Asymmetric Formal <i>trans</i>-Dihydroxylation and <i>trans</i>-Aminohydroxylation of α,β-Unsaturated Aldehydes via an Organocatalytic Reaction Cascade

This study demonstrates the first formal asymmetric <i>trans</i>-dihydroxylation and <i>trans</i>-aminohydroxylation of α,β-unsaturated aldehydes in an organocatalytic multibond forming one-pot reaction cascade. This efficient process converts α,β-unsaturated aldehydes into optically active <i>trans</i>-2,3-dihydroxyaldehydes and <i>trans</i>-3-amino-2-hydroxyaldehydes with the aldehyde moiety protected as an acetal. The elaborated one-pot protocol proceeds via the formation of 2,3-epoxy and 2,3-aziridine aldehyde intermediates, which subsequently participate in a novel NaOMe-initiated rearrangement reaction leading to the formation of acetal protected <i>trans</i>-2,3-dihydroxyaldehydes and <i>trans</i>-3-amino-2-hydroxyaldehydes in a highly stereoselective manner. Advantageously, this multibond forming reaction cascade can be performed one-pot, thereby minimizing the number of manual operations and purification procedures required to obtain the products. Additionally, for the purpose of <i>trans</i>-aminohydroxylation of the α,β-unsaturated aldehydes, a new enantioselective aziridination protocol using 4-methyl-<i>N</i>-(tosyloxy)benzenesulfonamide as the nitrogen source has been developed. The mechanism of the formal <i>trans</i>-dihydroxylation and <i>trans</i>-aminohydroxylation of α,β-unsaturated aldehydes is elucidated by various investigations including isotopic labeling studies. Finally, the products obtained were applied in the synthesis of numerous important molecules.