- Zirconium-redox-shuttled cross-electrophile coupling of aromatic and heteroaromatic halides
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Transition metal-catalyzed cross-electrophile coupling (XEC) is a powerful tool for forging C(sp2)–C(sp2) bonds in biaryl molecules from abundant aromatic halides. While the synthesis of unsymmetrical biaryl compounds through multimetallic XEC is of high synthetic value, the selective XEC of two heteroaromatic halides remains elusive and challenging. Herein, we report a homogeneous XEC method, which relies on a zirconaaziridine complex as a shuttle for dual palladium-catalyzed processes. The zirconaaziridine-mediated palladium (ZAPd)-catalyzed reaction shows excellent compatibility with various functional groups and diverse heteroaromatic scaffolds. In accord with density functional theory (DFT) calculations, a redox transmetallation between the oxidative addition product and the zirconaaziridine is proposed as the crucial elementary step. Thus, cross-coupling selectivity using a single transition metal catalyst is controlled by the relative rate of oxidative addition of Pd(0) into the aromatic halide. Overall, the concept of a combined reducing and transmetallating agent offers opportunities for the development of transition metal reductive coupling catalysis.
- Fu, Yue,Liu, Fang-Jie,Liu, Peng,Tang, Jian-Tao,Toste, F. Dean,Wu, Ting-Feng,Ye, Baihua,Zhang, Yue-Jiao
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supporting information
p. 1963 - 1974
(2021/07/07)
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- Suzuki-miyaura cross-coupling of 1,8-diaminonaphthalene (dan)-protected arylboronic acids
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We report a Suzuki-Miyaura cross-coupling reaction of 1,8-diaminonaphthalene (dan)-protected arylboronic acids in the presence of KOt-Bu, which does not require the removal of the dan moiety. Notably, the use of aryl-B(dan) in the Suzuki-Miyaura reaction provides a complementary solution to the protodeboronation problems. The base KOt-Bu plays a crucial role for the promotion of these cross-coupling reactions as it enables the formation of a borate salt. This reaction protocol was extended to the one-pot sequential Suzuki-Miyaura cross-coupling reaction of 4-[(pin)B]C6H4-B(dan), wherein the "less reactive" aryl-B(dan) moiety was cross-coupled preferentially.
- Mutoh, Yuichiro,Yamamoto, Kensuke,Saito, Shinichi
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p. 352 - 357
(2019/12/24)
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- LiCl-Accelerated multimetallic cross-coupling of aryl chlorides with aryl triflates
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While the synthesis of biaryls has advanced rapidly in the past decades, cross-Ullman couplings of aryl chlorides, the most abundant aryl electrophiles, have remained elusive. Reported here is the first general cross-Ullman coupling of aryl chlorides with aryl triflates. The selectivity challenge associated with coupling an inert electrophile with a reactive one is overcome using a multimetallic strategy with the appropriate choice of additive. Studies demonstrate that LiCl is essential for effective cross-coupling by accelerating the reduction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts. The modified conditions tolerate a variety of functional groups on either coupling partner (42 examples), and examples include a three-step synthesis of flurbiprofen.
- Huang, Liangbin,Ackerman, Laura K. G.,Kang, Kai,Parsons, Astrid M.,Weix, Daniel J.
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supporting information
p. 10978 - 10983
(2019/08/07)
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- Photoarylation of Pyridines Using Aryldiazonium Salts and Visible Light: An EDA Approach
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A metal-free methodology for the photoarylation of pyridines, in water, is described giving 2 and 4-arylated-pyridines in yields up to 96percent. The scope of the aryldiazonium salts is presented showing important results depending on the nature and position of the substituent group in the diazonium salt, that is, electron-donating or electron-withdrawing in the ortho, meta, or para positions. Further heteroaromatics were also successfully photoarylated. Mechanistic studies and comparison between our methodology and similar metal-catalyzed procedures are presented, suggesting the occurrence of a visible-light EDA complex which generates the aryl radical with no need for an additional photocatalyst.
