A new class of easily activated palladium precatalysts for facile C-N cross-coupling reactions and the low temperature oxidative addition of aryl chlorides

A new class of one-component Pd precatalysts bearing biarylphosphine ligands is described. These precatalysts are air- and thermally stable, are easily activated under normal reaction conditions at or below room temperature, and ensure the formation of the highly active monoligated Pd(0) complex necessary for oxidative addition. The use of these precatalysts as a convenient source of LPd(0) in C-N cross-coupling reactions is explored. The reactivity that is demonstrated in this study is unprecedented in palladium chemistry.     

4,4'-Disubstituted BINAPs for highly enantioselective Ru-catalyzed asymmetric hydrogenation of ketones

A family of tunable precatalysts Ru(4,4'-BINAP)(chiral diamine)Cl2 was synthesized and used for highly enantioselective hydrogenation of aromatic ketones. This result differs from previous chiral diphosphines that rely on the bis(xylyl)phosphino groups to control enantioselectivity. An X-ray structural study reveals that the bulky substituents on the 4,4'-positions of BINAP can effectively create a suitable chiral pocket in the transition state and thus provide a new mechanism for the enantiocontrol in such a remarkable asymmetric catalytic process.     

Catalytic asymmetric hydrogenation of aromatic ketones in room temperature ionic liquids

Polar bisphosphonic acid-derived Ru(BINAP)(DPEN)Cl₂ precatalysts were synthesized and immobilized in room temperature ionic liquids (RTILs) for asymmetric hydrogenation of aromatic ketones with ee values of up to 98.7%. The performance of the Ru catalysts is highly dependent on the nature of imidazolium ILs. For the imidazolium ILs without acidic protons, both ILs and Ru catalysts were recycled by simple extraction and reused. Such a simple immobilization approach also prevented the leaching of Ru (and Ru catalysts) into the chiral secondary alcohol products, and should prove desirable for the production of pharmaceutical intermediates that are free from metal contaminants.     

Electrochemical synthesis and catalytic activity of organonickel sigma-complexes

A new industrially applicable method of organonickel sigma-complexes production is developed. The technique is based on the reaction of the oxidative addition of ortho-substituted aromatic bromides to electrochemically generated nickel(0)-2,2′-bipyridyl complexes. Electrolysis is performed in undivided electrolyser supplied with sacrificial nickel anode with a periodic or continuous electrolyte loading. The electrochemically obtained organonickel sigma-complexes of type [NiBr(Ar)(bpy)], where Ar is 2,4,6-trimethylphenyl, 2,4,6-triisopropylphenyl, 2,6-dimethylphenyl, are highly effective precatalysts for ethylene oligomerization process, leading to the formation of linear alpha-olefines of C4–C12 fractions     

Rational Exploration of N‐Heterocyclic Carbene (NHC) Palladacycle Diversity: A Highly Active and Versatile Precatalyst for Suzuki–Miyaura Coupling Reactions of Deactivated Aryl and Alkyl Substrates

As less attention has been focussed on the design of highly efficient palladium precatalysts to ensure the smooth formation of the active catalyst for metal‐mediated cross coupling reactions, we herein demonstrate that combining the bulky N‐heterocyclic carbene (NHC) 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (IPr) with cyclopalladated acetanilide as the optimal palladium precatalyst leads to superior catalytic activity compared with the state‐of‐the‐art NHC–Pd catalysts. The complex was discovered through the evaluation of a small, rationally designed library of NHC–palladacycles prepared by a novel, practical and atom‐economic method, the direct reaction of IPr?HCl with palladacycle acetate dimers.     

New C2-symmetric 2,4-bis(1-hydroxycyclopentyl)azetidines derived from (S)-1-phenylethylamine and their application in the enantioselective catalysis

The synthesis of new tridental 2,4-bis(1-hydroxycyclopentyl)azetidines using (S)-1-phenylethylamine as starting material is described. These new structures have been successfully applied in the enantiocontrolled catalytic addition of diethylzinc to aromatic aldehydes reaching enantiomeric excesses of up to 85% for the resulting 1-arylpropan-1-ols. Attempts in the field of the enantioselective oxazaborolidine-catalyzed reduction of ketones employing azetidine alcohols as precatalysts are also included.     

Efficient and selective Al-catalyzed alcohol oxidation via Oppenauer chemistry

A highly active and selective Al-based catalytic Oppenauer (O) oxidation is reported. Quantitative and selective oxidations of a variety of benzylic, propargylic, allylic, and aliphatic primary and secondary alcohols were achieved using nitrobenzaldehyde derivatives as the oxidant and simple aluminum compounds as precatalysts.     

