162476-91-7

Upstream product

• 7031-93-8 2,2,6,6-tetramethylpiperidin-1-ol 
• 5259-72-3 cyclo-octa-1,5-diene 
• 67292-34-6 [1,1'-bis(diphenylphosphino)ferrocene]nickel(II) chloride 
• 1552-12-1 1,5-cis,cis-cyclooctadiene 
• 12150-46-8 1,1'-bis-(diphenylphosphino)ferrocene 
• 83864-14-6 nickel dichloride 
• 1295-35-8 bis(1,5-cyclooctadiene)nickel ⁽⁰⁾ 

Downstream Products

• 100-42-5 styrene 
• 637-50-3 1-phenylpropene 

Relevant academic research and scientific papers

Asymmetric Allylic Alkylation of β-Ketoesters via C-N Bond Cleavage of N-Allyl-N-methylaniline Derivatives Catalyzed by a Nickel-Diphosphine System

Nickel complexes bearing chiral diphosphine ligands, such as (S)-Tol-MeO-BIPHEP and (S)-H8-BINAP, serve as efficient catalysts for asymmetric allylic alkylation (AAA) of β-ketoesters, using allylic amines as allyl sources. The reactions proceed with high catalytic activity and high enantioselectivity. N-Methyl-N-phenyl allylic amines were indispensable to achieve the high catalytic activity, to achieve the high enantioselectivity, and to expand the substrate scope to 5-and 7-membered β-ketoesters, whose nickel-catalyzed AAA with allylic alcohols results in low enantioselectivity. On the basis of the kinetics using a catalyst system made of Ni(cod)2 and (S)-Tol-MeO-BIPHEP, and DFT calculations for the reaction pathway of the AAA reaction mediated by an isolated olefin-coordinated nickel-DPPF complex 4b, we propose a mechanism where protonation of the nitrogen atom of the coordinating allylic amine by β-ketoester is key to cleaving the C-N bond and delivering a cationic π-allyl nickel(II) intermediate.

Diboron-Promoted Reduction of Ni(II) Salts: Precatalyst Activation Studies Relevant to Ni-Catalyzed Borylation Reactions

The activation and reduction of nickel(II) salts under conditions relevant to Ni-catalyzed borylation reactions is reported. Methanolic solutions of NiCl2·6H2O reacted with >2 equiv of (iPr)2NEt were converted to polymeric Ni(OMe)2, which was characterized by IR spectroscopy, magnetic susceptibility measurements, and verified by independent synthesis from NaOMe. When diboron reagents such as bis(neopentylglycolato) diboron (B2(npg)2) were exposed to methanolic solutions of Ni(II) salts and (iPr)2NEt, nickel metal was deposited along with the evolution of hydrogen gas. A direct relationship between yield of nickel metal and equivalents of B2(npg)2 relative to [Ni] was also observed, reaching >99% yield at 8 equiv. Ni(0) coordination complexes were also isolated when a phosphine, phosphite, and/or diene ligand was present, all starting from NiCl2·6H2O, including the following: Ni[P(OPh)3]4 (74% yield), Ni[P(OiPr)3]4 (54% yield), Ni(PPh3)4 (75% yield), (dppp)2Ni + Ni(1,5-cod)2 (dppp = 1,3-bis(diphenylphosphine)propane) (91% yield), Ni(1,5-cod)2 (1,5-cod = 1,5-cyclooctadiene) (69% yield), and (dppf)Ni(1,5-cod) (dppf = 1,1′-bis(diphenylphosphino)ferrocene) (84% yield). The high yields observed indicated the efficient reduction of Ni(II) to Ni(0) and a likely route for precatalyst entry into the Ni-borylation catalytic cycle. These in situ reduction conditions were also successfully applied to a previously developed Ni-catalyzed alpha-arylation reaction where the requisite Ni(1,5-cod)2 precatalyst was substituted for NiCl2·6H2O and catalytic diboron. Comparable yields to the original report were observed under these conditions, further demonstrating that Ni(0) active species can be efficiently accessed with diboron reagents under protic conditions from Ni(II) salt hydrates.

Advancing Base-Metal Catalysis: Development of a Screening Method for Nickel-Catalyzed Suzuki-Miyaura Reactions of Pharmaceutically Relevant Heterocycles

Interest in replacing palladium catalysts with base metals resulted in the development of a 24-reaction screening platform for identifying nickel-catalyzed Suzuki-Miyaura reaction conditions. This method was designed to be directly applicable to process s

Nickel(I) Aryl Species: Synthesis, Properties, and Catalytic Activity

In this work, Ni(I) aryl species that are directly relevant to cross-coupling have been synthesized. Transmetalation of (dppf)NiIX (dppf = 1,1′-bis(diphenylphosphino)-ferrocene, X = Cl, Br) with aryl Grignard reagents or aryl boronic acids in t

Electronic Effect of Ligands on the Stability of Nickel-Ketene Complexes

Electronically variant (dppf)Ni(ketene) complexes were synthesized and characterized to perform kinetic analysis on their decomposition through a decarbonylation/disproportion process to Ni-CO complexes and alkenes. Ligands containing electron-donating groups stabilized such complexes, whereas an electron-withdrawing group was found to destabilize them. Hammett analysis on the decomposition reaction revealed the buildup of negative charges in the rate-determining step, which corroborates past computational models.

