- Cobalt-Catalyzed Kumada Coupling Forming Sterically Encumbered C-C Bonds
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A Co(acac)3/PN precatalyst was developed and optimized for catalytic Kumada coupling of aryl Grignard reagents to sterically encumbered alkyl halides. The substrate scope demonstrates excellent yields for primary alkyl chlorides and bromides, including good performance using neopentyl chloride and neophyl chloride. Secondary alkyl halides were also successfully arylated in good yields, and the presence of β-hydrogen atoms in a substrate did not inhibit product formation. An intermolecular functional group tolerance screen was conducted which indicates that ester and amide functionality are well tolerated by the reaction conditions. Electrophiles containing ester, pyridine, and nitrile functionality were all coupled with 2-mesitylmagnesium bromide in good yields, supporting tolerance screen results. The intermolecular screen also showed that functional groups which are typically reactive with Grignard reagents such as alcohols and terminal alkynes were not well-tolerated by the reaction.
- Brennan, Marshall R.,Darrow, William T.,Fout, Alison R.,Killion, Jack A.,Leahy, Clare A.
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- Cascade Reductive Friedel-Crafts Alkylation Catalyzed by Robust Iridium(III) Hydride Complexes Containing a Protic Triazolylidene Ligand
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The synthesis of complex molecules like active pharmaceutical ingredients typically requires multiple single-step reactions, in series or in a modular fashion, with laborious purification and potentially unstable intermediates. Cascade processes offer attractive synthetic remediation as they reduce time, energy, and waste associated with multistep syntheses. For example, triarylmethanes are traditionally prepared via several synthetic steps, and only a handful of cascade routes are known with limitations due to high catalyst loadings. Here, we present an expedient catalytic cascade process to produce triarylmethanes. For this purpose, we have developed a bifunctional iridium system as the efficient catalyst to build heterotriaryl synthons via reductive Friedel-Crafts alkylation from ketones, arenes, and hydrogen. The catalytically active species were generated in situ from a robust triazolyl iridium(III) hydride complex and acid and is composed of a metal-bound hydride and a proximal ligand-bound proton for reversible dihydrogen release. These complexes catalyze the direct hydrogenation of ketones at slow rates followed by dehydration. Appropriate adjustment of the conditions successfully intercepts this dehydration and leads instead to efficient C-C coupling and Friedel-Crafts alkylation. The scope of this cascade process includes a variety of carbonyl substrates such as aldehydes, (alkyl)(aryl)ketones, and diaryl ketones as precursor electrophiles with arenes and heteroarenes for Friedel-Crafts coupling. The reported method has been validated in a swift one-step synthesis of the core structure of a potent antibacterial agent. Excellent yields and exquisite selectivities were achieved for this cascade process with unprecedentedly low iridium loadings (0.02 mol %). Moreover, the catalytic activity of the protic system is significantly higher than that of an N-methylated analogue, confirming the benefit of the Ir-H/N-H hydride-proton system for high catalytic performance.
- Albrecht, Martin,Alshakova, Iryna D.
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p. 8999 - 9007
(2021/07/31)
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- Silver triflate mediated dehydration of benzylic alcohols and vinyl hydrovinylation of styrene
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The use of silver trifluoromethanesulfonate (silver triflate, AgOTf) as a halide abstraction reagent is pervasive in organometallic chemistry. However, recent reports suggest a “hidden” Br?nsted acid lurks within it that may catalyze purported metal-based catalysis. Presented herein are new reactions that are either catalyzed or promoted by the “hidden” acid, generated upon silver triflate degradation. 1-Phenylethanol dehydrates to styrene (1) upon reaction with AgOTf at 90 °C over 24 h, which slowly coverts to the vinyl hydrovinylation product (E)-1,3-diphenyl-1-butene, (2, 64%) over several days. While dehydration was observed with a number of benzylic alcohols to yield Zaitsev selective olefins, only 1-phenylethanol affords vinyl hydrovinylation products. Dehydration was not observed for primary and secondary alcohols, suggesting an acid catalyzed E1elimination reaction mechanism is at play. The degradation of silver triflate was found to be the source of the “hidden” Br?nsted acid, which demonstrated a dependence on the presence of light and oxygen. In the absence of light and oxygen, dehydration of 1-phenylethanol was severely stunted and 2 is not formed, but instead the ether product, oxy-bis(ethane-1,1-diyl)dibenzene (3), is afforded. The mesitylene internal standard also reacts with the in situ formed styrene to produce 2-(1-phenylethyl)mesitylene (4) through acid catalyzed electrophilic aromatic substitution. These reactions were monitored (products characterized) by GC-MS and/or 1H NMR spectroscopic methods. We present herein the details of these reactions and our characterization methods.