A comparison of low and high activity precatalysts: Do the calculated energy barriers during the self‐metathesis reaction of 1‐Octene correlate with the precatalyst metathesis activity?

The self‐metathesis reaction of 1‐octene with several well‐known Grubbs‐type precatalysts and the new Z‐selective Grubbs precatalyst were studied with molecular modeling. The obtained Gibbs‐free energy values for all the steps during the productive metathesis of 1‐octene were compared to the values obtained for some low catalytic activity precatalysts. Determining how the Gibbs‐free energy values of highly active precatalysts compare to that of low catalytic activity precatalysts gave a deeper insight into the mechanism. The questionable correlation of the theoretically observed trends with those obtained experimentally does point to the need to be very cautious when making assumptions from theoretical results without a sufficiently large dataset. © 2014 Wiley Periodicals, Inc.     

Discovery and evaluation of highly active imidotitanium ethylene polymerisation catalysts using high throughput catalyst screening

A family of ca. 50 imidotitanium precatalysts [Ti(NR)(Me(3)[9]aneN(3))Cl(2)](R = alkyl or aryl; Me(3)[9]aneN(3)= 1,4,7-trimethyltriazacyclononane) were prepared in good yields using semi-automated procedures; high-throughput screening techniques identified seven highly active ethylene polymerisation precatalysts with activities in the range ca. 3 400 to 10 000 kg(PE) mol(-1) h(-1) bar(-1).     

Yttrium (amidate) complexes for catalytic C-N bond formation. Rapid, room temperature amidation of aldehydes

Yttrium (amidate) precatalysts are highly active for the mild amidation of aldehydes with amines. Reactions occur at room temperature within 5 min in up to 98% isolated yield. These rare-earth systems are effective for this transformation in the absence of supplementary heat, light, base, or oxidants. The reaction proceeds with functionalized amines and/or aldehydes. A comparison of various amidate precatalysts in combination with reaction monitoring suggests that the targeted amide products formed during the reaction promote the formation of alternative catalytically active amidate species in situ.     

Convenient method for the rapid generation of highly active and enantioselective yttrium catalysts for asymmetric hydroamination

A facile method for the preparation of highly active and enantioselective yttrium precatalysts for asymmetric hydroamination of gem-disubstituted aminoalkenes, from the combination of YCl(3) or YCl(3)(THF)(3.5) with ligand (R)- and n-BuLi is described.     

Amidate complexes of titanium and zirconium: a new class of tunable precatalysts for the hydroamination of alkynes

A series of bis(amidate)group 4-bis(amido) complexes have been prepared, characterized and have been shown to be highly tunable precatalysts for both the intra- and intermolecular hydroamination of alkynes.     

Mechanistic basis for high reactivity of (salen)Co-OTs in the hydrolytic kinetic resolution of terminal epoxides

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co-OH catalyst and a Lewis acidic (salen)Co-X catalyst. The commonly used (salen)Co-OAc and (salen)Co-Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co-OH and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co-OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co-X precatalysts and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co-OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction.     

Palladium Complexes Based on Ylide-Functionalized Phosphines (YPhos): Broadly Applicable High-Performance Precatalysts for the Amination of Aryl Halides at Room Temperature

Palladium allyl, cinnamyl, and indenyl complexes with the ylide-substituted phosphines Cy₃P⁺−C⁻(R)PCy₂ (with R=Me ( L1 ) or Ph ( L2 )) and Cy₃P⁺−C⁻(Me)PtBu₂ ( L3 ) were prepared and applied as defined precatalysts in C−N coupling reactions. The complexes are highly active in the amination of 4-chlorotoluene with a series of different amines. Higher yields were observed with the precatalysts in comparison to the in situ generated catalysts. Changes in the ligand structures allowed for improved selectivities by shutting down β-hydride elimination or diarylation reactions. Particularly, the complexes based on L2 (joYPhos) revealed to be universal precatalysts for various amines and aryl halides. Full conversions to the desired products are reached mostly within 1 h reaction time at room temperature, thus making L2 to one of the most efficient ligands in C−N coupling reactions. The applicability of the catalysts was demonstrated for aryl chlorides, bromides and iodides together with primary and secondary aryl and alkyl amines, including gram-scale applications also with low catalyst loadings of down to 0.05 mol %. Kinetic studies further demonstrated the outstanding activity of the precatalysts with TOF over 10.000 h⁻¹.     

