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Article

Asymmetric Total Synthesis of (+)-Cannabisativine

Supporting Info

Jeffrey T. Kuethe and Daniel L. Comins*

Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204

J. Org. Chem., 2004, 69 (16), pp 5219–5231

DOI: 10.1021/jo049724+

Publication Date (Web): April 29, 2004

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, daniel_comins@ncsu.edu

Abstract

The asymmetric total synthesis of natural (+)-cannabisativine 1 was completed in 19 steps and 7% overall yield. The key synthetic intermediate 29 was prepared with a high degree of stereocontrol in 12 steps starting from chiral 1-acylpyridinium salt 10. Addition of zinc enolate 11 to pyridinium salt 10 furnished dihydropyridone 12 containing two contiguous stereocenters of the correct absolute configuration. Luche reduction of ketone 16 afforded diol 17 in high yield (96%) and excellent diastereoselectivity. The Mukaiyama−Michael reaction of pyridones 27a/b with O-silyl ketene acetal 32 gave phenyl selenyl ketones 33a/b with complete stereoselectivity. Elimination of cis-β-hydroxyselenides 34 and 35 effected the regiocontrolled preparation of tetrahydropyridine derivative 29. Several approaches to the macrocyclic ring closure of the 13-membered ring were investigated, ultimately leading to the completion of an asymmetric synthesis of the target compound with a high degree of stereocontrol.

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Published In Issue August 06, 2004
Received February 16, 2004

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Article

Asymmetric Total Synthesis of (+)-Cannabisativine

Abstract

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SciFinder Links

History

Recommend & Share

Related Content

Enantiopure 2,3-Dihydro-4-pyridones as Synthetic Intermediates: A Concise Asymmetric Synthesis of (+)-Allopumiliotoxin 267A

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A Direct and Efficient Total Synthesis of the Tubulin-Binding Agents Ceratamine A and B; Use of IBX for a Remarkable Heterocycle Dehydrogenation

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