Silylated chlorohydrins

In metal-free catalysis enantioselective ring-opening of epoxides according to Scheme 13.27 path B has been achieved both with chiral pyridine N-oxides and with chiral phosphoric amides. These compounds act as nucleophilic activators for tetrachlorosilane. In the work by Fu et al. the meso epoxides 71 were converted into the silylated chlorohydrins 72 in the presence of 5 mol% of the planar chiral pyridine N-oxides 73 (Scheme 13.36) [74]. As shown in Scheme 13.36, good yields... 

Chiral halohydrins epoxides.1 The esters (2) of the chiral alcohol 1 derived from camphor-10-sulfonic acid, are converted to a-chloro esters (3) by O-silylation and reaction with NCS with high diastereoselectivity. Reduction of 3 with Ca(BH4)2 results in the recovered auxiliary and the chlorohydrin 4 with clean retention. Cyclization of 4 to the terminal epoxide 5 proceeds with clean inversion. 

Although increasing the steric bulk of the nucleophile is necessary to improve selectivity, it has detrimental consequences on reactivity with aliphatic aldehydes (Scheme 7). In reactions with the bulky silyl ketene acetal 28e, aliphatic aldehydes are unreactive. Fortunately, reactivity can be recovered by decreasing the steric bulk of the ester group (from ferf-butyl 28e to ethyl 28b) and by changing the reaction medium. The addition of tetrabutylammonium iodide, which presumably increases the ionic strength of the reaction medium, shifts the equilibrium between the activated aldehyde and the trichlorosilyl chlorohydrin and allows carbon-carbon bond formation to proceed even in the case of aliphatic aldehydes [48]. 

A similar pattern is observed in the reactions of silyl enol ethers derived from aldehydes. Aldehyde-aldehyde aldol reactions had already been reduced to practice in the context of the Lewis base-catalyzed aldol reaction of trichlorosilyl enol ethers, thanks to the stabilizing effect of the trichlorosilyl chlorohydrin (Scheme 9) [25-27]. Because the product of the aldehyde-aldehyde aldol reaction is an aliphatic aldehyde, it can be quickly transformed into an umeactive chlorohydrin such... 

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