- Quillian, Brandon,Fields, Alexis E.,Chace, Desiree,Murrell Vickery, Amanda,Sharma, Mrinali,Zurwell, Dane,Bazemore, Joseph G.,Phan, Long,Thomas, Dorey,Padgett, Clifford W.
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p. 224 - 229
(2019/03/02)
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- Metal-Free C-O Bond Functionalization: Catalytic Intramolecular and Intermolecular Benzylation of Arenes
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A catalytic, metal-free intramolecular rearrangement of benzyl phenyl ethers using nitrosonium salt as a catalyst is described. The optimized reaction conditions enabled a catalytic and metal-free Friedel-Crafts alkylation reaction with benzylic alcohols, producing water as the stoichiometric byproduct. A comprehensive scope (>50 examples) for both approaches and application in drug synthesis were demonstrated. Mechanistic studies suggest a Lewis acid-based mechanism for the metal-free Friedel-Crafts reaction.
- Bering, Luis,Jeyakumar, Kirujan,Antonchick, Andrey P.
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supporting information
p. 3911 - 3914
(2018/07/22)
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- Graphene-Catalyzed Direct Friedel-Crafts Alkylation Reactions: Mechanism, Selectivity, and Synthetic Utility
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Transition-metal-catalyzed alkylation reactions of arenes have become a central transformation in organic synthesis. Herein, we report the first general strategy for alkylation of arenes with styrenes and alcohols catalyzed by carbon-based materials, exploiting the unique property of graphenes to produce valuable diarylalkane products in high yields and excellent regioselectivity. The protocol is characterized by a wide substrate scope and excellent functional group tolerance. Notably, this process constitutes the first general application of graphenes to promote direct C-C bond formation utilizing polar functional groups anchored on the GO surface, thus opening the door for an array of functional group alkylations using benign and readily available graphene materials. Mechanistic studies suggest that the reaction proceeds via a tandem catalysis mechanism in which both of the coupling partners are activated by interaction with the GO surface.
- Hu, Feng,Patel, Mehulkumar,Luo, Feixiang,Flach, Carol,Mendelsohn, Richard,Garfunkel, Eric,He, Huixin,Szostak, Michal
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supporting information
p. 14473 - 14480
(2015/11/27)
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- Iron-catalyzed arylation of aromatic ketones and aldehydes mediated by organosilanes
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A simple and efficient iron-catalyzed method for arylation of aromatic carbonyl compounds is reported. The use of 4-% FeCl3 or Fe(acac) 3 as the catalyst, in combination with a slight excess of chlorotrimethylsilane and triethylsilane, chlorination of benzylic ketones and aldehydes with subsequent Friedel-Crafts alkylation of arenes is achieved. Although the method is limited by the general constraints associated with Friedel-Crafts alkylation reactions, robust applications for the synthesis of pharmaceutical intermediates and so on can be envisioned. A robust one-pot, iron-catalyzed chlorination Friedel-Crafts alkylation reaction of benzylic carbonyl compounds, mediated by chlorotrimethylsilane and triethylsilane, has been developed to yield substituted diaryl and triaryl building blocks. Copyright
- Savela, Risto,Majewski, Marcin,Leino, Reko
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p. 4137 - 4147
(2014/07/08)
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- Iron-catalyzed friedel-crafts benzylation with benzyl TMS ethers at room temperature
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Friedel-Crafts benzylations between unactivated arenes and benzyl alcohol derivatives are clean and straightforward processes to construct biologically useful di- and triarylmethanes. We have established an efficient iron-catalyzed Friedel-Crafts benzylation method at room temperature that uses benzyl TMS ethers as substrates, which are poorly reactive under common nucleophilic substitution conditions. The reaction seems to progress through iron-catalyzed self-condensation of the benzyl TMS ether to the corresponding dibenzylic ether. The use of excess arene relative to benzyl TMS ether produced mono-benzylated arene (diand tri-arylmethane products), whereas the use of excess benzyl TMS ether versus arene provided bis-benzylated arene (polyarylated products) in high yields and regioselectivities. In previous methods, the latter double Friedel-Crafts benzylations hardly proceed.
