- Biaryls made easy: PEPPSI and the Kumada-Tamao-Corriu reaction
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An easily employed, highly versatile Kumada-Tamao-Corriu (KTC) protocol utilizing the PEPPSI (Pyridine, Enhanced, Precatalyst, Preparation, Stabilization and Initiation) precatalysts 1 and 2 is detailed. The ease-of-use of these catalysts and the synthesis of a wide range of hindered biaryls, large coupling partners and drug-like heterocycles, in high yield, makes the PEPPSI-KTC protocol very attractive. The high reactivity of the PEPPSI system allowed a tetra-ortho substituted heterocycle, 11 to be synthesized at room temperature for the first time using any protocol. The PEPPSI protocols also tolerated the Boc protecting group and phenols required no protection in modified conditions. A relatively large scale (10g) reaction was also performed with no loss in performance. Furthermore, PEPPSI IPr, 1, was compared to previously reported highly active phosphine ligands 42, 43, and 44 and was shown to result in significantly better yields under identical conditions. Finally, we demonstrated that the PEPPSI catalyst system is very adept at performing sequential KTC coupling reactions, analogous to multicomponent reactions, which allow complex polyaryl and polyheteroaryl architectures to be produced in one single operation.
- Organ, Michael G.,Abdel-Hadi, Mirvat,Avola, Stephanie,Hadei, Niloufar,Nasielski, Joanna,O'Brien, Christopher J.,Valente, Cory
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Read Online
- Processes for the Preparation of Zuclomiphene and Intermediates Thereof
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The present invention provides processes for the preparation of zuclomiphene, as well as intermediates useful in the preparation thereof. In particular, processes are provided for the carbometallation of diphenylacetylene with a compound of Formula (3) to afford either zuclomiphene or an intermediate which is converted to zuclomiphene.
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Paragraph 0140-0141
(2021/05/21)
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- Room-Temperature Palladium(II)-Catalyzed Direct 2-Arylation of Indoles with Tetraarylstannanes
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A palladium(II)-catalyzed direct 2-arylation of indoles by tetraarylstannanes with oxygen (balloon) as the oxidant at room temperature has been developed. Various tetraarylstannanes can be employed as aryl sources for 2-arylation of indoles in up to 89% yield, providing a practical and efficient catalytic protocol for accessing 2-arylindoles.
- Liu, Yuxia,Wang, Chao,Huang, Linjuan,Xue, Dong
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supporting information
p. 1613 - 1618
(2020/09/15)
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- Strain-Promoted 1,3-Dithiolium-4-olates–Alkyne Cycloaddition
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Reported here is the reactivity of mesoionic 1,3-dithiolium-4-olates towards strained alkynes, leading to thiophene cycloaddition products. In the process, the potential of these dipoles towards orthogonal reaction with azides, allowing efficient double ligation reactions, was discovered. A versatile process to access benzo[c]thiophenes, in an unprecedented divergent fashion, was developed and provides a new entry to unconventional polyaromatic thiophenes.
- Kumar, Ramar Arun,Pattanayak, Manas R.,Yen-Pon, Expédite,Eliyan, Jijy,Porte, Karine,Bernard, Sabrina,Riomet, Margaux,Thuéry, Pierre,Audisio, Davide,Taran, Frédéric
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supporting information
p. 14544 - 14548
(2019/09/17)
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- Chromium(II)-Catalyzed Diastereoselective and Chemoselective Csp2-Csp3 Cross-Couplings Using Organomagnesium Reagents
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A simple protocol for performing chromium-catalyzed highly diastereoselective alkylations of arylmagnesium halides with cyclohexyl iodides at ambient temperature has been developed. Furthermore, this ligand-free CrCl2 enables efficient electrophilic alkenylations of primary, secondary, and tetiary alkylmagnesium halides with readily available alkenyl acetates. Moreover, this chemoselective C-C coupling reaction with stereodefined alkenyl acetates proceeds in a stereoretentive fashion. A wide range of functional groups on alkyl iodides and alkenyl acetates are well tolerated, thus furnishing functionalized Csp2-Csp3 coupling products in good yields and high diastereoselectivity. Detailed mechanistic studies suggest that the in situ generated low-valent chromium(I) species might be the active catalyst for these Csp2-Csp3 cross-couplings.
