cas 1865-29-8, 2-PHENYL-ACRYLIC ACID METHYL ESTER

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Rhodium catalysed hydroformylation of unsaturated esters
Rhodium catalysed hydroformylation of unsaturated esters has been studied. A pronounced temperature dependence was observed on the regioselectivity and catalytic activity for these reactions, and under the appropriate conditions, it is possible to obtain preferentially either linear or quaternary products. A quaternary selective hydroformylation of methyl atropate to give 1,3-aldehydic esters has also been developed.
Clarke, Matthew L.
p. 4043 - 4045
(2004)
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Catalysis in supercritical CO2 using dendrimer-encapsulated palladium nanoparticles
Dendrimer-encapsulated nanoparticles are shown to be versatile catalysts for both the hydrogenation of styrene and Heck heterocoupling of iodobenzene and methacrylate in supercritical CO2 (scCO2).
Yeung,Lee C.T.,Johnston,Crooks
p. 2290 - 2291
(2001)
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Group 6 heteroatom- and non-heteroatom-stabilized carbene complexes. β,β′- and α,ββ′-Annulation reactions of cyclic enamines
Cyclization reactions of group 6 Fischer carbene complexes with cyclopentanone and cyclohexanone enamines are described. Enamine 3a undergoes thermal β,β′-annulation with alkenylcarbene complexes 1 and 2 (THF, 60 °C), affording semibullvalenes 5. The metalate intermediates 6, resulting from β,β′-annulation of the enamines 3a and 4a, were quantitatively formed by running the reaction in hexane at room temperature. Acid-promoted demetalation of 6 afforded endo-2-bicyclo[3.2.1]octen-8-ones 7 and endo/exo-2-bicyclo[3.3.1]nonen-9-ones 8 (endo/exo = 5:1). Using (S)-methoxymethylpyrrolidinederived enamines 3b and 4b,c allowed highly enantioenriched cycloadducts endo-(+)-7 as well as endo- (-)-8 and exo-(-)-8 to be accessed. The non -heteroatom -stabilized carbene complex 10 was formed from complex 6 by Me3SiOTf-promoted elimination of the methoxy group, characterized by 13C NMR, and transformed into the organic compounds 7, 7-d, and 11 as well as into bicyclo[3.2.1]octan-2,8-diones 14 and cycloheptanones 15, On the basis of this sequence, enantioenriched cycloheptanones (+)-15 were efficiently prepared in one pot from carbene complexes 2 and enamine 3b (51-55% yield, 91-96% ee). Extension of this work to simple Fischer carbene complexes 16 allowed an appropriate way to generate the nonstabilized pentacarbonyl[(phenyl(alkyl)carbene]tungsten complex 17 to be designed, for which the thermal and chemical behavior leading to compounds 18-21 is described.
Barluenga, Jose,Ballesteros, Alfredo,De la Rua, Ramon Bernardo,Santamaria, Javier,Rubio, Eduardo,Tomas, Miguel
p. 1834 - 1842
(2003)
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Room-temperature Pd-catalyzed methoxycarbonylation of terminal alkynes with high branched selectivity enabled by bisphosphine-picolinamide ligand
We report the room-temperature Pd-catalyzed methoxy-carbonylation with high branched selectivity using a new class of bisphosphine-picolinamide ligands. Systematic optimization of ligand structures and reaction conditions revealed the significance of both
Chen, Fen-Er,Ke, Miaolin,Liu, Ding,Ning, Yingtang,Ru, Tong
supporting information
p. 1041 - 1044
(2022/01/28)

Palladium-Catalyzed Asymmetric Hydroesterification of α-Aryl Acrylic Acids to Chiral Substituted Succinates
A palladium-catalyzed asymmetric hydroesterification of α-aryl acrylic acids with CO and alcohol was developed, preparing a variety of chiral α-substituted succinates in moderate yields with high ee values. The kinetic profile of the reaction progress revealed that the alkene substrate first underwent the hydroesterification followed by esterification with alcohol. The origin of the enantioselectivity was elucidated by density functional theory computation.
Ji, Xiaolei,Shen, Chaoren,Tian, Xinxin,Dong, Kaiwu
supporting information
p. 8645 - 8649
(2021/10/25)

Pyrrolidine integrin regulator and application thereof
Disclosed are a compound as represented by formula I, and a racemate, a stereoisomer, a tautomer, an isotopic marker, a nitrogen oxide, a solvate, a polymorph, a metabolite, an ester, and a prodrug thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising same, a preparation method therefor, and the medical use thereof. The structure of formula I is as follows:
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(2021/09/08)

Electrochemical oxidative: Z -selective C(sp2)-H chlorination of acrylamides
An electrochemical method for the oxidative Z-selective C(sp2)-H chlorination of acrylamides has been developed. This catalyst and organic oxidant free method is applicable across various substituted tertiary acrylamides, and provides access to a broad range of synthetically useful Z-β-chloroacrylamides in good yields (22 examples, 73% average yield). The orthogonal derivatization of the products was demonstrated through chemoselective transformations and the electrochemical process was performed on gram scale in flow.
Coles, Simon J.,Hareram, Mishra Deepak,Harnedy, James,Morrill, Louis C.,Tizzard, Graham J.
supporting information
p. 12643 - 12646
(2021/12/07)

Photocatalytic Hydromethylation and Hydroalkylation of Olefins Enabled by Titanium Dioxide Mediated Decarboxylation
A versatile method for the hydromethylation and hydroalkylation of alkenes at room temperature is achieved by using the photooxidative redox capacity of the valence band of anatase titanium dioxide (TiO2). Mechanistic studies support a radical-based mechanism involving the photoexcitation of TiO2 with 390 nm light in the presence of acetic acid and other carboxylic acids to generate methyl and alkyl radicals, respectively, without the need for stoichiometric base. This protocol is accepting of a broad scope of alkene and carboxylic acids, including challenging ones that produce highly reactive primary alkyl radicals and those containing functional groups that are susceptible to nucleophilic substitution such as alkyl halides. This methodology highlights the utility of using heterogeneous semiconductor photocatalysts such as TiO2 for promoting challenging organic syntheses that rely on highly reactive intermediates.
Zhu, Qilei,Nocera, Daniel G.
supporting information
p. 17913 - 17918
(2020/12/04)

