A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.

A concise and efficient synthesis of the marine natural products rubrolides B, I, K, and O was accomplished in 3–4 steps from commercially available 3,4‐dichloro‐2(5H)‐furanone. Key steps include: (i) a site‐selective Suzuki cross‐coupling, (ii) a vinylogous aldol condensation, and (iii) a late‐stage bromination. The latter reaction allowed functionalization of the aromatic rings in a highly regioselective fashion, enabling rapid access to the target rubrolides from common precursors.

The first synthesis of enhygrolide A, a scarce γ-alkylidenebutenolide antibiotic of the obligate marine myxobacterium Enhygromyxa salina, was achieved in five steps and 54% overall yield from tetronic acid. Key steps include (i) organocatalytic reductive alkylation, (ii) iron-catalyzed sp-sp cross-coupling, and (iii) vinylogous aldol condensation. Aside from its brevity and reliance on environmentally sustainable processes, the synthesis demonstrates the serviceability of butenolide pivalates in cross-coupling reactions.