Synthesis 2006(2): 247-256  
DOI: 10.1055/s-2005-924769
PAPER
© Georg Thieme Verlag Stuttgart · New York

Syntheses of Enantiopure 3,4-Diamino-1-Substituted Pyrrolidines

Charles M. Marson*a, Robert C. Mellingb
a Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H 0AJ, UK
Fax: +44(020)76797463; e-Mail: c.m.marson@ucl.ac.uk;
b Department of Chemistry, Queen Mary and Westfield College, University of London, London E1 4NS, UK
Further Information

Publication History

Received 5 July 2005
Publication Date:
21 December 2005 (online)

Abstract

A convenient and general route to enantiopure 3,4-diamino-1-substituted pyrrolidines has been devised. 1-Alkyl, 1-alkanoyl, 1-cycloalkyl and 1-aryl-3,4-diaminopyrrolidines of the (3R,4R)-configurations have all been prepared, the cycloalkyl and (mono)aryl being novel derivatives. A previous difficulty in the synthesis of such compounds is the observation that dimesylates undergo two-fold displacement with sodium azide in very poor yields (<10%), if at all. However, use of lithium azide permits satisfactory yields of the diazides 5 and hence the corresponding diamines 6 and their derivatives, and avoids the generation and use of hydrazoic acid, as previously required in a Mitsunobu procedure.

16

For displacement of a fluoro substituent on a quinolone ring by N,N′-bis-Boc derivatives of (3R,4R)-3,4-diamino-
pyrrolidine, see reference 3.