- Bartolomeu, Aloisio De A.,Brocksom, Timothy J.,De Oliveira, Kleber T.,No?l, Timothy,Silva, Rodrigo C.
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- Heterocyclic Allylsulfones as Latent Heteroaryl Nucleophiles in Palladium-Catalyzed Cross-Coupling Reactions
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Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant of the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents and, when treated with a Pd(0) catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents.
- Markovic, Tim,Murray, Philip R.D.,Rocke, Benjamin N.,Shavnya, Andre,Blakemore, David C.,Willis, Michael C.
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p. 15916 - 15923
(2018/11/23)
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- Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
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A range of 5- and 6-membered heterocycle-derived sulfinates are shown to be effective nucleophilic coupling partners with aryl chlorides and bromides using Pd(0) catalysis. The use of optimal reaction conditions, specifically incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed at moderate temperatures and enabled the inclusion of a variety of sensitive functional groups. Challenging heterocyclic sulfinates, including pyrazine, pyridazine, pyrimidine, pyrazole, and imidazole, were all shown to perform well.
- Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
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supporting information
p. 6033 - 6035
(2017/11/27)
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- Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides
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Pyridine rings are ubiquitous in drug molecules; however, the pre-eminent reaction used to form carbon-carbon bonds in the pharmaceutical industry, the Suzuki-Miyaura cross-coupling reaction, often fails when applied to these structures. This phenomenon is most pronounced in 2-substituted pyridines, and results from the difficulty in preparing, the poor stability of, and low efficiency in reactions of pyridine-2-boronates. We demonstrate that by replacing these boronates with pyridine-2-sulfinates, a cross-coupling process of unrivalled scope and utility is realized. The corresponding 3-And 4-substituted pyridine variants are also efficient coupling partners. In addition, we apply these sulfinates in a library format to the preparation of medicinally relevant derivatives of the drugs varenicline (Chantix) and mepyramine (Anthisan).
- Markovic, Tim,Rocke, Benjamin N.,Blakemore, David C.,Mascitti, Vincent,Willis, Michael C.
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p. 4437 - 4442
(2017/07/11)
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- Sustainable Fe-ppm Pd nanoparticle catalysis of Suzuki-Miyaura cross-couplings in water
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Most of today's use of transition metal-catalyzed cross-coupling chemistry relies on expensive quantities of palladium (Pd). Here we report that nanoparticles formed from inexpensive FeCl3 that naturally contains parts-per-million (ppm) levels of Pd can catalyze Suzuki-Miyaura reactions, including cases that involve highly challenging reaction partners. Nanomicelles are employed to both solubilize and deliver the reaction partners to the Fe-ppm Pd catalyst, resulting in carbon-carbon bond formation. The newly formed catalyst can be isolated and stored at ambient temperatures. Aqueous reaction mixtures containing both the surfactant and the catalyst can be recycled.
- Handa, Sachin,Wang, Ye,Gallou, Fabrice,Lipshutz, Bruce H.
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p. 1087 - 1091
(2015/09/21)
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- Phosphine-Free Suzuki Cross-Coupling Reaction Using an Efficient and Reusable Pd Catalyst in an Aqueous Medium under Microwave Irradiation
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We report here an improved, highly efficient, and general method for the ligand-free Suzuki cross-coupling reaction to the synthesis of biaryls, bipyridyls, thienylpyridine, and allylphenols. Microwave irradiation of (het)aryl halides and (hetaryl, allyl)arylboronic acid N-methyl-iminodiacetic acid (MIDA) ester, using polyurea microencapsulated palladium catalyst (Pd EnCat 30), gave the coupling adducts 1a-x in excellent yields in just 10-18 min.
- Da Silva, Joaquim F. M.,Yepes Perez, Andres F.,De Almeida, Natália P.
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supporting information
p. 1995 - 2004
(2015/08/18)
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- An efficient and new protocol for phosphine-free Suzuki coupling reaction using palladium-encapsulated and air-stable MIDA boronates in an aqueous medium
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A simple methodology that uses a system based on polyurea microencapsulated palladium (PdEnCat 30) and aryl or (2-pyridyl) MIDA boronates for Suzuki-Miyaura cross-coupling reactions of (hetero)aryl halides in water-alcohol under phosphine-free conditions was developed. This journal is the Partner Organisations 2014.
