biostudies-literatureZhao QAmerican Chemical SocietyNational Institutes of HealthNIH HHSNIGMS NIH HHSNational Science Foundatione202318703https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922840biostudies-literatureUnknown63(8)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-CH₂ Ar 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 %V_bur geometries ranging from 37.3 % to 52.7 %, with the latter representing the largest %V_bur described 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.Angewandte Chemie (International ed. in English)Wingtip-Flexible N-Heterocyclic Carbenes: Unsymmetrical Connection between IMes and IPr.PMC10922840DNI-55549R35GM133326R35 GM133326CHE-1650766Szostak MSzostak RZhao QZhou TLalancette RRahman MYang SfalseWingtip-Flexible N-Heterocyclic Carbenes: Unsymmetrical Connection between IMes and IPr.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-CH₂ Ar 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 %V_bur geometries ranging from 37.3 % to 52.7 %, with the latter representing the largest %V_bur described 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.2024-01-01T00:00:00Z2024 Feb2025-04-18T13:00:30.82Z2025-04-04T02:01:08.552ZS-EPMC109228403813566010.1002/anie.202318703