Total Synthesis of the Cephalotaxus Alkaloids. A Problem in Nucleophilic Aromatic Substitution

M. F. Semmelhack; B. P. Chong; R. D. Stauffer; T. D. Rogerson; A. Chong; Lawrence D. Jones

doi:10.1021/ja00842a031

Total Synthesis of the Cephalotaxus Alkaloids. A Problem in Nucleophilic Aromatic Substitution

M. F. Semmelhack, B. P. Chong, R. D. Stauffer, T. D. Rogerson, A. Chong, Lawrence D. Jones

Research output: Contribution to journal › Article › peer-review

200 Scopus citations

Abstract

The synthesis of cephalotaxine and cephalotaxinone has been achieved in 12-16% overall yield from pyrrolidone and 3,4-methylenedioxyphenylacetic acid. The strategy includes a key step which requires overall intramolecular nucleophilic aromatic substitution of an enolate anion onto an unactivated aromatic ring. Several methods give successful ring closure including addition to a transient aryne (15% yield), coupling via a σ-arylnickel complex (30%), and addition to a transient aryl radical generated from alkali metal reduction (45%) or from irradiation (94%).

Original language	English (US)
Pages (from-to)	2507-2516
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	97
Issue number	9
DOIs	https://doi.org/10.1021/ja00842a031
State	Published - Apr 1 1975
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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abstract = "The synthesis of cephalotaxine and cephalotaxinone has been achieved in 12-16% overall yield from pyrrolidone and 3,4-methylenedioxyphenylacetic acid. The strategy includes a key step which requires overall intramolecular nucleophilic aromatic substitution of an enolate anion onto an unactivated aromatic ring. Several methods give successful ring closure including addition to a transient aryne (15% yield), coupling via a σ-arylnickel complex (30%), and addition to a transient aryl radical generated from alkali metal reduction (45%) or from irradiation (94%).",

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AU - Rogerson, T. D.

AU - Chong, A.

AU - Jones, Lawrence D.

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AB - The synthesis of cephalotaxine and cephalotaxinone has been achieved in 12-16% overall yield from pyrrolidone and 3,4-methylenedioxyphenylacetic acid. The strategy includes a key step which requires overall intramolecular nucleophilic aromatic substitution of an enolate anion onto an unactivated aromatic ring. Several methods give successful ring closure including addition to a transient aryne (15% yield), coupling via a σ-arylnickel complex (30%), and addition to a transient aryl radical generated from alkali metal reduction (45%) or from irradiation (94%).

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Total Synthesis of the Cephalotaxus Alkaloids. A Problem in Nucleophilic Aromatic Substitution

Abstract

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