- Ni-Catalyzed Synthesis of Thiocarboxylic Acid Derivatives
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A Ni-catalyzed cross-coupling of readily accessible O-alkyl xanthate esters or thiocarbonyl imidazolides and organozinc reagents for the synthesis of thiocarboxylic acid derivatives has been developed. This method benefits from a fast reaction time, mild reaction conditions, and ease of starting material synthesis. The use of transition-metal catalysis to access a diverse range of thiocarbonyl-containing compounds provides a useful complementary approach when compared with previously established methodologies.
- Monteith, John J.,Scotchburn, Katerina,Mills, L. Reginald,Rousseaux, Sophie A. L.
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supporting information
p. 619 - 624
(2022/01/20)
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- Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters
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In this paper is described a synthesis of enantiomerically enriched, configurationally stable organozinc reagents by catalytic enantioselective carbozincation of a vinylboronic ester. This process furnishes enantiomerically enriched α-borylzinc intermediates that are shown to undergo stereospecific reactions, producing enantioenriched secondary boronic ester products. The properties of the intermediate α-borylzinc reagent are probed and the synthetic utility of the products is demonstrated by application to the synthesis of (-)-aphanorphine and (-)-enterolactone.
- Chen, Jingjia,Hu, Weipeng,Jin, Jing,Lovinger, Gabriel J.,Morken, James P.,Zhang, Chenlong
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supporting information
p. 14189 - 14195
(2021/09/11)
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- The Formation of P-C Bonds Utilizing Organozinc Reagents for the Synthesis of Aryl- A nd Heteroaryl-Dichlorophosphines
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Aryl- A nd heteroaryl-dichlorophosphines are mildly and selectively made in a one-pot synthesis in moderate to good yields starting from the respective aryl bromides or five-membered heterocycles, following lithiation with nBuLi, transmetalation with ZnCl
- Kirst, Christin,Tietze, Jonathan,Ebeling, Marian,Horndasch, Lukas,Karaghiosoff, Konstantin
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p. 17337 - 17343
(2021/11/18)
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- Ni-Catalyzed C(sp3)–O Arylation of α-Hydroxy Esters
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A Negishi cross-coupling of α-hydroxy ester derivatives and arylzinc reagents has been developed. This reaction tolerates both primary and secondary C(sp3)–O alcohol precursors and achieves efficient cross-coupling under Ni catalysis without the need for added external metal reductant, photocatalyst, or additives. The arylation of readily accessible C(sp3)–O electrophiles in this operationally simple, rapid, and mild reaction provides a complementary way of accessing desirable α-aryl ester products.
- Monteith, John J.,Rousseaux, Sophie A. L.
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supporting information
p. 9485 - 9489
(2021/12/09)
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- Oxidative Addition of Alkenyl and Alkynyl Iodides to a AuI Complex
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The first isolated examples of intermolecular oxidative addition of alkenyl and alkynyl iodides to AuI are reported. Using a 5,5′-difluoro-2,2′-bipyridyl ligated complex, oxidative addition of geometrically defined alkenyl iodides occurs readily, reversibly and stereospecifically to give alkenyl-AuIII complexes. Conversely, reversible alkynyl iodide oxidative addition generates bimetallic complexes containing both AuIII and AuI centers. Stoichiometric studies show that both new initiation modes can form the basis for the development of C?C bond forming cross-couplings.
- Bower, John F.,Cadge, Jamie A.,Russell, Christopher A.,Sparkes, Hazel A.
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supporting information
p. 6617 - 6621
(2020/03/13)
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- Asymmetric Synthesis of Alkylzincs by Rhodium-Catalyzed Enantioselective Arylative Cyclization of 1,6-Enynes with Arylzincs
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A chiral diene-rhodium complex was found to catalyze the reaction of 1,6-enynes with ArZnCl to give high yields of 2-(alkylidene)cyclopentylmethylzincs with high enantioselectivity (95–99 % ee). The enantioenriched alkylzincs were readily converted in a one-pot approach into a wide variety of functionalized products by taking advantage of their unique reactivity. The catalytic cylcle involves arylrhodation of alkyne, intramolecular alkenylrhodation of alkene, and transmetalation of the alkyl-rhodium intermediate into alkylzinc.
