Remote Asymmetric Bisvinylogous [4+2] Cycloaddition Reaction to Synthesize Spirocyclic Frameworks

Abstract

The highly enantioselective organocatalytic synthesis of spirocyclic compounds by Diels-Alder reactions via trienamine using cyclic 2,5-dienones as bisvinylogous precursors and different nitroalkenes as dienophiles is described. The use of cinchonidine-based primary amine as catalyst and benzoic acid as co-catalyst has allowed the construction of a wide variety of spiro compounds containing three stereogenic centres in good yields and excellent diastereo- and enantioselectivities. Additionally, other dienophiles have been evaluated exhibiting different behaviour depending on the electron withdrawing group nature. Subsequent transformations have yielded complex structures with up to five stereocentres. The plausible reaction mechanism has been investigated by computational methods.