Synergetic Catalysis for One-pot Bis-alkoxycarbonylation of Terminal Alkynes over Pd/Xantphos?Al(OTf)3 Bi-functional Catalytic System
Tandem bis-alkoxycarbonylation of alkynes allows for the preparation of 2-substituted succinates from alkynes and nucleophile alcohol via two successive alkoxycarbonylation with advantages of 100 % atomic economy and simplified one-pot operation. Herein, the one-pot tandem bis-alkoxycarbonylation of alkynes was accomplished over the bi-functional catalytic system containing Xantphos-modified Pd-complex and Lewis super-acid of Al(OTf)3. It was found that, via the synergetic catalysis, the involved Xantphos-modified Pd-complex was responsible for the activation of CO and the alkynes through coordination to Pd-center while Al(OTf)3 was in charge of the activation of the alcohol to facilitate the formation of [Pd?H]+ active species. The in situ high-pressure FT-IR analysis, coupled with 1H/13C NMR spectral characterizations, confirmed that the introduced Al(OTf)3 with intensive oxophilicity (via acid-base pair interaction) was able to activate nucleophilic MeOH to be a reliable proton-donor (i. e. hydride-source) to warrant the formation and stability of [Pd?H]+ species upon the oxidation of Pd0 by H+ (Pd0+H+→[PdII?H]+). Over the developed bi-functional catalytic system, the yields of the target diesters were obtained in the range of 36～86 % in this sequence with the wide substrate scope.
Guo, Wen-Di,Liu, Lei,Yang, Shu-Qing,Chen, Xiao-Chao,Lu, Yong,VO-Thanh, Giang,Liu, Ye
p. 1376 - 1384
(2020/01/24)

Palladium-catalyzed intermolecular C-H silylation initiated by aminopalladation
A Pd(ii)-catalyzed intermolecular C-H silylation reaction initiated by aminopalladation has been developed. The C-H bonds were activated by an alkyl Pd(ii) species generated through aminopalladation and then disilylated with hexamethyldisilane to form disilylated indolines as the final products. The reaction provides a new method for the introduction of silyl groups into complex organic molecules.
Ji, Xiaoming,Wei, Feng,Wan, Bin,Cheng, Cang,Zhang, Yanghui
p. 7801 - 7804
(2020/07/27)

Iridium complex-linked porous organic polymers for recyclable, broad-scope photocatalysis of organic transformations
Two rigid porous organic polymers (Ir-POP-1 and Ir-POP-2) were prepared from the coupling reactions of tetraphenylmethane tetraborate and two [Ir(ppy)2(dtbbpy)]+-based bitopic linkers and applied as heterogeneous visible-light photocatalysts for organic transformations. Ir-POP-2 was found to exhibit high catalytic activity for a wide range of organic reactions, which include Smiles-Truce rearrangement of alkyliodides, desulfurative conjugate addition to Michael acceptors, and aerobic oxidations of sulfides and arylboronic acids. For all the transformations, Ir-POP-2 could achieve heterogeneous photocatalytic efficiency that rivals that of the homogeneous prototype iridium complexes. This remarkably high photocatalytic performance has been attributed to the large pore size of the conjugated backbone. The new heterogeneous photocatalyst was also highly stable to achieve good recyclability for all the studied reactions and could be reused eight to nineteen times.
Xu, Zi-Yue,Luo, Yi,Zhang, Dan-Wei,Wang, Hui,Sun, Xing-Wen,Li, Zhan-Ting
supporting information
p. 136 - 143
(2020/01/21)

Catalytic Hydroetherification of Unactivated Alkenes Enabled by Proton-Coupled Electron Transfer
We report a catalytic, light-driven method for the intramolecular hydroetherification of unactivated alkenols to furnish cyclic ether products. These reactions occur under visible-light irradiation in the presence of an IrIII-based photoredox catalyst, a Br?nsted base catalyst, and a hydrogen-atom transfer (HAT) co-catalyst. Reactive alkoxy radicals are proposed as key intermediates, generated by direct homolytic activation of alcohol O?H bonds through a proton-coupled electron-transfer mechanism. This method exhibits a broad substrate scope and high functional-group tolerance, and it accommodates a diverse range of alkene substitution patterns. Results demonstrating the extension of this catalytic system to carboetherification reactions are also presented.
Knowles, Robert R.,Metrano, Anthony J.,Tsuchiya, Yuto,Tsui, Elaine
supporting information
p. 11845 - 11849
(2020/05/22)

Discovery of Oxygen α-Nucleophilic Addition to α,β-Unsaturated Amides Catalyzed by Redox-Neutral Organic Photoreductant
The conjugate additions of oxygen-centered nucleophiles to conjugate acceptors are among the most powerful C-O bond formation reactions. The conjugate addition normally takes place at the β-position carbon to the electron-withdrawing group, resulting in the formation of a stabilized carbanion intermediate that can be quenched by proton or electrophiles to form the β-addition (i.e., hetero-Michael addition) products. On the contrary, the formation of α-hydroxyl or alkoxyl amides through conjugate addition needs an α,β-inverse addition. Nevertheless, a regio-inversed nucleophilic α-addition of oxygen-centered nucleophiles to α,β-unsaturated carbonyl compounds still remains less explored because of the electronic mismatch. In this research, we discovered the first α-specific nucleophilic addition of α,β-unsaturated amides with oxygen and fluoride nucleophiles. This region-inversed nucleophilic addition is enabled by the catalysis of a novel redox-neutral nondonor-acceptor organic photoreductant (CBZ6). As low as 0.5 mol % of visible light photoreductant was employed. The mechanistic insights were also explored. The oxidative potential of the excited state of CBZ6 is obtained in -1.92 V (vs SCE), presenting a stronger reductive potential than representative metal-cored or organic photoredox catalysts. This feature enabled the umpolung of α,β-unsaturated amides to take place α-nucleophilic addition other than the normal β-addition.
Luan, Zi-Hong,Qu, Jian-Ping,Kang, Yan-Biao
supporting information
p. 20942 - 20947
(2020/12/22)

