Palladium-catalyzed cross-coupling reactions enable organic chemists to form C-C bonds in targeted positions and under mild conditions. Although phosphine ligands have been intensively researched, the search for even better catalysts attention has recently turned use of N-heterocyclic carbene (NHC) ligands, which a strong bond palladium center. PEPPSI (pyridine-enhanced precatalyst preparation, stabilization, initiation) precatalysts with bulky NHC established themselves as successful...

The synthesis of NHC-PdCl(2)-3-chloropyridine (NHC=N-heterocyclic carbene) complexes from readily available starting materials in air is described. 2,6-diisopropylphenyl derivative was found to be highly catalytically active alkyl-alkyl Suzuki and Negishi cross-coupling reactions. synthesis, ease-of-use, activity this complex are substantial improvements over situ catalyst generation all current Pd-NHC complexes. utilization 4 led the development a reliable, easily employed Suzuki-Miyama...

We have developed the first user-friendly Negishi protocol capable of routinely cross-coupling all combinations alkyl and aryl centers. The use an easily synthesized, air stable, highly active, well-defined precatalyst PEPPSI-IPr (1; PEPPSI=pyridine-enhanced preparation, stabilization initiation; IPr=diisopropylphenylimidazolium derivative) substantially increases scope, reliability, ease-of-use reaction. All organohalides used pseudohalides were excellent coupling partners, with chlorides,...

Incredible Bulk: A series of N-heterocyclic carbene catalysts (see picture) were prepared and evaluated in the Suzuki-Miyaura reaction. variety sterically encumbered tetra-ortho-substituted biaryl products formed from unreactive aryl chlorides using isopentyl-substituted catalyst at temperatures ranging 65 degrees C to room temperature. The cyclopentyl-substituted was virtually inactive, demonstrating that "flexible bulk" is essential promote these transformations.

Abstract Palladiumkatalysierte C‐C‐ und C‐N‐Kupplungen zählen zu den vielseitigsten leistungsfähigsten Syntheseverfahren. Seit 15 Jahren erfreuen sich die N‐heterocyclischen Carbene (NHCs) wachsender Beliebtheit als Liganden für palladiumvermittelte Kreuzkupplungen ähnliche Methoden. Sie sind in vielerlei Hinsicht üblichen tertiären Phosphanen überlegen. Weil NHCs stark σ‐elektronenschiebend sind, können sie auch anspruchsvolle Substrate oxidativen Insertionen bewegen. Andererseits führen...

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Carbon–Heteroatom Coupling Using Pd-PEPPSI ComplexesCory Valente†, Matthew Pompeo‡, Mahmoud Sayah‡, and Michael G. Organ*‡View Author Information† The Dow Chemical Company, 400 Arcola Road, Collegeville, Pennsylvania, United States 19426‡ Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada*E-mail: [email protected]Cite this: Org. Process...

ConspectusOver the past decade, use of Pd–NHC complexes in cross-coupling applications has blossomed, and reactions that were either not previously possible or only under very forcing conditions (e.g., > 100 °C, strong base) are now feasible mild room temperature, weak base). Access to tools such as computational chemistry facilitated a much greater mechanistic understanding catalytic cycles, which enabled design new NHC ligands accelerated advances cross-coupling. With these elements...

A capillary-based flow system has been developed for conducting microscale organic synthesis with the aid of microwave irradiation. The capillary internal diameter investigated ranged from 200 to 1200 μm, while rate was varied between 2 and 40 μL/min, which corresponds sample being irradiated approximately 4 min. Other parameters include reaction concentration power setting microwave. Excellent conversion observed in a variety cross coupling ring-closing metathesis (RCM) reactions employing...

A series of Pd-N-heterocyclic carbene (Pd-NHC) complexes with various NHC, halide and pyridine ligands (PEPPSI (pyridine, enhanced, precatalyst, preparation, stabilisation initiation) precatalysts) were prepared, the effects these on catalyst activation performance studied in Kumada-Tamao-Corriu (KTC), Negishi, Suzuki-Miyaura cross-coupling reactions. The lowered reactivity more hindered 2,6-dimethylpyridyl complex 4 Negishi KTC reactions is consistent slow reductive dimerisation...

An easily employed, highly versatile Kumada-Tamao-Corriu (KTC) protocol utilizing the PEPPSI (Pyridine, Enhanced, Precatalyst, Preparation, Stabilization and Initiation) precatalysts 1 2 is detailed. The ease-of-use of these catalysts synthesis a wide range hindered biaryls, large coupling partners drug-like heterocycles, in high yield, makes PEPPSI-KTC very attractive. reactivity system allowed tetra-ortho-substituted heterocycle, 11 to be synthesized at room temperature for first time...

Abstract Pd–N‐heterocyclic carbene (NHC)‐catalyzed Buchwald–Hartwig amination protocols mediated by Pd–PEPPSI precatalysts is described. These provide access to a range of hindered and functionalized drug‐like aryl amines in high yield with both electron‐deficient electron‐rich aryl‐ heteroaryl chlorides bromides. Variations solvent polarity, base temperature are tolerated, enhancing the scope utility this protocol. A mechanistic rationalization for strength (p K b ) requirements also provided.

