Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes

Polymer-bound allyl sulfones (cf. 9) were utilized in geminal cycloalkylati ons with epichlorohydrin to generate a cis-phenylsulfonylcyclobutanol deriv ative (cf. 11) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were scr eened to obtain an optimal protocol for "traceless" cleavage of cyclobutyli dene products from the resin. Among these, palladium-catalyzed allylic alky lation was the most efficient. In addition, highly regioselective nucleophi lic attack at the less hindered terminus of the allyl fragment (i.e., overa ll S(N)2' sulfinate displacement) was observed. Cyclobutylidene diversifica tion was demonstrated by incorporating different allylic substituents, O-fu nctionalizations, and C-nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4) in four steps an d 30-38% overall yield from lithium polystyrene/divinylbenzene sulfinate.