3041-40-5Relevant articles and documents
Industrial R&D on catalytic C-C and C-N coupling reactions: A personal account on goals, approaches and results
Blaser, Hans-Ulrich,Indolese, Adriano,Naud, Frederic,Nettekoven, Ulrike,Schnyder, Anita
, p. 1583 - 1598 (2004)
R&D issues for the application of Pd- and Ni-catalyzed C-C and C-N coupling reactions in the fine chemicals industry are discussed. In a first part, some background is given on industrial R&D and the role of C-C and C-N coupling for preparative applicatio
A novel and efficient arylation of malononitrile catalyzed by nickel(0) complexes
Cristau,Vogel,Taillefer,Gadras
, p. 8457 - 8460 (2000)
We report the first use of a nickel catalyst for the direct arylation of a β-difunctionalized compound, the malononitrile, from halogenated aromatic substrates. The catalytic system is quite simple: Ni(PPh3)3, generated in situ from
Single enantiomer, chiral donor-acceptor metal complexes from bisoxazoline pseudoracemates
Atkins, Jeffery M.,Moteki, Shin A.,DiMagno, Stephen G.,Takacs, James M.
, p. 2759 - 2762 (2006)
Single enantiomer, chiral donor-acceptor metal complexes were synthesized via the self-discriminating zinc(II) complexation of a pseudoracemic mixture of donor/acceptor-substituted bisoxazoline derivatives.
Design of an Electron-Withdrawing Benzonitrile Ligand for Ni-Catalyzed Cross-Coupling Involving Tertiary Nucleophiles
Edjoc, Racquel K.,Mills, L. Reginald,Rousseaux, Sophie A. L.
supporting information, p. 10422 - 10428 (2021/07/26)
The design of new ligands for cross-coupling is essential for developing new catalytic reactions that access valuable products such as pharmaceuticals. In this report, we exploit the reactivity of nitrile-containing additives in Ni catalysis to design a benzonitrile-containing ligand for cross-coupling involving tertiary nucleophiles. Kinetic and Hammett studies are used to elucidate the role of the optimized ligand, which demonstrate that the benzonitrile moiety acts as an electron-acceptor to promote reductive elimination over β-hydride elimination and stabilize low-valent Ni. With these conditions, a protocol for decyanation-metalation and Ni-catalyzed arylation is conducted, enabling access to quaternary α-arylnitriles from disubstituted malononitriles.
Structure-Activity Relationships of Pyrazolo[1,5- a]pyrimidin-7(4 H)-ones as Antitubercular Agents
Oh, Sangmi,Libardo, M. Daben J.,Azeeza, Shaik,Pauly, Gary T.,Roma, Jose Santinni O.,Sajid, Andaleeb,Tateishi, Yoshitaka,Duncombe, Caroline,Goodwin, Michael,Ioerger, Thomas R.,Wyatt, Paul G.,Ray, Peter C.,Gray, David W.,Boshoff, Helena I. M.,Barry, Clifton E.
, p. 479 - 492 (2021/01/26)
Pyrazolo[1,5-a]pyrimidin-7(4H)-one was identified through high-throughput whole-cell screening as a potential antituberculosis lead. The core of this scaffold has been identified several times previously and has been associated with various modes of actio
Preparation of O-Protected Cyanohydrins by Aerobic Oxidation of α-Substituted Malononitriles in the Presence of Diarylphosphine Oxides
Zhang, Dapeng,Lian, Mingming,Liu, Jia,Tang, Shukun,Liu, Guangzhi,Ma, Cunfei,Meng, Qingwei,Peng, Haisheng,Zhu, Daling
supporting information, p. 2597 - 2601 (2019/04/17)
A mild, reagent-cyanide-free, and efficient synthesis of O-phosphinoyl-protected cyanohydrins from readily available α-substituted malononitriles was realized using diarylphosphine oxides in the presence of O2. Mechanistic studies indicated that in addition to the initial aerobic oxidation of the malononitrile derivative notable features of this process include the formation of a tetrahedral intermediate and a subsequent intramolecular rearrangement. The phosphinoyl-protecting group can be removed by alcoholysis or by reduction with DIBAL-H.
Titanium(III)-Catalyzed Reductive Decyanation of Geminal Dinitriles by a Non-Free-Radical Mechanism
Weweler, Jens,Younas, Sara L.,Streuff, Jan
supporting information, p. 17700 - 17703 (2019/11/13)
A titanium-catalyzed mono-decyanation of geminal dinitriles is reported. The reaction proceeds under mild conditions, tolerates numerous functional groups, and can be applied to quaternary malononitriles. A corresponding desulfonylation is demonstrated as well. Mechanistic experiments support a catalyst-controlled cleavage without the formation of free radicals, which is in sharp contrast to traditional stoichiometric radical decyanations. The involvement of two TiIII species in the C?C cleavage is proposed, and the beneficial role of added ZnCl2 and 2,4,6-collidine hydrochloride is investigated.
A one-pot electrophilic cyanation–functionalization strategy for the synthesis of disubstituted malononitriles
Mills, L. Reginald,Rousseaux, Sophie A.L.
, p. 4298 - 4306 (2019/05/22)
Malononitriles are valuable synthetic intermediates for many applications, including the synthesis of herbicides and other biologically active molecules, and the synthesis of chiral ligands for asymmetric catalysis. This article describes the development of a procedure for the conversion of primary nitriles to malononitriles using dimethylmalononitrile, a commercial, non-toxic, carbon-bound source of electrophilic cyanide. This procedure avoids the use of toxic cyanide or malononitrile as a starting material. This protocol is further applied to the dicyanation of benzyl Grignard reagents, generated from benzyl bromides, yielding fully functionalized malononitriles from a nitrile-free precursor.
Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation
Mills, L. Reginald,Graham, Joshua M.,Patel, Purvish,Rousseaux, Sophie A. L.
supporting information, p. 19257 - 19262 (2019/12/02)
Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.
Design and evaluation of pyrazolopyrimidines as KCNQ channel modulators
Osuma, Augustine T.,Xu, Xiangdong,Wang, Zhi,Van Camp, Jennifer A.,Freiberg, Gail M.
, (2019/08/13)
Effective treatments of neuropathic pain have been a focus of many discovery programs. KCNQ (kv7) are voltage gated potassium channel openers that have the potential for the treatment of CNS disorders including neuropathic pain. Clinical studies have sugg
