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Stereoselective Palladium‐Catalyzed Functionalization of Homoallylic Alcohols: A Convenient Synthesis of Di‐ and Trisubstituted Isoxazolidines and β‐Amino‐δ‐Hydroxy Esters
Author(s) -
Malkov Andrei V.,
Barłóg Maciej,
MillerPotucká Lucie,
Kabeshov Mikhail A.,
Farrugia Louis J.,
Kočovský Pavel
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102716
Subject(s) - enantiopure drug , chemistry , palladium , stereoselectivity , diastereomer , catalysis , nucleophile , walden inversion , surface modification , stereochemistry , combinatorial chemistry , organic chemistry , enantioselective synthesis
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 CC bond ( 19 → 21 ), as revealed by the reaction of 15 , which afforded isoxazolidine 18 with high diastereoselectivity.