A cinchona-catalysed, enantioselective oxa-Michael reaction of α,β-unsaturated
aldehydes with either tert-butyl hydroperoxide or cumene hydroperoxide was developed.
The reaction was optimised by screening of solvents, modification of the catalyst framework
and variation of the acid co-catalysts. A strong relationship was noted between the pKa of
the acid co-catalyst and the degree of selectivity. Enantioselective peroxidation of α,β-
unsaturated aldehydes with tert-butyl hydroperoxide afforded β-peroxyaldehydes with good
enantioselectivities. In situ oxidation of the latter compounds furnished β-peroxycarboxylic
acids in high yields. Enantiomeric excesses were determined by derivitisation to their mandelate
esters and subsequent separation by chiral high performance liquid chromatography.
Peroxidation with cumene hydroperoxide was similarly successful with the products being
isolated as stable β-peroxyalcohols. These latter β-peroxyalcohols offer a direct route to 5-membered, chiral cycloperoxides
via a silver-mediated cyclisation. This reaction proceeds by trapping of the oxygen lone pair by the
incipient carbocation followed by loss of the cumyl or tert-butyl group and formation of the cycloperoxide product.
Keywords: Organocatalysis, cinchona, peroxidation, peroxyacids, peroxyesters, peroxyalcohols, cycloperoxides.
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