Jump to main content
Jump to site search

Issue 22, 2003
Previous Article Next Article

Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation–substitution of N-(tert-butoxycarbonyl)pyrrolidine

Author affiliations

Abstract

Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation–substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines {(1S*,2R*,8R*)-10-methyl-6,10-diazatricyclo[6.3.1.02,6]dodecane and (1S*,2R*,9R*)-11-methyl-7,11-diazatricyclo[7.3.1.02,7]tridecane} (via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[7.3.1.02,7]tridecane compound. An alternative route to (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.02,7]tridecane starting from the natural product, (−)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (−)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation–substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (−)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.02,7]tridecane is the first successful (+)-sparteine surrogate.

Graphical abstract: Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation–substitution of N-(tert-butoxycarbonyl)pyrrolidine

Back to tab navigation

Supplementary files

Article information


Submitted
22 Jul 2003
Accepted
18 Sep 2003
First published
07 Oct 2003

Org. Biomol. Chem., 2003,1, 3977-3988
Article type
Paper

Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation–substitution of N-(tert-butoxycarbonyl)pyrrolidine

J. R. Hermet, D. W. Porter, M. J. Dearden, J. R. Harrison, T. Koplin, P. O'Brien, J. Parmene, V. Tyurin, A. C. Whitwood, J. Gilday and N. M. Smith, Org. Biomol. Chem., 2003, 1, 3977 DOI: 10.1039/B308410H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.


Social activity

Search articles by author

Spotlight

Advertisements