- Sawama, Yoshinari,Shishido, Yuko,Kawajiri, Takahiro,Goto, Ryota,Monguchi, Yasunari,Sajiki, Hironao
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supporting information
p. 510 - 516
(2014/04/03)
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- Cationic Iron(III) porphyrin catalyzed dehydrative friedel-crafts reaction of alcohols with arenes
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Alcohols react with arenes in the presence of cationic iron(III) porphyrin catalyst. The reaction involves the formation of the C-C bond via dehydration, which is formal Lewis acid catalyzed Friedel-Crafts reaction. Georg Thieme Verlag Stuttgart, New York.
- Teranishi, Satoru,Kurahashi, Takuya,Matsubara, Seijiro
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supporting information
p. 2148 - 2152
(2013/10/21)
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- Synthesis of diarylmethanes via a Friedel-Crafts benzylation using arenes and benzyl alcohols in the presence of triphenylphosphine ditriflate
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Triphenylphosphine ditriflate (TPPD) was found to be an efficient promoter for the Friedel-Crafts benzylation of arenes with benzyl alcohols in CH 2Cl2 at room temperature. The good yields, the 1:1 molar ratio of arene and benzyl alcohol, the benzylation of chlorobenzene as a nonactivated aromatic compound at room temperature, and no by-product formation are the main advantages of this procedure.
- Khodaei, Mohammad Mehdi,Nazari, Ehsan
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experimental part
p. 5131 - 5135
(2012/09/22)
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- Zinc chloride enhanced arylations of secondary benzyl trifluoroacetates in the presence of b-hydrogen atoms
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Zinc or swim: Arylation of benzyl trifluoroacetates with arylzinc reagents in the presence of β- hydrogen atoms were realized under mild conditions. Both electron-rich and electron-deficient arene substrates were successfully arylated. This arylation method could offer a very versatile synthetic route to access a series of diversity-oriented diarylalkane motifs. TFA = trifluoroacetyl. Copyright
- Duan, Hui,Meng, Lingkui,Bao, Denghui,Zhang, Heng,Li, Yao,Lei, Aiwen
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supporting information; experimental part
p. 6387 - 6390
(2010/11/04)
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- Highly efficient gold(III)-catalyzed intermolecular hydroarylation of unactivated alkenes with arenes under mild conditions
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A simple and efficient method for functionalization of electron-rich arenes and heteroarenes with unactivated alkenes by Au(III)-catalyzed intermolecular hydroarylation under mild reaction conditions was developed. This method features a short reaction time (5 h) under mild conditions and has a broad substrate scope, including electron-rich arenes and heteroarenes, terminal and internal substituted aryl alkenes, and unactivated aliphatic alkenes.
- Xiao, Ya-Ping,Liu, Xin-Yuan,Che, Chi-Ming
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experimental part
p. 494 - 501
(2009/06/06)
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- An efficient iodine-catalyzed benzylation reaction of 1,3-dicarbonyl compounds
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Under mild conditions, iodine promotes the direct alkylation of 1,3-dicarbonyl compounds with benzylic alcohols or benzylic acetates. Georg Thieme Verlag Stuttgart.
- Li, Zhongxian,Duan, Zheng,Wang, Huaiqiu,Tian, Rongqiang,Zhu, Qianrui,Wu, Yangjie
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scheme or table
p. 2535 - 2539
(2009/05/07)
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- Selective one-pot synthesis of various phenols from diarylethanes
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Various substituted phenols were selectively synthesized by a one-pot reaction through the NHPI-catalyzed aerobic oxidation of 1,1-diarylethanes followed by treatment with dilute sulfuric acid. The Royal Society of Chemistry.
- Nakamura, Ryota,Obora, Yasushi,Ishii, Yasutaka
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supporting information; experimental part
p. 3417 - 3419
(2009/02/05)
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- An efficient and selective hydroarylation of styrenes with electron-rich arenes, catalyzed by bismuth(III) chloride and affording Markovnikov adducts
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In the presence of BiCl3, the hydroarylation of styrenes with electron-rich arenes afforded Markovnikov adducts selectively in good to high yields. Under arene-free conditions, the intermolecular hydroarylation of α-substituted styrenes and subsequent intramolecular hydroarylation produced the cyclic dimers of α-substituted styrenes in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Sun, Hong-Bin,Li, Biao,Hua, Ruimao,Yin, Gwu
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p. 4231 - 4236
(2007/10/03)
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