Allylic Sulfones in Solid-Phase Synthesis: Preparation of Cyclobutylidenes

Polymer-bound allyl sulfones (cf. 9 ) were utilized in geminal cycloalkylations with epichlorohydrin to generate a cis -phenylsulfonylcyclobutanol derivative (cf. 11 ) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were screened to obtain an optimal protocol for “traceless” cleavage of cyclobutylidene products from the resin. Among these, palladium-catalyzed allylic alkylation was the most efficient. In addition, highly regioselective nucleophilic attack at the less hindered terminus of the allyl fragment (i.e., overall S N 2‘ sulfinate displacement) was observed. Cyclobutylidene diversification was demonstrated by incorporating different allylic substituents, O -functionalizations, and C -nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4 ) in four steps and 30−38% overall yield from lithium polystyrene/divinylbenzene sulfinate.