Vinyl sulfones in solid-phase synthesis: Preparation of 4,5,6,7-tetrahydroisoindole derivatives

The preparation of functionalized 4,5,6,7-tetrahydroisoindole via a tracele ss solid-phase sulfone linker strategy is described. Thermolytic extrusion Of SO2 from polymer-bound 3-(phenylsulfonyl)3-sulfolene (7) generated polym er-bound 2-(phenylsulfonyl)-1,3-butadiene (9) in situ which underwent Diels -Alder cycloaddition with various dienophiles to furnish vinyl sulfone resi ns 10-14, To complete a traceless linker cleavage strategy, (p-tolysulfonyl )methyl isocyanide or ethyl isocyanoacetate was employed to react with the vinyl sulfone moiety to liberate functionalized. 4,5,6,7-tetrahydroisoindol e products from the resin. Using this chemistry, nine tetrahydroisoindole d erivatives (6, 15-22.) were prepared in 32-41% overall yields from polystyr ene/divinylbenzene sulfinate 1.