- Chen, Jiahua,Hayashi, Tamio
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supporting information
p. 18510 - 18514
(2020/08/21)
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- Modular Functionalization of Arenes in a Triply Selective Sequence: Rapid C(sp2) and C(sp3) Coupling of C?Br, C?OTf, and C?Cl Bonds Enabled by a Single Palladium(I) Dimer
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Full control over multiple competing coupling sites would enable straightforward access to densely functionalized compound libraries. Historically, the site selection in Pd0-catalyzed functionalizations of poly(pseudo)halogenated arenes has been unpredictable, being dependent on the employed catalyst, the reaction conditions, and the substrate itself. Building on our previous report of C?Br-selective functionalization in the presence of C?OTf and C?Cl bonds, we herein complete the sequence and demonstrate the first general arylations and alkylations of C?OTf bonds (in I dimer. This allowed the realization of the first general and triply selective sequential C?C coupling (in 2D and 3D space) of C?Br followed by C?OTf and then C?Cl bonds.
- Keaveney, Sinead T.,Kundu, Gourab,Schoenebeck, Franziska
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supporting information
p. 12573 - 12577
(2018/09/18)
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- An Enantioselective Iodolactonization/Cross-Coupling Protocol for the Synthesis of Highly Substituted Enol Lactones
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γ-Alkynoic acids readily undergo iodolactonization to give iodoenol lactones. Using commercially available (DHQD)2PHAL this transformation can be rendered asymmetric. In desymmetrization reactions of dialkynoic acids, good to very good enantioselectivities can be observed. Alternatively, kinetic resolution of already chiral, racemic γ-alkynoic acids can be carried out. The products of these iodolactonizations, iodoenol lactones, are suitable substrates for Palladium catalyzed cross-couplings. Negishi- as well as Sonogashira couplings can be carried out and allow the efficient synthesis of highly substituted enol lactones.
- Fricke, Christoph,Wilking, Michael,Daniliuc, Constantin G.,Hennecke, Ulrich
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p. 3158 - 3166
(2018/07/06)
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- Rhodium-Catalyzed Arylzincation of Alkynes: Ligand Control of 1,4-Migration Selectivity
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The addition of arylzinc reagents ArZnCl 1 to alkynes 2 was found to be catalyzed by rhodium complexes in the presence of a catalytic amount of zinc chloride. The selectivity in giving 2-arylalkenylzinc species 3 or ortho-alkenylarylzinc species 4, the la
- Ming, Jialin,Hayashi, Tamio
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p. 6188 - 6192
(2018/10/02)
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- Nickel-Catalyzed Negishi Cross-Coupling of N -Acylsuccinimides: Stable, Amide-Based, Twist-Controlled Acyl-Transfer Reagents via N-C Activation
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This paper reports a room temperature, nickel-catalyzed Negishi cross-coupling of N -acylsuccinimides with arylzinc reagents via selective N-C bond cleavage enabled by amide bond twist. The reaction proceeds using a commercially available, air-stable Ni(II) precatalyst in the absence of additives under exceedingly mild conditions. Of broad interest, this report introduces N -acylsuccinimides as stable, crystalline, electrophilic, cost-effective, benign, amide-based acyl transfer reagents via acyl metal intermediates. The reaction selectivity is governed by half-twist of the amide bond in N -acylsuccinimides, thus opening the door for applications in metal-catalyzed manifolds via redox-neutral reaction pathways tuneable by amide bond distortion.
- Shi, Shicheng,Szostak, Michal
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supporting information
p. 3602 - 3608
(2017/08/15)
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- Transition-Metal-Free Cross-Coupling of Aryl and Heteroaryl Thiols with Arylzinc Reagents
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Cross-coupling of (hetero)arylthiols with arylzinc reagents via C-S cleavage was performed under transition-metal-free conditions. The reaction displays a wide scope of substrates and high functional-group tolerance. Electron-rich and -deficient (hetero)arylthiols and arylzinc reagents can be employed in this transformation. Mg2+ and Li+ ions were demonstrated to facilitate the reaction.
