Synthesis of Cembranolides by SE′ Cyclization of Enantioenriched α-Alkoxy Allylstannanes

A total synthesis of the unnamed cembranolide 35 is described starting from enal XV , an intermediate derived from geraniol. Key transformations include asymmetric reduction of stannyl ketone 1 with (R)-(+)-BINAL-H to give the hydroxy stannane 2 of high ee, and cyclization of the derived MOM ether 6 to the cis-(Z) hydroxy enol ether 7 in high yield. Further elaboration of 7 to the natural product was achieved by OH-directed hydroalanation-iodination of the derived diol 17 , methylation of iodide 17 with methyl cuprate and selective protection, oxidation, lactonization, and α-methylenation. The resulting product was identified by comparison of ¹H NMR, ¹³C NMR, IR, and optical rotation with an authentic sample. The synthesis defines the absolute configuration of the natural cembranolide.