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