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

Abstract

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-S(E)' additions to the nitrogen-based electrophiles to give the (E)-olefin isosteves 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.

Department(s)

Chemistry

Keywords and Phrases

Peptide Derivative; Silane Derivative; chemical Bond; Chemical Reaction; Peptide Analysis; Protein Analysis; Protein Structure; Structure Analysis

International Standard Serial Number (ISSN)

0002-7863

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 1997 American Chemical Society (ACS), All rights reserved.

Publication Date

01 Jul 1997

Link to Full Text

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