Asymmetric Synthesis Of α-fluoromethyl Vicinal Diamines Induced By Chiral Auxiliary

Because of the widely application of fluorinated amines in lifesciences field, the development of efficient synthetic methods forfluorinated amines become much more important. Schiff bases assynthetic precursors of fluorinated amines have attracted much attention.This thesis focused on the asymmetric synthesis of-fluoromethylvicinal diamines from N-tert-butanesulfinyl fluoroacetaldimines andSchiff bases.Firstly, two classes of Schiff base1and2were synthesizedaccording to literature method. Schiff bases1were prepared bydehydration condensation of benzophenone and benzylamines in yield of49-85%. Schiff bases2were prepared by dehydration condensation ofbenzhydrylamine and benzaldehydes in yield of70-86%. The reactioncondition between fluoroacetaldimine and Schiff base1or2wasoptimized. The desired-fluoromethyl vicinal diamine products wereobtained stereoselectively in yield of53-84%with n-BuLi as base, THFas solvent at-78oC for Schiff base1or t-BuOK as base, DMSO assolvent at room temperature for Schiff base2. The structure of the fluorinated diamines achieved from the two conditions are exactly same,and their steric configuration was determined by single crystal X-raydiffraction analyses. The mechanism for the steric outcome of thenucleophilic addition was proposed. The developed methodology can beapplied in the asymmetric synthesis of fluorinated vicinal diamines.