Insights into the spontaneous emergence of enantioselectivity in an asymmetric Mannich reaction carried out without external catalyst

ESI-MS, chiral HPLC, time-resolved ¹H NMR and optical rotation measurements were performed to gain insights into the nature of spontaneous mirror symmetry breaking in the catalyst-free Mannich reaction of PMP protected α-iminoethylglyoxylate with hydroxyacetone. Spontaneous temporary generation of enantiomeric excesses of up to 7.4% in the major syn diastereomer is reproducibly observed in aqueous phosphate buffers, starting from achiral conditions. The syn-product ee values for both enantiomers (2S,3S) and (2R,3R)], although not with stochastic distribution, have been observed with no clear preference for either enantiomer.