the structure of 3-PPP.An improved me
- Grayson, Neile A.,Bowen, Wayne D.,Rice, Kenner C.
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p. 2281 - 2292
(2007/10/02)
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- THE PYRIDYL CATION AS A REACTIVE INTERMEDIATE IN THE PHOTOREACTION OF IODOPYRIDINES WITH BENZENES
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The electrophilic behavior of the reactive entity in the photosubstitution of benzenes with 2-iodopyridine was found to be ascribable to the intermediary 2-pyridyl cation, rather than the electrophilic 2-pyridyl radical.
- Ohkura, Kazue,Seki, Koh-ichi,Terashima, Masanao,Kanaoka, Yuichi
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p. 3433 - 3436
(2007/10/02)
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- PHOTO-ARYLATION. II. PHOTO-REACTION OF HALOPYRIDINES WITH BENZENE
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Photolysis of halopyridines in benzene afforded corresponding phenylpyridines.The reactivities of halopyridines in the reactions increased in the order of Cl3>4 for bromo- and iodopyridines, 3>2>4 for chloropyridines were observed.Effects of bases and solvents on the reaction were investigated.Homolytic mechanism of the present reaction would be suggested by the photolysis of halopyridines in anisole.
- Terashima, Masanao,Seki, Kohichi,Yoshida, Chihiro,Kanaoka, Yuichi
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p. 1075 - 1078
(2007/10/02)
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- 3-Phenylpiperidines. Central Dopamine-Autoreceptor Stimulating Activity
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Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity.The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity.Introduction of an additional hydroxyl group into the 4-position of the aromatic ring gives a compound with dopaminergic activity but lacking selectivity for autoreceptors. 3-(3-Hydroxyphenyl)-N-n-propylpyrrolidine, 3-(3-hydroxy)-N-n-propylperhydroazepine, and 3-(3-hydroxyphenyl)quinuclidine were all inactive.The most potent compounds were the N-isopropyl-, N-n-butyl-, N-n-pentyl-, and N-phenethyl-substituted 3-(3-hydroxyphenyl)piperidine derivatives.None of the compounds investigated seemed to have central noradrenaline- or serotonin-receptor stimulating activity.
- Hacksell, Uli,Arvidsson, Lars-Erik,Svensson, Uno,Nilsson, J. Lars G.
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p. 1475 - 1482
(2007/10/02)
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