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Total Synthesis of Thromboxane B2 via a Key Bicyclic Enal Intermediate

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journal contribution
posted on 07.08.2020 by Changcheng Jing, Varinder K. Aggarwal
A 12-step asymmetric synthesis of thromboxane B2 (TxB2) from 2,5-dimethoxytetrahydrofuran is described. The synthesis employs our organocatalytic aldol reaction of succinaldehyde to give a key bicyclic enal intermediate. From here, the synthetic strategy involves a conjugate addition of an alkenyl side chain to the bicyclic enal, Baeyer–Villiger oxidation, and a highly Z-selective Wittig olefination of a hemiacetal. Key to success was minimizing redox operations and the manipulation of functional groups in the correct order.