A Broadly Applicable Strategy for Entry into Homogeneous Nickel(0) Catalysts from Air-Stable Nickel(II) Complexes

A series of air-stable nickel complexes of the form L[subscript 2]Ni(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl[subscript 2]·6H[subscript 2]O or NiBr[subscript 2]·3H[subscript 2]O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni(cod)[subscript 2]. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions.National Institute of General Medical Sciences (U.S.) (GM63755)National Science Foundation (U.S.). Graduate Research Fellowshi

Nickel precatalysts as enabling tools for catalytic coupling reactions

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.Cataloged from PDF version of thesis.Includes bibliographical references.[Chemical formula] A series of air-stable nickel complexes of the form L₂Ni(aryl)X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl₂-6H₂O or NiBr₂-3H₂O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. [Chemical formula] The air-stable nickel(II) complex trans-(PCy₂Ph)₂Ni(o-tolyl)Cl was employed as a precatalyst for the Mizoroki-Heck-type, room temperature, internally selective coupling of substituted benzyl chlorides with terminal alkenes. This reaction, which employs a terminal alkene as an alkenylmetal equivalent, provides rapid, convergent access to substituted allylbenzene derivatives in high yield and with regioselectivity greater than 95:5 in nearly all cases. The reaction is operationally simple, can be carried out on the benchtop with no purification or degassing of solvents or reagents, and requires no exclusion of air or water during setup. Synthesis of the precatalyst is accomplished through a straightforward procedure that employs inexpensive, commercially available reagents, requires no purification steps, and proceeds in high yield. [Chemical formula] The nickel-catalyzed cross-coupling of aliphatic N-tosylaziridines with aliphatic organozinc reagents is described. The reaction protocol displays complete regioselectivity for reaction at the less hindered C-N bond, and the products are furnished in good to excellent yield for a broad selection of substrates. An air-stable nickel(II) chloride/ligand precatalyst was also developed and employed for the reaction. In addition to increasing the activity of this catalyst system, this also greatly improves the practicality of this reaction, as the use of the very air-sensitive Ni(cod)₂ is avoided. Finally, mechanistic investigations, including deuterium-labeling studies, show that the reaction proceeds with overall inversion of configuration at the terminal position of the aziridine by way of aziridine ring opening by Ni (inversion), transmetallation (retention), and reductive elimination (retention).by Eric A. Standley.Ph. D. in Organic Chemistr

Simplifying Nickel(0) Catalysis: An Air-Stable Nickel Precatalyst for the Internally Selective Benzylation of Terminal Alkenes

The synthesis and characterization of the air-stable nickel­(II) complex <i>trans</i>-(PCy₂Ph)₂Ni­(<i>o</i>-tolyl)Cl is described in conjunction with an investigation of its use for the Mizoroki–Heck-type, room temperature, internally selective coupling of substituted benzyl chlorides with terminal alkenes. This reaction, which employs a terminal alkene as an alkenylmetal equivalent, provides rapid, convergent access to substituted allylbenzene derivatives in high yield and with regioselectivity greater than 95:5 in nearly all cases. The reaction is operationally simple, can be carried out on the benchtop with no purification or degassing of solvents or reagents, and requires no exclusion of air or water during setup. Synthesis of the precatalyst is accomplished through a straightforward procedure that employs inexpensive, commercially available reagents, requires no purification steps, and proceeds in high yield

Simplifying Nickel(0) Catalysis: An Air-Stable Nickel Precatalyst for the Internally Selective Benzylation of Terminal Alkenes

The synthesis and characterization of the air-stable nickel­(II) complex <i>trans</i>-(PCy₂Ph)₂Ni­(<i>o</i>-tolyl)Cl is described in conjunction with an investigation of its use for the Mizoroki–Heck-type, room temperature, internally selective coupling of substituted benzyl chlorides with terminal alkenes. This reaction, which employs a terminal alkene as an alkenylmetal equivalent, provides rapid, convergent access to substituted allylbenzene derivatives in high yield and with regioselectivity greater than 95:5 in nearly all cases. The reaction is operationally simple, can be carried out on the benchtop with no purification or degassing of solvents or reagents, and requires no exclusion of air or water during setup. Synthesis of the precatalyst is accomplished through a straightforward procedure that employs inexpensive, commercially available reagents, requires no purification steps, and proceeds in high yield

