- Pd-Catalyzed Regioselective Branched Hydrocarboxylation of Terminal Olefins with Formic Acid
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A regioselective Pd-catalyzed hydrocarboxylation of terminal olefins with HCOOH is described. A wide variety of branched carboxylic acids can readily be obtained with high regioselectivities under mild reaction conditions. The reaction is operationally simple and requires no handling of toxic CO. The ligand and LiCl are important factors for reaction reactivity and selectivity.
- Chu, Jianxiao,Guo, Jianqiong,Ren, Wenlong,Shi, Yian,Shi, Yuan,Wang, Mingzhou,Zhou, Jintao
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supporting information
p. 886 - 891
(2022/02/07)
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- Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C-H/C-H Coupling: Four-Step Total Synthesis of (±)-Russujaponol F
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The development of practical C-H/C-H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C-C bonds. Herein we report a cyclative C(sp3)-H/C(sp2)-H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-N-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na2CO3·1.5H2O2) as the sole oxidant and generates water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, can be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through sequential functionalizations of four C-H bonds.
- Zhuang, Zhe,Herron, Alastair N.,Liu, Shuang,Yu, Jin-Quan
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p. 687 - 692
(2021/01/25)
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- Intramolecular Oxidative Coupling between Unactivated Aliphatic C-H and Aryl C-H Bonds
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Direct oxidative coupling of different inert C-H bonds is the most straightforward and environmentally benign method to construct C-C bonds. In this paper, we developed a Pd-catalyzed intramolecular oxidative coupling between unactivated aliphatic and aryl C-H bonds. This chemistry showed great potential to build up fused cyclic scaffolds from linear substrates through oxidative couplings. Privileged chromane and tetralin scaffolds were constructed from readily available linear starting materials in the absence of any organohalides and organometallic partners.
- Liao, Yang,Zhou, Yi,Zhang, Zhen,Fan, Junzhen,Liu, Feng,Shi, Zhangjie
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supporting information
p. 1251 - 1257
(2021/03/03)
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- Palladium-Catalyzed C(sp3)-H Nitrooxylation with tert-Butyl Nitrite and Molecular Oxygen
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Herein, we report a Pd(II)-catalyzed nitrooxylation of unactivated methyl C(sp3)-H bonds using commercial available and easily manageable tert-butyl nitrite as the precursor of ONO2 radical under aerobic conditions. Environmentally benign molecular oxygen is used to initiate the generation of active radical reactant; it is also used as the terminal oxidant. A broad range of nitrooxylated aliphatic carboxamides were prepared in moderate to good yields under mild conditions.
- Han, Ye-Qiang,Li, Bo,Shi, Bing-Feng,Yang, Xu
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supporting information
p. 9719 - 9723
(2020/12/21)
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- Pd(ii)/Zn co-catalyzed chemo-selective hydrogenation of α-methylene-γ-keto carboxylic acids
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An efficient Pd/Zn co-catalyzed chemo-selective hydrogenation of α-methylene-γ-keto carboxylic acids is described. This methodology offers a divergent synthesis of α-methyl-γ-keto carboxylic acids, α-methylcarboxylic acids, and lactones starting from α-me
- Zhang, Xuexin,Gao, Yang,Laishram, Ronibala Devi,Li, Kangkui,Yang, Yong,Zhan, Yong,Luo, Yang,Fan, Baomin
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p. 2174 - 2181
(2019/02/27)
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- Synthesis of Carboxylic Acids by Palladium-Catalyzed Hydroxycarbonylation
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The synthesis of carboxylic acids is of fundamental importance in the chemical industry and the corresponding products find numerous applications for polymers, cosmetics, pharmaceuticals, agrochemicals, and other manufactured chemicals. Although hydroxycarbonylations of olefins have been known for more than 60 years, currently known catalyst systems for this transformation do not fulfill industrial requirements, for example, stability. Presented herein for the first time is an aqueous-phase protocol that allows conversion of various olefins, including sterically hindered and demanding tetra-, tri-, and 1,1-disubstituted systems, as well as terminal alkenes, into the corresponding carboxylic acids in excellent yields. The outstanding stability of the catalyst system (26 recycling runs in 32 days without measurable loss of activity), is showcased in the preparation of an industrially relevant fatty acid. Key-to-success is the use of a built-in-base ligand under acidic aqueous conditions. This catalytic system is expected to provide a basis for new cost-competitive processes for the industrial production of carboxylic acids.
- Sang, Rui,Kucmierczyk, Peter,Dühren, Ricarda,Razzaq, Rauf,Dong, Kaiwu,Liu, Jie,Franke, Robert,Jackstell, Ralf,Beller, Matthias
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supporting information
p. 14365 - 14373
(2019/09/06)
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- Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals
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In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.
- Wu, Fu-Peng,Li, Da,Peng, Jin-Bao,Wu, Xiao-Feng
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supporting information
p. 5699 - 5703
(2019/08/01)
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- Cooperative iodine and photoredox catalysis for direct oxidative lactonization of carboxylic acids
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A new method for the formation of γ- and δ-lactones from carboxylic acids through direct conversion of benzylic C-H to C-O bonds is described. The reaction is conveniently induced by visible light and relies on a mild cooperative catalysis by the combination of molecular iodine and an organic dye.
