Chiral NHCs secondary alcohols

In 2003, Sigman et al. reported the use of a chiral carbene ligand in conjunction with the chiral base (-)-sparteine in the palladium(II) catalyzed oxidative kinetic resolution of secondary alcohols [26]. The dimeric palladium complexes 51a-b used in this reaction were obtained in two steps from N,N -diaryl chiral imidazolinium salts derived from (S, S) or (R,R) diphenylethane diamine (Scheme 28). The carbenes were generated by deprotonation of the salts with t-BuOK in THF and reacted in situ with dimeric palladium al-lyl chloride. The intermediate NHC - Pd(allyl)Cl complexes 52 are air-stable and were isolated in 92-95% yield after silica gel chromatography. Two diaster corners in a ratio of approximately 2 1 are present in solution (CDCI3). 

In a interesting example of organocatalysis, Suzuki et al. studied the enantioselective acylation of secondary alcohols using chiral NHCs [11,12]. The approach was partly based on the work of Nolan and Hedrick who had independently reported NHC-catalyzed transesterifications [13,14]. The enantioselective acylation was subsequently improved by using more sterically hindered acylating agents such as diphenylacetate derivatives (Scheme 4), leading to selectivity factors (s = kn, ) of up to 80 [15,16]. 

Chiral N-arylated imidazolinylidene ligands have been employed in the palladium(II) catalyzed aerobic oxidation of secondary alcohols to the corresponding ketones [55]. The chiral variant of this reaction, which does not generate a new element of chirality, is again based on the kinetic resolution of racemic mixtures. The active catalyst is formed in situ by a combination of two precursors, a dinuclear NHC-palladium(II) complex and an achiral (acetate) or chiral base ((-)-sparteine) (Scheme 18). 

Preceeding this work, palladium/NHC complexes had been used in the aerobic oxidative kinetic resolution of secondary alcohols [93]. The reaction was explored as a measure of match-mismatch interaction between a supporting NHC ligand and an exogenous chiral base. The NHC ligands met two essential criteria compatibility under oxidation conditions and stability toward dis-... 

Since this reaction produces secondary alcohols, an asymmetric version using a chiral NHC ligand is conceivable. However, only one report by Bolm and co-workers has appeared to date, in which a catalyst bearing an enantio-pure paracyclophane-containing NHC was employed, but only gave low enantioselectivities (up to 38% ee). ... 

Given that the reaction produces secondary alcohols, an asymmetric version using a chiral NHC ligand is possible however, only a few reports have... 

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