Asymmetric C−N Bond Constructions via Crotylsilane Addition Reactions:  A Stereocontrolled Route to Dipeptide Isosteres

• Published in: Journal of the American Chemical Society Vol. 119; no. 26; pp. 6040 - 6047
• Main Authors: Masse, Craig E, Knight, Bradford S, Stavropoulos, Pericles, Panek, James S
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.07.1997; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; COPPER-COMPLEXES; TRANS-ALKENE ISOSTERES; CHIRAL (E)-CROTYLSILANES; AZIRIDINATION; CYCLOPROPANATION; MEDIATED REACTION; OLEFINS; ALLYLSILANES; STEREOSELECTIVE SYNTHESIS; PEPTIDE
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja964364w

A new approach to the asymmetric synthesis of (E)-olefin dipeptide isosteres is described based on asymmetric C−N bond constructions resulting from nitronium tetrafluoroborate (NO2BF4) promoted electrophilic nitrations of chiral (E)-crotylsilanes and from a copper(I)-catalyzed enantioselective aziridination of chiral (E)-crotylsilanes. The silane reagents undergo efficient anti-SE‘ additions to the nitrogen-based electrophiles to give the (E)-olefin isosteres in >96% de. The topological bias is principally controlled by the facial bias of the silane reagent. The scope of the methodology was explored via several related crotylsilane derivatives. The (E)-olefin isosteres are nonhydrolyzable, rigid analogs of the peptide linkage in biologically active peptides. The new methodology will facilitate the preparation and study of peptidomimetics since the crotylsilane reagents allow for incorporation of a wide range of functionality on the resulting isosteres.