Protecting-group-free and catalysis-based total synthesis of the ecklonialactones.
A concise and protecting-group-free total synthesis of optically pure ecklonialactones A (1) and B (2) is described. The successful route to these oxylipins isolated from various brown algae involves five transition-metal-catalyzed transformations in the longest linear sequence of 13 steps. The first chiral center was set by a rhodium-catalyzed 1,4-addition of an alkenyl boronate to the commercial butenolide 11, which was controlled by Carreira's carvone-derived diene ligand 21. Other key steps involve a ring-closing olefin metathesis effected by the ruthenium indenylidene complex 22 for the formation of the five-membered carbocycle, a vanadium-catalyzed, hydroxy-directed epoxidation, and a ring-closing alkyne metathesis (RCAM) to forge the macrocyclic ring. Because of the unusually high propensity of the oxirane of the ecklonialactones for ring-opening, this transformation was best achieved with [(Ph(3)SiO)(3)Mo[triple bond]CPh].OEt(2) (34) as the catalyst, which is a representative of a new generation of highly tolerant yet remarkably efficient molybdenum alkylidyne complexes. The ancillary triphenylsilanolate ligands in 34 temper the Lewis acidity of the molybdenum center and are not able to nucleophilically open the fragile epoxide ring. The final reduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene was accomplished either by Lindlar reduction or with the aid of nickel boride.
Hickmann
Volker
V
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany.
Alcarazo
Manuel
M
Fürstner
Alois
A
D002384:Catalysis; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D055620:Optical Phenomena
D007783:Lactones; D008670:Metals