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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Asymmetric Total Synthesis of the Rearranged Steroid Phomarol Enabled by a Biomimetic SN2' Cyclization
Xudong Wang1, Ganlin Huang1, Yun Wang1
1CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Abstract:
Phomarol is a structurally unusual 1(10 → 19)abeo-steroid with a pseudo-symmetrical cycloheptene-1,3-diol motif, an aromatic B ring, and a densely functionalized tetrahydropyran ring. Herein, we report a 13-step synthesis of this natural product from inexpensive sitolactone by means of a convergent fragment-coupling approach. Key transformations include a diastereoselective allylboration, a decarboxylative elimination, a Schönecker-Baran C-H hydroxylation, a biomimetic SN2' cyclization, and a late-stage 6π electrocyclization. Mechanistic studies indicate that the pivotal formation of the tetrahydropyran ring occurs via a silyl migration/intramolecular SN2' cyclization cascade rather than via an epoxide-opening process.
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