- Li, Jie,Ren, Qianyi,Cheng, Xinyi,Karaghiosoff, Konstantin,Knochel, Paul
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supporting information
p. 18127 - 18135
(2019/11/19)
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- Nickel-Catalyzed Cross-Coupling of Functionalized Organo manganese Reagents with Aryl and Heteroaryl Halides Promoted by 4-Fluorostyrene
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A catalytic system consisting of Ni(acac) 2 (5 mol%) and 4-fluorostyrene (20 mol%) allows a convenient cross-coupling of functionalized organomanganese reagents with a variety of aryl and heteroaryl halides leading to polyfunctionalized diaryl- and arylheteroarylmethane derivatives.
- Benischke, Andreas D.,Desaintjean, Alexandre,Juli, Thomas,Cahiez, Gérard,Knochel, Paul
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supporting information
p. 5396 - 5412
(2017/12/14)
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- A Short Access to Symmetrically α,α-Disubstituted α-Amino Acids from Acyl Cyanohydrins
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A straightforward synthesis of symmetrically α,α-disubstituted α-amino acids is presented. The key step of this process relies on the efficient double addition of Grignard reagents to acyl cyanohydrins to provide N-acyl amino alcohols selectively in good yields. The chemoselectivity of the reaction was modulated by the nature of the acyl moiety. Eleven amino acids were prepared, including the particularly simple divinylglycine, which is not easily accessible by using conventional methods.
- Boukattaya, Fatma,Caillé, Julien,Ammar, Houcine,Rouzier, Florian,Boeda, Fabien,Pearson-Long, Morwenna S. M.,Bertus, Philippe
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p. 906 - 916
(2016/03/12)
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- Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates
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Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate.
- Eno, Meredith S.,Lu, Alexander,Morken, James P.
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supporting information
p. 7824 - 7827
(2016/07/11)
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- Facile Hydrogenolysis of C(sp3)–C(sp3) σ Bonds
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The modification of benzylic quaternary, tertiary, and secondary carbon centers through palladium-catalyzed hydrogenolysis of C(sp3)–C(sp3) σ bonds is presented. When benzyl Meldrum's acid derivatives bearing quaternary benzylic centers are treated under mild hydrogenolysis conditions – palladium on carbon and atmospheric pressure of hydrogen – aromatics substituted with tertiary benzylic centers and Meldrum's acid are obtained with good to excellent yield. Analogously, substrates containing tertiary or secondary benzylic centers yield aromatics substituted with secondary benzylic centers or toluene derivatives, respectively. Furthermore, this strategy is used for the high yielding synthesis of diarylmethanes. The scope of the reductive dealkylation reaction is explored and the limitations with respect to steric and electronic factors are determined. A mechanistic analysis of the reaction is described that consisted of deuterium labelling experiments and hydrogenolysis of enantioenriched derivatives. The investigation shows that the C(sp3)–C(sp3) σ bond-cleaving events occur through a hybrid SN1/SN2 mechanism, in which the palladium center displaces a carbon-based leaving group, namely Meldrum's acid, with inversion of configuration, followed by reductive elimination of palladium to furnish a C?H bond. (Figure presented.).
- Fillion, Eric,Beaton, Eric,Nguyen, Yen,Wilsily, Ashraf,Bondarenko, Ganna,Jacq, Jér?me
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supporting information
p. 3422 - 3434
(2016/11/13)
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- Bismuth-catalyzed synthesis of polycyclic aromatic hydrocarbons (PAHs) with a phenanthrene backbone via cyclization and aromatization of 2-(2-arylphenyl)vinyl ethers
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The reaction of 2-(2-arylphenyl)vinyl ethers in the presence of a catalytic amount of bismuth(III) triflate gave substituted phenanthrenes in excellent yields under mild reaction conditions. The reaction was also applied to the construction of other polycyclic aromatic hydrocarbons (PAHs), such as chrysene, helicene, and pyrene having a phenanthrene backbone, via regioselective cyclization. This method has the advantages of easy availability of the cyclization precursors, operational simplicity, and high reaction efficiency.
- Murai, Masahito,Hosokawa, Naoki,Roy, David,Takai, Kazuhiko
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supporting information
p. 4134 - 4137
(2014/09/30)
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- Synthesis of 4-silapiperidine building blocks with N-H groups using the Staudinger reaction
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4-Silapiperidines are important skeletons for drug design. In this context, a novel acid-free method for the synthesis of 4-silapiperidine building blocks with N-H groups has been developed, using the Staudinger reaction as the key step. As a proof of principle, the model compounds 13 and 14 were synthesized, starting from Ph2SiCl2 and MeSi(OMe)3, respectively.
