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. 2011 Mar 30;133(12):4260-3.
doi: 10.1021/ja2008906. Epub 2011 Mar 9.

Enantioselective α-arylation of aldehydes via the productive merger of iodonium salts and organocatalysis

Anna E Allen  1 , David W C MacMillan
Affiliations

Enantioselective α-arylation of aldehydes via the productive merger of iodonium salts and organocatalysis

Anna E Allen et al. J Am Chem Soc. .

Abstract

The enantioselective α-arylation of aldehydes has been accomplished using diaryliodonium salts and a combination of copper and organic catalysts. These mild catalytic conditions provide a new strategy for the enantioselective construction and retention of enolizable α-formyl benzylic stereocenters, a valuable synthon for the production of medicinal agents. As one example, this new asymmetric protocol has been applied to the rapid synthesis of (S)-ketoprofen, a commercially successful oral and topical analgesic.

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Figures

Scheme 1
Scheme 1
Initial Hypothesis for the α-Arylation of Aldehydes
Scheme 2
Scheme 2
Revised Mechanism for the Aldehyde α-Arylation
Scheme 3
Scheme 3
Rapid Enantioselective Synthesis of (S)-Ketoprofen
See this image and copyright information in PMC

References

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