Ketene silyl acetals, fluorine-substituted

This review describes the first catalytic asymmetric Mukaiyama-aldol reaction of fluorine-substituted ketene silyl acetals with aldehydes and the catalytic asymmetric He (nitroaldol) reaction of 2,2-difluoroaldehydes with nitromethane to provide the optically active aldols and nitroaldols, respectively, which must be versatile synthetic intermediates for the fluorinated protease inhibitors. 

Catalytic Asymmetric Aldol Reaction of Fluorine-Substituted Ketene Silyl Acetals... 

We propose two different reaction courses for the aldol reactions of the fluorine-substituted ketene silyl acetals 1 and 2 at -78°C and at higher temperatures (-45 C and -20 C). As shown in Scheme 2, the reaction at -78 C preferentially proceeds through the extended open transition states in which the attack of the acetals occurs on the Si face of the aldehyde 29,31)- From transition state 8, the nn -aldol is obtained, while transition state 9 provides the syn-isomer. 

The uncatalyzed aldol reaction of highly reactive enoxysilanes such as enoxysilacyclobutanes has previoudy been reported to proceed through six-membeied cyclic transition states (32,55), and the torsional structure of the difluoroketene acetal 5 is considered to be more suitable for the uncatalyzed aldol reaction tfian the planar geometry of 4 because the acetal 5 has a geometrical similarity to the ketene acetal in die cyclic transition states. As mentioned above (Scheme 1), a 60 40 mixture of the syn- and anri-aldols was obtained at 40°C from the bromofluoroketene silyl acetal 2 (E/Z =62/38), suggesting that the uncatalyzed aldol reaction of the fluorine-substituted ketene acetals 1 and 2 proceeds preferentially through boat-like cyclic transition states. Denmark et aL proposed diat the boat-like transition states are extremely predominant in the uncatalyzed aldol reaction of enoxysilacyclobutanes and trichlorosilyl enolates (55,54). 

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