The First Negishi Cross-Coupling Reaction of Two Alkyl Centers Utilizing a Pd−N-Heterocyclic Carbene (NHC) Catalyst

Hadei, Niloufar; Kantchev, Eric Assen B.; O'Brien, and Christopher J.; Organ, Michael G.

doi:10.1021/ol0514909

Cited by 155 publications

(79 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[157] Our research group found that IPr·HCl (9) performed much better in this reaction (Table 1, Schemes 6 and 18). [158] Under optimized conditions, the coupling of functionalized alkyl bromides and alkylzinc reagents was achieved in high yield at room temperature without the need for NMI (Scheme 52). Notably, branching at the b-position to the reactive functionality (198, Scheme 53) was also well tolerated.…”

Section: The Negishi Reactionmentioning

confidence: 99%

Palladium Complexes of N‐Heterocyclic Carbenes as Catalysts for Cross‐Coupling Reactions—A Synthetic Chemist's Perspective

2007

View full text Add to dashboard Cite

Palladium-catalyzed C-C and C-N bond-forming reactions are among the most versatile and powerful synthetic methods. For the last 15 years, N-heterocyclic carbenes (NHCs) have enjoyed increasing popularity as ligands in Pd-mediated cross-coupling and related transformations because of their superior performance compared to the more traditional tertiary phosphanes. The strong sigma-electron-donating ability of NHCs renders oxidative insertion even in challenging substrates facile, while their steric bulk and particular topology is responsible for fast reductive elimination. The strong Pd-NHC bonds contribute to the high stability of the active species, even at low ligand/Pd ratios and high temperatures. With a number of commercially available, stable, user-friendly, and powerful NHC-Pd precatalysts, the goal of a universal cross-coupling catalyst is within reach. This Review discusses the basics of Pd-NHC chemistry to understand the peculiarities of these catalysts and then gives a critical discussion on their application in C-C and C-N cross-coupling as well as carbopalladation reactions.

show abstract

Section: The Negishi Reactionmentioning

confidence: 99%

Palladium Complexes of N‐Heterocyclic Carbenes as Catalysts for Cross‐Coupling Reactions—A Synthetic Chemist's Perspective

2007

View full text Add to dashboard Cite

show abstract

“…[157] Wir fanden heraus, dass IPr·HCl (9) in dieser Reaktion erheblich besser abschneidet (Tabelle 1, Schema 6 und 18). [158] Unter optimierten Bedingungen konnten bei Raumtemperatur und ohne NMI (Schema 52) funktionalisierte Alkylbromide und Alkylzinkreagentien mit hoher Ausbeute gekuppelt werden. Dabei konnten Verzweigungen in b-Stellung zur reaktiven Funktion vorliegen (198,Schema 53).…”

Section: Die Negishi-reaktionunclassified

Aus der Sicht des Synthetikers: Palladiumkomplexe N‐heterocyclischer Carbene als Katalysatoren für Kreuzkupplungen

2007

View full text Add to dashboard Cite

Palladiumkatalysierte C‐C‐ und C‐N‐Kupplungen zählen zu den vielseitigsten und leistungsfähigsten Syntheseverfahren. Seit 15 Jahren erfreuen sich die N‐heterocyclischen Carbene (NHCs) wachsender Beliebtheit als Liganden für palladiumvermittelte Kreuzkupplungen und ähnliche Methoden. Sie sind in vielerlei Hinsicht den üblichen tertiären Phosphanen überlegen. Weil NHCs stark σ‐elektronenschiebend sind, können sie auch anspruchsvolle Substrate zu oxidativen Insertionen bewegen. Andererseits führen ihre Sperrigkeit und ihre besondere Topologie zu einer raschen reduktiven Eliminierung. Schließlich tragen die starken Pd‐NHC‐Bindungen zur hohen Stabilität der aktiven Spezies bei – auch bei niedrigen Ligand/Pd‐Verhältnissen und hohen Temperaturen. Wenn erst stabile, anwenderfreundliche und leistungsstarke NHC‐Pd‐Präkatalysatoren kommerziell verfügbar sind, liegt das Ziel eines universellen Kreuzkupplungskatalysators in greifbarer Nähe. Dieser Aufsatz beschreibt zunächst die chemischen Grundlagen zu den NHC‐Pd‐Komplexen, um ihre Besonderheiten kennenzulernen. Anschließend folgt eine umfassende Diskussion zur Anwendung dieser Katalysatoren in C‐C‐ und C‐N‐Kreuzkupplungen sowie in der Carbopalladierung.

show abstract

“…[8,17] Cross-couplings of alkyl substrates are considered to be particularly challenging due to retardation of both oxidative addition and reductive elimination (compared to the unsaturated systems), in addition to the existence of a major competing pathway, b-hydride elimination that would lead to products resembling 5 and 6, for instance, in Table 1. [18] Recently, we discovered that Pd ligated by a bulky NHC, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) (1 Table 1), prepared either in situ [19,20] or from a well-defined complex [21,22] efficiently catalyzes the alkyl-alkyl Negishi cross-coupling of alkylbromides and chlorides possessing bhydrogen atoms at room temperature.…”

mentioning

confidence: 99%

Density Functional Theory Investigation of the Alkyl–Alkyl Negishi Cross‐Coupling Reaction Catalyzed by N‐Heterocyclic Carbene (NHC)–Pd Complexes

Chass

O’Brien

Hadei

et al. 2009

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

A novel mechanism is proposed for the Pd-1,3-(2,6-diisopropylphenyl)imidazolyl-2-ylidene (1) catalyzed Negishi reaction. DFT computations supported by atoms-in-molecules (AIM) analyses of non-truncated models show that a "steric wall" created by the N-substituent on the ligand guides reactants to and from the Pd center. Notably, transmetalation and not oxidative addition is found to be rate-limiting. Additionally, a key Pd-Zn interaction (approximately = 2.4 A, rho(b) approximately = 0.0600 au) is identified in the mechanism. This interaction persists beyond reductive elimination and, in combination with the ligand, facilitates reductive elimination by creating a highly sterically crowded environment in the coordination sphere of the Pd center.

show abstract

The First Negishi Cross-Coupling Reaction of Two Alkyl Centers Utilizing a Pd−N-Heterocyclic Carbene (NHC) Catalyst

Cited by 155 publications

References 37 publications

Palladium Complexes of N‐Heterocyclic Carbenes as Catalysts for Cross‐Coupling Reactions—A Synthetic Chemist's Perspective

Palladium Complexes of N‐Heterocyclic Carbenes as Catalysts for Cross‐Coupling Reactions—A Synthetic Chemist's Perspective

Aus der Sicht des Synthetikers: Palladiumkomplexe N‐heterocyclischer Carbene als Katalysatoren für Kreuzkupplungen

Density Functional Theory Investigation of the Alkyl–Alkyl Negishi Cross‐Coupling Reaction Catalyzed by N‐Heterocyclic Carbene (NHC)–Pd Complexes

Contact Info

Product

Resources

About