Versatile and efficient solid-phase syntheses of pyrazoles and isoxazoles

Condensation of aromatic or aliphatic esters with resin-supported acetyl ca rboxylic acids 2, followed by cyclization with hydrazines or hydroxylamine, activation of the linker, and cleavage using amines provides highly substi tuted, isomeric pyrazoles or isoxazoles 5, This general method gives produc ts in excellent yields and purities in which the ratio of the two isomers c an be easily controlled. A variation of this scheme generates 1,4,5- and 1, 3,4-trisubstituted pyrazoles and related isoxazoles. Post-cleavage reductio n with borane converts pyrazole amides to amines such as 11.