- Fischer, Markus,Tacke, Reinhold
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p. 7181 - 7185
(2014/01/06)
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- Selective introducing of aryl and amino groups: Reaction of benzanthrone and organometallic reagents
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The reaction of benzanthrone and aryl magnesium bromides produced 6-aryl-substituted benzanthrones in moderate to good yields. Similarly, 6-alkylaminobenzanthrones were selectively prepared by the reaction of benzanthrone and lithium alkylamides. In contrast, for the lithium arylamides, the arylamino groups were selectively introduced at the 4-position of the benzanthrone.
- Umeda, Rui,Namba, Teruaki,Yoshimura, Tomohiro,Nakatsukasa, Masamichi,Nishiyama, Yutaka
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p. 1526 - 1531
(2013/02/23)
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- Copper-catalyzed difluoromethylation of β,γ-unsaturated carboxylic acids: An efficient allylic difluoromethylation
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Not one but two! A new strategy for the regiospecific construction of compounds with allylic CF2H groups has been developed. The decarboxylative (phenylsulfonyl)difluoromethylation of β,γ- unsaturated carboxylic acids is catalyzed by a Lewis acid (CuCl 2·2 H2O), and the resulting product easily undergoes desulfonylation. Copyright
- He, Zhengbiao,Hu, Mingyou,Luo, Tao,Li, Lingchun,Hu, Jinbo
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supporting information
p. 11545 - 11547
(2013/01/15)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE ALCOHOL
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Disclosed is a method for producing an optically active alcohol including reacting a titanium compound, an aromatic magnesium compound and a carbonyl compound in the presence of an optically active biphenol compound having a predetermined structure and an ether compound having a predetermined structure.
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Page/Page column 20
(2012/02/14)
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- Cross-coupling of aryl/alkenyl silyl ethers with grignard reagents through nickel-catalyzed CO bond activation
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CO activation and its application have drawn much attention since oxygen-based electrophiles are easily available, less toxic, and more environmentally benign. This letter presents systematically results on the Ni-catalyzed KumadaTamaoCorriu coupling based on siloxy arenes/alkenes, which provides a new strategy of silyl protection/CC bond formation sequence in organic synthesis.
- Zhao, Fei,Yu, Da-Gang,Zhu, Ru-Yi,Xi, Zhenfeng,Shi, Zhang-Jie
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supporting information; experimental part
p. 1001 - 1003
(2011/12/05)
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- Use of73Ge NMR Spectroscopy and X-ray Crystallography for the Study of electronic interactions in substituted tetrakis(phenyl)-, -(phenoxy)-, and -(thiophenoxy)germanes
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NMR chemical shifts of 1H, 13C, and 73Ge, molecular modeling, and single-crystal X-ray diffraction results are reported for a series of substituted tris- and tetrakis(phenyl)germanes of the type (XC6H4)3GeY and (XC6H 4)4Ge, where X = o-, m-, and p-OCH3, o-, m-, and p-OC2H5, m- and p-CF3, H, p-C(CH 3)3, p-Cl; and Y = Cl and H. Chemical shifts and X-ray data are also reported for o-CH3 and o-OCH3 tetrakis(phenoxy)- ((XC6H4O)4Ge) and thiophenoxygermanes ((XC6H4S)4Ge). For tetrakis derivatives, 73Ge resonances are observed for all but the o-methoxyphenoxy compound, for which the inability to detect a resonance is attributed to rapid quadrupolar relaxation caused by intramolecular interactions of the methoxy oxygen with the central atom. The observation of a relatively broad, slightly upfield 73Ge resonance in the analogous phenyl and thiophenoxy derivatives suggests, as do the results of molecular modeling, that in these compounds there is some hypercoordination. The solid-state structures show bond angles at the aromatic carbon bearing the alkoxy group that suggest an interaction of the alkoxy oxygen with germanium. Oxygen-germanium bond distances are about 17% shorter than the sum of the van der Waals radii.
- Yoder, Claude H.,Agee, Tamara M.,Griffith, Allison K.,Schaeffer Jr., Charles D.,Carroll, Mary J.,Detoma, Alaina S.,Fleisher, Adam J.,Gettel, Cameron J.,Rheingold, Arnold L.
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experimental part
p. 582 - 590
(2010/04/25)
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- COMPOUNDS AND METHODS FOR CHELATING METALS IN AQUEOUS SOLUTIONS
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The present invention relates to a new class of organic compounds and their use, for example, to sequester metal ions, including actinides (such as uranium and plutonium), precious metals (such as gold, silver and platinum) and all other metals (such as transition metals), from aqueous solutions, such as bodies of water (including but not limited to ocean water, seawater, river water) and all other aqueous solutions. Specifically, the present invention relates to a new class of polydentate organic chelating agents and methods for their use to recover metals from aqueous solutions, such as uranium from seawater.
