Synthesis of Spiroheterocycles by Palladium-Catalyzed Domino Cycloisomerization/Cross-Coupling of α-Allenols and Baylis-Hillman Acetates

A new domino hetero-cyclization/cross-coupling reaction of α-allenols and BH acetates that includes [(2,5-dihydrofuran-3-yl)methyl]acrylate derivatives, was prepared. The domino reaction provides a facile access to functionalized spiroindolinones, which prompted to test it using enantiopure 2-azetidinone-tethered allenic alcohols. When α-allenol 1c and BH acetate containing nitrile 2c were subjected to this PdII-catalyzed protocol, the reaction did not produce the expected adduct 6e. The configurational assignment at the benzylic-like carbon atom was made taking into account mechanistic considerations. The difference in reactivity between both types of BH acetates could be explained by the different inductive and resonating capacities of the ester and cyano groups. The presence of a cyano substituent in the BH adduct probably strengthened the reactivity of the benzylic-like carbon, thus favoring the SN1 substitution over the SN2 substitution.