- Suzuki-Miyaura cross-coupling of esters by selective O-C(O) cleavage mediated by air- And moisture-stable [Pd(NHC)(μ-Cl)Cl]2precatalysts: Catalyst evaluation and mechanism
-
The cross-coupling of aryl esters has emerged as a powerful platform for the functionalization of otherwise inert acyl C-O bonds in chemical synthesis and catalysis. Herein, we report a combined experimental and computational study on the acyl Suzuki-Miyaura cross-coupling of aryl esters mediated by well-defined, air- and moisture-stable Pd(ii)-NHC precatalysts [Pd(NHC)(μ-Cl)Cl]2. We present a comprehensive evaluation of [Pd(NHC)(μ-Cl)Cl]2 precatalysts and compare them with the present state-of-the-art [(Pd(NHC)allyl] precatalysts bearing allyl-type throw-away ligands. Most importantly, the study reveals [Pd(NHC)(μ-Cl)Cl]2 as the most reactive precatalysts discovered to date in this reactivity manifold. The unique synthetic utility of this unconventional O-C(O) cross-coupling is highlighted in the late-stage functionalization of pharmaceuticals and sequential chemoselective cross-coupling, providing access to valuable ketone products by a catalytic mechanism involving Pd insertion into the aryl ester bond. Furthermore, we present a comprehensive study of the catalytic cycle by DFT methods. Considering the clear advantages of [Pd(NHC)(μ-Cl)Cl]2 precatalysts on several levels, including facile one-pot synthesis, superior atom-economic profile to all other Pd(ii)-NHC catalysts, and versatile reactivity, these should be considered as the 'first-choice' catalysts for all routine applications in ester O-C(O) bond activation.
- Cavallo, Luigi,Nolan, Steven P.,Poater, Albert,Szostak, Michal,Yang, Shiyi,Zhou, Tongliang
-
p. 3189 - 3197
(2021/05/25)
-
- Water Phase, Room Temperature, Ligand-Free Suzuki–Miyaura Cross-Coupling: A Green Gateway to Aryl Ketones by C–N Bond Cleavage
-
We report herein a green strategy for synthesis of aryl ketones from twisted amides by using Pd(OAc)2 as catalysts. This method shows high functional group tolerance to offer a variety of ketones in good yields under mild conditions (up to 94 %). Notably, this methodology demonstrates the first water phase, room temperature, ligand-free Suzuki–Miyaura coupling through C–N bond cleavage, which is environmentally friendly and might facilitate the development of amide based green chemistry.
- Zhang, Yuqi,Wang, Zijia,Tang, Zhao,Luo, Zhongfeng,Wu, Hongxiang,Liu, Tingting,Zhu, Yulin,Zeng, Zhuo
-
p. 1620 - 1628
(2020/03/04)
-
- Decarboxylative Oxygenation via Photoredox Catalysis
-
The direct conversion of aliphatic carboxylic acids to their dehomologated carbonyl analogues has been accomplished through photocatalytic decarboxylative oxygenation. This transformation is applicable to an array of carboxylic acid motifs, producing ketones, aldehydes, and amides in excellent yields. Preliminary results demonstrate that this methodology is further amenable to aldehyde substrates via in situ oxidation to the corresponding acid and subsequent decarboxylative oxygenation. We have exploited this strategy for the sequential oxidative dehomologation of linear aliphatic chains.
- Faraggi, Tomer M.,Li, Wei,MacMillan, David W. C.
-
p. 410 - 415
(2019/12/24)
-
- FeCl3-catalyzed oxidative decarboxylation of aryl/heteroaryl acetic acids: Preparation of selected API impurities
-
There is an ever-increasing demand for impurity compounds for use in impurity profiling as regulatory agencies seek information during registration. Herein, we report the FeCl3-catalyzed oxidative decarboxylation of aryl- and heteroaryl acetic acids to the corresponding carbonyl compounds. A variety of useful aldehydes and ketones were prepared in a simple one-pot transformation by employing an environmentally benign, low-cost, and readily available iron salt. The utility of this method has been demonstrated by preparing five valuable API impurities including a multi-gram-scale synthesis of ketorolac impurity B for the first time. This journal is
- Gangadurai, Chinnakuzhanthai,Illa, Giri Teja,Reddy, D. Srinivasa
-
p. 8459 - 8466
(2020/11/05)
-
- Photoredox-Catalyzed Decarboxylative Oxidation of Arylacetic Acids
-
A photoredox-catalyzed decarboxylative oxidation of arylacetic acids, which are privileged scaffolds in pharmaceuticals, is reported herein. The established method is operationally simple and a variety of substrates are applicable, providing rapid access to dehomologated bioisosteres of common pharmaceuticals.
