- Copper-Catalyzed Regioselective Coupling of Tosylhydrazones and 2-Pyridones: A Strategy for the Production of N-Alkylated Compounds
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The highly regioselective N-alkylation reaction of 2-pyridones was achieved through hydrazone chemistry, especially for substrates with bulky secondary alkyl groups. Described herein is a copper-catalyzed coupling reaction of pyridone derivatives with tosylhydrazones.
- Wu, Ye-Bin,Wu, You-Zhi,Wu, Jian,Xu, Dan,Jiang, Hui,Chang, Wen-Wu,Ma, Chang-You
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p. 6918 - 6926
(2021/05/06)
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- Cross coupling of sulfonyl radicals with silver-based carbenes: A simple approach to β-carbonyl arylsulfones
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A coupling reaction between sulfonyl radicals and silver-based carbenes has been well established. This simple radical-carbene coupling (RCC) process provided an efficient approach to a variety of β-carbonyl arylsulfones from sodium arylsulfinates and diazo compounds, and was characterized by wide substrate scope, easy scale-up, simple manipulation, accessible starting materials, and mild reaction conditions.
- Li, Jingjing,Lian, Pengcheng,Wan, Xiaobing,Wang, Hanghang,Zheng, Yonggao
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supporting information
p. 2163 - 2169
(2020/03/27)
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- Copper-catalyzed oxyvinylation of diazo compounds
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A copper(I)-catalyzed vinylation of diazo compounds with vinylbenziodoxolone reagents (VBX) as partners is reported. The transformation tolerates diverse functionalities on both reagents delivering polyfunctionalized vinylated products. The strategy was successfully extended to a three-component/intermolecular version with alcohols. The obtained products contain synthetically versatile functional groups, such as an aryl iodide, an ester, and an allylic leaving group, enabling further modification.
- Pisella, Guillaume,Gagnebin, Alec,Waser, Jerome
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supporting information
p. 3884 - 3889
(2020/05/14)
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- Three-Component Reaction for the Synthesis of Highly Functionalized Propargyl Ethers
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Multicomponent reactions provide efficient means to access molecular complexity. Herein, we report a copper-catalyzed three-component reaction of diazo compounds, alcohols and ethynyl benziodoxole (EBX) reagents for the synthesis of propargyl ethers. Extensive variations of the three partners of the reaction is possible, leading to highly functionalized and structurally diverse products under mild conditions. Alkynylation of a copper ylide intermediate is postulated as key step for this transformation.
- Pisella, Guillaume,Gagnebin, Alec,Waser, Jér?me
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supporting information
p. 10199 - 10204
(2020/07/17)
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- Supramolecularly regulated copper-bisoxazoline catalysts for the efficient insertion of carbenoid species into hydroxyl bonds
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The catalytic insertion of copper carbenoids into O-H bonds affords synthetically useful α-alkyl/aryl-α-alkoxy/aryloxy derivatives. Herein, the design, preparation and application of supramolecularly regulated copper(i) complexes of bisoxazoline ligands is reported. We have demonstrated that the catalytic performance of these systems can be modulated by the use of an external molecule (i.e.the regulation agent), which interacts with a polyethyleneoxy chain on the ligand (i.e.the regulation site)viasupramolecular interactions. This approach has been applied to an array of structurally diverse alcohols (cycloalkyl, alkyl and aryl derivatives). Moreover, we have used this methodology to synthesise advanced synthetic intermediates of biologically relevant compounds.
- Iniesta, Ester,Vidal-Ferran, Anton
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supporting information
p. 6364 - 6367
(2020/06/21)
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- Enantioselective Formal Synthesis of (+)-Cycloclavine and Total Synthesis of (+)-5- epi-Cycloclavine
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Starting from the commercially available 4-bromoindole, a concise and efficient enantioselective formal synthesis of (+)-cycloclavine (1) in 13 steps with 2.0% overall yield and a total synthesis of (+)-5-epi-cycloclavine (2) in 14 steps with 3.3% overall yield were achieved. Key features of the syntheses include the addition of a Grignard reagent to the C-N/Heck reaction sequence to construct the fused 6-5-6 ring systems, cyclopropanation, an ester aminolysis reaction, and the first example of the construction of a 3-azabicyclo[3,1,0]hexane through an intramolecular [3 + 2] cycloaddition/nitrogen extrusion.
