Asymmetric synthesis of (−)-(S,S)-homaline

The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps 18% overall yield, from commercially available starting materials, using the diastereoselective conjugate addition of lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate as the key step. The asymm...

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Bibliographic Details
Published in:Tetrahedron letters 2012-02, Vol.53 (9), p.1119-1121
Main Authors: Davies, Stephen G., Lee, James A., Roberts, Paul M., Stonehouse, Jeffrey P., Thomson, James E.
Format: Article
Language:English
Subjects:
(−)-(S,S)-Homaline
Amides
Asymmetric synthesis
Asymmetry
Conjugate addition
Conjugates
Esters
Homalium alkaloids
Lithium
Lithium amide
Resultants
Synthesis (chemistry)
Tetrahedrons
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Summary:The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps 18% overall yield, from commercially available starting materials, using the diastereoselective conjugate addition of lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate as the key step. The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps from commercially available starting materials using the diastereoselective conjugate addition of the novel lithium amide reagent lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate to install the correct stereochemistry. Subsequent functional group manipulation of the resultant β-amino ester and Sb(OEt)3-mediated macrolactamisation was followed by homodimerisation to give (−)-(S,S)-homaline in 18% overall yield, representing the first asymmetric, and by far the most efficient synthesis of this natural product reported to date.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2011.12.088