Ag(I)-Catalyzed Nucleophilic Substitution of Baylis-Hillman Adduct with Indoles

Significance

Reported is a development of an efficient and highly α-regioselective AgOTf-catalyzed condensation of allylic acetates with indole derivatives. The allylic acetates of type A and B are readily available via the Baylis-Hillman methodology. Although DABCO-promoted direct nucleophilic α-substitutions of Baylis-Hillman adducts are known, alternative S_N2′-type behavior has also been reported. Furthermore, Pd-catalyzed nucleophilic substitution of acyclic Baylis-Hillman adducts favors a γ-substituted product (S_N2′) where the E-isomer predominates, while for cyclic substrates α-substitution (S_N2) appears to be the preferred mode of reactivity (G. W. Kabalka et al. J. Org. Chem. 2005, 70, 9207). The present method represents a mild and direct nucleophilic α-substitution. A mechanism involving coordination of Ag(I) with acetate and carbonyl groups has been proposed. The present method shows a limited substitution pattern on indole and is restricted to cyclic Baylis-Hillman adducts. Some of the C3-substituted products were converted into azepinoindole derivatives.