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Page/Page column 21-23
(2010/12/26)
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- NON-STEROIDAL PROGESTERONE RECEPTOR MODULATORS
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The present invention relates to non-steroidal progesterone receptor modulators of the general formula 1, the use of the progesterone receptor modulators for the manufacture of medicaments, and pharmaceutical compositions which comprise these compounds. The compounds according to the invention are suitable for the therapy and prophylaxis of gynaecological disorders such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhoea, and for the therapy and prophylaxis of hormone-dependent tumours and for use for female fertility control and for hormone replacement therapy.
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Page/Page column 63-64
(2009/04/24)
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- N-(3-(IMIDAZO [1,5-A]PYRIMIDIN-4-YL)PHENYL]-SULFONAMIDES AND N-[3-(IMIDAZO[1,5-A]PYRIMIDIN-4-YL)-PHENYL]-CARBOXAMIDES AND THEIR USE AS GABAA RECEPTOR MODULATORS
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The present invention relates to compounds of formula I wherein R1, R2, R3 and X are as defined in the claims. The compounds have specific affinity for the GABAA receptor and are therefore useful in the treatment and prevention of diseases modulated by the 1 and 2-GABAA receptors.
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Page/Page column 33
(2008/06/13)
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- Arylzinc species by microwave assisted Grignard formation-transmetallation sequence: Application in the Negishi coupling
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Arylmagnesium species can be efficiently generated from magnesium turnings and aryl chlorides or aryl bromides under dielectric heating conditions. Subsequent microwave assisted transmetallation using ZnCl2-TMEDA afforded the corresponding arylzinc reagents. A sequential microwave assisted arylmagnesium formation-transmetallation-Negishi coupling protocol suitable for automated multiple parallel synthesis has been developed.
- Mutule, Ilga,Suna, Edgars
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p. 11168 - 11176
(2007/10/03)
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- Novel chromogenic substances and use thereof for the determination of carboxypeptidase activities
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The invention relates to chromogenic compounds and the use thereof for the determination of enzymes of the family of carboxypeptidases N and carboxypeptidases U. The above is more specifically a compound of formula (I) in which A=(1), (2), (3), (4) or (5). R1. R2=H. —CH3, —CH(CH3)2, —OCH3, —Cl.—CF3,—OCF3,—SCH3, R3=an amino acid group which may be hydrolysed by a carboxypeptidase A and R4=a basic amino acid group.
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Page/Page column 10;21;22
(2008/06/13)
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- Method of preparing organomagnesium compounds
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The present invention is directed to a reagent for use in the preparation of organomagnesium compounds as well as to a method of preparing such organomagnesium compounds. The present invention furthermore provides a method of preparing functionalized or unfunctionalized organic compounds as well as the use of the reagents of the present invention in the preparation of organometallic compounds and their reaction with electrophiles. Finally, the present invention is directed to the use of lithium salts - LiY in the preparation of organometallic compounds and their reactions with electrophiles and to an organometallic compound which is obtainable by the disclosed method.
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- Coating compositions stabilized against damage by light, heat and oxygen
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Coatings comprisingA) a binder based on an organic polymer andB) as stabilizer against damage by light, heat and oxygen, a 2-(2′-hydroxyphenyl)-1,3-pyrimidine of the formula I ?in which the radicals R1 to R6 are as defined in claim 1 have an outstanding resistance to the damaging effects of light, oxygen and heat. Compounds of the formula Ib defined in claim 18 are suitable in general for the stabilization of organic material.
