Total Synthesis of Phorboxazole B

Abstract
An efficient and highly convergent total synthesis of the potent antitumor agent phorboxazole B has been achieved. The synthetic strategy of this synthesis features: 1) a highly efficient substrate‐controlled hydrogenation to construct the functionalized cis‐tetrahydropyrane unit; 2) iterative crotyl addition to synthesize the segment that contains alternating hydroxyl and methyl substituents; 3) Hg(OAc)2/I2‐induced cyclization to establish the cis‐tetrahydropyrane moiety; 4) 1,3‐asymmetric induction in the Mukaiyama aldol reaction to afford the stereogenic centers at C9 and C3; and 5) the exploration of the Still–Gennari olefination reaction to complete the macrolide ring of phorboxazoloe B.

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