Novel multi-dentate phosphines for Pd-catalyzed alkoxycarbonylation of alkynes promoted by H2O additive
A series of novel multi (bi-/tri-/tetra-)-dentate phosphines with good robustness against water and oxygen were synthesized and fully characterized. It was found that the developed ionic tri-dentate phosphine (L2′) enabled Pd-catalyzed alkoxycarbonylation of alkynes most efficiently while H2O was used as an additive instead of acid. As for L2′, its unique steric configuration with two types of potential P-P chelation modes (P?P distance of 4.31 ? and 4.36 ? respectively) to Pd-centre rendered the corresponding Pd-catalyst high activity and good stability for alkoxycarbonylation of alkynes. The in situ FT-IR analysis also verified that the formation and stability of Pd–H active species were greatly facilitated with the presence of L2′ as well as H2O additive. In addition, as an ionic phosphine, L2′ based PdCl2(MeCN)2 system immobilized in RTIL of [Bmim]NTf2 could be recycled for 7 runs without obvious activity loss or metal leaching.
Yang, Da,Liu, Lei,Wang, Dong-Liang,Lu, Yong,Zhao, Xiao-Li,Liu, Ye
p. 236 - 244
(2019/02/19)

Iridium-Catalyzed α-Methylation of α-Aryl Esters Using Methanol as the C1 Source
IrCl(cod)2]/dppe-catalyzed α-methylation of aryl esters using methanol as the C1 source was developed. This methylation process is useful in several fields including organic chemistry, biochemistry, and medicinal chemistry. Readily available methanol as methylation reagent was successfully adapted. The reaction processed high atom economy and efficient. By applying the reaction system, the synthesis method of naproxen was provided.
Tsukamoto, Yuya,Itoh, Satoshi,Kobayashi, Masaki,Obora, Yasushi
supporting information
p. 3299 - 3303
(2019/05/10)

Palladium-catalysed alkyne alkoxycarbonylation with P,N-chelating ligands revisited: A density functional theory study
A revised in situ base mechanism of alkyne alkoxycarbonylation via a Pd catalyst with hemilabile P,N-ligands (PyPPh2, Py = 2-pyridyl) has been fully characterised at the B3PW91-D3/PCM level of density functional theory. Key intermediates on thi
Ahmad, Shahbaz,Lockett, Ashley,Shuttleworth, Timothy A.,Miles-Hobbs, Alexandra M.,Pringle, Paul G.,Bühl, Michael
p. 8543 - 8552
(2019/05/06)

Tandem Remote Csp3-H Activation/Csp3-Csp3 Cleavage in Unstrained Aliphatic Chains Assisted by Palladium(II)
We report here a proof-of-concept for the cleavage of unstrained remote Csp3-Csp3 bonds at room temperature assisted by a directing group, opening up new possibilities to use aliphatic carboxylic acids as suitable alkenyl coupling partners. This strategy involves the Pd-mediated Csp3-H activation directed by a tethered 8-aminoquinoline group, followed by a concerted asynchronous carbene insertion into the Pd-C bond, and an unexpected β-carbon-carbon bond splitting. The insertion of a coupling partner into a Pd-C bond is a novel route to promote C-C bond cleavage, which in contrast to most common methodologies does not rely on the use of strained carbocycles.
Pérez-Gómez, Marta,Azizollahi, Hamid,Franzoni, Ivan,Larin, Egor M.,Lautens, Mark,García-López, José-Antonio
supporting information
p. 973 - 980
(2019/03/04)

Enantioselective Construction of Quaternary All-Carbon Centers via Copper-Catalyzed Arylation of Tertiary Carbon-Centered Radicals
An enantioselective copper-catalyzed arylation of tertiary carbon-centered radicals, leading to quaternary all-carbon stereocenters, has been developed herein. The tertiary carbon-centered radicals, including both benzylic and nonbenzylic radicals, were produced by the addition of trifluoromethyl radical to α-substituted acrylamides, and subsequently captured by chiral aryl copper(II) species to give C-Ar bonds with excellent enantioselectivity. Importantly, an acylamidyl (CONHAr) group adjacent to the tertiary carbon radical is essential for the asymmetric radical coupling. The reaction itself features broad substrate scope, excellent functional group compatibility and mild conditions.
Wu, Lianqian,Wang, Fei,Chen, Pinhong,Liu, Guosheng
p. 1887 - 1892
(2019/02/05)

Efficient Synthesis of Spirooxindole Pyrrolones by a Rhodium(III)-Catalyzed C?H Activation/Carbene Insertion/Lossen Rearrangement Sequence
A rhodium(III)-catalyzed domino annulation of simple olefins with diazo oxindoles to give spirooxindole pyrrolone products is described. This reaction can be formally viewed as the result of an anomalous tandem C?H activation, carbene insertion, Lossen rearrangement, and a nucleophilic addition process. The potential utility of this reaction was further demonstrated by the late-stage diversification of drug molecules.
Ma, Biao,Wu, Peng,Wang, Xing,Wang, Zhengyu,Lin, Hai-Xia,Dai, Hui-Xiong
p. 13335 - 13339
(2019/08/20)

Catalyst-Free Deaminative Functionalizations of Primary Amines by Photoinduced Single-Electron Transfer
The use of pyridinium-activated primary amines as photoactive functional groups for deaminative generation of alkyl radicals under catalyst-free conditions is described. By taking advantage of the visible light absorptivity of electron donor–acceptor complexes between Katritzky pyridinium salts and either Hantzsch ester or Et3N, photoinduced single-electron transfer could be initiated in the absence of a photocatalyst. This general reactivity platform has been applied to deaminative alkylation (Giese), allylation, vinylation, alkynylation, thioetherification, and hydrodeamination reactions. The mild conditions are amenable to a diverse range of primary and secondary alkyl pyridiniums and demonstrate broad functional group tolerance.
Wu, Jingjing,Grant, Phillip S.,Li, Xiabing,Noble, Adam,Aggarwal, Varinder K.
supporting information
p. 5697 - 5701
(2019/03/21)

Dehydroxymethylation of alcohols enabled by cerium photocatalysis
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
supporting information
p. 10556 - 10564
(2019/08/20)

Dehydroxymethylation of Alcohols Enabled by Cerium Photocatalysis
Dehydroxymethylation, the direct conversion of alcohol feedstocks as alkyl synthons containing one less carbon atom, is an unconventional and underexplored strategy to exploit the ubiquity and robustness of alcohol materials. Under mild and redox-neutral reaction conditions, utilizing inexpensive cerium catalyst, the photocatalytic dehydroxymethylation platform has been furnished. Enabled by ligand-to-metal charge transfer catalysis, an alcohol functionality has been reliably transferred into nucleophilic radicals with the loss of one molecule of formaldehyde. Intriguingly, we found that the dehydroxymethylation process can be significantly promoted by the cerium catalyst, and the stabilization effect of the fragmented radicals also plays a significant role. This operationally simple protocol has enabled the direct utilization of primary alcohols as unconventional alkyl nucleophiles for radical-mediated 1,4-conjugate additions with Michael acceptors. A broad range of alcohols, from simple ethanol to complex nucleosides and steroids, have been successfully applied to this fragment coupling transformation. Furthermore, the modularity of this catalytic system has been demonstrated in diversified radical-mediated transformations including hydrogenation, amination, alkenylation, and oxidation.
Zhang, Kaining,Chang, Liang,An, Qing,Wang, Xin,Zuo, Zhiwei
supporting information
p. 10556 - 10564
(2019/08/28)

Rhenium-Catalyzed Decarboxylative Tri-/Difluoromethylation of Styrenes with Fluorinated Carboxylic Acid-Derived Hypervalent Iodine Reagents
Herein, unprecedented rhenium-catalyzed decarboxylative oxytri-/difluoromethylation and Heck-type trifluoromethylation of styrenes have been developed by using hypervalent iodine(III) reagents derived from cheap, stable, and easy-handling fluorinated carboxylic acids. Mechanistic studies revealed a radical decarboxylative trifluoromethylation pathway occurring in these reactions.
Wang, Yin,Yang, Yunhui,Wang, Congyang
supporting information
p. 1229 - 1233
(2019/11/21)

Selective Palladium-Catalyzed Carbonylation of Alkynes: An Atom-Economic Synthesis of 1,4-Dicarboxylic Acid Diesters
A class of novel diphosphine ligands bearing pyridine substituents was designed and synthesized for the first time. The resulting palladium complexes of L1 allow for chemo- and regioselective dialkoxycarbonylation of various aromatic and aliphatic alkynes affording a wide range of 1,4-dicarboxylic acid diesters in high yields and selectivities. Kinetic studies suggest the generation of 1,4-dicarboxylic acid diesters via cascade hydroesterification of the corresponding alkynes. Based on these investigations, the chemo- and regioselectivities of alkyne carbonylations can be controlled as shown by switching the ligand from L1 to L3 or L9 to give α,β-unsaturated esters.
Liu, Jiawang,Dong, Kaiwu,Franke, Robert,Neumann, Helfried,Jackstell, Ralf,Beller, Matthias
supporting information
p. 10282 - 10288
(2018/08/03)

Co-catalysis over a bi-functional ligand-based Pd-catalyst for tandem bis-alkoxycarbonylation of terminal alkynes
A bi-functional ligand (L1) containing a diphosphino fragment and sulfonic acid group (-SO3H) enabled PdCl2(MeCN)2 to efficiently catalyze the tandem bis-alkoxycarbonylation of terminal alkynes to produce aryl-/alkyl-substituted succinate (α,ω-diesters). It was found that the -SO3H incorporated in L1 indispensably assisted the Pd-catalyst in accomplishing this tandem reaction via intramolecular synergic effects. Co-catalysis over the L1-based Pd-catalyst was not due to the physical mixture of Xantphos and MeSO3H. In situ FTIR analysis verified that the formation and stability of Pd-H active species were facilitated by the presence of L1. The formation of stabilized diacylpalladium intermediate (F) was the critical driving force for the second-step methoxycarbonylation. DFT calculation was carried out to optimize the geometric structure of F, which indicated that the developed intramolecular O?H hydrogen bonds were an important structural feature to stabilize F. In addition, the L1-based Pd-catalyst could be recycled successfully for at least 3 runs in the ionic liquid [Bmim]NTf2 without obvious activity loss and detectable metal leaching.
Yang, Da,Liu, Huan,Wang, Dong-Liang,Luo, Zhoujie,Lu, Yong,Xia, Fei,Liu, Ye
supporting information
p. 2588 - 2595
(2018/06/11)

From small molecules to polymeric catalysts in the oscillatory carbonylation reaction: Multiple effects of adding HI
The oscillatory palladium-catalysed carbonylation reaction opens new horizons for applications in smart materials due to the versatility of its conditions and substrates, as well as the adjustability of amplitude and period of pH oscillations. A variety o
Isakova, Anna,Murdoch, Billy J.,Novakovic, Katarina
p. 9281 - 9288
(2018/04/14)

Macrolide Synthesis through Intramolecular Oxidative Cross-Coupling of Alkenes
A RhIII-catalyzed intramolecular oxidative cross-coupling between double bonds for the synthesis of macrolides is described. Under the optimized reaction conditions, macrocycles containing a diene moiety can be formed in reasonable yields and with excellent chemo- and stereoselectivity. This method provides an efficient approach to synthesize macrocyclic compounds containing a 1,3-conjugated diene structure.
Jiang, Bing,Zhao, Meng,Li, Shu-Sen,Xu, Yun-He,Loh, Teck-Peng
p. 555 - 559
(2018/02/21)

Palladium-Catalyzed C?H Silylation through Palladacycles Generated from Aryl Halides
A highly efficient palladium-catalyzed disilylation reaction of aryl halides through C?H activation has been developed for the first time. The reaction has broad substrate scope. A variety of aryl halides can be disilylated by three types of C?H activation, including C(sp2)?H, C(sp3)?H, and remote C?H activation. In particular, the reactions are also unusually efficient. The yields are essentially quantitative in many cases, even in the presence of less than 1 mol % catalyst and 1 equivalent of the silylating reagent under relatively mild conditions. The disilylated biphenyls can be converted into disiloxane-bridged biphenyls.
Lu, Ailan,Ji, Xiaoming,Zhou, Bo,Wu, Zhuo,Zhang, Yanghui
p. 3233 - 3237
(2018/02/23)

Palladium-Catalyzed Tandem Reaction of Three Aryl Iodides Involving Triple C-H Activation
A novel palladium-catalyzed tandem reaction of N-(2-iodoaryl)acrylamides with two aryl iodides for the synthesis of spirooxindole has been achieved. The reaction underwent the process of triple C-H activation and four C-C bond formations based on the double trapping of transient spirocyclic palladacycles which are obtained through remote C-H activation.
Luo, Xiai,Xu, Yankun,Xiao, Genhua,Liu, Wenjuan,Qian, Cheng,Deng, Guobo,Song, Jianxin,Liang, Yun,Yang, Chunming
p. 2997 - 3000
(2018/05/28)

Cyanomethyl anion transfer reagents for diastereoselective Corey-Chaykovsky cyclopropanation reactions
A readily available and bench-stable cyanomethyl sulfonium salt was used in highly diastereoselective Corey-Chaykovsky cyclopropanation reactions of electron-poor olefins. This efficient method provides a rapid route to access densely functionalized cyclopropyl nitriles.
Hommelsheim, Renè,Hock, Katharina J.,Schumacher, Christian,Hussein, Mohanad A.,Nguyen, Thanh V.,Koenigs, Rene M.
supporting information
p. 11439 - 11442
(2018/10/20)

Bifunctional ligands for Pd-catalyzed selective alkoxycarbonylation of alkynes
Catalytic carbonylations of alkynes represent straightforward and atom-economic synthesis of α,β-unsaturated carbonyl compounds. One of the issues associated with the currently known catalytic systems is insufficient efficiency. In this context, Pd/ligand-catalyzed regioselective and efficient alkoxycarbonylation of terminal alkynes is desirable for the synthesis of α,β-unsaturated esters. Herein, we present the use of a newly designed bifunctional ligand for efficient Pd-catalyzed alkoxycarbonylation of alkynes. Both aliphatic and aromatic alkynes were smoothly transformed to the branched desired products with high selectivity (28 examples, 45–96% yields, 95.0–99.9% selectivity).
Qi, Huimin,Huang, Zijun,Wang, Menglan,Yang, Peiju,Du, Chen-Xia,Chen, Shu-Wei,Li, Yuehui
p. 63 - 68
(2018/05/04)

An approach to spirooxindoles: Via palladium-catalyzed remote C-H activation and dual alkylation with CH2Br2
A facile and efficient approach for the synthesis of spirooxindoles has been developed via the coupling of spirocyclic C,C-palladacycles with CH2Br2. The key spirocyclic palladacycles are generated catalytically via remote C-H activation. A range of spirooxindoles can be synthesized in good to excellent yields from readily available starting material.
Shao, Changdong,Wu, Zhuo,Ji, Xiaoming,Zhou, Bo,Zhang, Yanghui
supporting information
p. 10429 - 10432
(2017/09/25)

Structural insights into the ene-reductase synthesis of profens
Reduction of double bonds of α,β-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.
Waller,Toogood,Karuppiah,Rattray,Mansell,Leys,Gardiner,Fryszkowska,Ahmed,Bandichhor,Reddy,Scrutton
p. 4440 - 4448
(2017/07/10)

2-Pyridyl substituents enhance the activity of palladium-phospha-adamantane catalysts for the methoxycarbonylation of phenylacetylene
The synthesis of a series of CgPAr ligands is reported, where CgP is the 6-phospha-2,4,8-trioxa-1,3,5,7-tetramethyladamant-6-yl moiety and Ar = 2-pyridyl (L2), 3-pyridyl (L3), 2-pyrimidyl (L4), 4-R-2-pyridyl [R = Me (L5a), CF3 (L6a), SiMe3 (L7a)] or 6-R-2-pyridyl [R = Me (L5b), CF3 (L6b), SiMe3 (L7b). Testing of these ligands in the Pd-catalysed methoxycarbonylation of phenylacetylene reveals that the activity and branched selectivity of the catalysts derived from these ligands varies as a function of the N-heterocycle, with the catalyst derived from L5b being the most active of those tested. This, together with the poor performance of catalysts derived from L3 supports the hypothesis that the catalysis proceeds by a “proton shuttling” mechanism, an idea that previously had only been applied to arylphosphines. Reaction of [PtCl2(cod)] with L where L = L2 or L4-7 yields a rac/meso mixture of the trans-[PtCl2(L)2] (1a-h) complexes, three of which are structurally characterised. 31P NMR spectroscopy shows that reaction of L3 with [PtCl2(cod)] gives a mixture of mononuclear and binuclear metal complexes in solution. The complex trans-[PdCl2(L2)2] (4) reacts with AgBF4 to give the [PdCl(κ1-L2)(κ2-L2)]BF4 (5) with spectroscopic and structural characterisation confirming the presence of a P,N-chelate. 1H and 31P NMR evidence supports the assignment of a pyridyl-protonated species being formed upon treatment of 4 with TsOH·H2O in CD2Cl2; both the protonated species and chelate 5 are observed when the reaction is carried out in MeOH.
Shuttleworth, Timothy A.,Miles-Hobbs, Alexandra M.,Pringle, Paul G.,Sparkes, Hazel A.
p. 125 - 137
(2016/12/28)

Water as a Hydride Source in Palladium-Catalyzed Enantioselective Reductive Heck Reactions
Pd-catalyzed intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by reduction of C(sp3)-Pd intermediate using diboron–water as a hydride source afforded enantioenriched 3,3-disubstituted oxindoles in high yields and enantioselectivities. When heavy water was used as a deuterium donor in combination with bis(catecholato)diboron (Cat2B2), deuterium was incorporated into the products with high synthetic efficiency. The ligand determined both the enantioselectivity of the reaction and the reaction pathways, thereby affording either hydroarylation (reductive Heck) or carboborylation products.
Kong, Wangqing,Wang, Qian,Zhu, Jieping
p. 3987 - 3991
(2017/03/27)

A Methylidene Group in the Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia-Lyases
Aromatic amino acid ammonia-lyases and aromatic amino acid 2,3-aminomutases contain the post-translationally formed prosthetic 3,5-dihydro-4-methylidene-5H-imidazol-5-one (MIO) group. MIO enzymes catalyze the stereoselective synthesis of α- or β-amino acid enantiomers, making these chemical processes environmentally friendly and affordable. Characterization of novel inhibitors enables structural understanding of enzyme mechanism and recognizes promising herbicide candidates as well. The present study found that both enantiomers of the aminophosphonic acid analogue of the natural substrate phenylalanine and a novel derivative bearing a methylidene at the β-position inhibited phenylalanine ammonia-lyases (PAL), representing MIO enzymes. X-ray methods unambiguously determined the absolute configuration of all tested enantiomers during their synthesis. Enzyme kinetic measurements revealed the enantiomer of the methylidene-substituted substrate analogue as being a mirror image relation to the natural l-phenylalanine as the strongest inhibitor. Isothermal titration calorimetry (ITC) confirmed the binding constants and provided a detailed analysis of the thermodynamic driving forces of ligand binding. Molecular docking suggested that binding of the (R)- and (S)-enantiomers is possible by a mirror image packing. (Figure presented.).
Bata, Zsófia,Qian, Renzhe,Roller, Alexander,Horak, Jeannie,Bencze, László Csaba,Paizs, Csaba,Hammerschmidt, Friedrich,Vértessy, Beáta G.,Poppe, László
supporting information
p. 2109 - 2120
(2017/06/23)

Screening for covalent inhibitors using DNA-display of small molecule libraries functionalized with cysteine reactive moieties
DNA-encoded chemical libraries are increasingly used to identify leads for drug discovery or chemical biology. Despite the resurging interest in covalent inhibitors, libraries are typically designed with synthon filtered out for reactive functionalities that can engage a target through covalent interactions. Herein, we report the synthesis of two libraries containing Michael acceptors to identify cysteine reactive ligands. We developed a simple procedure to discriminate between covalent and high affinity non-covalent inhibitors using DNA display of the library in a microarray format. The methodology was validated with known covalent and high affinity non-covalent kinase inhibitors. Screening of the library revealed novel covalent inhibitors for MEK2 and ERBB2.
Zambaldo,Daguer,Saarbach,Barluenga,Winssinger
supporting information
p. 1340 - 1351
(2016/07/21)

Multifunctional Single-Site Catalysts for Alkoxycarbonylation of Terminal Alkynes
A multifunctional copolymer (PyPPh2–SO3H@porous organic polymers, POPs) was prepared by combining acidic groups and heterogeneous P,N ligands through the copolymerization of vinyl-functionalized 2-pyridyldiphenylphosphine (2-PyPPh2) and p-styrene sulfonic acid under solvothermal conditions. The morphology and chemical structure of the copolymer were evaluated using a series of characterization techniques. Compared with traditional homogeneous Pd(OAc)2/2-PyPPh2/ p-toluenesulfonic acid catalyst, the copolymer supported palladium catalyst (Pd–PyPPh2–SO3H@POPs) exhibited higher activity for alkoxycarbonylation of terminal alkynes under the same conditions. This phenomenon could be attributed to the synergistic effect between the single-site Pd centers, 2-PyPPh2 ligands, and SO3H groups, the outstanding swelling properties as well as the high enrichment of the reactant concentration by the porous catalyst. In addition, the catalyst could be reused at least 4 times without any apparent loss of activity. The excellent catalytic reactivity and good recycling properties make it an attractive catalyst for industrial applications. This work paves the way for advanced multifunctional porous organic polymers as a new type of platform for heterogeneous catalysis in the future.
Chen, Xingkun,Zhu, Hejun,Wang, Wenlong,Du, Hong,Wang, Tao,Yan, Li,Hu, Xiangping,Ding, Yunjie
p. 2451 - 2459
(2016/10/24)

New palladium-bis(oxazoline)-phosphine complexes: Synthesis, characterization and catalytic application in alkoxycarbonylation of alkynes
New cationic palladium-bis(oxazoline)-phosphine (Pd-BOX-PR3) complexes (Pd-BOX-B and Pd-BOX-C) have been synthesized and characterized using 1H, 13C and 31P NMR, FTIR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). The new complexes were used as catalysts in the alkoxycarbonylation of alkynes with various alcohols as nucleophiles. The carbonylation has produced the gem-α,β-unsaturated ester isomer (3) in high regioselectivity and excellent yields. The catalyst systems have been optimized by screening the type of palladium complexes and also by varying the reaction parameters including the reaction time, solvent, and temperature. A mechanism of the catalytic cycle based on a N-protonated palladium bis(oxazoline) phosphine active species was proposed for the alkoxycarbonylation reaction. (Figure Presented.).
Ibrahim, Mansur B.,Suleiman, Rami,El Ali, Bassam
p. 1346 - 1357
(2017/10/16)