- Wang, Wei,Mi, Yang,Cao, Xiao-Ping,Shi, Zi-Fa
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supporting information
p. 6603 - 6607
(2019/09/07)
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- Metal-Free Tandem Rearrangement/Lactonization: Access to 3,3-Disubstituted Benzofuran-2-(3H)-ones
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A novel metal-free synthesis of 3,3-disubstituted benzofuran-2-(3H)-ones through reacting α-aryl-α-diazoacetates with triarylboranes is presented. Initially, triarylboranes were successfully investigated in α-arylations of α-diazoacetates, however in the presence of a heteroatom in the ortho position, the boron enolate intermediate undergoes an intramolecular rearrangement to form a quaternary center. The intermediate cyclizes to afford valuable 3,3-disubstituted benzofuranones in good yields.
- Santi, Micol,Ould, Darren M. C.,Wenz, Jan,Soltani, Yashar,Melen, Rebecca L.,Wirth, Thomas
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supporting information
p. 7861 - 7865
(2019/04/25)
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- Synthesis of spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives: Via a multi-component cascade reaction of α-diazo esters, water, isatins and malononitrile/ethyl cyanoacetate
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We report a green synthesis of spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives which are of potential value in medicinal chemistry. We are able to access spiro[2,3-dihydrofuran-3,3′-oxindole] derivatives via a Cu(OTf)2-catalyzed or Cu(OTf)2/Rh2(OAc)4-cocatalyzed multi-component cascade reaction of α-diazo esters, water, isatins and malononitrile/ethyl cyanoacetate. The reaction can be accomplished in good to excellent yields (60-99%), and the structure of products 6a and 6k was supported by X-ray crystallography. The catalyst Cu(OTf)2 can be recycled 4 times without a sharp loss of the yield of 6a. 6q can be easily synthesized in gram scale. In brief, the reaction is characterized by step economy, a harmless solvent, and a recyclable catalyst.
- Shi, Taoda,Teng, Shenghan,Wei, Yajie,Guo, Xin,Hu, Wenhao
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supporting information
p. 4936 - 4940
(2019/09/30)
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- A sustainable catalytic enantioselective synthesis of norstatine derivatives
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Norstatine derivatives are of important value in pharmaceutical science. However, their catalytic asymmetric synthesis is rare. We developed a sustainable method via chiral phosphoric acid (CPA)-[Rh(OAc)2]2 co-catalyzed multi-component reactions (MCR) of diazoacetates with alcohol/water and imines. This method allows us to synthesize a library of 45 norstatines with excellent enanotioselectivites and broad substrate scope which includes anti-α-aryl-norstatines 11-1, anti-α-alkyl-norstatines 11-2, syn-α-hydro-norstatines 11-3 and syn-α-aryl-norstatines 11-4. The sustainability of this method lies in the reliable scalability, improved safety, and reusable [Rh(OAc)2]2 catalyst. The synthetic value of norstatine derivatives was demonstrated by preparing oxazolinone 14, ezetimibe analogue 15, and Taxol C-13 chain 16. Mechanistic study reveals that the synergetic catalysis of CPA and [Rh(OAc)2]2 is essential to maintain chemo- and enantioselectivity. Control experiments support the mechanism where the reactions proceed through the trapping of hyper-reactive oxonium ylides with imines. Shortly, we report herein the sustainable catalytic enantioselective synthesis of both syn- and anti-norstatine derivatives. We believe that this method might shed light on the sustainable synthesis of norstatine derivative-based drug candidates.
