Chirality wingtip groups

Advantage Usually better chiral resolution (% ee) of the product compared with unsaturated NHC with chiral wingtip groups. 

Bohn and coworkers introduced an additional central chiral wingtip group (CHPhMe) onto the other side of the imidazole ring [11] in an attempt to increase the chiral resolution in the product of asymmetric catalysis. For this effect, they reacted phenyl boronic acid with 4-chlorobenzaldehyde to give the corresponding chiral diarylmethanol. Chiral resolution was modest at best with no clear trend as to the additive or competitive nature of the two chiral elements present in the ligand. 

To summarise, a large variety of different chiral elements and chiral wingtip groups were used in the synthesis and application of chiral NHC hgands. No clear trend can be... 

It seems that the racemic mixture of A-hydroxycyclohexyl imidazole is used in further reactions, normally even without mention of chirality [14,15]. Double functionalisation is facile, as the two wingtip groups need to be introduced stepwise. Ray et al. [14] used this opportunity to introduce a keto group in the second step by reacting iV-hydroxycyclohexyl imidazole with chloracetophenone (see Figure 4.2). 

In a comparative study, an unfunctionalised wingtip group chiral NHC, a backbone chiral saturated NHC and the hydroxyethyl functionalised saturated NHC (chiral centre on the... 

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. 

In a more conventional ligand design, Ros et al. used chiral A -tra 5-2,5-diphenylpyr-rolidinyl imidazole as the starting point to introduce a thioether functionality on a primary alkyl halide carrier (see Figure 4.85) [261], The thioether functionality becomes chiral upon coordination to palladium and the remote chirality effect of the other, the pyrrolidine wingtip group ensures that only one of the two possible sulfur based enantiomers is realised. 

Figure 5.2 Synthesis of NHC with central chirality in the wingtip groups.

Note The protocol can also be applied to 1,2-diaminoethane to form the corresponding imidazolidine system [29]. If the carbon atoms of the ethane (propane) backbone are chosen to be asymmetric, chirality is introduced into the ring rather than the wingtip groups. 

We would like to introduce at this point a few examples of wingtip group chiral imidazo-lium salts that are somewhat outside the mainstream. 

Another interesting approach to an NHC ligand with a chiral, bridging wingtip group was introduced by Perry et al. [45] and uses enantiomerically pure 1,2-diamino-cyclohexane as the scaffold. Reaction with chloroacetic acid chloride and subsequently with DIPP-imidazole yields the imidazolium salt that can be reacted with silver(I) oxide [46] to the respective silver(I) NHC complex. Subsequent carbene transfer to palladium(II) renders the chiral palladium(II) carbene transfer that can be used in catalysis (see Figure 5.9). 

Advantage Sterically more demanding wingtip groups than mesityl can be introduced into the carbene alongside chiral centres in the backbone (O and O). 

It is, of course, possible to combine endocyclic (asymmetric centres in the imidazole ring) with exocycUc (asymmetric centres in the wingtip groups) chirality. The easiest way to do this is to combine the major protocols for each variety within a common synthetic sequence. Figure 5.18 shows a selection of popular and more recent examples for this kind of chiral carbenes [54,63-69]. The list of examples is astonishingly short. 

The stereodirecting effect of the axially chiral 1,1 -binaphthyl ligand is assisted by the bulky wingtip group of the carbene (Mes) and the additional substituents of the benzylide-nyl ligand that features prominently in the Grubbs catalyst (see Figure 5.12). 

It is not strictly necessary to introduce the 1,1 -binaphthyl backbone. For axial chirality, the biphenyl scaffold is sufficient, provided that rotation around the phenyl-phenyl axis is sufficiently hindered. Hoveyda combined this reduced axial chiral motif with additional central chirality in the imidazole backbone (O and C ) [6,7], Synthetically, the task is accomplished by Buchwald-Hartwig amination of enantiomerically pure (H ,21 )-diphenylethylenediamine with 1-methoxy-I -iodo-biphenyl and subsequent reaction with mesityl bromide to introduce the bulky wingtip group on the second amino group of the chiral starting material. Ring closure reaction with triethyl orthoformate and hydrolysis of... 

For planar chirality, the only convincing example up to date is the use of [2,2]-paracyclophane wingtip groups and here auxiliary substituents on the paracyclophane enhance the chiral resolution, probably due to an additional atropisomeric effect, hindrance of rotation aronnd the C-N bond. 

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