Title:Asymmetric Peroxidation of α,β-Unsaturated Aldehydes under Diarylprolinol Ether Catalysis
Volume: 21
Issue: 19
Author(s): K. O’Reilly, M.K. Gupta, H. Gandhi, V.P. Kumar*T.P. O’Sullivan
Affiliation:
- Department of Chemistry, University College Cork, Cork,Ireland
Keywords:
Organocatalysis, prolinol, asymmetric, peroxidation, peroxyacids, peroxyesters.
Abstract: Background: Chiral peroxides, many of which are biologically active, are an attractive target in organic
synthesis. Organocatalysts have been used for some time in the asymmetric epoxidation of α,β-
unsaturated carbonyls. More recently, cinchona-derived organocatalysts have been adapted to effect the asymmetric
peroxidation of unsaturated ketones. We successfully applied this catalyst system to the stereoselective
peroxidation of more challenging α,β-unsaturated aldehydes with moderate enantioselectivity observed. Herein
we describe our efforts to improve upon the overall stereoselectivity using prolinol-derived organocatalysts.
Objective: To determine whether diarylprolinol silyl ethers are effective catalysts in the asymmetric peroxidation
of α,β-unsaturated aldehydes.
Methods: Using trans-2-butenal as the test substrate, peroxidation with tert-butyl hydroperoxide was attempted
in a range of different solvents. The resulting β-peroxyaldehydes were oxidised in situ to afford stable
β-peroxyesters. The reaction was further optimised by varying the co-catalyst and by changing the silyl ether
group on the prolinol catalyst. A number of short-chain substrates were subjected to peroxidation under optimised
conditions.
Results: Diarylprolinol ethers were found to be effective catalysts for the enantioselective peroxidation of unsaturated
aldehydes. The degree of enantioselectivity was influenced both by the choice of solvent and acid cocatalyst.
Furthermore, a clear trend emerged where the level of enantioselectivity increased with increasing
steric bulk of the silyl group.
Conclusion: Diarylprolinol ethers are effective catalysts for the asymmetric peroxidation of α,β-unsaturated
aldehydes. Under optimised conditions, short-chain substrates may be converted to the corresponding β-
peroxyesters in good yields and excellent enantioselectivities.