- Shi, Taoda,Jing, Changcheng,Qian, Yu,Xu, Xinfang,Alavala, Gopi Krishna Reddy,Lv, Xinxin,Hu, Wenhao
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p. 9792 - 9798
(2019/12/02)
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- Au Nanoparticle-Catalyzed Insertion of Carbenes from α-Diazocarbonyl Compounds into Hydrosilanes
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Supported Au nanoparticles on TiO2 catalyze the insertion of carbenes from α-diazocabonyl compounds into hydrosilanes. It is proposed that the transformation involves two modes of catalytic activation: formation of nucleophilic Au carbenes on the surface of nanoparticle via expulsion of N2 and activation of the Si-H bond of hydrosilane on Au nanoparticle, followed by coupling of the chemisorbed species. No external ligands or additives are required, while the process is purely heterogeneous, thus allowing the recycling and reuse of the catalyst.
- Kidonakis, Marios,Stratakis, Manolis
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supporting information
p. 4086 - 4089
(2018/07/15)
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- Rh(III)-Catalyzed Regio- and Chemoselective [4 + 1]-Annulation of Azoxy Compounds with Diazoesters for the Synthesis of 2H-Indazoles: Roles of the Azoxy Oxygen Atom
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A Rh(III)-catalyzed tandem C-H alkylation/intramolecular decarboxylative cyclization of azoxy compounds with diazoesters for the synthesis of 3-acyl-2H-indazoles is disclosed. The azoxy instead of the azo group enables a distinct approach for cyclative capture, leading to a [4 + 1]-annulation rather than a classic [4 + 2] manner. The azoxy oxygen atom is traceless after annulation, and further removal from the product is not required. This reaction features a complete regioselectivity for unsymmetrical azoxybenzenes and a compatibility of monoaryldiazene oxides.
- Long, Zhen,Wang, Zhigang,Zhou, Danni,Wan, Danyang,You, Jingsong
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supporting information
p. 2777 - 2780
(2017/06/07)
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- Iron-Catalyzed Carbene Insertion Reactions of α-Diazoesters into Si-H Bonds
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An efficient iron-catalyzed carbene insertion reaction of α-diazo carbonyl compounds into the Si-H bond was developed. A wide range of α-silylesters was obtained in high yields (up to 99%) from α-diazoesters using a simple iron(II) salt as catalyst.
- Keipour, Hoda,Ollevier, Thierry
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supporting information
p. 5736 - 5739
(2017/11/10)
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- Ru(ii)-Pheox-catalyzed Si-H insertion reaction: construction of enantioenriched carbon and silicon centers
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We established a highly enantioselective Si-H insertion reaction to construct chiral centers at the carbon and silicon atoms, using a Ru(ii)-pheox catalyst. The catalytic asymmetric Si-H insertion reaction of α-methyl-α-diazoesters proceeded smoothly with excellent stereoinduction at both the neighboring carbon and silicon atoms (up to 99% yield and 99% ee).
- Nakagawa, Yoko,Chanthamath, Soda,Fujisawa, Ikuhide,Shibatomi, Kazutaka,Iwasa, Seiji
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supporting information
p. 3753 - 3756
(2017/04/03)
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- Trifluoromethylthiolation and Trifluoromethylselenolation of α-Diazo Esters Catalyzed by Copper
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α-Diazo esters are smoothly converted into the corresponding trifluoromethyl thio- or selenoethers by reaction with Me4NSCF3or Me4NSeCF3, respectively, in the presence of catalytic amounts of copper thiocyanate. This straightforward method gives high yields under neutral conditions at room temperature and is applicable to a wide range of functionalized molecules, including diverse α-amino acid derivatives. It is well-suited for the late-stage introduction of trifluoromethylthio or -seleno groups into drug-like molecules.
- Matheis, Christian,Krause, Thilo,Bragoni, Valentina,Goossen, Lukas J.
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supporting information
p. 12270 - 12273
(2016/08/24)
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- Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds with Hypervalent Iodine Reagents
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Alkynes have found widespread applications in synthetic chemistry, biology, and materials sciences. In recent years, methods based on electrophilic alkynylation with hypervalent iodine reagents have made acetylene synthesis more flexible and efficient, but they lead to the formation of one equivalent of an iodoarene as side-product. Herein, a more efficient strategy involving a copper-catalyzed oxy-alkynylation of diazo compounds with ethynylbenziodoxol(on)e (EBX) reagents is described, which proceeds with generation of nitrogen gas as the only waste. This reaction is remarkable for its broad scope in both EBX reagents and diazo compounds. In addition, vinyl diazo compounds gave enynes selectively as single geometric isomers. The functional groups introduced during the transformation served as easy handles to access useful building blocks for synthetic and medicinal chemistry.
- Hari, Durga Prasad,Waser, Jerome
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supporting information
p. 2190 - 2193
(2016/03/08)
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- Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds
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Highly reactive metal carbenes, generated from simple ketones via diazo compounds, including diazoamides and -phosphonates, using a recyclable reagent inflow, are transient but versatile electrophiles for heteroatom alkylation reactions and for epoxide formation. The method produces no organic waste, with the only byproducts being water, KI and nitrogen, without the attendant hazards of isolation of intermediate diazo compounds.
- Nicolle, Simon M.,Hayes, Christopher J.,Moody, Christopher J.
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supporting information
p. 4576 - 4579
(2015/03/18)
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- Direct Synthesis of Chiral Allenoates from the Asymmetric CH Insertion of α-Diazoesters into Terminal Alkynes
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The asymmetric CH insertion of α-diazoesters into 1-alkynes was achieved using chiral cationic guanidinium salts and copper(I) complexes. Optically active 2,4-disubstituted allenoates were generated under mild reaction conditions from various α-diazoesters and 1-alkynes in high yield (up to 99‰) and enantioselectivity (up to 97:3 e.r.). Control experiments excluded the possibility of an asymmetric isomerization of alkynoates. Salt down: The title reaction was achieved using chiral cationic guanidinium salts with copper(I) complexes. Optically active 2,4-disubstituted allenoates were generated under mild reaction conditions from various α-diazoesters and 1-alkynes in high yield and enantioselectivity. Control experiments excluded the possibility of an asymmetric isomerization.
- Tang, Yu,Chen, Quangang,Liu, Xiaohua,Wang, Gang,Lin, Lili,Feng, Xiaoming
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supporting information
p. 9512 - 9516
(2015/08/11)
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- Palladium(II)/Lewis acid synergistically catalyzed allylic C-H olefination
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The first allylic C-H olefination with α-diazo esters synergistically catalyzed by a palladium(II) complex and (salen)CrCl has been established to directly generate conjugated polyene derivatives in moderate to high yields and with excellent stereoselectivities.
- Wang, Pu-Sheng,Lin, Hua-Chen,Zhou, Xiao-Le,Gong, Liu-Zhu
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supporting information
p. 3332 - 3335
(2014/07/08)
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- Potassium N-iodo p-toluenesulfonamide (TsNIK, iodamine-T): A new reagent for the oxidation of hydrazones to diazo compounds
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A new reagent for the oxidation of hydrazones to diazo compounds is described. N-Iodo p-toluenesulfonamide (TsNIK, iodamine-T) allows the preparation of α-diazoesters, α-diazoamides, α-diazoketones and α-diazophosphonates in good yield and in high purity after a simple extractive work-up. α-Diazoesters were also obtained in high yield from the corresponding ketones through a one-pot process of hydrazone formation/oxidation. Diazo compounds: N-Iodo p-toluenesulfonamide (TsNIK, iodamine-T), readily prepared from p-toluenesulfonamide and iodine in aqueous KOH, is a new reagent for the oxidation of hydrazones to diazo compounds in good yields and high purity (see scheme).
- Nicolle, Simon M.,Moody, Christopher J.
