Bidirectional Strategy Applied to the Synthesis of Bis(spiroketal)butenolides Using Bismuth(III) Triflate as Catalyst

ABSTRACT

Highly functionalized polyspirocompounds have scarcely been described in the literature. To prepare such derivatives according to a straightforward manner, a bidirectional synthesis of trispiro derivatives was developed. In a single step, a bis(acetylenic)diol ‐ readily available from diethyl malonate ‐ can be converted into a chiral spirobis(enolether); the latter reacts directly with two molecules of a α‐ketoester present in the reaction mixture. This tandem reaction catalyzed by a nontoxic bismuth salt yields the products as a mixture of three diastereomers. The major adduct was isolated from methyl pyruvate in 44% yield, and its structure was fully characterized by x‐ray diffraction. Its relative configuration was established as (R*,s*,R*) and, based on NMR data comparisons, assigned to all other major isomers obtained with the tested α‐ketoesters. These compounds exhibit D ₄ ‐symmetry, a fully rationalized by the selective attack of the enol ether on the ketoesters.