Total Synthesis of Gymnothelignan K via a One-Pot Homologative γ-Butyrolactonization.

The first total synthesis of tetrahydrofuran dilignan gymnothelignan K is disclosed. The approach is based on implementing an early stage one-carbon homologative lactonization, which we recently disclosed, for constructing the γ-butyrolactone scaffold with the requisite β,γ- trans -vicinal stereocenters. Other salient features of the synthesis include the acid-promoted dimerization and the Suzuki-Miyaura cross-coupling reaction to install the challenging diaryl skeleton that permits the effective assembly of the optically active gymnothelignan K in 8 steps from commercially available materials.