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3-Aryl-5-isoxazolecarboxaldehyde undergoes fast Baylis-Hillman reaction with a variety of activated alkenes to yield the corresponding adducts in excellent yields. Some of the Baylis-Hillman adducts reported herein have been subsequently modified to obtain isoxazole substituted pyrazolin-3-ones and g-butyrolactones.The Baylis-Hillman reaction and its synthetic utility is one of the most attractive and extensively studied subject of recent times. 2 Its importance in solution and solid phase synthetic organic chemistry is enormous as it leads to synthetically useful multifunctional molecules. 2a,3 However, the inherent drawbacks associated with this reaction are the slow reaction rates and limited scope of substrate. To circumvent these shortcomings various alterations in the reaction conditions, both physical and chemical, have been attempted with excellent results. 4 On the other hand, the search for fast reacting electrophiles has led to the identification of diethyl ketomalonate, furfuraldehyde, glyoxalate, 2-cycloalkene-1-ones, etc. as substrates, which all undergo a fast Baylis-Hillman reaction. Indeed, it has also been reported that even simple aldehydes can react very fast either with excess of a,b-unsaturated cycloketones in the presence of TiCl 4 or with activated alkenes in presence of DABCO at low temperatures to furnish Baylis-Hillman adducts. 4c,e In our efforts directed towards studying the chemical transformations of 3-aryl-5-isoxazolecarboxaldehyde, we observed that these molecules undergo extremely fast Baylis-Hillman reactions under ordinary conditions. Substituted isoxazoles are considered to be one of the most versatile heteroaromatic synthons because they can Reagents and conditions: (a) CH 2 =CHR ' , DABCO, r.t.; (b) AcCl, pyridine, DMAP (cat.), CH 2 Cl 2 , r.t.; (c) NH 2 NH 2 .H 2 O, MeOH, r.t.; (d) (CH 3 CO) 2 CH 2 , K 2 CO 3 , EtOH, reflux; (e) 20% TFA in CH 2 Cl 2 , r.t.; (f) HTIB, CH 2 Cl 2 , r.t. SchemeDownloaded by: National University of Singapore. Copyrighted material.

This study indicates that 5- and 3-substituted isoxazolecarbaldehydes are 'first generation' multifunctional, spermicidal molecules that hold promise for development as topical contraceptives with useful associated activities that can add considerably to their effectiveness, safety and prophylaxis.

Fast and practical access to azides of Baylis-Hillman adducts, from the corresponding acetates in aqueous media and in excellent yields is described. The solution phase methodology has been successfully translated to the solid phase for applications toward combinatorial synthesis.