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Page column 44
(2008/06/13)
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- Attempts to find a solution to the problem of atropisomer interconversion in 1,8-diarylnaphthalenes and 5,6-diarylacenaphthenes
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A series of sterically restricted 5,6-diarylacenaphthenes 5, 11, 12, 13 and 14 have been prepared via Suzuki crosscouplings of the appropriate boronic acids with 5,6-dibromoacenaphthene 3 in an attempt to prevent atropisomer interconversion in these systems. Attempts to further functionalise bis(p-methoxyphenyl) system 5 in the position ortho to the methyl ethers by Friedel-Crafts acylation or metallation were unsuccessful; however, two unexpected products were obtained, p,p′-Dimethoxybiphenyl 6 results from an unexpected rearrangement of 5 under strongly basic conditions and is dependent on the base used, whilst acylated derivative 7 results from a Friedel-Crafts acylation of the acenaphthene scaffold in the 3-position, rather than the desired functionalisation of the peri-aryl rings, presumably due to the difficulty in forming a tetrahedral intermediate. The oxygen functionality in 5 has been used, following methyl ether cleavage via diphenol 8 and allylation via 9, to demonstrate the viability of a double Claisen rearrangement yielding 11 after acetylation. However, the broad 1H NMR exhibited by 11 clearly showed that this system is not configurationally stable, hence steps were required to access more sterically demanding systems which would be configurationally stable. Molecular mechanics and semi-empirical simulations were carried out on related biaryl systems to determine if a single bulky substituent in the 3-position of the peri-aryl rings would be sufficient to prevent atropisomer interconversion. The modelling showed that the energies of the syn- and antiatropisomeric forms, e.g. for 12-14, were surprisingly similar. With the objective of preparing conformationally stable molecules in this class in mind, 12-14 were prepared in remarkable yield for such a hindered system. In spite of extensive attempts to determine whether 13 was configurationally stable, enantiomeric separation could not be achieved. Unsuccessful attempts were thus made to detect the presence of stable atropisomeric forms of 13 through the synthesis of bis(benzyl ether) 19, in which the benzylic protons could act as enantiotopic reporters. In addition mandelate ester 20 was prepared and it was shown by 1H NMR that a mixture of anti- and syn-diastereoisomers had been obtained. It was therefore concluded that steric groups in the 3-position of the peri-aryl rings cannot be used to prevent atropisomer interconversion in 1,8-diarylnaphthalenes and 5,6-diarylacenaphthenes. During attempts to access diphenols 18 and 24, other by-products were isolated, i.e. 21 and 25 respectively, resulting from a steric strain-induced 1,2-aryl shift.
- Steele, Melanie,Watkinson, Michael,Whiting, Andrew
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p. 588 - 598
(2007/10/03)
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- Endothelin receptor antagonists
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Novel indane and indene derivatives are described which are endothelin receptor antagonists.
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- A convenient method for the synthesis of (3S,4R)-3-p-methoxyphenyl-4- hydroxy-1,5-hexadiene
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A new procedure for the synthesis of (3S, 4R)-3-p-methoxyphenyl-4- hydroxy-1,5-hexadiene is described using D-mannitol as chiral source.
- Yang, Bing-Hui,Zhao, Jing-Jing,Chen, Guo-Nan
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p. 2583 - 2591
(2007/10/03)
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- Triazole derivatives
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The present invention relates to a novel glycerol derivative and a process for preparing the same, and a process for preparing a triazole derivative. According to the present invention, an optical active 2-arylglycerol derivative which is a novel and useful as a synthetic intermediate of medicament can be provided and furthermore, (R)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)-propane-1,2-diol which is useful as an antifungal agent can be prepared.
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- Palladium catalyzed vinylic substitution reactions with 2-substituted-pyridines
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This invention involves a coupling reaction involving an organo-metallic catalyst, preferably a palladium catalyst involving reacting 2-halo-3-hydroxy-6-hydroxymethylpyridine, acrylic acid or its alkali metal salt and benzyl or a phenylalkyl derivative in presence of a dipolar aprotic solvent producing none other than the expected 2-propenoate-3-benzyl or phenylalkylether-6-hydroxymethyl-pyridine product. Said products are converted into medicaments useful for treating psoriasis.
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- Hydro-ethano-indeno-pyridines
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A compound of formula I STR1 wherein X, V, W, Y, Z, R, a, b, c, and d are as described herein. These compounds are useful in the treatment of tumors, allergies, bronchoconstriction and CNS diseases and conditions.
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- Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid
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A process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid comprising the reaction of an organometallic derivative with a suitable substituted benzene in the presence of a transition-metal based catalyst is described.
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- Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid
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A process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid comprising the reaction of an organometallic derivative with a suitable substituted benzene in the presence of a transition-metal based catalyst is described.
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- Liquid crystal compounds
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Novel liquid crystal compounds are disclosed, which are chiral esters based upon the phenol STR1 Typical examples are: STR2 and mixtures of these compounds have a helical pitch such that the mixtures reflect light of a specific wavelength when illuminated with ordinary light and the pitch is temperature sensitive so that the mixtures can be used in temperature indicating devices. Specific examples are given as are samples of mixtures that can be used in phase change electro-optic display devices.
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- N-Acyl-3-azetidinone
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Disclosed herein are novel N-acyl-3-aryl-3-azetidinols useful as intermediates. A method is provided for their direct preparation from acyclic starting materials. These N-acyl-3-aryl-azetidinols provide a convenient route to the 3-azetidinol series.
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- Diarylcyclobutanes
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1,3-bis(p-Hydroxyphenyl)cyclobutane and its monomethyl ether are estrogenic agents having antifertility action.
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