Crystallization-Induced Dynamic Resolution of Fox Chiral Auxiliary and Application to the Diastereoselective Electrophilic Fluorination of Amide Enolates

A highly efficient crystallization-induced dynamic resolution (CIDR) of <i>trans</i>-<b>Fox</b> (fluorinated oxazolidine) chiral auxiliary is reported. This chiral auxiliary was used for highly diastereoselective (>98% <i>de</i>) electrophilic fluorination of amide enolates. After removal of the chiral auxiliary, highly valuable enantiopure α-fluorocarboxylic acids and β-fluoroalcohols are obtained

Synthesis of Enantiopure <i>trans</i>-2,5-Disubstituted Trifluoromethylpyrrolidines and (2<i>S</i>,5<i>R</i>)‑5-Trifluoromethylproline

Enantiopure <i>trans</i>-2,5-disubstituted trifluoromethylpyrrolidines were prepared on a several gram scale starting from a readily available chiral fluorinated oxazolidine (Fox). A pure oxazolopyrrolidine intermediate could be obtained after an efficient separation by selective diastereomer destruction. The addition of various Grignard reagents on this oxazolopyrrolidine provided disubstituted pyrrolidines with moderate to complete <i>trans</i> diastereoselectivity. The highly valuable compound (2<i>S</i>,5<i>R</i>)-5-trifluoromethylproline could be synthesized from the same oxazolopyrrolidine intermediate via a Strecker-type reaction

Synthesis of Enantiopure <i>trans</i>-2,5-Disubstituted Trifluoromethylpyrrolidines and (2<i>S</i>,5<i>R</i>)‑5-Trifluoromethylproline

Enantiopure <i>trans</i>-2,5-disubstituted trifluoromethylpyrrolidines were prepared on a several gram scale starting from a readily available chiral fluorinated oxazolidine (Fox). A pure oxazolopyrrolidine intermediate could be obtained after an efficient separation by selective diastereomer destruction. The addition of various Grignard reagents on this oxazolopyrrolidine provided disubstituted pyrrolidines with moderate to complete <i>trans</i> diastereoselectivity. The highly valuable compound (2<i>S</i>,5<i>R</i>)-5-trifluoromethylproline could be synthesized from the same oxazolopyrrolidine intermediate via a Strecker-type reaction