IMes (IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene) and IPr (IPr=1,3‐ bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) represent by far the most frequently used N‐heterocyclic carbene ligands in homogeneous catalysis, however, despite numerous advantages, these ligands are limited by the lack of steric flexibility of catalytic pockets. We report a new class of unique unsymmetrical N‐heterocyclic carbene ligands that are characterized by freely‐rotatable N‐aromatic wingtips in the imidazol‐2‐ylidene architecture. The combination of rotatable N−CH2Ar bond with conformationally‐fixed N−Ar linkage results in a highly modular ligand topology, entering the range of geometries inaccessible to IMes and IPr. These ligands are highly reactive in Cu(I)‐catalyzed β‐hydroboration, an archetypal borylcupration process that has had a transformative impact on the synthesis of boron‐containing compounds. The most reactive Cu(I)‐NHC in this class has been commercialized in collaboration with MilliporeSigma to enable broad access of the synthetic chemistry community. The ligands gradually cover %Vburgeometries ranging from 37.3 % to 52.7 %, with the latter representing the largest %Vburdescribed for an IPr analogue, while retaining full flexibility of N‐wingtip. Considering the modular access to novel geometrical space in N‐heterocyclic carbene catalysis, we anticipate that this concept will enable new opportunities in organic synthesis, drug discovery and stabilization of reactive metal centers.
This content will become publicly available on December 22, 2024
IMes (IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene) and IPr (IPr=1,3‐ bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) represent by far the most frequently used N‐heterocyclic carbene ligands in homogeneous catalysis, however, despite numerous advantages, these ligands are limited by the lack of steric flexibility of catalytic pockets. We report a new class of unique unsymmetrical N‐heterocyclic carbene ligands that are characterized by freely‐rotatable N‐aromatic wingtips in the imidazol‐2‐ylidene architecture. The combination of rotatable N−CH2Ar bond with conformationally‐fixed N−Ar linkage results in a highly modular ligand topology, entering the range of geometries inaccessible to IMes and IPr. These ligands are highly reactive in Cu(I)‐catalyzed β‐hydroboration, an archetypal borylcupration process that has had a transformative impact on the synthesis of boron‐containing compounds. The most reactive Cu(I)‐NHC in this class has been commercialized in collaboration with MilliporeSigma to enable broad access of the synthetic chemistry community. The ligands gradually cover %Vburgeometries ranging from 37.3 % to 52.7 %, with the latter representing the largest %Vburdescribed for an IPr analogue, while retaining full flexibility of N‐wingtip. Considering the modular access to novel geometrical space in N‐heterocyclic carbene catalysis, we anticipate that this concept will enable new opportunities in organic synthesis, drug discovery and stabilization of reactive metal centers.
more » « less- NSF-PAR ID:
- 10486881
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 63
- Issue:
- 8
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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