NHC-Based Pd Catalysts and Ligands for C–C Bond Formation

Aldrich ChemFiles 2006, 6.1, 8.

Aldrich ChemFiles 2006, 6.1, 8.

Sigma-Aldrich, in collaboration with Umicore,1 is pleased to offer a series of robust Pd(II) and Pd(0) complexes employed as efficient catalysts in C–C bond forming reactions. The high performance Pd catalysts reviewed below can rapidly couple alkyl and aryl chlorides with organoboron compounds on large scale (100 g–100 t/a).2 The high TONs, mild reaction conditions, and economic viability/availability of aryl chlorides, make this methodology attractive to industrial scale applications. Catalysts 11 and 12 (Scheme 14) should exhibit superior activity in C–C coupling reactions, because they are formally Pd(0) and are rare examples of well-characterized monocarbene palladium precursors to 12‑electron complexes. Indeed, the Umicore NHC-Pd system performs Suzuki and Kumada couplings as well as a-arylation reactions at mild temperatures.


[Pd(pr)(NQ)]2 and [PD(Mass)(NQ)]2 should exhibit superior activity in C-C coupling reactions

Scheme 14. (660388) (660272)

In the latter case, (NHC)Pd(allyl)Cl (13),2 a reactive, formally 16‑electron complex, mediates the a-arylation of an array of aryl ketones (Scheme 15).3 The air-stable catalyst, short reaction times, and high conversions prove the usefulness of this NHC technology over previous Pd systems. This system can be optimized by utilizing excess aryl halides which, in turn, increases the reaction rates and ensures high product yields in as little as 15 min. Reactivity of both alkyl–alkyl and alkyl–aryl ketones was studied in the early NHC-Pd article from Nolan and co-workers.


(NHC)Pd(allyl)Cl (13), a reactive, formally 16‑electron complex, mediates the a-arylation of an array of aryl ketones

Scheme 15.

[Pd(IMes)(NQ)]2 catalyst 12 demonstrated high reactivity and selectivity in sp3–sp2 Kumada couplings.4 The generality of this methodology extends to both electron-rich and electron-poor aryl magnesium reagents. Furthermore, a broad spectrum of functionalized alkyl chlorides was employed to afford complex organic building blocks (Scheme 16). The high product yields at room temperature validates the robustness of this catalytic system versus well-known Pd-phosphine catalysts Pd(PPh3)4 and Pd2(dba3) as a function of reaction conditions.


a broad spectrum of functionalized alkyl chlorides was employed to afford complex organic building blocks

Scheme 16.

The related [Pd(IPr)(NQ)]2 catalyst 11 exhibited impressive activity in the Suzuki–Miyaura coupling of aryl chlorides with phenyl boronic acid (Scheme 17). At 50 °C, the high-yielding (88%) reaction was complete in one hour at a catalyst loading of 0.5 mol %.5 Interestingly, Pd(0) catalyst 11 produced lower yields of coupled biaryl product at room temperature, whereas analogous catalyst 12 gave 86% yields of 4-Me-biphenyl at both room temperature and 50 °C under identical loadings conditions. Presumably, catalyst 11 needs additional energy to climb over the activation barrier and enter the catalytic cycle as a naked Pd-NHC species. It should be noted that the reactivity of [Pd(IPr)(NQ)]2 was also shown to be high in the coupling of sterically encumbered 2,6-diphenyl chloride and 1‑naphthalene boronic acid (Scheme 18).


the reactivity of [Pd(IPr)(NQ)]2 was also shown to be high in the coupling of sterically encumbered 2,6-diphenyl chloride and 1‑naphthalene boronic acid

Scheme 17.

Scheme 18.

Beller and co-workers succeeded in establishing a reactivity profile for NHC-Pd naphtholquinone catalysts in Heck reactions (Table 4).6 The outstanding capacity of this system is illustrated in Scheme 19, wherein good stillbene yields were obtained at 140 °C in an ionic liquid media. The low catalyst loading (0.5 mol %), cheap aryl chloride reagents, and a stabilized ionic liquid environment all contribute to the potential advancement of this chemistry to the industrial fine chemical arena.


Table 4.


Scheme 19.

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NHC Ligands

It is well known that the activity of Pd catalysts can be modified by the introduction of sterically encumbered groups approximate to the metal center. Sigma-Aldrich now offers two NHC ligands that contain bulky, dissimilar moieties that will impart greater catalyst design flexibility. These asymmetric ligands expand our commercial line of NHC ligands, granting ready access to a range of highly active catalysts in various important organic transformations when combined with metal precursors. More information related to our NHC ligand technology, including relevant ordering details, can be found at sigma-aldrich.com/carbeneligands.

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Materials

     

References

  1. These products are sold in collaboration with Umicore. For questions please contact Aldrich or UMICORE.
  2. Nolan, S. P. et al. Organometallics 2002, 21, 5470.
  3. Nolan, S. P. et al. Org. Lett. 2002, 4053.
  4. Beller, M. et al. Angew. Chem., Int. Ed. Engl. 2005, 44, 674.
  5. Nolan, S. P. et al. J. Organometallic. Chem. 2004, 3722.
  6. Beller, M. et al. Org. Lett. 2002, 4, 3031.

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