- Yang, Bo,Wang, Zhong-Xia
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supporting information
p. 6220 - 6223
(2017/11/24)
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- Efficient Synthesis of Diaryl Ketones by Nickel-Catalyzed Negishi Cross-Coupling of Amides by Carbon–Nitrogen Bond Cleavage at Room Temperature Accelerated by a Solvent Effect
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The first Negishi cross-coupling of amides for the synthesis of versatile diaryl ketones by selective C?N bond activation under exceedingly mild conditions is reported. The cross-coupling was accomplished with bench-stable, inexpensive precatalyst [Ni(PPh3)2Cl2] that shows high functional-group tolerance and enables the synthesis of highly functionalized diaryl ketone motifs. The coupling occurred with excellent chemoselectivity favoring the ketone (cf. biaryl) products. Notably, this process represents the mildest conditions for amide N?C bond activation accomplished to date (room temperature, 10 min). Considering the versatile role of polyfunctional biaryl ketone linchpins in modern organic synthesis, availability, and excellent functional-group tolerance of organozinc reagents, this strategy provides a new platform for amide N?C bond/organozinc cross-coupling under mild conditions.
- Shi, Shicheng,Szostak, Michal
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supporting information
p. 10420 - 10424
(2016/07/21)
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- Rh-Catalyzed Conjugate Addition of Arylzinc Chlorides to Thiochromones: A Highly Enantioselective Pathway for Accessing Chiral Thioflavanones
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A highly efficient asymmetric synthesis of chiral thioflavanones is developed via conjugate addition of arylzinc reagents to thiochromones using Rh(COD)Cl2/(R)-3,4,5-MeO-MeOBIPHEP catalyst. This method overcomes catalyst poisoning and substrate inertness and affords a series of chiral thioflavanones (2-arylthiochroman-4-ones) in good yields (up to 91% yield) with excellent ee values (up to 97% ee). The established asymmetric synthesis paves the way for further pharmaceutical studies.
- Meng, Ling,Jin, Ming Yu,Wang, Jun
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supporting information
p. 4986 - 4989
(2016/10/14)
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- Nickel-catalyzed diaryl ketone synthesis by N-C cleavage: Direct negishi cross-coupling of primary amides by site-selective N,N-Di-boc activation
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A general Negishi acylation of primary amides enabled by a combination of site-selective N,N-di-Boc activation and nickel catalysis is reported for the first time. The reaction is promoted by a bench-stable, inexpensive Ni catalyst. The reaction shows excellent functional group compatibility, affording functionalized diaryl ketones by selective N-C cleavage. Most notably, this protocol represents the first amide cross-coupling by direct metal insertion of simple and readily available primary amides. The overall strategy by N,N-di-Boc activation/metal insertion is suitable for a broad range of coupling protocols via acylmetals. Mechanistic experiments suggest high reactivity of N,N-di-Boc activated 1° amides in direct amide C-N cross-couplings.
- Shi, Shicheng,Szostak, Michal
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supporting information
p. 5872 - 5875
(2016/11/29)
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- One-pot synthesis of aryl sulfones from organometallic reagents and iodonium salts
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A transition-metal-free arylation of lithium, magnesium, and zinc sulfinates with diaryliodonium salts is described. The sulfinic acid salts were prepared from the reaction of the corresponding organometallic reagents and sulfur dioxide. Combination of the three single steps (preparation of the organometallic compound, sulfinate formation, and arylation) leads to a one-pot sequence for the synthesis of aryl sulfones from simple starting materials. The chemoselectivity of unsymmetrical diaryliodonium salts has been investigated. Potential and limitations of this method will be discussed.