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supporting information
p. 4420 - 4425
(2014/05/06)
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- Asymmetric N-H Insertion of secondary and primary anilines under the catalysis of palladium and chiral guanidine derivatives
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Efficient enantioselective N-H insertion reactions of secondary and primary anilines were catalyzed by palladium(0) in combination with chiral guanidine derivatives. A broad range of substituted anilines were tolerated, and the corresponding products were obtained in high yield (up to 99 %) with good enantioselectivity (up to 94 % ee) under mild reaction conditions. The N-H insertion mechanism was examined by the study of kinetic isotope effects, control experiments, HRMS, and spectroscopic analysis. Hidden talents: Chiral guanidine derivatives were developed as useful ligands for the enantioselective insertion of carbenoids into the N-H bonds of secondary and primary anilines in combination with palladium(0), which was not previously known to promote asymmetric N-H insertion (see scheme; dba=dibenzylideneacetone). The N-H insertion mechanism was examined by kinetic isotope studies, control experiments, HRMS, and spectroscopic analysis. Copyright
- Zhu, Yin,Liu, Xiaohua,Dong, Shunxi,Zhou, Yuhang,Li, Wei,Lin, Lili,Feng, Xiaoming
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supporting information
p. 1636 - 1640
(2014/03/21)
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- Enantioselective synthesis of α-alkyl-β-ketoesters: Asymmetric Roskamp reaction catalyzed by an oxazaborolidinium ion
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Breaking kamp: A catalytic route toward chiral α-alkyl-β- ketoesters using the title reaction of α-alkyl diazoester with aldehydes has been developed (see scheme). The reaction proceeds with high to excellent enantioselectivities and this methodology was applied to a concise two-step synthesis of the natural pheromone sitophilate. Copyright
- Gao, Lizhu,Kang, Byung Chul,Hwang, Geum-Sook,Ryu, Do Hyun
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supporting information; experimental part
p. 8322 - 8325
(2012/09/08)
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- Catalytic asymmetric synthesis of trisubstituted aziridines
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A method is described which provides for the direct asymmetric catalytic synthesis of trisubstituted aziridines from imines and diazo compounds. While unactivated imines were not reactive to α-diazo carbonyl compounds in which the diazo carbon was disubstituted, N-Boc imines react with both α-diazo esters and α-diazo-N-acyloxazolidinones to give trisubstituted aziridines with excellent diastereo- and enantioselectivities.
- Huang, Li,Wulff, William D.
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supporting information; experimental part
p. 8892 - 8895
(2011/08/04)
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- AZABICYCLIC COMPOUNDS AS SEROTONINE, DOPAMINE AND NOREPINEPHRINE RE-UPTAKE INHIBITORS
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The present invention relates to novel compounds of Formula (I)' or pharmaceutically acceptable salts or a solvates thereof: wherein A is and K is a mono or bicyclic aryl group; R1 is selected from a group consisting of: halogen, C1-4alkyl and C1-4alkoxy, and such R1 may assume different meanings on the basis of p value; p is an integer from 0 to 5; R2 is a group P wherein P is and R3 is hydrogen, C1-4alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-3alkyl, haloC1-2alkyl or an optionally substituted phenyl group; X is oxygen, -NR8- or sulphur; n is 0 or 1; R7 is hydrogen or methyl; R4 is hydrogen or methyl; R5 is hydrogen or C1-4alkyl; R6 is hydrogen or C1-4alkyl; and R8 is hydrogen or C1-4alkyl; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as serotonin (5-HT), dopamine (DA) and norepinephrine (NE), re-uptake inhibitors.
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Page/Page column 69-70
(2008/12/06)
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- Cu(I)-carbenoid- and Ag(I)-Lewis acid-catalyzed asymmetric intermolecular insertion of α-diazo compounds into N-H bonds
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Chiral Cu(I)-bisoxazoline- and Cu(I)-PN-complexes were found to catalyze the intermolecular insertion of α-diazo compounds into N-H bonds. The insertion reactions proceed with enantioselectivities of up to 28% ee for the different α-diazo acetates into one of the N-H bonds of different amines. Analogous chiral Ag(I) complexes were found to give higher enantioselectivities of up to 48% ee, however, lower yields were obtained. There are indications, that the Ag(I)-mediated reactions follow a different reaction mechanism compared to the Cu(I)-catalyzed insertions. It is demonstrated that different α-amino acid derivatives can be obtained via this approach in good yields and with low to moderate enantioselectivities. However, the results obtained are the highest asymmetric inductions obtained for an intermolecular N-H insertion via chiral carbene complexes or chiral Lewis acid catalysis.
