Total synthesis of (+)-cocaine via desymmetrization of a meso-dialdehyde.
[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.
Mans
Douglas M
DM
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.
Pearson
William H
WH
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D003042:Cocaine / Q000032:analysis / Q000138:chemical synthesis*; D003500:Cyclization; D015394:Molecular Structure; D011392:Proline / Q000378:metabolism*; D011759:Pyrrolidines / Q000138:chemical synthesis; D013237:Stereoisomerism
D000447:Aldehydes; D011759:Pyrrolidines; D011392:Proline; D003042:Cocaine; C032519:pyrrolidine