Asymmetric peroxidation of α,β-unsaturated aldehydes under diarylprolinol ether catalysis

O'Reilly, Kate; Gupta, Manoj K.; Gandhi, Hirenkumar; Kumar, Vydyula P.; O'Sullivan, Timothy P.

Asymmetric peroxidation of α,β-unsaturated aldehydes under diarylprolinol ether catalysis

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Accepted version

Date

2017

Authors

O'Reilly, Kate

Gupta, Manoj K.

Gandhi, Hirenkumar

Kumar, Vydyula P.

O'Sullivan, Timothy P.

Publisher

Bentham Science Publishers

Published Version

10.2174/1385272821666170412113323

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.

Keywords

Organocatalysis , Prolinol , Asymmetric , Peroxidation , Peroxyacids , Peroxyesters

Citation

O’Reilly, K., Gupta, M. K., Gandhi, H., Kumar*, V. P. and O’Sullivan, T. P. (2017) 'Asymmetric peroxidation of α,β-unsaturated aldehydes under diarylprolinol ether catalysis', Current Organic Chemistry, 21(19), pp. 2013-2016. doi: 10.2174/1385272821666170412113323