title: Synthesis of enantioenriched aza-proline derivatives through gold(I)-catalyzed cyclization of chiral α-hydrazino esters.
abstract: A selective gold(I)-catalyzed synthesis of chiral aza-proline derivatives has been developed by ring closure of enantioenriched α-hydrazino esters bearing an alkyne group. These are easily prepared through a synthetic strategy involving two key steps: organocatalyzed electrophilic amination of pent-4-ynal with dialkyl azodicarboxylate promoted by l-proline and functionalization of the triple bond by Sonogashira cross-coupling. This strategy allowed the preparation of a range of enantioenriched α-hydrazino esters that underwent ring closure by using Ph(3)PAuCl/AgBF(4) as a catalytic system. Under these conditions, 5-exo-dig cyclization was favored over 6-endo-dig and aza-proline derivatives were obtained in good yields without epimerization at the stereogenic center. Influence of the catalytic system, hydrazine protecting group and alkyne substitution on the cyclization step has also been investigated.
authors.affiliation: Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles-St-Quentin-en-Yvelines, 45 Avenue des États-Unis, 78035 Versailles cedex, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bouvet
authors.forename: Xavier
authors.initials: X
authors.lastname: Moreau
authors.forename: Vincent
authors.initials: V
authors.lastname: Coeffard
authors.forename: Christine
authors.initials: C
authors.lastname: Greck
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D004952:Esters; D006046:Gold / Q000737:chemistry*; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000480:Alkynes; D001372:Aza Compounds; D004952:Esters; D006834:Hydrazines; D006046:Gold; D011392:Proline