Substituted isoxazolidinium salts 6-14 undergo ring-opening reaction when treated with lithium iodide to yield 13-amino alcohols 15-23 having multiple c h i d centres. The overall process proceeds through a probable single-electron-transfer mechanism with the redox system being the N,O-heterocyclic cations and the iodide anion.
Isoxazolidines 'I, 1,3-dipolar cycloadduct products of nitrones to olefines '), are versatile intermediates in organic synthesis for ~i m p l e ~-~' and complex molecules having biological interest 3,7-11'. This remarkably powerful approach to the formation of carboncarbon and carbon-oxygen bonds involves the initial condensation of carbonyl compounds with N-substituted hydroxylamines to nitrones'' or other alternative procedure^'^-^^), followed by the inter-3-9) or intramolecular '0.11.'51 1,3-dipolar cycloaddition to double bonds.
Essentially all the recent applications of such N,O-heterocyclic intermediates to the total synthesis of natural products depend on the subsequent facility with which the chemical modification of the N -0 bond in the five-membered ring can be performed under mild conditions producing open-chain derivatives. Many chemical methods rely on catalytic hydrogenation of the isoxazolidine nucleus, which is regioselectively cleaved at the N -0 bond by hydrogenolysis2,'6-z21 to unmask the 1,3-amino alcohol moiety. Thus, reductive scission of substituted isoxazolidines to acyclic derivatives takes place in the presence of 10% Pd/C with uptake of only one equivalent of hydrogen leading to variable yield of products16-z2'. Reductive procedures other than catalytic hydrogenation have also to be applied in some cases, owing to the obvious limitation imposed by schemes which include hydrogenation, i.e. double bonds present in the molecules are clearly not amenable. The reduction with zinc in acetic a c i d / ~a t e r ~. ' ~-' ~) has, therefore, also been used, while the oxidation with rn-chloroperbenzoic acidz6"') has been exploited in order to achieve the chemical transformation of the initial N,O-heterocycles. Some peculiar isoxazolidine structures are ring-opened by LiAIH4 treatment 27.2R), by heating in methanolz9', in toluene with potassium tert-butoxidez8', in methanol with sodium methoxide"', and by the reaction with dilute hydrogen fluoride "I.
Since there has been a continuing search of simple and different procedures for functional group transformation to the open ring products, the quaternary ammonium cations of isoxazolidinium structure 1 (Scheme 1) have also been used for the chemical conversion of the primary 1,3-dipolar cycloadducts. N,O-Heterocyelen, 24'). -Eine new Uatersuchung der Ringiiffnung von Isoxamlidiaiumsalzen zu 1,3-Aminoalkoholen Die Umsetzung der substituierten Isoxazolidiniumsalze 6 -14 mit Lithiumiodid fihrt zur Ringoffnung, aus der 1,3-Aminoalkohole 15-23 entstehen, die verschiedene chirale Atome enthalten. Vermutlich verlauft die Reaktion uber einen Single-electron-transfer-Mechanismus, in dem das Redoxsystem aus dem N,O-heterocyclischen Kation und dem Iodid-Ion besteht. The isoxazolidinium salts can undergo chemical modifications leading to opening of the five-membered ring as shown in Schemc 1 by basic reagent^'.^.^.^^.^^', by hydrogen~lysis'~.'~ 35), by zinc dust in acetic acidi.R.26b.36-401 , and LiAIH, treatment4.5~7~9.'hh.4''. Scheme 1