- Bachmann, Stephan,Fielenbach, Doris,Jorgensen, Karl Anker
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p. 3044 - 3049
(2007/10/03)
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- Reactions of benzocyclic β-keto esters with sulfonyl azides. 2. Further insight into the influence of azide structure and solvent on the reaction course
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The reactions of 2-ethoxycarbonyl-1-benzosuberone with 4- methoxybenzenesulfonyl, 2,4,6-triiso-propylbenzenesulfonyl, methanesulfonyl, and trifluoromethanesulfonyl azide, in the presence of triethylamine, have been investigated in N,N-dimethylformamide, a
- Benati, Luisa,Nanni, Daniele,Spagnolo, Piero
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p. 5132 - 5138
(2007/10/03)
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- 11. Selectivity in Rhodium(II)-Catalyzed Rearrangements of Cycloprop-2-ene-1-carboxylates
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The course of the thermocatalytic rearrangement of cycloprop-2-ene-1-carboxylates in the presence of dirhodium(II) tetrakis(perfluorobutyrate) (Rh2(pfb)4>) was investigated by varying the substituents of the cyclopropene ring.Product composition is markedly influenced by the number, nature, and position of the substituents, which determine the regio- and stereoselectivity of the cyclopropene-ring cleavage.A mechanism is proposed in which attack of the electrophilic RhII species is concerted with disrotatory ring opening of the incipient cyclopropyl cation and affords a metal-complexed vinylcarbene.The chemoselectivity of the latter is consistent with that of other carbenes generated in the presence of .
- Mueller, Paul,Graenicher, Christian
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p. 129 - 144
(2007/10/02)
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- NITROSATION OF PEPTIDE BONDS. CLEAVAGE OF NITROSATED PEPTIDES BY PYRROLIDINE AND α-AMINO ESTERS
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The reaction of several α-amino acids and peptides (containing Gly, L-Ala, L-Leu, L- or DL-Phe, and/or L- or D-Val) with air-diluted nitrogen oxides has been studied to roughly mimic the N-nitrosation of peptide bonds that the contaminated urban air might produce in pulmonary tissues. Most N-protected α-amino acids give practically quantitative yields of N-nitroso derivatives. N-Protected dipeptides afford either dinitrosated peptides, mixtures of di- and mononitrosated compounds, selectively mononitrosated products, or no reaction at all, depending mainly on steric effects. The same trends are observed for some higher peptides.The (poly)nitrosated peptides, which retain the chirality of the starting materials, have been characterized by 1H and 13C NMR spectroscopy and are cleaved by pyrrolidine and amino esters under mild conditions to give (new) amides or peptides plus diazo derivatives.
- Garcia, Jordi,Gonzalez, Javier,Segura, Ramon,Vilarrasa, Jaume
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p. 3121 - 3128
(2007/10/02)
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- Polymer Anchored Sulfonylazide for Deformylating Diazo Group Transfer and the Synthesis of Diazo-cyclopolyenes
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Polymer anchored sulfonylazide is compared with its efficiency in the diazogroup transfer reaction of tosylazide.The resulting yields with the polymeric reaction are slihgtly lower than with tosylazide.However the greater thermostability of polymeric sulfonyl azide and its workup procedure make this alternative very attractive for synthesis.The reaction of polymeric sulfonyl azide with cyclic polyenes gives very small yields compared with the monomeric reaction.The attempt to generate diazocyclononatetraene by an alternative route leads only to the secondary product namely indene.At low temperature, and intermediate diazocompound is, however, observed, which is tentatively assigned to structure 12. - Key words: Polymer-bound Sulfonylazide, Azogroup Transfer, Synthesis of Diazo-cyclopolyenes
- Duerr, Heinz,Hauck, Gerhard,Brueck, Wolfgang,Kober, Helge
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p. 1149 - 1152
(2007/10/02)
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