Palladium–NHC complex explained

In organometallic chemistry, palladium-NHC complexes are a family of organopalladium compounds in which palladium forms a coordination complex with N-heterocyclic carbenes (NHCs). They have been investigated for applications in homogeneous catalysis,[1] particularly cross-coupling reactions.[1] [2]

Synthesis

See main article: article and Transition metal NHC complex. The synthesis of Pd-NHC complexes follows the methods used for the synthesis of transition metal NHC complexes. The synthesis of Pd-NHC complexes can also be achieved through substitution of a labile ligand L in a Pd-L complex. Labile ligands typically include cyclooctadiene, dibenzylideneacetone, bridging halides, or phosphines. This process can be used in conjunction with the in situ generation of free carbenes. Pd-NHC complexes can also be synthesized through transmetalation with silver-NHC complexes. The transmetallated NHCs can either be isolated for subsequent reaction with palladium in a two-step method, or generated in the presence of palladium in a one-pot reaction. However, generation of Pd-NHC complexes by Ag transmetallation is cost-prohibitive and hampered by Ag complexes’ light sensitivity.[1]

Pd-NHC complexes in catalytic cross-coupling

The utility of palladium-catalyzed cross-coupling reactions is enhanced by the use of N-heterocyclic carbene ligands. Indeed, Pd-NHC complexes have been proven effective in Suzuki-Miyaura, Negishi, Sonogashira, Kumada-Tamao-Corriu, Hiyama, and Stille cross-coupling. Compared to the corresponding Pd-phosphine catalysts, Pd-NHC catalysts can be faster, exhibit broader substrate scope, all with higher turnover numbers.[1]

Suzuki-Miyaura cross-coupling

In Suzuki-Miyaura cross-couplings, the traditional coupling partners are organobromides and organoboron compounds. While Suzuki-Miyaura cross-couplings typically employ organobromides as coupling partners, organochlorides are more desirable electrophiles for cross-coupling due to their lower cost. The sluggish reactivity of the C-Cl bond is often a problem. With the advent of Pd-NHC complexes, organochlorides have emerged as viable partners in Suzuki-Miyaura cross coupling.[1] [3]

Negishi coupling

The use of NHC-Pd-PEPPSI complexes in Negishi cross-coupling has resulted in high turnover numbers and turnover frequencies.[4] Additionally, NHC-Pd complexes can be used to couple sp3 centers to sp3 centers in higher yield than their non-NHC Pd analogs.[5] However, studies of Pd-NHC complexes and their utility in Negishi coupling are currently lacking despite these promising results.

Sonogashira coupling

Pd-NHC complexes used in Sonogashira cross-coupling effect temperature stability in the complex.[6] As in other Pd-NHC mediated cross-coupling reactions, the use of Pd-NHC complexes also allow higher turnover numbers than their NHC-free counterparts.[7] NHC-palladacycles permit copper-free Sonogashira reactions to be carried out.[8] [9]

Heck-Mizoroki coupling

The use of Pd-NHC complexes in Heck-Mizoroki cross-coupling permits the use of cheaper, ample supplies of aryl chloride substrates.[1] Additionally, the activity and stability of the catalyst in Heck-Mizoroki coupling can be enhanced by adjusting the 1,3 substituents on the imidazole ring.[10]

Notes and References

  1. Fortman. George. Nolan. Steven. N-Heterocyclic carbene (NHC) ligands and palladium in homogeneous cross-coupling catalysis: a perfect union. Chemical Society Reviews. 2011. 40. 10. 5151–5169. 10.1039/C1CS15088J. 21731956.
  2. Web site: Eastman. K. N-Heterocyclic Carbenes (NHCs). www.scripps.edu.
  3. Gstöttmayr. Christian. Volker. Böhm. Eberhardt. Herdtweck. Grosche. Manja. Herrmann. Wolfgang. A Defined N-Heterocyclic Carbene Complex for the Palladium-Catalyzed Suzuki Cross- Coupling of Aryl Chlorides at Ambient Temperatures. Angewandte Chemie International Edition. 2002. 41. 8. 1363–1365. 10.1002/1521-3773(20020415)41:8<1363::aid-anie1363>3.0.co;2-g.
  4. Nasielski. J.. Hadei. N.. Achonduh. G. E. A. B.. Kantchev. O'Brien. C.J.. Structure–Activity Relationship Analysis of Pd–PEPPSI Complexes in Cross-Couplings: A Close Inspection of the Catalytic Cycle and the Precatalyst Activation Model. Chemistry: A European Journal. 2010. 16. 35. 10844–10853. 10.1002/chem.201000138. 20665575.
  5. Niloufar. Hadei. Kantchev. Eric. O'Brien. Christopher. The First Negishi Cross-Coupling Reaction of Two Alkyl Centers Utilizing aPd − N-Heterocyclic Carbene (NHC) Catalyst. Organic Letters. 2005. 7. 17. 3805–3807. 10.1021/ol0514909. 16092880.
  6. Batey. Robert. Shen. Ming. Lough. Alan. Carbamoyl-Substituted N-Heterocyclic Carbene Complexes of Palladium(II): Application to Sonogashira Cross-Coupling Reactions. Organic Letters. 2002. 14. 9. 1411–1414. 10.1021/ol017245g.
  7. Kim. Jong-Ho. Lee. Dong-Ho. Jun. Bong-Hyun. Lee. Yoon-Sik. Copper-free Sonogashira cross-coupling reaction catalyzed by polymer-supported N-heterocyclic carbene palladium complex. Tetrahedron Letters. 2007. 48. 40. 7079–7084. 10.1016/j.tetlet.2007.08.015.
  8. Chinchilla. Rafael. Nàjera. Carmen. The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry. Chemical Reviews. 2007. 107. 3. 874–922. 10.1021/cr050992x. 17305399.
  9. McGuinness. David. Cavell. Kingsley. Donor-Functionalized Heterocyclic Carbene Complexes of Palladium(II): Efficient Catalysts for C - C Coupling Reactions. Organometallics. 2000. 19. 5. 741–748. 10.1021/om990776c.
  10. Taige. Maria. Zeller. Alexander. Ahrens. Sebastian. Goutal. Sigrid. Hardtweck. Eberhardt. New Pd–NHC-complexes for the Mizoroki–Heck reaction. Journal of Organometallic Chemistry. 2006. 692. 7. 1519–1529. 10.1016/j.jorganchem.2006.11.050.