Synergy between Experimental and Computational Chemistry Reveals the Mechanism of Decomposition of Nickel-Ketene Complexes

A series of (dppf)Ni(ketene) complexes were synthesized and fully characterized. In the solid state, the complexes possess η2-(C,O) coordination of the ketene in an overall planar configuration. They display similar structure in solution, except in some cases, the η2-(C,C) coordination mode is also detected. A combination of kinetic analysis and DFT calculations reveals the complexes undergo thermal decomposition by isomerization from η2-(C,O) to η2-(C,C) followed by scission of the C=C bond, which is usually rate limiting and results in an intermediate carbonyl carbene complex. Subsequent rearrangement of the carbene ligand is rate limiting for electron poor and sterically large ketenes, and results in a carbonyl alkene complex. The alkene readily dissociates, affording alkenes and (dppf)Ni(CO)2. Computational modeling of the decarbonylation pathway with partial phosphine dissociation reveals the barrier is reduced significantly, explaining the instability of ketene complexes with monodentate phosphines.

Fundamental studies and development of nickel-catalyzed trifluoromethylthiolation of aryl chlorides: Active catalytic species and key roles of ligand and traceless MeCN additive revealed

A catalytic protocol to convert aryl and heteroaryl chlorides to the corresponding trifluoromethyl sulfides is reported herein. It relies on a relatively inexpensive Ni(cod)2/dppf (cod = 1,5-cyclooctadiene; dppf = 1,1′-bis(diphenylphosphino)ferrocene) catalyst system and the readily accessible coupling reagent (Me4N)SCF3. Our computational and experimental mechanistic data are consistent with a Ni(0)/Ni(II) cycle and inconsistent with Ni(I) as the reactive species. The relevant intermediates were prepared, characterized by X-ray crystallography, and tested for their catalytic competence. This revealed that a monomeric tricoordinate Ni(I) complex is favored for dppf and Cl whose role was unambiguously assigned as being an off-cycle catalyst deactivation product. Only bidentate ligands with wide bite angles (e.g., dppf) are effective. These bulky ligands render the catalyst resting state as [(P-P)Ni(cod)]. The latter is more reactive than Ni(P-P)2, which was found to be the resting state for ligands with smaller bite angles and suffers from an initial high-energy dissociation of one ligand prior to oxidative addition, rendering the system unreactive. The key to effective catalysis is hence the presence of a labile auxiliary ligand in the catalyst resting state. For more challenging substrates, high conversions were achieved via the employment of MeCN as a traceless additive. Mechanistic data suggest that its beneficial role lies in decreasing the energetic span, therefore accelerating product formation. Finally, the methodology has been applied to synthetic targets of pharmaceutical relevance.

PROCESS FOR PREPARING 2-AMINO-5-CYANOBENZOIC ACID DERIVATIVES

Disclosed is a method for preparing a compound of Formula 1 comprising contacting a compound of Formula 2 with at least one alkali metal cyanide of Formula 3 and a compound of Formula 4 wherein R1 is NHR3 or OR4; R2 is CH3 or Cl; R3 is H, C1-C4 alkyl, cyclopropyl, cyclopropylcyclopropyl, cyclopropylmethyl or methylcyclopropyl; R4 is H or C1-C4 alkyl; X is Br, Cl or I; and R5, R6, R7, R8, R9 and R10 are as defined in the disclosure. Also disclosed is a method for preparing a compound of Formula 4 wherein R9 and R10 together are a cycloalkadiene bidentate ligand, comprising contacting a compound of Formula 5 wherein Y is Cl, Br or I, with a cycloalkadiene bidentate ligand, at least one metal reducing agent and a nitrile solvent. Also disclosed is a method for preparing a compound of Formula 1 comprising preparing a compound of Formula 4 by contacting a compound of Formula 5 with a cycloalkadiene bidentate ligand and at least one metal reducing agent, and then contacting the reaction mixture comprising the compound of Formula 4 with a compound of Formula 2 and at least one alkali metal cyanide of Formula 3; and further disclosed is a method for preparing a compound of Formula 6 wherein R15, R16, R17 and Z are as defined in the disclosure using a compound of Formula 1, characterized by preparing the compound of Formula 1 by a method disclosed above.