Stereoselective palladium-catalyzed functionalization of homoallylic alcohols: a convenient synthesis of di- and trisubstituted isoxazolidines and β-amino-δ-hydroxy esters

Malkov, A.V., Barłóg, M., Miller-Potucká, L., Kabeshov, M.A., Farrugia, L.J. and Kocovsky, P. (2012) Stereoselective palladium-catalyzed functionalization of homoallylic alcohols: a convenient synthesis of di- and trisubstituted isoxazolidines and β-amino-δ-hydroxy esters. Chemistry: A European Journal, 18(22), pp. 6873-6884. (doi: 10.1002/chem.201102716)

Abstract

Enantiopure, Boc-protected alkoxyamines 12 and 13, derived from the readily available homoallylic alcohols 4 via a reaction that involves either inversion or retention of configuration, undergo a diastereoselective Pd-catalyzed ring-closing carbonylative amidation to produce isoxazolidines 16/17 (≤50:1 diastereoisomer ratio (d.r.)) that can be readily converted into the N-Boc-protected esters of β-amino-δ-hydroxy acids and their γ-substituted homologues 37. The key carbonylative cyclization proceeds through an unusual syn addition of the palladium and the nitrogen nucleophile across the C[DOUBLE BOND]C bond (19→21), as revealed by the reaction of 15, which afforded isoxazolidine 18 with high diastereoselectivity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Malkov, Dr Andrei and Farrugia, Dr Louis and Kocovsky, Professor Pavel
• Authors: Malkov, A.V., Barłóg, M., Miller-Potucká, L., Kabeshov, M.A., Farrugia, L.J., and Kocovsky, P.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Chemistry: A European Journal
• Journal Abbr.: Chem. Eur J.
• ISSN: 0947-6539
• ISSN (Online): 1521-3765