Asymmetric construction of a quaternary carbon center by tandem [4 + 2]/[3 + 2] cycloaddition of a nitroalkene. The total synthesis of (-)-mesembrine

Scott E. Denmark, Lawrence R. Marcin

Research output: Contribution to journalArticle

Abstract

An efficient, total synthesis of the Sceletium alkaloid (-)-mesembrine is accomplished in seven steps and 19% yield from a functionalized nitroalkene (itself prepared in six steps and 34% yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.

Original languageEnglish (US)
Pages (from-to)1675-1686
Number of pages12
JournalJournal of Organic Chemistry
Volume62
Issue number6
DOIs
StatePublished - Jan 1 1997

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Cycloaddition
Carbon
Cyclohexanols
Biological Products
Alkaloids
mesembrine
vinyl ether

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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abstract = "An efficient, total synthesis of the Sceletium alkaloid (-)-mesembrine is accomplished in seven steps and 19{\%} yield from a functionalized nitroalkene (itself prepared in six steps and 34{\%} yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.",
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T1 - Asymmetric construction of a quaternary carbon center by tandem [4 + 2]/[3 + 2] cycloaddition of a nitroalkene. The total synthesis of (-)-mesembrine

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AU - Marcin, Lawrence R.

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N2 - An efficient, total synthesis of the Sceletium alkaloid (-)-mesembrine is accomplished in seven steps and 19% yield from a functionalized nitroalkene (itself prepared in six steps and 34% yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.

AB - An efficient, total synthesis of the Sceletium alkaloid (-)-mesembrine is accomplished in seven steps and 19% yield from a functionalized nitroalkene (itself prepared in six steps and 34% yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.

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