English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Significance: A convenient route to enantiopure a-trifluoromethyl proline is reported. Lewis acid catalyzed allylation of an easily accessible oxazolidinone derived from (R)-phenylglycinol generates a morpholin-2-one derivative in 86–92% yields as a diastereomeric mixture (dr = 69:31 to 75:25), independent of the diastereomeric ratio of the educt. Following PTSA-catalyzed lactonization, hydroboration, and mesylation, the pyrrolidine lactone is obtained as a diastereomeric mixture which may be separated by column chromatography. Standard hydrogenolysis affords both enantiomers of trifluoromethyl proline in five steps and up to 36% overall yield. Comment: The growing interest of fluorinated analogues of proline is based on control of the cis– trans isomerization of prolyl bonds in oligopeptides (R. Golbik et al. Biochemistry 2005, 44, 16026-16034) and for the design and synthesis of enzyme inhibitors (L. Chen et al. J. Org. Chem. 2006, 71, 5468-5473; D. D. Staas et al. Bioorg. Med. Chem. 2006, 14, 6900-6916). Among the available methods for the synthesis of fluoro-substituted prolines (e.g., J. R. Del Valle, M. Goodman Angew. Chem. Int. Ed. 2002, 41, 1600-1602), few are known for the introduction of a fluorinated group in the a-position (M. Eckert et al. Org. Lett. 2005, 7, 3741-3743). The synthesis of racemic ethyl a-difluoromethylproline ester has been recently reported (J. Zhu et al. Tetrahedron Lett. 2005, 46, 2795-2797). The current method appears to be unique for the synthesis of both enantiopure a-trifluoromethyl prolines and may contribute to further studies of these unnatural amino acids. HN O

Synthesis of Enantiopure (S)- and (R)-α-Trifluoromethyl Proline