Highly Regioselective Nickel-Catalyzed Cross-Coupling of <i>N</i>‑Tosyl­aziridines and Alkylzinc Reagents

Herein, we report the first ligand-controlled, nickel-catalyzed cross-coupling of aliphatic <i>N</i>-tosyl­aziridines with aliphatic organo­zinc reagents. The reaction protocol displays complete regio­selectivity for reaction at the less hindered C–N bond, and the products are furnished in good to excellent yield for a broad selection of substrates. Moreover, we have developed an air-stable nickel­(II) chloride/ligand precatalyst that can be handled and stored outside a glovebox. In addition to increasing the activity of this catalyst system, this also greatly improves the practicality of this reaction, as the use of the very air-sensitive Ni­(cod)₂ is avoided. Finally, mechanistic investigations, including deuterium-labeling studies, show that the reaction proceeds with overall inversion of configuration at the terminal position of the aziridine by way of aziridine ring opening by Ni (inversion), transmetalation (retention), and reductive elimination (retention)

A Broadly Applicable Strategy for Entry into Homogeneous Nickel(0) Catalysts from Air-Stable Nickel(II) Complexes

A series of air-stable nickel complexes of the form L₂Ni­(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi­(aryl)­X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl₂·6H₂O or NiBr₂·3H₂O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni­(cod)₂. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions

Synthesis of Zinc and Cadmium \u3cem\u3eO\u3c/em\u3e-Alkyl Thiocarbonate and Dithiocarbonate Complexes and a Cationic Zinc Hydrosulfide Complex

Treatment of Zn(II) and Cd(II) hydroxide complexes of the tris(2-pyridylmethyl)amine (TPA) ligand with COS or CS2 in protic solvents (MeOH or EtOH) resulted in [(TPA)Zn–SC(S)OCH3]ClO4 (1), [(TPA)Zn–SC(O)OCH3]BF4 (2), [(TPA)Zn–SC(O)OCH3]ClO4 (3), [(TPA)Zn–SC(O)OCH2CH3]BF4 (4), [(TPA)Cd–SC(S)OCH3]ClO4 (5) and [(TPA)Cd–SC(O)OCH3]ClO4 (6). The molecular structures of 1, 2, 5 and 6 were determined by X-ray crystallography. Complexes 2, 3 and 4, unlike 1, 5 and 6, are easily hydrolyzed upon treatment with water in CH3CN to give zinc hydrosulfide complexes of the form [(TPA)Zn–SH]X (X = BF4− (7) and ClO4− (8)), as evidenced by spectroscopic methods and the crystal structure of 7. These complexes may be prepared more directly by (a) reacting equimolar amounts of TPA, Zn(ClO4)2·6H2O and Me4NOH·5H2O with COS in CH3CN or (b) treating [((TPA)Zn)2(μ-OH)2](ClO4)2 with H2S. Moreover, reactivity and density functional theory computational studies comparing the cationic hydrosulfide complexes 7 and 8 with the neutral zinc hydrosulfide complexes supported by tris(pyrazolyl)borate ligands have been conducted and subtle differences between the two types of hydrosulfide complexes have been determined

Accelerated Discovery in Photocatalysis by a Combined Screening Approach Involving MS Tags

International audienceHerein, we report on the development of a MS-tag screening strategy that accelerates the discovery of photocatalytic reactions. By efficiently combining mechanism-and reaction-based screening dimensions, the respective advantages of each strategy were retained, while the drawbacks inherent to each screening approach could be eliminated. The covalent installation of a suitable MS-tag in discovered quenchers facilitated both the identification of formed products and enabled a significant reduction in the amount of reagents, catalysts and solvents required. Applying this approach led to the discovery of a mild photosensitized decarboxylative hydrazide synthesis from mesoionic sydnones and carboxylic acids as starting materials