Stereoselectivity chiral hydroperoxide synthesis

Also of significant preparative potential is the kinetic resolution of chiral hydroperoxides in the presence of sulfides or guaiacol [253-261]. The reaction has been shown to occur with CPO, HRP and CiP and provides good to excellent results for a multitude of different substrates. Whereas usually the back-reaction of Compound I to the resting state is used for organic synthesis, Compound I is formed upon the stereoselective decomposition of alkylhydroperoxides here. Scheme 2.20 illustrates the first example described in the literature [253] where CPO and different aryl methyl sulfides have been employed and where it has been found that mainly the R-form of the chiral hydroperoxide is reduced to the corresponding alcohol. 

The authors also investigated the mode of activation of these BINOL-derived catalysts. They proposed an oligomeric structure, in which one Ln-BINOL moiety acts as a Brpnsted base, that deprotonates the hydroperoxide and the other moiety acts as Lewis acid, which activates the enone and controls its orientation towards the oxidant . This model explains the observed chiral amplification effect, that is the ee of the epoxide product exceeds the ee of the catalyst. The stereoselective synthesis of cw-epoxyketones from acyclic cw-enones is difficult due to the tendency of the cw-enones to isomerize to the more stable fraw5-derivatives during the oxidation. In 1998, Shibasaki and coworkers reported that the ytterbium-(f )-3-hydroxymethyl-BINOL system also showed catalytic activity for the oxidation of aliphatic (Z)-enones 129 to cw-epoxides 130 with good yields... 

An enantioselective route to 1,3-dithiane 1-oxide (33) (R = R = H) was subsequently developed [69]. It involves asymmetric oxidation of (32) (R = pivaloyl, R = H) by cumene hydroperoxide in presence of the chiral titanium complex. The syn/anti mixture (around 90% ee for each diastereoisomer) is recrystallized and then deacylated, giving the desired product in 80% yield. A recent application of this chemistry is the asymmetric synthesis of enantiopure (R)-(-)-2,6-dimethylheptanoic acid in two steps from (33) (R = C(0)Et, R = Et) [70]. The reaction involves a fully stereoselective methylation in the a-position of the keto group, followed by basic deacylation, which also regenerates enantiopure 2-ethyl-l,3-dithiane 1-oxide (33) (Ri = H, R = Et). A range of a-arylpropanoic acids have since been prepared by similar routes in high ee s. [162]... 

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