Amide chiral NHCs

Whilst the addition of a chiral NHC to a ketene generates a chiral azolium enolate directly, a number of alternative strategies have been developed that allow asymmetric reactions to proceed via an enol or enolate intermediate. For example, Rovis and co-workers have shown that chiral azolium enolate species 225 can be generated from a,a-dihaloaldehydes 222, with enantioselective protonation and subsequent esterification generating a-chloroesters 224 in excellent ee (84-93% ee). Notably, in this process a bulky acidic phenol 223 is used as a buffer alongside an excess of an altemativephenoliccomponentto minimise productepimerisation (Scheme 12.48). An extension of this approach allows the synthesis of enantiomericaUy emiched a-chloro-amides (80% ee) [87]. 

Enantioselective oxidative esterification, thioesterification, and amidation of aldehydes have been achieved using a combined organocatalyst system of a chiral NHC and riboflavin, with dioxygen as terminal oxidant." ... 

In 2011, Murakami and coworkers [82] reported that chiral NHC ligands having a 2,2 -bisquinoline-based Cj symmetric skeleton were efficient ligands in the palladium-catalyzed intramolecular a-arylation of amides to afford 3,3-disubstituted oxindoles with good yield and enantioselectivity (Scheme 8.44). The two fused rings attached to the NHC core played an important role in the reaction mechanism. 

Scheme 8.43 Chiral NHCs in the palladium-catalyzed intramolecular cyclization of amides to oxindoles, as described by Kiindig and coworkers [78a,b].

The same group accomplished the enantioselective silyl transfer to a,p-unsamrated lactams and acyclic amides with the same chiral NHC-copper(I) catalyst that is formed from L12 (Scheme 12, upper) [39]. y-Butyrolactams having... 

Chiral hydroxy-amide-functionalized NHC-Ir complexes 199 facilitated efficient asymmetric hydrosilylation of ketones using HSiMe(OEt)2 under ambient conditions (Figure 13.25). A chiral NHC containing an isobutyl stereodirecting group was found to be the best ligand in the examined functionalized NHC-Ir complexes and <96% ee was obtained for the hydrosilylation of aromatic ketones. 

DFT computations for BuLi addition to PhCHO in the presence of chiral A,P-amides R NHC H(R)CH2PPh2 derived from amino acids have reproduced the enantioselectiv-... 

Recently, Trapp and coworkers presented a series of six-membered NHC-Pd complexes 69 [63]. Steric demand increases from 69a to 69c while retaining natural rf-(+)-camphor as the chiral motif. The complexes showed different catalytic profiles in the intramolecular asymmetric a-arylation of amides (Scheme 3.38). Whereas catalyst 69a showed no enantiodiscrimination and 69c gave dehaloge-nation products in attempted oxindole synthesis, 69b proved to be more effective producing the 3,3-disubstituted oxindoles in high yields (up to 98%) and moderate enantioselectivities (68% ee). 

The exclusive access to the particular diastereomer of the NHC ligand (Ra,Ra) that behaves well in catalysis was later reported by the same group. After testing several substitution patterns, Dorta and coworkers foimd that placing a relatively rigid cydooctyl group at the 2-position of the naphthyl moieties lead to the dia-stereomerically pure NHC salt 74 and subsequently the palladium complex 75 (Scheme 3.41) [67]. The palladium complex 75 was tested in the a-arylation of amide for the synthesis of chiral 3-aryl-3-fluoro-oxindole 76. While moderate to... 

Besides chiral amines, also phosphines, sulfides, A(-heterocyclic carbenes (NHCs), phosphoramides, and form-amides have been impressively utilized as chiral Lewis base catalysts in numerous case studies [14, 88]. Chiral phosphines have been mainly used for BayUs-Hillman-type reactions and allenoate activations in this context [88, 94]. 

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