- Duhamel, Thomas,Mu?iz, Kilian
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supporting information
p. 933 - 936
(2019/01/23)
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- 1-Aminopyridinium Ylides as Monodentate Directing Groups for sp3 C-H Bond Functionalization
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1-Aminopyridinium ylides are efficient directing groups for palladium-catalyzed β-arylation and alkylation of sp3 C-H bonds in carboxylic acid derivatives. The efficiency of these directing groups depends on the substitution at the pyridine moiety. The unsubstituted pyridine-derived ylides allow functionalization of primary C-H bonds, while methylene groups are unreactive in the absence of external ligands. 4-Pyrrolidinopyridine-containing ylides are capable of C-H functionalization in acyclic methylene groups in the absence of external ligands, thus rivaling the efficiency of the aminoquinoline directing group. Preliminary mechanistic studies have been performed. A cyclopalladated intermediate has been isolated and characterized by X-ray crystallography, and its reactivity was studied.
- Le, Ky Khac Anh,Nguyen, Hanh,Daugulis, Olafs
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supporting information
p. 14728 - 14735
(2019/10/11)
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- CATALYTIC CARBOXYLATION OF ACTIVATED ALKANES AND/OR OLEFINS
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The present invention relates to a method of reacting starting materials with an activating group, namely alkanes carrying a leaving group and/or olefins, with carbon dioxide under transition metal catalysis to give carboxyl group-containing products. It is a special feature of the method of the present invention that the carboxylation predominantly takes place at a preferred position of the molecule irrespective of the position of the activating group. The carboxylation position is either an aliphatic terminus of the molecule or it is a carbon atom adjacent to a carbon carrying an electron withdrawing group. The course of the reaction can be controlled by appropriately choosing the reaction conditions to yield the desired regioisomer.
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Page/Page column 64; 72; 73
(2018/02/28)
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- Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
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Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
- Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 9067 - 9089
(2017/11/14)
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- Site-Selective Catalytic Carboxylation of Unsaturated Hydrocarbons with CO2 and Water
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A catalytic protocol that reliably predicts and controls the site-selective incorporation of CO2 to a wide range of unsaturated hydrocarbons utilizing water as formal hydride source is described. This platform unlocks an opportunity to catalytically repurpose three abundant, orthogonal feedstocks under mild conditions.
- Gaydou, Morgane,Moragas, Toni,Juliá-Hernández, Francisco,Martin, Ruben
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p. 12161 - 12164
(2017/09/12)
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- Unactivated C(sp3)-H hydroxylation through palladium catalysis with H2O as the oxygen source
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A novel palladium catalyzed hydroxylation of unactivated aliphatic C(sp3)-H bonds was successfully developed. Different from conventional methods, water serves as the hydroxyl group source in the reaction. This new reaction demonstrates good reactivity and broad functional group tolerance. The C-H hydroxylated products can be readily transformed into various highly valuable chemicals via known transformations. Based on experimental and theoretical studies, a mechanism involving the Pd(ii)/(iv) pathway is proposed for this hydroxylation reaction.
- Hu, Jiantao,Lan, Tianlong,Sun, Yihua,Chen, Hui,Yao, Jiannian,Rao, Yu
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supporting information
p. 14929 - 14932
(2015/10/06)
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- CARBOXYLIC DERIVATIVES FOR USE IN THE TREATMENT OF CANCER
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The invention provides novel compounds of formula (I), wherein: R1 is a radical derived from one of the known ring systems; R2 is a phenyl radical optionally substituted; Xn represents a birradical selected from the group consisting of: -(CH2)1-4-, (C2-C4)-alkenyl, (C2-C4)alkynyl, -S-(CH2)1-3-#, and -(CH2)1-3-O-#; wherein the symbol # indicates the position at which Xn is attached to R1; Yn is a birradical selected from the group consisting of: -(CH2)2-4-, -S-(CH2)1-3#, and -O-(CH2)1-3-#,; where in the symbol # indicates the position at which Yn is attached to R2; and R3 is a radical selected from the group consisting of: -OR4. The compounds of formula (I) are useful in the treatment of cancer
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Page/Page column 25
(2009/07/25)
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- New Methods and Reagents in Organic Synthesis. 26. Reductive Desulfonylation of α-Sulfonylacetates
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α-Acyl-benzylsulfonyldiazomethanes (2a-d) have been converted to α-benzylsulfonyl-α-substituted-acetic acids (7a-d) by means of the Wolff rearrangement.Reductive removal of the benzylsulfonyl group of 7b-d can be achieved by the use of sodium-ethanol in tetrahydrofuran. α-Benzylsulfonyl-α-substituted-propionic acids (9a-d), prepared from benzyl α-benzylsulfonyl-α-substituted-acetates (3a-d), were also debenzylsulfonylated under similar reductive conditions.The overall process, in combination with the Arndt-Eistert synthesis of α-sulfonylacetates from acyl chlorides and benzylsulfonyldiazomethane (1), provides a new, safe method for the homologation of carboxylic acids.Keywords-reductive desulfonylation; Wolff rearrangement; sodium amalgam reduction; catalytic debenzylation; sodium-ethanol reduction; methylation; α-substituted propionic acid; α-sulfonylacetate
- Kuo, Ying-Che,Aoyama, Toyohiko,Shioiri, Takayuki
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p. 2787 - 2792
(2007/10/02)
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