Applications of Palladium N-Heterocyclic Carbene (NHC) Catalysts
Created on 01.22
1. Overview and Significance
Palladium N-heterocyclic carbene (NHC) catalysts are a class of transition metal catalysts featuring NHC ligands and a palladium center. Leveraging the strong σ-donor ability of NHCs, excellent stability, and tunable steric/electronic properties, these catalysts have become indispensable tools in organic synthesis, particularly for constructing C–C and C–heteroatom bonds. They are widely employed in cross-coupling, C–H activation, carbonylation, and defluoroalkylation reactions.
2. Representative Applications
Case 1: Direct Alkynylation of Amines via Sonogashira Cross-Coupling
Catalyst: SIPr-PdCl₂-Py
Reaction: Coupling of terminal alkynes with aryltrimethylammonium triflates
Advantage: Enables one-pot alkynylation of amines without pre-isolation of ammonium salts
Ref.: ACS Catal. 2019, 9, 3730
Case 2: N–C/O–C Bond Activation of Amides and Esters
Catalyst: [Pd(NHC)(acac)Cl]
Reaction: Suzuki-Miyaura and Buchwald-Hartwig cross-coupling via selective N–C/O–C cleavage
Significance: Activates inert carboxylic acid derivatives for coupling reactions
Ref.: Org. Lett. 2019, 21, 3304
Case 3: Allylic Alkylation for Vicinal Tertiary/Quaternary Centers
Catalyst: Pd(OAc)₂/S-IPr
Reaction: Allylic alkylation of ketones with (E)-gem-dialkyl/aryl-substituted allylic carbonates
Stereoselectivity: Diastereoselective construction of vicinal tertiary and quaternary carbon centers
Ref.: ACS Catal. 2018, 8, 3317
Case 4: C–N Coupling under Aerobic Conditions
Catalyst: Pd-PEPPSI-IPentᴬⁿ
Reaction: Buchwald-Hartwig amination of (hetero)aryl chlorides with amines
Practicality: Proceeds efficiently under aerobic conditions, enhancing operational simplicity
Ref.: J. Org. Chem. 2018, 83, 9144
Case 5: C–O Bond Activation of Aryl Esters
Catalyst: Pd(IPr)(cinnamyl)Cl
Reaction: Suzuki-Miyaura coupling of aryl esters with boronic acids
Innovation: Utilizes stable esters as alternatives to aryl halides for ketone synthesis
Ref.: J. Am. Chem. Soc. 2017, 139, 1311
Case 6: C–N Bond Activation of Aryl Amides
Catalyst: Pd-PEPPSI-IPr
Reaction: Suzuki-Miyaura coupling of aryl amides with arylboronic acids
Breakthrough: Demonstrates the feasibility of amides as electrophilic coupling partners
Ref.: J. Org. Chem. 2017, 82, 6638
Case 7: Hydrodefluorination of gem-Difluorocyclopropanes
Catalyst: Pd/IPrᴮᴵᴰᴱᴬ
Reagent: 3,3-Dimethylallyl pinacol boronate as a hydride donor
Product: Regioselective synthesis of thermodynamically unstable terminal fluoroalkenes
Mechanism: Proceeds via direct 3,4'-hydride transfer
Ref.: J. Am. Chem. Soc. 2024, 146, 24
3. Key Advantages of NHC-Pd Catalysts
- Strong Metal–Ligand Bonding: High stability under heating, functional group interference, and air/moisture
- Reaction Diversity: Applicable to classical cross-couplings, C–H functionalization, and inert bond activation
- Tunability: Catalytic activity and selectivity can be optimized by modifying NHC substituents
- Practicality: Most systems tolerate aerobic conditions, improving reproducibility and scalability
4. References
- Q. Chen et al., ACS Catal.2019, 9, 3730.
- T. Zhou et al., Org. Lett.2019, 21, 3304.
- F.-L. Yu et al., ACS Catal.2018, 8, 3317.
- F.-D. Huang et al., J. Org. Chem.2018, 83, 9144.
- T. B. Halima et al., J. Am. Chem. Soc.2017, 139, 1311.
- P. Lei et al., J. Org. Chem.2017, 82, 6638.
- H. Qian et al., J. Am. Chem. Soc.2024, 146, 24.