Organic Letters 2004-09-16

Total synthesis of (+)-cocaine via desymmetrization of a meso-dialdehyde.

Douglas M Mans, William H Pearson

Index: Org. Lett. 6(19) , 3305-8, (2004)

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Abstract

[reaction: see text] The total synthesis of (+)-cocaine is described. An extension of the recently reported proline catalyzed intramolecular enol-exo-aldol reaction to a meso-dialdehyde provided the tropane ring skeleton directly with good enantiomeric excess. The meso-dialdehyde was prepared using a 2-azaallyllithium [3 + 2] cycloaddition to generate a cis-2,5-disubstituted pyrrolidine. Overall, the synthesis proceeded in 6.5% yield and 86% ee over 14 linear steps starting from commercially available 3-benzyloxy-1-propanol.