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Eight-Step Enantioselective Total Synthesis of (-)-Cycloclavine.

ABSTRACT: The first enantioselective total synthesis of (-)-cycloclavine was accomplished in 8?steps and 7.1?% overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh2 (S-TBPTTL)4 , and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels-Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99?% ee after crystallization. The synthesis of (-)-1 was completed by a late-stage intramolecular Diels-Alder furan (IMDAF) cycloaddition to install the indole.

SUBMITTER: McCabe SR

PROVIDER: S-EPMC5195887 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Eight-Step Enantioselective Total Synthesis of (-)-Cycloclavine.

McCabe Stephanie R SR Wipf Peter P

Angewandte Chemie (International ed. in English) 20161118 1

The first enantioselective total synthesis of (-)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh<sub>2</sub> (S-TBPTTL)<sub>4</sub> , and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels-Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee af ...[more]

PMID: 27860203

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