Chirality bis-carbenes

In practical terms, axial chirality often occurs when free rotation along an axis in the molecule is sufficiently hindered. A well known example is the binaphthyl system where free rotation around the common bond can be prevented by introducing bulky substituents in the 2,2 -positions. If these substituents are NHC, then an axial chiral bis-carbene results... 

A much more complex but still chiral bis-carbene ligand system was introduced by Veige and coworkers [352,353] based on the tra 5-9,10-dihydro-9,10-ethanoanthracene scaffold (see Figure 3.111) that has been used previously as a platform for chiral bidentale ligands [354,355]. 

Figure 3.110 Synthesis of a chiral bis-carbene complex of palladium(ll) using the 1,2-diami-...

Figure 3.111 Synthesis of chiral bis-carbenes based on a 9,10-ethanoanthracene scaffold and their transition metal complexes.

Figure 3,113 Synthesis of an axial chiral bis-carbene on a binaphthyl scaffold.

Figure 5.19 Axial chiral bis-carbene ligands based on the 1,1 -binaphthyl scaffold.

Despite the planar conformation of nitrogens, several possibilities are available for the introduction of chirality. It is possible to prepare benzim-idazolylidenes, triazolylidenes, imidazolylidenes or unsubstituted-backbone imidazolinylidenes with a stereogenic center on one or two N-substituents (carbenes I and II). The other possibility is to relay the imidazolinylidenes backbone stereogenecity via the N-substituents or to combine stereogenic N-substituents with a chiral backbone (carbenes III or IV). It is at least possible to prepare bis-carbenes of type V with one (or two) stereogenic link between the two carbenes (Fig. 7). 

Mono or bis-carbene complexes are possible depending on the carbene/ metal precursor ratio and the steric bulk of the carbene. Most of the metal precursors and bases used for the synthesis of chiral complexes are presented below Metal precursors ... 

Among the transition-metal catalysts that have been used, only those of Pd(II) are productive with diazomethane, which may be the result in cyclopropanation reactions [7,9,21] of a mechanism whereby the Pd-coordinated alkene undergoes electrophilic addition to diazomethane rather than by a metal carbene transformation in any case, asymmetric induction does not occur by using Pd(II) complexes of chiral bis-oxazolines [22],... 

A stereoselective insertion of phenyldiazoacetate-derived carbene into the a-C-H bond of tetrahydrofuran, catalyzed by a laponite clay-immobilized chiral bis(oxazoline) copper complex, depicted below, was also described <07OL731>. 

A totally different approach to bis-carbene ligands on a cyclic scaffold comes from Burgess and coworkers [351], They start from AA -dimethyl-l,2-diaminocyclohexane and acetylate this compound with chloroacetic acid chloride. Addition of an N-substituted imidazole yields the chiral bis-imidazolium salt (see Figure 3.110). Reaction with silver(I) oxide and carbene transfer to palladium(II) completes the reaction sequence. 

A third example comes from Clyne et al. [358] and concerns the axial chiral binaphthyl backbone [359,360], itself known from phosphorus chemistry [361]. The synthesis starts from the trifluoromethylsulfonato substituted binaphthyl with a Kumada coupling reaction [291,292] with methytmagnesiumbromide. Oxidation with NBS yields the methyl brominated derivative that can be attached to the imidazole ring. Subsequent methylation results in the bis-imidazolium salt that is deprotonated to the bis-carbene and coordinated to the transition metal halide (Pd, Ni), a rather straightforward reaction sequence (see Figure 3.113). The overall yield for the four-step reaction to the bis-imidazolium salt is surprisingly good (65%). 

The concept can be adapted to the introduction of only one (chiral) carboxylic acid wingtip group, even without the introduction of a second one [94]. The adaptation comprises the drop-wise addition of a mixture of ammonia, sodium hydroxide and the a-amino acid in water to a solution of glyoxal and formaldehyde in water at 50°C. Yields are moderate (but excellent compared with the 40-50% achieved by the parent protocol [97]). In the event, Strassner and coworkers [94] used the chiral carboxylic acid functionalised imidazole for the synthesis of the corresponding ester functionalised bis-carbene ligand and their palladium(ll) complexes. 

The ability of chiral bis(camphorquinone-a-dioximato)cobalt(Il) complexes (Section 1.2.1.2.4.2.6.3.1.) to catalyze carbene transfer from diazocarbonyl compounds (diazoacetic esters, 2-diazo-l-phenylethan-l-one) to terminal alkenes conjugated with vinyl, aryl, carbonyl, and cyano groups, has already been mentioned. The ee-values are 75-88 /o at best, often lower. The highest values are again obtained with bulky diazoacetic esters. The significance of these catalysts, however, is their ability to promote cyclopropanation of electron-deficient alkenes, such as acrylates and acrylonitriles, in contrast to the rhodium and copper catalysts discussed above. 

Besides Rh, Cu is another transition metal widely used to catalyze carbene transformations. Early on, intramolecular insertions of carbenoids have been realized by copper complexes ligated with chiral bis(oxazolines) and... 

In 2005, Enders et al. [22] reported the first enantioselective intramolecular crossed-benzoin reaction catalyzed by novel chiral bi- or tetracyclic triazolium carbenes 9a, 9b, or 10. A number of benzoin products with a quaternary chiral carbon were obtained in high yields with good to high enantioselectivities (Scheme 7.7). 

More recently Wulff and coworkers introduced a method based on the reaction of diynes 4 with bis(carbene) complexes 3 (Eq. 4.2) [6]. In contrast to the classical fragment condensation method, two phenol rings are formed during the key cyclization step. Since bonds to the substituted methylenes are not cleaved in the cyclization step, this method allows the preparation of chiral, optically active methylene-substituted calix[4]arenes, starting from the appropriate enantiopure precursors. 

Bridging of two carbene donor groups with the 1,1 -binaphthyl moiety led to ligands with axial chirality. Bis-imidazolium salt 56 and the analogous benzimidazolium derivative belong to these ligand precursors as well as the hydroxyl substituted mono-imidazolium derivative 57. Additional examples for carbenes and carbenes precursors with chiral modified N-heterocycles are presented in Schemes 1.7 and 1.8. 

Liu L-J, Wang F, Shi M. Synthesis of chiral bis(N-heterocyclic carbene) palladium and rhodium complexes with 1,1 -biphenyl scaffold and their application in asymmetric catalysis. Organometallics. 2009 28 4416-4420. 

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