- Margraf, Natalie,Manolikakes, Georg
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p. 2582 - 2600
(2015/03/18)
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- Stereoconvergent negishi arylations of racemic secondary alkyl electrophiles: Differentiating between a CF3 and an alkyl group
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In this report, we establish that a readily available nickel/bis(oxazoline) catalyst accomplishes a wide array of enantioconvergent cross-couplings of arylzinc reagents with CF3-substituted racemic secondary alkyl halides, a process that necessitates that the chiral catalyst be able to effectively distinguish between a CF3 and an alkyl group in order to provide good ee. We further demonstrate that this method can be applied without modification to the catalytic asymmetric synthesis of other families of fluorinated organic compounds.
- Liang, Yufan,Fu, Gregory C.
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supporting information
p. 9523 - 9526
(2015/08/18)
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- Catalytic asymmetric synthesis of tertiary alkyl fluorides: Negishi cross-couplings of racemic α,α-dihaloketones
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The development of new approaches to the construction of fluorine-containing target molecules is important for a variety of scientific disciplines, including medicinal chemistry. In this Article, we describe a method for the catalytic enantioselective syn
- Liang, Yufan,Fu, Gregory C.
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supporting information
p. 5520 - 5524
(2014/05/06)
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- Synthesis of α-amino amides via N,O-acetals derived from Weinreb amides
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(Chemical Equation Presented) An easy and straightforward synthesis of α-amino amides via a base-mediated rearrangement of modified Weinreb amides into N,O-acetals is presented. Subsequent arylation, alkylation, alkenylation, or alkynylation of this intermediate affords the corresponding R-amino amides in excellent yields. Furthermore, a more generalized protocol for the α-arylation of Weinreb amides lacking an R-amino moiety is also discussed.
- Hirner, Sebastian,Somfai, Peter
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experimental part
p. 7798 - 7803
(2009/12/29)
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- An improved and scalable process for the synthesis of ezetimibe: An antihypercholesterolemia drug
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An efficient, cost-effective and large-scale synthesis of ezetimibe 1, an antihypercholesterolemia drug, is described. Chiral oxazolidinone chemistry was used to fix the required stereochemistry of the β-lactam ring, and the chiral oxazaborolidine chemistry was used to fix the hydroxyl group stereochemistry. The synthesis significantly lowers the cost and provides easy access to ezetimibe on large scale.
- Sasikala,Padi, Pratap Reddy,Sunkara, Vishnuvardhan,Ramayya, Pattabhi,Dubey,Uppala, Venkata Bhaskar Rao,Praveen, Cherukupally
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experimental part
p. 907 - 910
(2010/04/22)
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- 4-halogeno-1,1,1-trifluorobut-3-yn-2-one [4+2] cycloadducts and their cross-coupling with organozinc compounds
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The reactions of 4-chloro-1,1,1-trifluorobut-3-yn-2-one and 4-bromo-1,1,1-trifluorobut-3-yn-2-one with conjugated dienes afford [4+2] cycloadducts in high yields. The halogen atom in the products is readily replaced by a (het)aryl residue in the cross-coupling with organozinc compounds.
- Koldobskii,Tsvetkov,Shilova,Solodova,Kalinin
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p. 2271 - 2275
(2014/05/06)
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- PROCESS FOR THE PREPARATION OF N-[4-(4-FLUOROPHENYL)-5-FORMYL-6-ISOPROPYL-PYRIMIDIN-2-YL]-N-METHYLMETHANESULFONAMIDE
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The present invention is directed to a method for the preparation of N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide and its use in the preparation of rosuvastatin or a pharmaceutically acceptable salt thereof.
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Page/Page column 10
(2008/06/13)
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- Cyclic and acyclic propenones for treating CNS disorders
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The invention relates to novel cyclic and non-cyclic propenone derivatives as well as their pharmaceutically acceptable slats. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are useful as medicaments.
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Page/Page column 24
(2008/06/13)
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- Combinations of lipid modulating agents and substituted azetidinones and treatments for vascular conditions
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The present invention provides compositions, therapeutic combinations and methods including: (a) at least one lipid modulating agent; and (b) at least one substituted azetidinone or substituted β-lactam sterol absorption inhibitor which can be useful for treating vascular conditions, diabetes, obesity and lowering plasma levels of sterols or 5α-stanols.
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Page/Page column 23-24
(2008/06/13)
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