- Sakakibara, Yota,Cooper, Phillippa,Murakami, Kei,Itami, Kenichiro
-
supporting information
p. 2410 - 2413
(2018/06/04)
-
- General Method for the Suzuki-Miyaura Cross-Coupling of Primary Amide-Derived Electrophiles Enabled by [Pd(NHC)(cin)Cl] at Room Temperature
-
A general, highly selective method for the room temperature Suzuki-Miyaura cross-coupling of commonly encountered primary benzamides is reported. A combination of site-selective N,N-di-Boc-activation (tert-butoxycarbonyl activation) of the amide nitrogen with practical air- and moisture-stable, well-defined, and highly reactive [Pd(NHC)(cin)Cl] (NHC = N-heterocyclic carbene; cin = cinnamyl) provides a highly effective route to biaryl ketones from primary amides in high yields. For the first time, a TON of >1000 has been achieved in amide acyl cross-coupling.
- Lei, Peng,Meng, Guangrong,Ling, Yun,An, Jie,Nolan, Steven P.,Szostak, Michal
-
supporting information
p. 6510 - 6513
(2017/12/26)
-
- N-Acylsuccinimides: Twist-controlled, acyl-transfer reagents in Suzuki-Miyaura cross-coupling by N-C amide bond activation
-
The palladium-catalyzed Suzuki-Miyaura cross-coupling of N-acylsuccinimides as versatile acyl-transfer reagents via selective amide N-C bond cleavage is reported. The method is user-friendly since it employs commercially-available, air-stable reagents and catalysts. The cross-coupling is enabled by half-twist of the amide bond in N-acylsuccinimides. These highly effective, crystalline acyl-transfer reagents present major advantages over perpendicularly twisted N-acylglutarimides, including low price of the succinimide activating ring, selective metal insertion under redox neutral conditions and high stability of the amide bond towards reaction conditions. Mechanistic studies indicate that oxidative addition is the rate limiting step in this widely applicable protocol.
- Osumi, Yuki,Liu, Chengwei,Szostak, Michal
-
supporting information
p. 8867 - 8871
(2017/11/09)
-
- Preparation process of ketoprofen
-
The invention discloses a preparation process of ketoprofen. A method takes benzoyl chloride and acetanilide as starting raw materials, and the ketoprofen is prepared through the steps of acylating, carting out acylation, de-protecting, hydrolyzing, carrying out diazotization reduction, carrying out Darzens reaction, oxidizing and the like. According to the method disclosed by the invention, the raw materials have cheap prices and are easy to obtain; the process is easy to realize and a hazardous process does not exist in the reaction; the yield is high and reaction conditions are moderate; the preparation method is simple and convenient to operate and has low requirements on equipment.
- -
-
Paragraph 0069; 0070
(2017/07/19)
-
- Palladium-catalyzed Suzuki-Miyaura coupling of aryl esters
-
The Suzuki-Miyaura coupling is among the most important C-C bond-forming reactions available due to its reliability, chemoselectivity, and diversity. Aryl halides and pseudohalides such as iodides, bromides, and triflates are traditionally used as the electrophilic coupling partner. The expansion of the reaction scope to nontraditional electrophiles is an ongoing challenge to enable an even greater number of useful products to be made from simple starting materials. Herein, we present how an NHC-based Pd catalyst can enable Suzuki-Miyaura coupling where the C(acyl)-0 bond of aryl esters takes on the role of electrophile, allowing the synthesis of various ketone-containing products. This contrasts known reactions of similar esters that provide biaryls via nickel catalysis. The underlying cause of this mechanistic divergence is investigated by DFT calculations, and the robustness of esters compared to more electrophilic acylative coupling partners is analyzed.
- Halima, Taoufik Ben,Zhang, Wanying,Yalaoui, Imane,Hong, Xin,Yang, Yun-Fang,Houk, Kendall N.,Newman, Stephen G.
