The discovery of NHCs (NHC = N‐heterocyclic carbenes) as ancillary ligands in transition‐metal‐catalysis ranks as one of the most important developments in synthesis and catalysis. It is now well‐recognized that the strong σ‐donating properties of NHCs along with the ease of scaffold modification and a steric shielding of the N‐wingtip substituents around the metal center enable dramatic improvements in catalytic processes, including the discovery of reactions that are not possible using other ancillary ligands. In this context, although the classical NHCs based on imidazolylidene and imidazolinylidene ring systems are now well‐established, recently tremendous progress has been made in the development and catalytic applications of BIAN‐NHC (BIAN = bis(imino)acenaphthene) class of ligands. The enhanced reactivity of BIAN‐NHCs is a direct result of the combination of electronic and steric properties that collectively allow for a major expansion of the scope of catalytic processes that can be accomplished using NHCs. BIAN‐NHC ligands take advantage of (1) the stronger σ‐donation, (2) lower lying LUMO orbitals, (3) the presence of an extended π‐system, (4) the rigid backbone that pushes the N‐wingtip substituents closer to the metal center by buttressing effect, thus resulting in a significantly improved control of the catalytic center and enhanced air‐stability of BIAN‐NHC‐metal complexes at low oxidation state. Acenaphthoquinone as a precursor enables facile scaffold modification, including for the first time the high yielding synthesis of unsymmetrical NHCs with unique catalytic properties. Overall, this results in a highly attractive, easily accessible class of ligands that bring major advances and emerge as a leading practical alternative to classical NHCs in various aspects of catalysis, cross‐coupling and C−H activation endeavors.
IPr# – highly hindered, broadly applicable N-heterocyclic carbenes
IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) represents the most important NHC (NHC = N-heterocyclic carbene) ligand throughout the field of homogeneous catalysis. Herein, we report the synthesis, catalytic activity, and full structural and electronic characterization of novel, sterically-bulky, easily-accessible NHC ligands based on the hash peralkylation concept, including IPr#, Np# and BIAN-IPr#. The new ligands have been commercialized in collaboration with Millipore Sigma: IPr#HCl, 915653; Np#HCl; 915912; BIAN-IPr#HCl, 916420, enabling broad access of the academic and industrial researchers to new ligands for reaction optimization and screening. In particular, the synthesis of IPr# hinges upon cost-effective, modular alkylation of aniline, an industrial chemical that is available in bulk. The generality of this approach in ligand design is demonstrated through facile synthesis of BIAN-IPr# and Np#, two ligands that differ in steric properties and N-wingtip arrangement. The broad activity in various cross-coupling reactions in an array of N–C, O–C, C–Cl, C–Br, C–S and C–H bond cross-couplings is demonstrated. The evaluation of steric, electron-donating and π-accepting properties as well as coordination chemistry to Au( i ), Rh( i ) and Pd( ii ) is presented. Given the tremendous importance of NHC ligands in homogenous catalysis, we expect that this new class of NHCs will find rapid and widespread application.
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- Award ID(s):
- 1650766
- NSF-PAR ID:
- 10323766
- Date Published:
- Journal Name:
- Chemical Science
- Volume:
- 12
- Issue:
- 31
- ISSN:
- 2041-6520
- Page Range / eLocation ID:
- 10583 to 10589
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
ItBu (ItBu = 1,3-di- tert -butylimidazol-2-ylidene) represents the most important and most versatile N -alkyl N-heterocyclic carbene available in organic synthesis and catalysis. Herein, we report the synthesis, structural characterization and catalytic activity of ItOct (I t Octyl), C 2 -symmetric, higher homologues of ItBu. The new ligand class, including saturated imidazolin-2-ylidene analogues has been commercialized in collaboration with MilliporeSigma: ItOct, 929 298; SItOct, 929 492 to enable broad access of the academic and industrial researchers within the field of organic and inorganic synthesis. We demonstrate that replacement of the t -Bu side chain with t -Oct results in the highest steric volume of N -alkyl N-heterocyclic carbenes reported to date, while retaining the electronic properties inherent to N-aliphatic ligands, such as extremely strong σ-donation crucial to the reactivity of N -alkyl N-heterocyclic carbenes. An efficient large-scale synthesis of imidazolium ItOct and imidazolinium SItOct carbene precursors is presented. Coordination chemistry to Au( i ), Cu( i ), Ag( i ) and Pd( ii ) as well as beneficial effects on catalysis using Au( i ), Cu( i ), Ag( i ) and Pd( ii ) complexes are described. Considering the tremendous importance of ItBu in catalysis, synthesis and metal stabilization, we anticipate that the new class of ItOct ligands will find wide application in pushing the boundaries of new and existing approaches in organic and inorganic synthesis.more » « less
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We describe the development of [(NHC)Pd(cinnamyl)Cl] complexes of ImPy (ImPy = imidazo[1,5- a ]pyridin-3-ylidene) as a versatile class of precatalysts for cross-coupling reactions. These precatalysts feature fast activation to monoligated Pd(0) with 1 : 1 Pd to ligand ratio in a rigid imidazo[1,5- a ]pyridin-3-ylidene template. Steric matching of the C5-substituent and N2-wingtip in the catalytic pocket of the catalyst framework led to the discovery of ImPyMesDipp as a highly reactive imidazo[1,5- a ]pyridin-3-ylidene ligand for Pd-catalyzed cross-coupling of nitroarenes by challenging C–NO 2 activation. Kinetic studies demonstrate fast activation and high reactivity of this class of well-defined ImPy–Pd catalysts. Structural studies provide full characteristics of this new class of imidazo[1,5- a ]pyridin-3-ylidene ligands. Computational studies establish electronic properties of sterically-restricted imidazo[1,5- a ]pyridin-3-ylidene ligands. Finally, a scalable synthesis of C5-substituted imidazo[1,5- a ]pyridin-3-ylidene ligands through Ni-catalyzed Kumada cross-coupling is disclosed. The method obviates chromatographic purification at any of the steps, resulting in a facile and modular access to ImPy ligands. We anticipate that well-defined [Pd–ImPy] complexes will find broad utility in organic synthesis and catalysis for activation of unreactive bonds.more » « less
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Over the last decades, advances in Ni catalysis have expanded the chemical reactivity of cross-coupling reactions and led to the discovery of catalytic systems that are now widely applied in industrial and academic research. Herein, we report the cross-coupling of aryl tosylates by Ni–NHC catalysis using bulky N-heterocyclic carbene ligands. A notable feature of this operationally-simple method is the combination of ‘fluoride effect’ to minimize homocoupling and bulky NHC ligands, such as IPr* and IPr* MeO , that enhance the activity of Ni in cross-coupling and prevent hydrolysis of sensitive oxygen electrophiles. A broad range of aryl and heteroaryl tosylates underwent cross-coupling with high efficiency. The finding that easily accessible, bulky NHCs with flexible CHPh 2 wingtips enhance the reactivity in Ni–NHC cross-coupling represents a powerful approach for catalysis.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D1SC02619D
