Further insights into the organocatalytic reaction of 2,2-dimethyl-1,3-dioxan-5-one with α-silyloxy aldehydes

Abstract

Proline-catalysed reactions of dihydroxyacetone isopropylidene acetal, 1, with enantiopure α-silyloxy aldehydes 2/4/6/8 afford 90–95% yields of cross-aldol products (only one stereoisomer in each case), provided that 15±10equiv of H2O are present in the medium. Individual reaction steps have been monitored by NMR spectroscopy to gain insight into the cause of these remarkable results. It is confirmed that proline ‘protects’ 2 as oxazolidinone 2-ox, but it means that proline—the catalyst—is trapped by 2; several equiv of H2O are required to avoid it. Moreover, H2O mediates prolyl group exchanges and goes against the dehydration of aldols. For the first time, we detected by NMR one ‘wanted’ intermediate (an enamine of the adduct).