One-Step Palladium-Catalyzed Synthesis of Substituted Dihydrofurans from the Carbonate Derivatives of γ-Hydroxy-α,β-unsaturated Sulfones

The palladium-catalyzed nucleophilic allylic substitution of the carbonate derivatives of γ-hydroxy-α,β-unsaturated sulfones (2) with soft carbon nucleophiles such as malonates, β-keto esters, 1,3-diketones, and α-sulfonyl ketones took place cleanly and with full regiocontrol (γ-substitution). Typical optimized conditions are Pd2(dba)3 (5 mol %), dppe (20 mol %), molecular sieves, in toluene−THF at 100 °C. Unexpectedly, when β-keto esters, 1,3-diketones, and α-sulfonyl ketones were used as nucleophiles a cascade process occurred, via initial γ-regioselective allylic substitution and further intramolecular conjugate addition of the enol moiety to the α,β-unsaturated sulfone, to give 2,3,4,5-tetrasubstituted dihydrofurans (13−25) in moderate to good yields. Moreover, the cyclization step is highly stereoselective giving predominantly or exclusively the 4,5-dihydrofuran of trans configuration. From readily available enantiopure (S)-2, this one-step procedure of synthesis of substituted dihydrofurans has been applied to the synthesis of enantiomerically pure tetrasubstituted tetrahydrofurans.