- Mendes Da Silva, Joaquim Fernando,Yepes Perez, Andres Felipe,Pinto De Almeida, Natalia
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p. 28148 - 28155
(2014/07/21)
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- Synthesis of mono- and diaza-'pyridones' via stille coupling of alkoxystannanes
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Various alkoxy-substituted heterocyclic stannanes provide access to the corresponding substituted 'pyridone' moieties via Stille cross-coupling. Both pyridyl and a series of diazinyl stannanes are prepared, and options for unmasking (via demethylation or debenzylation) of the pyridone unit are evaluated. Georg Thieme Verlag Stuttgart. New York.
- Smith, Charlotte L.,Hirschh?user, Christoph,Malcolm, Georgia K.,Nasrallah, Daniel J.,Gallagher, Timothy
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p. 1904 - 1908
(2014/08/18)
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- Transforming Suzuki-Miyaura cross-couplings of MIDA boronates into a green technology: No organic solvents
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New technology has been developed that enables Suzuki-Miyaura couplings involving widely utilized MIDA boronates to be run in water as the only medium, mainly at room temperature. The protocol is such that no organic solvent is involved at any stage; from the reaction through to product isolation. Hence, using the E factor scale as a measure of greenness, the values for these cross-couplings approach zero.
- Isley, Nicholas A.,Gallou, Fabrice,Lipshutz, Bruce H.
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supporting information
p. 17707 - 17710
(2014/01/06)
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- Kumada coupling of aryl, heteroaryl, and vinyl chlorides catalyzed by amido pincer nickel complexes
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A series of amido pincer complexes of nickel were examined for their catalysis in the Kumada cross-coupling reaction. The P,N,O-pincer nickel complexes tested are active catalysts for the cross-coupling of aryl, heteroaryl, and vinyl chlorides with aryl Grignard reagents. The reactions can proceed at room temperature and tolerate functional groups in aryl chlorides with the aid of LiCl and ZnCl2 additives (Figure presented).
- Liu, Ning,Wang, Zhong-Xia
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experimental part
p. 10031 - 10038
(2012/02/05)
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- Negishi cross-coupling reactions catalyzed by an aminophosphine-based nickel system: A reliable and general applicable reaction protocol for the high-yielding synthesis of biaryls
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Treatment of NMP solutions of NiCl2 with 1,1′,1″- (phosphanetriyl)tripiperidine (≈2.05 equiv), dissolved in THF, in air at 25°C forms a highly active catalytic system for the cross-coupling of a large variety of electronically activated, non-activated, deactivated, and ortho-substituted, heterocyclic, and functionalized aryl bromides and aryl chlorides with diarylzinc reagents. Very high levels of conversion and yields were obtained within 2 h at 60°C in the presence of only 0.1 mol% of catalyst (based on nickel) and thus at catalyst loadings far lower than typically reported for nickel-catalyzed versions of the Negishi reaction. Various aryl halides-which may contain trifluoromethyl groups, fluorides, or other functional groups such as acetals, ketones, ethers, esters, lactones, amides, imines, anilines, alkenes, pyridines, quinolines, and pyrimidines-were successfully converted into the corresponding biaryls. Electronic and steric variations are tolerated in both reaction partners. Experimental observations indicate that a molecular (NiI/NiIII) mechanism is operative.
- Gerber, Roman,Frech, Christian M.
