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Abstract The development of a concise total synthesis of (±)‐phyllantidine (1), a member of thesecurinegafamily of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen‐oxygen (N−O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early‐stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N−O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide.
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Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of Bromobenzene
Abstract The total synthesis of lycoricidine and narciclasine is enabled by an arenophile‐mediated dearomative dihydroxylation of bromobenzene. Subsequent transpositive Suzuki coupling and cycloreversion deliver a key biaryl dihydrodiol intermediate, which is rapidly converted into lycoricidine through site‐selectivesyn‐1,4‐hydroxyamination and deprotection. The total synthesis of narciclasine is accomplished by the late‐stage, amide‐directed C−H hydroxylation of a lycoricidine intermediate. Moreover, the general applicability of this strategy to access dihydroxylated biphenyls is demonstrated with several examples.
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- Award ID(s):
- 1654110
- PAR ID:
- 10045388
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 56
- Issue:
- 47
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 15049-15052
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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