-
p. 1311 - 1318
(2017/05/16)
-
- Metal-free efficient cross coupling of aromatic aldehydes with aryldiazonium tetrafluoroborates using DTBP as a radical initiator
-
A highly efficient, metal-free, one-pot radical route to access diaryl ketones from aromatic aldehydes is reported. The protocol renders cross coupling of aromatic aldehydes with aryl diazonium tetrafluoroborates using inexpensive di-tert-butylperoxide (DTBP) as a radical initiator under mild conditions. The reaction offers a convenient alternative to the Friedel-Crafts acylation for the synthesis of diaryl ketones.
- Tripathi, Shubhangi,Singh, Sachchida N.,Yadav, Lal Dhar S.
-
supporting information
p. 4211 - 4214
(2015/06/22)
-
- Simple preparation of aryltributylstannanes and its application to one-pot synthesis of diaryl ketones
-
Transfer of aryl group from boron to tin can be achieved by simple treatment of arylboronic acids with tributyltin methoxide at 100 °C for 1 h under neat conditions. The resulting aryltributylstannanes are applicable to one-pot synthesis of diaryl ketones. Thus, Pd-catalyzed cross-coupling reaction with aroyl chlorides is allowed to proceed without isolation step to produce the corresponding diaryl ketones in good to high yields.
- Oikawa, Asuka,Kindaichi, Gan,Shimotori, Yasutaka,Okimoto, Mitsuhiro,Hoshi, Masayuki
-
p. 1705 - 1711
(2015/03/30)
-
- Unmasked acyl anion equivalent from acid chloride with indium: Reversed-polarity synthesis of unsymmetric aryl aryl and alkenyl aryl ketone through palladium-catalyzed cross-coupling reaction
-
A reversed-polarity synthetic method of a range of unsymmetric aryl aryl and alkenyl aryl ketones has been developed through Pd-catalyzed cross-coupling reaction of acylindium reagents generated in situ from easily available acid chlorides and indium with various electrophiles such as aryl iodide and triflate and alkenyl triflate.
- Lee, Dohyung,Ryu, Taekyu,Park, Youngchul,Lee, Phil Ho
-
supporting information
p. 1144 - 1147
(2014/03/21)
-
- Application of complementary mass spectrometric techniques to the identification of ketoprofen phototransformation products
-
Ketoprofen (KP) is a nonsteroidal anti-inflammatory drug, which during UV irradiation rapidly transforms into benzophenone derivatives. Such transformation products may occur after topical application of KP, which is then exposed to sunlight resulting in a photo-allergic reaction. These reactions are mediated by the benzophenone moiety independently of the amount of allergen. The same reactions will also occur during wastewater or drinking water treatment albeit their effect in the aqueous environment is yet to be ascertained. In addition, only a few such transformation products have been recognised. To enable the detection and structural elucidation of the widest range of KP transformation products, this study applies complementary chromatographic and mass spectrometric techniques including gas chromatography coupled to single quadrupole or ion trap mass spectrometry and liquid chromatography hyphenated with quadrupole-time-of-flight mass spectrometry. Based on structural information gained in tandem and multiple MS experiments, and on highly accurate molecular mass measurements, chemical structures of 22 transformation products are proposed and used to construct an overall breakdown pathway. Among the identified transformation products all but two compounds retained the benzophenone moietya€"a result, which raises important issues concerning the possible toxic synergistic effects of KP and its transformation products. These findings trigger further research into water treatment technologies that would limit their entrance into environmental or drinking waters. Copyright
- Kosjek, Tina,Perko, Silva,Heath, Ester,Kralj, Bogdan,Zigon, Dusan
-
experimental part
p. 391 - 401
(2011/11/12)
-
- Pd(II)-Catalyzed decarboxylative cross-coupling of potassium aryltrifluoroborates with α-oxocarboxylic acids at room temperature
-
A novel Pd-catalyzed decarboxylative cross-coupling of potassium aryltrifluoroborates with R-oxocarboxylic acids is performed at room temperature. This reaction provides an efficient access to aryl ketones under mild conditions.
- Li, Mingzong,Wang, Cong,Ge, Haibo
-
supporting information; experimental part
p. 2062 - 2064
(2011/06/19)
-
- Efficient synthesis of alkyl aryl ketones & ketals via palladium-catalyzed regioselective arylation of vinyl ethers
-
The combination of Pd(OAc)2 with 1,3-bis(diphenylphosphino) propane (dppp) in ethylene glycol constitutes a high-performance catalytic system for highly regioselective arylation of a range of electron-rich vinyl ethers by aryl bromides to provide, upon hydrolysis, alkyl aryl ketones and cyclic ketals in good yields with up to 3.75 × 105 TON and 15625 h-1 TOF.