Rhodium-Catalyzed Hydrocarboxylation of Olefins with Carbon Dioxide
The catalytic hydrocarboxylation of styrenes derivatives and α,β-unsaturated carbonyl compounds with CO2(101.3 kPa) in the presence of an air-stable rhodium catalyst was explored. The combination of [RhCl(cod)]2(cod = cyclooctadiene) as a catalyst and diethylzinc as a hydride source allowed for effective hydrocarboxylation and provided the corresponding α-aryl carboxylic acids in moderate to excellent yields. In this catalytic process with carbon dioxide, intervention of the RhI–H species, which could be generated from the RhIcatalyst and diethylzinc, was clarified. Significantly, the catalytic asymmetric hydrocarboxylation of α,β-unsaturated esters with carbon dioxide was also performed by employing a cationic rhodium complex possessing (S)-(–)-4,4′-bi-1,3-benzodioxole-5,5′-diylbis(diphenylphosphine) [(S)-SEGPHOS] as a chiral diphosphine ligand. A plausible model for asymmetric induction was proposed by determination of the absolute configuration of the product.
Kawashima, Shingo,Aikawa, Kohsuke,Mikami, Koichi
supporting information
p. 3166 - 3170
(2016/07/19)

Investigating molecular dynamics-guided lead optimization of EGFR inhibitors
The epidermal growth factor receptor (EGFR) is part of an extended family of proteins that together control aspects of cell growth and development, and thus a validated target for drug discovery. We explore in this work the suitability of a molecular dynamics-based end-point binding free energy protocol to estimate the relative affinities of a virtual combinatorial library designed around the EGFR model inhibitor 6{1} as a tool to guide chemical synthesis toward the most promising compounds. To investigate the validity of this approach, selected analogs including some with better and worse predicted affinities relative to 6{1} were synthesized, and their biological activity determined. To understand the binding determinants of the different analogs, hydrogen bonding and van der Waals contributions, and water molecule bridging in the EGFR-analog complexes were analyzed. The experimental validation was in good qualitative agreement with our theoretical calculations, while also a 6-dibromophenyl-substituted compound with enhanced inhibitory effect on EGFR compared to the reference ligand was obtained.
Lavecchia, Martin J.,Puig De La Bellacasa, Raimon,Borrell, José I.,Cavasotto, Claudio N.
p. 768 - 778
(2016/02/09)

Metal-Free Synthesis of 3-Arylquinolin-2-ones from N,2-Diaryl- acrylamides via Phenyliodine(III) Bis(2,2-dimethylpropanoate)- Mediated Direct Oxidative C?C Bond Formation
Treatment of N,2-diarylacrylamides with the organoiodine(III) compound phenyliodine(III) bis(2,2-dimethylpropanoate) [PhI(O2C-t-Bu)2] and boron trifluoride etherate (BF3?Et2O) resulted in a direct and selective oxidative C(sp2)?C(sp2) bond formation leading to a convenient assemblage, under mild conditions, of the biologically important 3-arylquinolin-2-one skeleton. Differing from the five-membered oxindole products from oxidative cyclizations mediated by transition metals, this metal-free approach realized a direct annulation of the N-arylacrylamide into a six-membered 3-arylquinolin-2-one skeleton. (Figure presented.).
Cao, Yang,Zhao, Hui,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
supporting information
p. 3610 - 3615
(2016/11/25)

P(NMe2)3-Mediated Umpolung Alkylation and Nonylidic Olefination of α-Keto Esters
A commercial phosphorus-based reagent (P(NMe2)3) mediates umpolung alkylation of methyl aroylformates with benzylic and allylic bromides, leading to either Barbier-type addition or ylide-free olefination products upon workup. The reaction sequence is initiated by a two-electron redox addition of the tricoordinate phosphorus reagent with an α-keto ester compound (Kukhtin-Ramirez addition). A mechanistic rationale is offered for the chemoselectivity upon which the success of this nonmetal mediated C-C bond forming strategy is based.
Wang, Sunewang Rixin,Radosevich, Alexander T.
p. 3810 - 3813
(2015/08/18)

Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions
Chemoselective synthesis of N-protected β-amino esters involving lipase-catalyzed aza-Michael additions and α,β-unsaturated precursors is mainly hampered by the two electrophilic sites present on these compounds. In order to control the chemoselectivity a solvent engineering strategy based on the thermodynamic behaviour of products in media of different polarity was designed. This strategy allowed to obtain aza-Michael adducts from benzylamine and different acrylates with high selectivity. In almost all reactions carried out in n-hexane, a non-polar solvent, aminolysis was avoided while the corresponding Michael adducts were exclusively synthesized in 53-78% yields. On the contrary, in reactions carried out in a polar solvent such as 2-methyl-2-butanol the aminolysis products were favoured. Thermodynamic analyses of these processes using the COSMO-RS method helped to understand some of the key factors affecting chemoselectivity and confirmed that a reliable estimation of the thermodynamic interactions of solutes and solvents allows an adequate selection of a reaction media that may lead to chemoselectivity.
Rivera-Ramírez, José Domingo,Escalante, Jaime,López-Munguía, Agustín,Marty, Alain,Castillo, Edmundo
supporting information
p. 76 - 82
(2015/01/30)

Electron-deficient olefin ligands enable generation of quaternary carbons by Ni-catalyzed cross-coupling
A Ni-catalyzed Negishi cross-coupling with 1,1-disubstituted styrenyl aziridines has been developed. This method delivers valuable β-substituted phenethylamines via a challenging reductive elimination that affords a quaternary carbon. A novel electron-deficient olefin ligand, Fro-DO, proved crucial for achieving high rates and chemoselectivity for C-C bond formation over β-H elimination. This ligand is easy to access, is stable, and presents a modular framework for reaction discovery and optimization. We expect that these attributes, combined with the fact that the ligands impart distinct electronic properties to a metal, will support the invention of new transformations not previously possible using established ligands.
Huang, Chung-Yang,Doyle, Abigail G.
supporting information
p. 5638 - 5641
(2015/05/20)

