Synthesis of Enantioenriched Fluorinated Enol Silanes Enabled by Asymmetric Reductive Coupling of Fluoroalkylacylsilanes and 1,3-Enynes and Brook Rearrangement

Fluorinated enol silanes are broadly useful in various synthetic transformations such as Mukaiyama aldol, Michael, and Mannich reactions. However, previous methods to these intermediates are limited to racemic synthesis. Therefore, the development of access to enantioenriched ones is of great value. We now describe an enantioselective reductive coupling reaction of fluoroalkylacylsilanes and 1,3-enynes. The coupling products were easily transformed to fluorinated enol silanes with the retention of enantiopurity though Brook rearrangement. The practicality of our methodology was demonstrated by the multisteps-one-isolation processes for the synthesis of alkynyl, alkenyl, and alkyl substituted enantioenriched beta,beta-difluoro enol silanes. The applications of the enantiopure beta,beta-difluoro enol silane in the synthesis of valuable chiral organofluorine compounds demonstrated the synthetic potential of our reaction.

Automated summary

Fluorinated enol silanes are widely used in synthetic transformations, but previous methods only allowed for the synthesis of racemic products. In this study, an enantioselective reductive coupling reaction was developed to access enantioenriched fluorinated enol silanes. The practicality of this methodology was demonstrated through multistep-one-isolation processes, and the synthetic potential of enantioenriched fluorinated enol silanes in the synthesis of valuable chiral organofluorine compounds was also shown.