Isoxazolidine library

The isoxazolidine library prepared according to Scheme 16.1 was embedded in a KBr window by pressing. An area of 3x3 mm2 was automatically mapped. When the polystyrene absorption at 1942 cm 1 was used to visualize the IR map, all resin beads on the surface were detected (Fig. 16.14). 

Figure 16.14. IR map of an area (3x3 mm) of a KBr window in which resin beads of the isoxazolidine library are embedded. By application of the polystyrene absorption at 1942 cm 1 all resin beads were detected. White region KBr window gray region resin beads. There is a total of 297 resin beads in the scanned area.

To demonstrate the potential of this method, a model library of isoxazolidines on Rink amide resin was synthesized by the split-and-combine method [25] (Scheme 16.1). The polymer-bound library obtained consists of a total of 18 compounds. If one considers the different building blocks of the synthesis, a nitro group or the carboxamidomethyl residue is found in 50 % each of the compounds, a cyano, N,N-dimethylamino, or trifluoromethyl group in 33 % each and a succinimide, N-methylsuccinimide, or sulfone group in 33 % each. 

A small library of AT-aryl-5-trifluoromethylisoxazolidines was prepared through a three-component 1,3-DC of a nitroso arene, an electron-deficient alkene, and (trifluoromethyl)-diazomethane (86), which was obtained from the reaction of 2,2,2-trifluoroethylamine hydrochloride with sodium nitrite in a mixture of dichloromethane and water. The reaction is highly diastereoselective and afforded isoxazolidines such as 87 and 88 in high yield (19 examples, 62-91% yield) (130L3166). 

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