Direct Access to α-Aryl-β-Amino Aldehydes via Hypervalent Iodine-Mediated Oxidative Rearrangement of Cinnamyl Amines

Selective synthesis of α-aryl-β-amino aldehydes remains less developed despite considerable progress in Mannich reactions, aza-Michael additions and asymmetric hydroformylation. Here we report a phenyliodine(III) bis(trifluoroacetate) (PIFA)-mediated oxidative rearrangement of cinnamyl amines through formal 1,2-aryl migration. The reaction proceeds at 0 °C under ambient air and accommodates diverse nitrogen substituents, migrating aryl groups and pharmaceutical-derived substrates. A 6-gram preparation and subsequent transformations to β-amino acids, 1,3-amino alcohols, 1,3-diamines and azetidines, together with the synthesis of a valifenalate isomer, demonstrate the synthetic utility of the aldehyde products. Mechanistic experiments suggest a pathway involving a bis(trifluoroacetate) intermediate. An initial asymmetric variant using chiral iodine(III) reagents furnished a celecoxib-derived chiral aldehyde, with up to 77% ee measured for its reduced chiral alcohol derivative.