Copper-Catalyzed Aerobic Decarboxylation/Ketooxygenation of Electron-Deficient Alkenes
A copper-catalyzed ketooxygenation of electron-deficient alkenes was developed. This approach combines O-H alkylation, aerobic decarboxylation, and oxygenation in one transformation. Mechanistic investigation of this reaction showed that the copper salt is responsible for both generating the amidoxyl radical and promoting aerobic decarboxylation.
Lu, Qingquan,Peng, Pan,Luo, Yi,Zhao, Ying,Zhou, Minxian,Lei, Aiwen
supporting information
p. 18580 - 18583
(2016/01/25)

Regioselective hydromethoxycarbonylation of terminal alkynes catalyzed by palladium(II)-tetraphos complexes
An in situ generated dinuclear palladium hydride complex bearing cis,trans,cis-1,2,3,4-tetrakis(diphenylphosphanyl)cyclobutane catalyzed the hydromethoxycarbonylation of terminal alkynes, giving the corresponding branched α,β-unsaturated ester (A) with high regioselectivity.
Oberhauser, Werner,Ienco, Andrea,Vizza, Francesco,Trettenbrein, Barbara,Oberhuber, Dennis,Strabler, Christof,Ortner, Teresa,Brueggeller, Peter
experimental part
p. 4832 - 4837
(2012/10/08)

Ene reductase-catalysed synthesis of (R)-profen derivatives
Enantiomerically pure (R)-profen derivatives and intermediates are synthesised utilising the enzyme YqjM, an ene reductase from Bacillus subtilis. After optimisation of the reaction conditions, the chemoenzymatic approach was applied for the first time in the synthesis of (R)-flurbiprofen methyl ester. Copyright
Pietruszka, Joerg,Schoelzel, Melanie
p. 751 - 756
(2012/04/23)

Synthesis of 4-azepanones and heteroaromatic-fused azepines
Two syntheses of versatile intermediate azepinones 2 and 3 are described. A 6-step intramolecular Dieckmann cyclization and decarboxylation led to the intermediate 3 while an alternate 4-step synthesis of 2 was developed and used for scale-up. The highlight of the second synthesis is the one-step per-bromination/elimination protocol from readily available azepinone 13a to provide a versatile scaffold in vinyl bromide 5, which enables SAR around the aryl moiety. An example of the elaboration of the intermediate 2 toward a heteroaryl azepinone is also described.
Sakya, Subas M.,Flick, Andrew C.,Coe, Jotham W.,Gray, David L.,Liang, Sidney,Ferri, Fabiola,Van Den Berg, Michel,Pouwer, Kees
supporting information; experimental part
p. 723 - 725
(2012/02/17)

Synthesis of dialkyl and diaryl benzylphosphonates through a ZnI 2-mediated reaction
Several trialkyl and two triaryl phosphites have been tested for their reactivity in the zinc iodide mediated conversion of benzyl alcohol to the corresponding phosphonates. Most react smoothly to afford the desired phosphonate diesters, including hindered and nonracemic phosphites. The implications of this reactivity on the reactions involved in the transformation are discussed.
Richardson, Rebekah M.,Barney, Rocky J.,Wiemer, David F.
supporting information
p. 6682 - 6684
(2013/01/15)

Scaffold-inspired enantioselective synthesis of biologically important spiro[pyrrolidin-3,2'-oxindoles] with structural diversity through catalytic isatin-derived 1,3-dipolar cycloadditions
Catalytic asymmetric construction of the biologically important spiro[pyrrolidin-3,2'-oxindole] scaffold with contiguous quaternary stereogenic centers in excellent stereoselectivities (up to >99:1 d.r., 98 % ee) has been established by using an organocat
Shi, Feng,Tao, Zhong-Lin,Luo, Shi-Wei,Tu, Shu-Jiang,Gong, Liu-Zhu
supporting information; experimental part
p. 6885 - 6894
(2012/07/27)

The synthesis and stereospecific solid-state photodecarbonylation of hexasubstituted meso- and d,l-ketones
Tertiary carbanions were trapped with half an equivalent of diphosgene to give meso- and d,l-hexasubstituted ketones in moderate yields and modest diastereoselectivities. The ketones were also synthesized by a step-wise synthesis in which the carbonyl group was first installed as an acid before activation and the second nucleophilic attack. This second method gave lower yields but similar diastereoselectivites. Steric limits of both methods were also determined. The photolysis of the resulting crystalline ketones gave a mixture of products in solution, but took place chemoselectively and diastereospecifically in the solid-state. The Royal Society of Chemistry and Owner Societies.
Shiraki, Saori,Natarajan, Arunkumar,Garcia-Garibay, Miguel A.
p. 1480 - 1487
(2012/06/01)

Recyclable Pd(OAc)2/ligand/Al(OTf)3 catalyst for the homogeneous methoxycarbonylation and hydrocarboxylation reactions of phenylacetylene
The Pd-catalyzed methoxycarbonylation reaction of phenylacetylene was studied making use of various promoters, including aluminum triflate and several other acid-type promoters of this reaction. The influence of the ligand (bidentate-type ligands and monodentate analogues) was found to be determinative of the success of the reaction. The catalyst was found to be recyclable through 10 catalytic runs. The unique results when using BINAP, relating to the selectivity for the branched product and the stability of the catalyst produced, led to a study on the sulfonated analogue thereof, with the intention of performing hydrocarboxylation reactions to directly prepare the carboxylic acid. The product obtained accordingly may be varied between the methyl ester or its carboxylic acid equivalent, depending on the solvent medium and the ligand employed.
Williams, D. Bradley G.,Shaw, Megan L.,Hughes, Tanya
experimental part
p. 4968 - 4973
(2011/11/05)