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experimental part
p. 11893 - 11904
(2011/11/29)
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- Homoleptic zincate-promoted room-temperature halogen-metal exchange of bromopyridines
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Homoleptic lithium tri- and tetraalkyl zincates were reacted with a set of bromopyridines. Efficient and chemoselective bromine-metal exchanges were realized at room temperature with a substoichiometric amount of nBu 4ZnLi2·TMEDA reagent (1/3 equiv; TMEDA=N,N,N′,N′-tetramethylethylenediamine). This reactivity contrasted with that of tBu4ZnLi2·TMEDA, which was inefficient below one equivalent. DFT calculations allowed us to rationalize the formation of N...Li stabilized polypyridyl zincates in the reaction. The one-pot difunctionalization of dibromopyridines was also realized using the reagent stoichiometrically. The direct creation of C-Zn bonds in bromopyridines enabled us to perform efficient Negishi-type cross-couplings. Mild zincation! nBu4ZnLi2·TMEDA (in substoichiometric amounts) promoted efficient and chemoselective room-temperature bromine-metal exchange of a range of bromopyridines (see scheme). DFT calculations strongly supported the formation of a stabilized tripyridylzincate, which could be reacted with electrophiles or be directly involved in palladium-catalyzed cross-coupling reactions.
- Chau, Nguyet Trang Thanh,Meyer, Maxime,Komagawa, Shinsuke,Chevallier, Floris,Fort, Yves,Uchiyama, Masanobu,Mongin, Florence,Gros, Philippe C.
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experimental part
p. 12425 - 12433
(2011/01/05)
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- Palladium-catalyzed Suzuki-Miyaura coupling of pyridyl-2-boronic esters with aryl halides using highly active and air-stable phosphine chloride and oxide ligands
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(Chemical Equation Presented) The palladium-catalyzed Suzuki-Miyaura coupling of pyridyl-2-boronic esters provided an efficient approach to useful biaryl building blocks containing a 2-pyridyl moiety. The convenient reaction protocol demonstrates its pote
- Yang, David X.,Colletti, Steven L.,Wu, Kevin,Song, Maoying,Li, George Y.,Shen, Hong C.
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supporting information; experimental part
p. 381 - 384
(2009/07/11)
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- Palladium-catalyzed cross-coupling reactions of 2-pyridylborates with air-stable HASPO religands
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A novel, air-stable TADDOLP(O)H derivative bearing electron-withdrawing substituents allows for efficient Suzuki-Miyaura cross-couplings with challenging electron-deficient 2-pyr-idylborates as nucleophiles.
- Ackermann, Lutz,Potukuchi, Harish K.
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experimental part
p. 2852 - 2856
(2010/03/26)
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- Synthesis of functionalized 2-arylpyridines from 2-halopyridines and various aryl halides via a nickel catalysis
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An efficient nickel-catalyzed method devoted to the direct formation of functionalized 2-arylpyridines is described avoiding the prior preparation of organometallic species. Various functionalized 2-arylpyridines are obtained in moderate to excellent yields by a one-step chemical procedure from corresponding halides. The NiBr2(2,2′-bipyridine) complex appears to be an extremely suitable catalyst for the activation in the presence of manganese dust of aromatic halides and pyridyl halides functionalized by reactive groups. The versatility of this original process represents a simple alternative to most known methods using organometallic reagents.
- Gosmini, Corinne,Bassene-Ernst, Carine,Durandetti, Muriel
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experimental part
p. 6141 - 6146
(2011/03/19)
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- A general and efficient method for the Suzuki-Miyaura coupling of 2-pyridyl nucleophiles
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(Chemical Equation Presented) One of the most general systems for the cross-coupling of aryl and heteroaryl bromides and chlorides with 2-pyridyl-derived nucleophiles has been developed, for which catalysts comprising [Pd2(dba)3] and either diaryl (1) or dialkyl phosphine oxide (2) supporting ligands were found to be ideal (see scheme).
- Billingsley, Kelvin L.,Buchwald, Stephen L.
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supporting information; experimental part
p. 4695 - 4698
(2009/02/06)
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- Electrosynthesis of functionalized 2-arylpyridines from functionalized aryl and pyridine halides catalyzed by nickel bromide 2,2'-bipyridine complex
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2-Arylpyridines substituted on aryl and/or on pyridine nuclei can be obtained in good to high yields in one step by electroreduction of mixtures of the corresponding aryl and pyridyl halides using the sacrificial iron anode process and a nickel 2,2'-bipyr
- Gosmini, Corinne,Nédélec, Jean Yves,Périchon, Jacques
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p. 5039 - 5042
(2007/10/03)
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