title: A practical synthesis of trans-3-substituted proline derivatives through 1,4-addition.
abstract: A practical four-step synthesis of 3-alkyl-, vinyl-, and aryl-substituted proline derivatives, which are important building blocks for conformationally restrained peptide analogs, was developed. The method relies on a Cu-catalyzed 1,4-addition of Grignard reagents to N-protected 2,3-dehydroproline esters, efficiently prepared in a new one-pot protocol. The 1,4-addition products are obtained with good trans-selectivity (dr 5:1 to 25:1). A nonracemic sample of N-Cbz-3-vinylproline (74% ee) was obtained using Evans oxazolidinone as a chiral auxiliary.
authors.affiliation: Department of Chemistry, University of Cologne, Greinstr. 4, 50939 Köln, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Huy
authors.forename: Jörg-Martin
authors.initials: JM
authors.lastname: Neudörfl
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Schmalz
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D003300:Copper; D011392:Proline