Mizoroki-Heck coupling using immobilized molecular precatalysts: leaching active species from Pd pincers, entrapped Pd salts, and Pd NHC complexes

The Mizoroki-Heck reaction is a palladium-catalyzed reaction of both practical importance and scientific significance. Two challenges currently faced by practitioners of the Heck and other palladium-catalyzed coupling reactions are (i) minimizing the costs associated with this reaction by developing high TON catalysts or facilitating catalyst recovery and (ii) elucidating the nature of the active species when using various different precatalysts. These two challenges, one practical and one fundamental, served as our motivation in our studies of immobilized molecular palladium(II) complexes as precatalysts in Mizoroki-Heck reactions. This Forum Article describes our investigations in this area, highlighting our approach to the elucidation of the active catalyst by combining kinetic and poisoning studies of several different related precatalysts, our development of new, selective catalyst poisons, and our quest for stable, recyclable supported Heck, Suzuki, and Sonogashira coupling catalysts. Under high-temperature conditions (120 degrees C), all precatalysts studied are conclusively shown to decompose, liberating soluble, active palladium(0) species that are the true catalysts. Techniques for the elucidation of the nature of the truly active Pd species are enumerated.     

Ionic Liquids as Precatalysts in the Highly Stereoselective Conjugate Addition of α,β‐Unsaturated Aldehydes to Chalcones

Imidazolium‐based ionic liquids (ILs) serve both as recyclable reaction media and as precatalysts for the N‐heterocyclic carbene‐catalyzed conjugate addition of α,β‐unsaturated aldehydes to chalcones. The reaction produces a broad scope of 1,6‐ketoesters incorporating an anti‐diphenyl moiety in high yields and with high stereoselectivity. In recycling experiments, the IL can be reused up to five times with retained reactivity and selectivity. Moreover, the 1,6‐ketoesters form self‐assembled organogels in aliphatic hydrocarbons. The reaction protocol is robust, easily operated, scalable and highly functionalized compounds can be obtained from inexpensive and readily accessible starting materials.     

Selective iron-catalyzed cross-coupling reactions of grignard reagents with enol triflates, acid chlorides, and dichloroarenes

Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)(3) are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C-C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron-ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)(2)](n) generated in situ. Control experiments using the ate-complex [Me(4)Fe]Li(2) corroborate this interpretation.     

Comparison of dppf‐Supported Nickel Precatalysts for the Suzuki–Miyaura Reaction: The Observation and Activity of Nickel(I)

Ni‐based precatalysts for the Suzuki–Miyaura reaction have potential chemical and economic advantages compared to commonly used Pd systems. Here, we compare Ni precatalysts for the Suzuki–Miyaura reaction supported by the dppf ligand in 3 oxidation states, 0, I and II. Surprisingly, at 80 °C they give similar catalytic activity, with all systems generating significant amounts of Ni^I during the reaction. At room temperature a readily accessible bench‐stable Ni^II precatalyst is highly active and can couple synthetically important heterocyclic substrates. Our work conclusively establishes that Ni^I species are relevant in reactions typically proposed to involve exclusively Ni⁰ and Ni^II complexes.     

Supported copper precatalysts for ligand-free, palladium-free Sonogashira coupling reactions

Copper(II) oxide and Cu metal, highly dispersed on inert oxides (silica, alumina), have been employed as precatalysts in ligand-free, palladium-free Sonogashira coupling reactions. Best results were obtained with highly dispersed Cu metal on alumina, which exhibited high reactivity with aryl iodides. Electron-rich alkynes, in particular arylacetylenes, act as the most effective alkyne substrates. The present catalytic system appears attractive in view of its ease of application and low cost, due to the use of a readily available non-noble metal catalyst combined with the absence of ligands.     

Mechanistic study of asymmetric oxidative biaryl coupling: evidence for self-processing of the copper catalyst to achieve control of oxidase vs oxygenase activity

Copper(I) and copper(II) 1,5-diaza-cis-decalin complexes [(N2)Cu] are effective precatalysts for aerobic oxidative coupling of naphthol substrates. Mechanistic studies, however, reveal that these complexes are not the reactive form of the catalyst under steady-state conditions. Rather, the active catalyst forms in a presteady-state self-processing step that involves oxygenation of the naphthol substrate. The oxygenated substrate, NapHOX, serves as a cofactor that combines with the (N2)Cu complexes to achieve highly selective, steady-state oxidase reactivity (aerobic oxidative biaryl coupling).