SOLID-PHASE SYNTHESIS OF DIVERSE ISOXAZOLIDINES VIA 1,3-DIPOLAR CYCLOADDITION

Diverse substituted isoxazolidines 2-4 are assembled on solid phase by condensing hydroxylamines with aldehydes and trapping the resulting n itrones with various dipolarophiles. The one-pot three-component cyclo addition reaction yields the isoxazolidines in good to excellent yield . Three different reaction pathways - each dealing with one of the thr ee components attached to the solid support - are evaluated with respe ct to versatility and yield of the synthesized isoxazolidines. Structu res and relative configurations of representative isoxazolidines are e lucidated with H-1-NMR, TOCSY, HSQC and NOESY. The reaction of polymer -bound hydroxylamines with aldehydes and alkenes is found to be the mo st successful. The kinetics of the solid phase reaction are determined by FT-IR-ATR spectroscopy. polymer-bound nitrones are stable for the split/combine synthesis. A library of isoxazolidines is synthesized by the split/combine method and analyzed by means of HPLC-MS. (C) 1998 E lsevier Science Ltd. All rights reserved.