Connecting Neutral and Cationic Pathways in Nickel-Catalyzed Insertion of Benzaldehyde into a C–H Bond of Acetonitrile

Abstract

Nickel catalysts supported by diethylamine-or aza-crown ether-containing aminophosphinite (NCOP) pincer ligands catalyze the insertion of benzaldehyde into a C−H bond of acetonitrile. The catalytic activity of neutral (NCOP)Ni(O t Bu) and cationic [(NCOP)Ni(NCCH 3 )] + are starkly different. The neutral tert-butoxide precatalysts are active without any added base and give good yields of product after 24 h, while the cationic precatalysts require a base cocatalyst and still operate much more slowly (120 h in typical runs). A series of in situ spectroscopic studies identified several intermediates, including a nickel cyanoalkoxide complex that was observed in all of the reactions regardless of the choice of precatalyst. Reaction monitoring also revealed that the neutral tert-butoxide precatalysts decompose to form the cationic acetonitrile complex during catalysis; this deactivation involves alkoxide abstraction and can be hastened by the addition of lithium salts. While the deactivated cationic species is inactive under standard base-free conditions, catalysis can be reinitiated by the addition of catalytic amounts of base. ■ INTRODUCTIONOrganonickel complexes orchestrate an array of molecular elaborations, 1−8 but nickel catalysts have lagged behind precious metals in the functionalization of C−H bonds. 6−8 The choice of substrate can be a deciding factor in nickelmediated C−H functionalization: substrates containing a directing group can hold a C−H bond in close proximity to the metal center, 9−13 or substrates containing relatively acidic C−H bonds can facilitate pathways that rely on deprotonation. 14,15 Acetonitrile is an attractive substrate for nickel-catalyzed C− C bond-forming reactions because the sp 3 C−H bond is relatively acidic (pK a = 25 in H 2 O) 16 and the products would contain a valuable nitrile functionality. Direct deprotonation of acetonitrile is often impractical or not tolerated by nearby functional groups, motivating the development of catalytic methods that avoid stoichiometric amounts of strong base.This article describes the insertion of benzaldehyde into a C−H bond of acetonitrile (Scheme 1) catalyzed by asymmetric Ni aminophosphinite (NCOP) pincer complexes with little or no base added. Only two nickel catalysts are found among the handful 17−22 of late-transition-metal catalysts known to carry out this cyanomethylation reaction, 23,24 which produces synthetically useful β-hydroxy nitriles. 25−27 In 2005, Ozerov and co-workers reported a cationic Ni catalyst that required stoichiometric base to couple nitriles and aldehydes. 23 In 2013, Guan and co-workers isolated a C-bound cyanomethyl species (Ni−CH 2 CN) that proved to be a highly active catalyst (turnover number (TON) of up to 82 000) for C−H insertion without added base. 24 The two Ni catalysts were proposed to operate through quite different mechanisms, despite the fact that both are supported by pincer ligands. The cationic, base-promoted catalyst was proposed to react through the Lewis acid mechanism shown in Scheme 2A: nitril...

Installation of internal electric fields by non-redox active cations in transition metal complexes

“…Electric elds generated by internal dipoles have been increasingly cited in selective or increased reactivity for organic synthesis. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Kanan et al have demonstrated that the eld generated by ion pairing modies the regioselectivity of Au(I)-catalyzed hydroarylation of 3-substituted phenyl propargyl ethers. 31 Coote et al have also reported using pH switchable elds that rely on protonationdeprotonation to vary radical stability.…”

Reaction Medium as the Installing Reservoir for Key Functionalities in the Molecules

“…Similarly generation of CN − anion was achieved using various systems such as Cu, NaH . Formation of metal‐cyano complexes were also observed during the cyanation and cyanomethylation using ACN with the various metals such as Ni, Ir‐PNP pincer, [70 NiNCOP Pincer, Cu, Cu/Ag and Ag . Shen and coworkers demonstrated that in presence of copper and TEMPO in a reaction, both cyanide anion as well as cyanide radical formations are possible …”

“…Pincer complexes were also studied for the cyanomethylation. Smith and Miller (2016) explored the Nickel‐NCOP type pincer complex for the hydrocyanomethylation of benzaldehyde using ACN (Scheme ). Two pathways were proposed (neutral and cationic) under present conditions.…”

An Ion‐Responsive Pincer‐Crown Ether Catalyst System for Rapid and Switchable Olefin Isomerization

“…[15][16][17][18] With am acrocycle as hemilabile ligand, dissociation of the chelate reveals ar eceptor for cation binding.W ith iridium pincer-crown ether complexes,cations in solution can adjust the extent of acetonitrile binding and the rate of H 2 activation. [15][16][17][18] With am acrocycle as hemilabile ligand, dissociation of the chelate reveals ar eceptor for cation binding.W ith iridium pincer-crown ether complexes,cations in solution can adjust the extent of acetonitrile binding and the rate of H 2 activation.…”

“…Considering the lack of methods for controlling substrate binding in small organometallic catalysts,w eh ave initiated ap rogram to develop ligands with ion-tunable hemilability. [15][16][17][18] With am acrocycle as hemilabile ligand, dissociation of the chelate reveals ar eceptor for cation binding.W ith iridium pincer-crown ether complexes,cations in solution can adjust the extent of acetonitrile binding and the rate of H 2 activation. [15] Only degenerate H/D exchange was observed, rather than productive catalysis,w ith mechanistic studies suggesting at unable continuum between two different activity states.…”