Stereoselective Palladium‐Catalyzed Functionalization of Homoallylic Alcohols: A Convenient Synthesis of Di‐ and Trisubstituted Isoxazolidines and β‐Amino‐δ‐Hydroxy Esters |
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| Authors: | Prof Dr Andrei V Malkov Dr Maciej Barłóg Dr Lucie Miller‐Potucká Dr Mikhail A Kabeshov Dr Louis J Farrugia Prof Dr Pavel Kočovský |
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| Institution: | 1. Department of Chemistry, WestChem, University of Glasgow, Glasgow G12 8QQ (UK), Fax: (+44)?141‐330‐4888;2. Present address: Department of Chemistry, Loughborough University, Loughborough, Leics LE11 3TU (UK), Fax: (+44)?1509‐22‐3925;3. Present address: College of Science, Texas A&M University at Qatar, P.O.Box 23874, Doha 23874 (Qatar);4. Present address: AstraZeneca, Silk Road Business Park, Charter Way, Macclesfield, Cheshire, SK10 2NA (UK) |
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| 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?C bond ( 19 → 21 ), as revealed by the reaction of 15 , which afforded isoxazolidine 18 with high diastereoselectivity. |
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| Keywords: | amidopalladation amino acids carbonylation palladium stereocontrol |
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