Abstract An overview of Pd‐PEPPSI complexes in the Negishi cross‐coupling reaction is presented. Preliminary evaluations differentially substituted imidazolium salts that generate highly active catalysts situ provide foundation for development an air‐ and moisture‐stable NHC‐based precatalyst: Pd‐PEPPSI‐IPr. The application Pd‐PEPPSI‐IPr sp 3 –sp , 2 (and vice versa), cross‐couplings reviewed. This allowed systematic Pd‐PEPPSI‐IPent, a more sterically demanding, second‐generation catalyst...

This review concentrates on the results obtained thus far in cross-coupling reactions utilising Pd-PEPPSI-IPr (pre)catalyst. Results from computational studies expose possible factors behind high reactivity of this complex, as well mechanistic details for IPr-Pd-mediated alkyl-alkyl Negishi cross-coupling.

Suzuki reactions of aryl chlorides and arylboronic acids with a range electronically different N-heterocyclic carbene ligands derived from N,N-diadamantylbenzimidazolium salts are reported. Results indicate that an electron-rich NHC ligand enhances the rate oxidative addition. However, reductive elimination is unchanged by electronic nature supporting primarily affected steric environment.

No migration? problem! A series of new N-heterocyclic carbene based Pd complexes has been created and evaluated in the Negishi cross-coupling aryl heteroaryl chlorides, bromides, triflates with a variety secondary alkylzinc reagents (see scheme). The direct elimination product is nearly exclusively formed; most examples there no migratory insertion at all. Detailed facts importance to specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not...

Cool couplings: Complex, hindered biaryls have been prepared at temperatures ranging from 0°C to room temperature, or with gentle heating. The Pd-PEPPSI-IPent catalyst (see scheme) nicely couples starting materials containing acidic moieties and routinely prepares biaryl derivatives where one both rings comprising the are heterocyclic. Ar1=hindered aryl heteroaryl, Ar2=unactivated heteroaryl. Detailed facts of importance specialist readers published as "Supporting Information". Such...

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Abstract Palladiumkatalysierte Kreuzkupplungen versetzten Organiker in die Lage, C‐C‐Bindungen gezielt und unter milden Reaktionsbedingungen zu einzuführen. Während Phosphanliganden diesen Umsetzungen am intensivsten erforscht wurden, sind seit kurzem auf der Suche nach leistungsfähigeren Katalysatoren für auch N‐heterocyclische Carbenliganden (NHC), eine starke Bindung zum Palladiumzentrum bilden, beachtet worden. PEPPSI‐Pd‐Präkatalysatoren (“Pyridin‐verstärkte Präkatalysatorherstellung,...

Aryl thiols made cool and quick: The coupling of alkyl, aryl, silyl to hindered, deactivated aryl bromides chlorides has been achieved under the most mild temperatures yet reported (i.e., room temperature 40 °C). bulk afforded by di-2,6-(3-propylphenyl)imidazolium-derived Pd-PEPPSI-IPent catalyst is believed actively promote critical reductive elimination step catalytic cycle, thereby eliminating formation poisonous off-cycle dimeric resting states that have plagued Pd-catalyzed sulfination...

The cross-coupling reactions of allylboronic acid pinacol ester derivatives with aryl and heteroaryl halides occurred high selectivity (>97%) at the α-carbon allylboron reagent in presence Pd-PEPPSI-IPent precatalyst 5 M KOH refluxing THF. In case trisubstituted allylboronates different substituents on olefin, minor olefin geometry isomerization was observed (E/Z ≈ 80/20).

Pd-PEPPSI-IPent, a recently-developed N-heterocyclic carbene (NHC) complex, has been evaluated in amination reactions with secondary amines and it shown superb reactivity under the most mildly basic reaction conditions. Rate computational studies were conducted to provide insight into mechanism of transformation. The IPent catalyst coordinates amine much more strongly than IPr variant, thus favouring deprotonation comparatively weak bases. Indeed is first order base only slightly zeroth amine.

Pd-PEPPSI-IPent has proven to be an excellent catalyst for the Negishi cross-coupling reaction of secondary alkylzinc reagents with a wide variety aryl/heteroaryl halides. Importantly, β-hydride elimination/migratory insertion organometallic leading production isomeric coupling products been significantly reduced using highly-hindered Ipent ligand.

Abstract Current state‐of‐the‐art protocols for the coupling of unreactive amines (e.g., electron‐poor anilines) with deactivated oxidative‐addition partners electron‐rich and/or hindered aryl chlorides) involve strong heating (usually >100 °C) tert ‐butoxide base, and even then not all couplings are successful. The aggressive base reacts in many instances destroys typical functional groups that necessary function most organic molecules, such as carbonyl groups, esters, nitriles, amides,...

The role of halide salt additives has been investigated in the Negishi reaction involving aryl zinc reagents. Diarylzincs readily transmetallate to Pd relatively non-polar media (e.g., THF) with zero present and coupling proceeds. Arylzinc halides (ArZnX) fail couple THF without salt, but do it. However, unlike alkylzincs that form higher-order zincates order facilitate transmetallation, all is required arylzincs an increase solvent dielectric as even ZnX2 works additive, which completely...