The in vogue N-heterocyclic carbenes (NHCs) have attracted attention largely for its new found popularity in chemical catalysis and also for displaying promising traits in biomedical applications. The current perspective provides an account of our efforts in exploring the utility of N/O-functionalized N-heterocyclic carbenes in these two areas. On the catalysis front, we have employed the N/O-functionalized N-heterocyclic carbene based precatalysts for the C–C and C–N bond forming reactions like the Suzuki–Miyaura, Sonogashira and Hiyama cross-couplings, the base-free Michael addition, the alkene and alkyne hydroamination reactions and the ring-opening polymerization (ROP) of L-lactides that produce biodegradable polylactide polymers while on the biomedical application front, the anticancer and antimicrobial properties of these N/O-functionalized N-heterocyclic carbene complexes were evaluated. Towards this objective, the N-heterocyclic carbene chemistry of a variety of transition metals like Ag, Au, Ni and Pd has been investigated.

Fascinating frontiers of N/O-functionalized N-heterocyclic carbene chemistry: from chemical catalysis to biomedical applications

A chiral bicyclic guanidine was developed as a versatile Bronsted base catalyst for the enantioselective Michael reactions of dithiomalonates and β-keto thioesters using a range of acceptors including maleimides, cyclic enones, furanone and acyclic 1,4-dicarbonylbutenes.

Chiral Bicyclic Guanidine as a Versatile Brønsted Base Catalyst for the Enantioselective Michael Reactions of Dithiomalonates and β‐Keto Thioesters

Low valent ruthenium hydride complexes are excellent catalysts which act as either redox Lewis acid or base catalysts. Nitriles are substrates which have strong coordination ability towards transition metals, so new types of catalytic transformations of nitriles have been explored using these catalysts. As redox Lewis acid catalysts, hydration of nitriles, amidation of amines, and esterification of alcohols with nitriles can be achieved. The same catalyst can be used for direct formation of carbon nucleophiles by C–H activation of pronucleophiles, such as nitriles and carbonyl compounds, hence catalytic aldol-type reactions and Michael-type additions can be performed under neutral and mild conditions.

A New Way for Efficient Catalysis by Using Low Valent Ruthenium Complexes as Redox Lewis Acid and Base Catalysts

Cu(SbF6)2-AdamBox and copper(II) bis-(5-tert-butylsalicylaldehydate) catalyze the Michael addition in neutral media. Mechanistic studies, based on UV−vis, IR, and electrospray ionization mass spectrometry (ESI-MS), suggest that copper enolates of the β-dicarbonyl formed in situ are the active nucleophilic species.

Ionic and covalent copper(II)-based catalysts for Michael additions. The mechanism.

A series of several new nickel precatalysts supported overN/O-functionalized N-heterocyclic carbenes (NHC) for the Michael reactions of β-dicarbonyl, β-keto ester, β-diester, and α-cyano ester compounds with α,β-unsaturated carbonyl compounds in air at ambient temperature under the much preferred base-free conditions are reported. Specifically, the nickel complexes, [1-(R1-aminocarbonylmethyl)-3-R2-imidazol-2-ylidene]2Ni [R1 = 2-C6H4(OMe); R2 = Me (1b), iPr (2b), CH2Ph (3b) and R1 = 2-CH2C4H3O; R2 = Me (4b), CH2Ph (5b)] carried out the highly convenient base-free Michael addition of the activated C–H compounds across α,β-unsaturated carbonyl compounds in air at room temperature. The complexes 1b–5b were synthesized by the direct reaction of the respective imidazolium chloride salt with NiCl2·6H2O in CH3CN in the presence of K2CO3 as a base. The exceptional stability of 1b–5b has been attributed to the deeply buried nickel–NHC σ-bonding molecular orbitals as evidenced from the density functional theory (DFT) studies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Nickel Complexes of N/O-Functionalized N-Heterocyclic Carbenes as Precatalysts for Michael Reactions in Air at Room Temperature Under the Much Preferred Base-Free Conditions

In Gegenwart von Nickelacetylacetonat bilden Acetylaceton (I) und Vinylmethylketon (II) in hoher Ausbeute das Michael-Addukt (III), das bisher nur in 45%iger Ausbeute zuganglich war.

NICKEL-CATALYZED MICHAEL ADDITIONS OF β-DICARBONYLS

Substitutionally inert metal β-diketonates undergo typical aromatic electrophilic substitution reactions1, though it has recently been convincingly argued2 that these systems possess little aromatic character. The relatively acidic methine hydrogens on the chelate rings are stoichiometrically replaced in a stepwise manner to yield mixtures of mono-, di- and tri-substituted products as schematically illustrated in reaction (1).

George C. DeLullo

Papers

NICKEL-CATALYZED MICHAEL ADDITIONS OF β-DICARBONYLS

Catalytic Addition of Electrophiles to β-Dicarbonyls