N-Heterocyclic Carbenes (NHCs)

1. N-Heterocyclic Carbenes (NHCs) Ming-Liang Lou 1/16/2016

2. Outline • Introduction • Features of NHCs • Coordination to Transition Metals • NHCs as Organocatalysts --take Yonggui Robin Chi’s work for example

3. Introduction 1) Prior to 1960, people thought carbenes were too reactive to be isolated. 2) In the early 1960's Wanzlick first investigated the reactivity and stability of N-heterocyclic carbenes. 3) Shortly thereafter, Wanzlick reported the first application of NHCs as ligands for metal complexes. 4) Surprisingly, the field of NHCs as ligands in transition metal chemistry remained dormant for 23 years. 5)In 1991, a report by Arduengo and co-workers on the extraodinary stability, isolation and storablility of crystalline NHC IAd. Angew. Chem. Int. Ed. 1962, 1, 75-80 Angew. Chem. Int. Ed. 1968, 7, 141-142 J. Am. Chem. Soc. 1991,113, 361-363

4. Features of NHCs 1) Different from traditional carbenes, NHCs are electron rich 2) NHCs own remarkable stability a) steric effects of the bulky substituents b) σ-electron-withdrawing: lowering the energy of the occupied σ-orbital c) p-electron-donating：donating electron density into the empty p-orbital d) cyclic nature of NHCs also helps to favour the singlet state by forcing the carbene carbon into a bent ,more sp2-like rearrangement 3) Comparative ease to prepare diverse analogues:benefit from centuries of research on the preparation of heterocyclic compounds Nature,2014,510,485-496

5. Coordination to Transition Metals • Difference between carbene ligands and phosphine ligands : • 1) NHCs are in general more electron-donating than phosphineswhich leads to thermodynamically stronger metal–ligand bonds: typically greater bond dissociation energies and shorter metal–ligand bond • 2)The stronger metal–ligand interaction renders NHC–metal coordination less labile than metal–phosphine binding and the complexes are more thermally and oxidativelystable. • 3) independently modify the steric and electronic properties of NHCs.

6. NHCs as Ligands in Palladium Catalysed Cross-coupling Features: a) electron richness of NHCs can lead to improved oxidative addition b) steric bulkiness of NHCs can aid reductive elimination c) both steric and electronic factors help to stabilize the active Pd0 catalyst Nature,2014,510,485-496

7. NHCs as Organocatalysts Organic Letters,2014,16,3272-3275

8. Synthesis of Spirocyclicγ‑Lactams Organic Letters,2012,14, 5412–5415

9. Access to Chiral Quaternary Aminooxindoles Organic Letters,2014,16,3272-3275

10. Explanation to Different Results an NHC catalyst with an electron-rich, sterically bulky substituent such as the N-mesityl group on the triazolium ring favors homoenolatereactions; the electron-deficient, less hindered azoliumsalts, such as the N- pentafluorophenyl derivatives, are preferred for acyl anion reactions

11. Concise Access to β2-Amino Acids Angew. Chem. 2015, 127, 5250 –5254

12. Carbon–carbon Bond Activation of Cyclobutenones Nature Communications,2015, DOI: 10.1038/ncomms7207

13. NHC-Catalyzed Radical Reactions J. Am. Chem. Soc. 2015, 137, 2416−2419

14. Thank you for your attention!