Tetrahedron Letters,Vol.29,No.41,pp 5313-5316,1988 0040-4039/88 $3.00 + .OO Printed in Great Britain Pergamon Press plc INTRAMOLECULAR OXIME OLEFIN CYCLOADDITIONS. STEREOSPECIFIC FORMATION OF FUECTIONALIEED PYRROLIDIMRS.l Alfred Hassner*, Rakesh Maurya, Eszter Mesko Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel Abstract. Allylamines possessing a properly positioned aldoxime or ketoxime chain undergo thermally induced dipolar cycloaddition to bicylic isoxazoli- dines, with stereospecific introduction of three stereo centers. This provides an entry into stereospecifically functionalized pyrrolidines. Intramolecular nitrile oxide olefin cycloadditions (INOC) have been of considerable synthetic and mechanistic interesta, especially since the resulting isoxazoline ring can serve as a precursor to hydroxy ketones3 or to other functional groups.4 The related nitrone olefin cycloadditions lead to saturated isoxazolidines5 hence to the introduction of an additional stereochemical center. Both types of cycloaddition reaction have been used increasingly in stereoselective syntheses.6 However, nitrones react more sluggishly with alkenes than do nitrile oxides and the products contain a substituent on nitrogen which may not be desirable. In recent elegant work, Grigg & a7 were able to form N-substituted isoxazolidines both in inter as well as in intramolecular additions of oximes to olefins. This was achieved by converting the oximes b situ into nitrones by means of olefins bearing electron withdrawing substituents (see eq.1). Though 2-oximes of 1,2,3_tricarbonyl systems have been shown to undergo an unassisted proton transfer from 0 to N to generate a 1,3-dipole as a reactive intermediate, attempts to extend this cycloaddition process to simple aldehyde or keto oximes were unsuccessful.8 CO2 Me J CO2 Me 7 R -C=N-OH We now found undergoes smooth zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 1: t + ‘34 Me Q R eq 1 R’ COzMe that a, an allylamine containing an aldoxime chain, intramolecular cycloaddition to the pyrrolidino isoxazolidine J.= simply on heating at 80-llO°C or even upon standing for long periods of time at room temperature. This ring closure proceeded stereospecifically to generate three adjacent stereochemical centers that provide an entry into functionalized pyrrolidines, for instance amino alcohols that do not bear a substituent on the amine function. Apparently these reactions proceed via a thermal equilibration of the oxime to its nitrone tautomer 2, which undergoes subsequent intramolecular dipolar cycloaddition. 5313