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DOI: 10.1055/s-0036-1588602
The Wender Cedrene Synthesis Revisited: A Catalytic Enantioselective Entry to the Chiral Key Intermediate
Publication History
Received: 29 August 2016
Accepted: 01 September 2016
Publication Date:
26 September 2016 (online)
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Dedicated to Prof. Dr. Dieter Enders
Abstract
The seminal synthesis of the sesquiterpene (±)-α-cedrene reported by Wender in 1981 offers a uniquely short and elegant access to the bridged-tricyclic target compound by exploiting an intramolecular arene-olefin photocycloaddition. However, the synthesis was performed only in the racemic series so far. This synthesis was now re-investigated and the catalytic methods for the enantioselective preparation of the chiral key intermediate were evaluated. It was found that Cu-catalyzed allylic substitution of a cinnamyl chloride with MeMgBr in the presence of a Taddol-derived chiral phosphine-phosphite ligand affords the corresponding (1-methylallyl)arene with high enantioselectivity (94% ee). Hydroboration and subsequent Suzuki coupling gave (R)-curcuphenol methyl ether from which (–)-α-cedrene was prepared along the route paved by Wender.
Key words
terpenoids - total synthesis - enantioselectivity - asymmetric catalysis - allylation - photochemistry - copper - chiral P,P-ligandsSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588602. NMR spectra and chromatograms are included.
- Supporting Information
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For reviews, see:
For a recent application of such a ligand in enantioselective 1,4-addition, see:
For recent reviews on hydrovinylation, see:
For reviews on asymmetric Cu-catalyzed allylic substitution using Grignard reagents, see:
For an early key publication, see also: