Studies On The Application Of α-fluoroamides In The Construction Of Chiral Carbon-fluorine Stereocenters

In this paper,the application ofα-fluoro-substituted amides as fluorinated blocks in the construction of chiral C（sp³）-F bonds are introduced.A diastereoselective Mannich reaction has been developed for the construction of stereogenic C–F bonds by the reaction ofα-fluoro-substituted amides,including highly activated 3-fluoro-oxindoles,and simple linear fluoroacetamides with N-tert-butylsulfinylimines.Under the condition of base（for example Li HMDS）,α-fluoroenolates and imide occured an addition reaction at-70℃.Theα-fluoro-β-amino amides containing fluorinated quaternary carbon chiral ceters were obtained in high diastereoselectivities and good yields.Further research ofα-fluoro-substituted amides indicated the fluorinatedα-carbon centers is stable under mild acidic or basic conditions.An Aldol reaction has been developed for the construction of stereogenic C–F bonds by the reaction of alphafluoro Thioester with aldehydes,Under the action of Mg Br₂·Et₂O/i Pr₂NEt,an addition reaction ofα-fluoroenolates to aldehydes occured at room temperature.Theα-fluoro-β-hydroxyl Thioester containing fluorinated carbon chiral centers were obtained.This paper provides a concise route to a variety of structurally diverseα-fluoro-β-amino amides andα-fluoro-β-hydroxyl thioester containing stereogenic fluorinated carbon centers.It is able to provide assistance for the synthesis of related fluoro-active molecules。...