Asymmetric Base‐Free Michael Addition at Room Temperature with Nickel‐Based Bifunctional Amido‐Functionalized N‐Heterocyclic Carbene Catalysts

Abstract

A series of nickel‐based chiral bifunctional catalysts (1d–3d) with N‐heterocyclic carbene (NHC) ligands derived from (1R)‐(–)‐menthol, (1S)‐(–)pinene, and (1R)‐(+)‐camphor have been successfully designed for asymmetric Michael addition reactions under base‐free conditions. The NHC complexes, namely, [1‐R‐3‐{N‐(phenylacetamido)}imidazol‐2‐ylidene]2Ni [R = (1S)‐menthyl (1d), (1S)‐pinane (2d), and (1R)‐isobornyl (3d)], bearing chiral ancillaries on the amido‐functionalized side arms of the NHC ligands, performed the bifunctional catalysis of the asymmetric base‐free Michael addition reaction of the α‐methyl cyano ester substrates ethyl 2‐cyanopropanoate (4), isopropyl 2‐cyanopropanoate (5), and tert‐butyl 2‐cyanopropanoate (6) with the activated olefinic substrates methyl vinyl ketone (7) and acrylonitrile (8) in 63–98 % yields with enantiomeric excess (ee) values of 2–75 % at room temperature in 8 h. More interestingly, only the longest of the three catalysts, the menthol derivative 1d, showed significant chiral induction of up to 75 % ee; this has been attributed to the reduction of the steric influence owing to the relatively distant dispositions of the chiral ancillaries from the catalytically active metal center that arise as a consequence of the cis geometries of 1d–3d.

New Chiral Ebselen Analogues with Antioxidant and Cytotoxic Potential

“…The mixture was stirred at 60 °C for 20 h. Ethanol was evaporated and the precipitated oxime filtrated under reduce pressure. The product was used without further purification [ 44 ].…”

Chiral Oxazolidine‐Fused N‐Heterocyclic Carbene Complexes of Rhodium and Iridium and Their Utility in the Asymmetric Transfer Hydrogenation of Ketones

“…Despite their promise, the multistep sequences required for the synthesis of these fused bicyclic oxazolidine N‐heterocyclic carbene ligands has somewhat restricted the larger applicability of these ligands, and this has attracted our attention. Specifically, owing to our interest in the exploration of the catalytic utility N‐heterocyclic carbene ligands with different ring types, spanning from the ubiquitous five‐membered cyclic imidazole‐ and triazole‐based ones to less common varieties such as acyclic six‐membered N‐heterocyclic carbenes, bicyclic imidazo[1,2‐ a ]pyridines,, and tricyclic triazolooxazine‐derived ones, we became interested in exploring the catalytic exploits of one such less frequently encountered type, that is, chiral bicyclic oxazolidine‐fused N‐heterocyclic carbene ligands. Furthermore, as much of the catalytic studies reported for these bicyclic oxazolidine‐fused N‐heterocyclic‐carbene‐based systems were performed under in situ LAC conditions and there are no known examples of well‐defined transition‐metal complexes, we decided to employ structurally characterized molecular complexes for our study in asymmetric catalysis to obtain a better insight into the mode of action of these catalysts.…”

The Developing Concept of Bifunctional Catalysis with Transition Metal N‐Heterocyclic Carbene Complexes

“…Towards this purpose, a series of bis‐chelating amido‐functionalized N‐heterocyclic carbene complexes of nickel of the type (NHC) 2 Ni ( 1 – 3 ,23 4 – 8 ,24 11 – 12 25 and 13 –1 5 26) were synthesized, and in the process of which two rare examples of the terminal‐[Ni–OH] complexes 9 and 10 25 were structurally characterized (Figure 1). Significantly enough, all of these nickel complexes 1 – 15 of the amido‐functionalized NHC ligands carried out the bifunctional catalysis of the base‐free Michael addition reaction under ambient conditions at room temperature Scheme (A–C).…”

“…The asymmetric version of the base‐free Michael addition was also tried with the following chiral bifunctional Ni–NHC catalysts 13 – 15 26. Quite interestingly, of the three bifunctional catalysts derived from the (1 R )‐(–)‐menthol ( 13 ), (1 S )‐(–)pinene ( 14 ) and (1 R )‐(+)‐camphor ( 15 ) scaffolds, only the menthyl derivative 13 exhibited asymmetric induction exhibiting enantionselectivity of up to 75 % ( ee ) even though all of the three catalysts carried out the base‐free Michael addition in an efficient fashion.…”