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Synfacts 2013; 9(1): 0011
DOI: 10.1055/s-0032-1317720
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (R)-Rolipram

Contributor(s):
Philip Kocienski
Yang X.-F, Ding C.-H, Li X.-H, Huang J.-Q, Hou X.-L, * Dai L.-X, Wang P.-J. Shanghai Institute of Organic Chemistry, P. R. of China
Regio- and Enantioselective Palladium-Catalyzed Allylic Alkylation of Nitromethane with Monosubstituted Allyl Substrates: Synthesis of (R)-Rolipram and (R)-Baclofen.

J. Org. Chem. 2012;
77: 8980-8985
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Publication History

Publication Date:
17 December 2012 (online)

 
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Key words

(R)-rolipram - (R)-baclofen - asymmetric allylic alkylation - nitromethane - allyl carbonates - palladium

Significance

Rolipram is a phosphodiesterase-4 (PDE-4) inhibitor that displays potentially useful anti-inflammatory, antidepressant and antipsychotic effects. The key step in the micro-scale synthesis depicted is the palladium-catalyzed asymmetric allylic alkylation of nitromethane with the allylic carbonate A. High regio- and enantio­selectivities were observed using the ferrocene-based SIOCPhox chiral ligand B.


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Comment

The scope of the asymmetric allylic ­alkylation of nitromethane was explored using eleven aryl-substituted allyl methyl carbonates giving yields of 80–92% (one exception) and enantiomeric excesses of 90–98%. The reaction was also applied to an asymmetric synthesis of the anti-spasmodic agent (R)-baclofen.


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