- Liu, Mingcui,Hyder, Zeynab,Sun, Yawei,Tang, Weijun,Xu, Lijin,Xiao, Jianliang
-
supporting information; experimental part
p. 2012 - 2015
(2010/07/04)
-
- A new practical ketone synthesis directly from carboxylic acids: First application of coupling reagents in palladium catalysis
-
A new palladium-catalyzed cross-coupling reaction between arylboronic acids and carboxylic acids, activated in situ for the oxidative addition to a tricyclohexylphosphine palladium(0) catalyst by treatment with di(N-succinimidyl) carbonate (DSC) is disclosed, which allows the high-yielding synthesis of various functionalized arylketones under mild conditions.
- Goossen,Ghosh
-
p. 2084 - 2085
(2007/10/03)
-
- Photochemical and photobiological properties of ketoprofen associated with the benzophenone chromophore.
-
Irradiation of ketoprofen in neutral aqueous medium gave rise to 3-ethylbenzophenone as the major photoproduct. Its formation is justified via protonation of a benzylic carbanion or hydrogen abstraction by a benzylic radical. Minor amounts of eight additional compounds were isolated. Four of them are derived from the benzylic radical: 3-(1-hydroperoxyethyl)benzophenone, 3-(1-hydroxyethyl)benzophenone, 3-acetylbenzophenone and 2,3-bis-(3-benzoylphenyl)butane. The other four products involve initial hydrogen abstraction by the excited benzophenone chromophore of ketoprofen: 1,2-bis-(3-ethylphenyl)-1,2-diphenyl-1,2-ethanediol, 2-(3-benzoylphenyl)-1-(3-ethylphenyl)-1-phenylpropan-1-ol, alpha-(3-ethylphenyl)phenylmethanol, 1,2-bis-[3-(2-hydroxycarbonylethyl) phenyl]-1,2-diphenyl-1,2-ethanediol. The latter process was found to mediate the photoperoxidation of linoleic acid through a type I mechanism, as evidenced by the inhibition produced by the radical scavengers butylated hydroxyanisole and reduced glutathione. The major photoproduct, which contains the benzophenone moiety but lacks the propionic acid side chain, also photosensitized linoleic acid peroxidation. Because lipid peroxidation is indicative of cell membrane lysis, the above findings are highly relevant to explain the photobiological properties of ketoprofen.
- Bosca,Miranda,Carganico,Mauleon
-
-
- OXIDATIVE DECARBOXYLATION OF CARBOXYLIC ACIDS BY IRON PORPHYRIN - IODOSYLBENZENE SYSTEM
-
An iodosylbenzene - iron tetraarylporphyrin catalyst system decarboxylated α-aryl carboxylic acids and α,α,α-trisubstituted acetic acids efficiently to give the corresponding alcohol and carbonyl derivatives.
- Komuro, Masakatsu,Nagatsu, Yoshio,Higuchi, Tsunehiko,Hirobe, Masaaki
-
p. 4949 - 4952
(2007/10/02)
-
- ENANTIOSELECTIVE SYNTHESIS AND ABSOLUTE CONFIGURATION OF (+)-α-(3-BENZOYLPHENYL)PROPIONIC ACID
-
Asymmetric homogeneous hydrogenation of α-(3-benzoylphenyl)acrylic acid (4), which is preparared in 90percent overall yield from (3-benzoylphenyl)acetic acid (1), affords (+)-α-(3-benzoylphenyl)propionic acid, (+)-5, in 93.7percent chemical and 67.4percent optical yield.The absolute configuration of (+)-5 is correlated with that of (+)-(S)-hydratropic acid via (+)-α-(3-benzylphenyl)propionic acid, (+)-6.The origin of the CD bands of (+)-6 is discussed and comparison of chiroptical data with those of (+)-(S)-hydratropic acid, reveals that (+)-6 has an S configuration.Since (+)-6 is chemically correlated with (+)-5, the absolute S configuration of this enantiomer is confirmed.
- Comisso, Giovanni,Mihalic, Mladen,Kajfez, Franjo,Sunjic, Vitomir,Snatzke, Guenther
-
p. 123 - 128
(2007/10/02)
-