Chiral N-heterocyclic Carbene Gold Complexes: Synthesis and Applications in Catalysis

Abstract

N-Heterocyclic carbenes have found many applications in modern metal catalysis, due to the formation of stable metal complexes, and organocatalysis. Among a myriad of N-heterocyclic carbene metal complexes, gold complexes have gained a lot of attention due to their unique propensity for the activation of carbon-carbon multiple bonds, allowing many useful transformations of alkynes, allenes, and alkenes, inaccessible by other metal complexes. The present review summarizes synthetic efforts towards the preparation of chiral N-heterocyclic gold(I) complexes exhibiting C 2 and C 1 symmetry, as well as their applications in enantioselective catalysis. Finally, the emerging area of rare gold(III) complexes and their preliminary usage in asymmetric catalysis is also presented. Scheme 3. The synthesis of a gold(I) complex from (R)-1-aminotetralin.An elegant approach to C2-symmetric gold(I) complexes was described by Czekelius et al. [72] (Scheme 4), inspired by previous Herrmann's work [73]. The synthetic approach involves chiral amines 24, readily available from the corresponding phenylacetic acid 22 via the Friedel-Crafts reaction of bromobenzene and fractional crystallization of the corresponding tartaric acid amine salt upon reductive amination. The resulting amine 24 was further formylated and subjected to Bischler-Napieralski cyclization to give 3-aryl-substituted dihydroisoquinoline 25. Subsequent reductive coupling afforded the basic diamine skeleton 26 into a single diastereomer, which appeared a perfect platform for structural ligand diversification via Suzuki coupling. The functionalized diamines 26 were then cyclized into imidazolium salts 27 with triethyl orthoformate to give the products with yields in the range of 49-94% (for selected examples, see Scheme 4). The formation of gold(I) complexes 28 was accomplished under rather unusual conditions, by the reaction of gold(I) chloride with a carbene generated by the action of KOtBu. Scheme 4. The synthesis of C2-symmetric gold(I) complexes accessible via a reductive coupling. The application of other chiral building blocks has recently been reported by the Toste group (Scheme 5) [74]. Besides chiral amines, amino alcohols 29 were also utilized in the synthesis of C2-Scheme 3. The synthesis of a gold(I) complex from (R)-1-aminotetralin.An elegant approach to C 2 -symmetric gold(I) complexes was described by Czekelius et al. [72] (Scheme 4), inspired by previous Herrmann's work [73]. The synthetic approach involves chiral amines 24, readily available from the corresponding phenylacetic acid 22 via the Friedel-Crafts reaction of bromobenzene and fractional crystallization of the corresponding tartaric acid amine salt upon reductive amination. The resulting amine 24 was further formylated and subjected to Bischler-Napieralski cyclization to give 3-aryl-substituted dihydroisoquinoline 25. Subsequent reductive coupling afforded the basic diamine skeleton 26 into a single diastereomer, which appeared a perfect platform for structural ligand diversification via Suzuki...

Recent Advances in the Development of Chiral Gold Complexes for Catalytic Asymmetric Catalysis

“…In enantioselective homogenous gold catalysis, N‐heterocyclic carbenes have been adopted for gold(I) catalysts [1y,50] and gold(III) catalysts [51] . Apart from NHC ligands, acyclic diaminocarbenes (ADC) have also proved its high potential in asymmetric gold catalysis [1w,y,52] …”

“…One of the strategies is chirality transfer from substrates to products in gold‐catalyzed reactions, which enables obtaining enantioenriched compounds utilizing memory of chirality in organic synthesis [2] . Another important strategy is adopting gold catalysts with chiral ligands, obtaining chiral compounds by chiral resolution or constructing new chiral centers from achiral substrates [1r,w,y –aa,3] . Merging organocatalysis and gold catalysis, using chiral auxiliaries including Brønsted acids (e. g., chiral phosphoric acids), primary/secondary amines, and hydrogen‐bonding reagents (e. g., sulfonamides), is also a promising strategy [1v,4] …”

“…Most of the electron‐rich tertiary phosphine and amine ligands are not suitable for gold(III) ion because of the possible reduction. Electron‐deficient nitrogen‐containing ligands such as pyridines, Schiff bases, N‐heterocyclic carbenes and triazole derivatives, were adopted for stable gold(III) complexes [1x–z] . On the other hand, too stable gold(III) complexes tend to exhibit poor catalytic activity.…”

Chiral Gold(III) Complexes: Synthesis, Structure, and Potential Applications

“…[31] In 2011, Michelet summarized the progress made in asymmetric gold catalysis, which then mostly focused on gold(I) complexes along with few existing examples based on gold(III). [32] More recently, two reviews focusing on asymmetric gold catalysis have been published: one on the recent advances in the field and the other on the use of chiral NHC-type ligands, [33,34] both mixing gold(I) and (III) compounds. However, there is no review dedicated to the synthesis of chiral gold(III) complexes despite an increasing amount of published reports in the last years.…”

Rapid and mild synthesis of Au–NHC complexes in a simple two-phase flow reactor

“…1,2 NHC complexes of gold have been shown to catalyse a wide variety of reactions, and Au(I)-NHC complexes especially are important in gold catalysis. 3,4 Au(III) has found considerably less use than Au(I)-NHC complexes, despite being readily available from the Au(I) precursors by a simple oxidation. This is most likely due to Au(III)'s propensity towards reduction to Au(I) or Au(0) 5 .…”