A Novel Solid-Phase Synthesis of Carboxypyrrolinones

A solid-phase organic synthesis method has been developed for the preparation of 3-carboxypyrrolinones 9 . Treatment of polymer-bound malonic acid with amino alcohols afforded the malonamide resin products 6 . Benzyl and alkyl amino alcohols were prepared in solution via a two-step procedure without purification and were coupled to the resin directly using a resin capture strategy. Polymer loadings and product conversions were determined by direct cleavage of resin-bound materials and analysis by 1 H NMR spectroscopy with an internal standard. Treatment of the polymer-bound malonamides with TFA released the malonamic acids, 10, which underwent further reaction to afford the trifluoroacetate derivatives 11 . Secondary amides underwent an additional cyclization to afford oxazoles 12 . The malonamide resins 6 can be oxidized to the corresponding ketones 7 by treatment with CrO 2 (O- t -Bu) 2, which can in turn be cyclized in the presence of LDA or LHMDS to afford the carboxypyrrolinones 8 . TFA treatment releases the free carboxypyrrolinones, 9, in 43−80% overall yield.