Amino-zinc-enolate carbometalation reactions: application to ring closure of terminally substituted olefin for the asymmetric synthesis of cis- and trans-3-prolinoleucine.
The amino-zinc-enolate cyclization reaction is a straightforward route for the synthesis of 3-substituted prolines. As classical intramolecular carbometalation reactions, the applicability of the addition of zinc to a double bond was limited to a substrate in which the terminal alkene carbon was unsubstituted. Being interested in the synthesis of cis- and trans-3-prolinoleucine derivatives for our structure-activity relation (SAR) studies, we focused our effort on the preparation of these compounds by amino-zinc-enolate cyclization of terminally substituted double bonds. Herein we report that the attachment of an activating group such as cyclopropyl to the terminal olefin carbon allows the amino-zinc-enolate cyclization of a terminally substituted alkene. The reaction is stereospecific, leading to a trans-3-substituted proline derivative, whereas a cis stereochemistry was observed with the amino-zinc-enolate cyclization of terminally nonsubstituted olefins. Absolute configurations obtained for the 3-prolinoleucine were established by X-ray analysis, NMR, and optical activity comparison of the cis and trans derivatives obtained by an unambiguous pathway.
Karoyan
Philippe
P
UMR CNRS 7613, Structure et Fonction de Molécules Bioactives, Université Paris VI, France. karoyan@ccr.jussieu.fr
Quancard
Jean
J
Vaissermann
Jacqueline
J
Chassaing
Gérard
G
D000588:Amines / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D003500:Cyclization; D004151:Dipeptides / Q000138:chemical synthesis*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
D000588:Amines; D004151:Dipeptides; C018170:prolylleucine; D011392:Proline; D015032:Zinc