Asymmetric Skeletal Rearrangement of Symmetrically α,α-Disubstituted α-Amino Aldehydes: A New Entry to Optically Active α-Hydroxy Ketones

A unique asymmetric skeletal rearrangement of symmetrically α,α-disubstituted α-amino aldehydes has been accomplished for the first time using a chiral organoaluminum Lewis acid 1. For instance, treatment of (S)-2,2'-bis(trifluoromethanesulfonylamino)-1,1'-binaphthyl with Me3Al (1.0 equiv) in toluene at room temperature for 15 min and at 110 °C for an additional 15 min produced (S)-1, and a subsequent reaction with α -amino aldehyde 2a (R = CH2Ph) at −78 °C for 4 h and at −40 °C for 12 h resulted in the smooth rearrangement to the zwitterionic iminium intermediate A, which furnished the α-hydroxy ketone 3a (R = CH2Ph) in 93% isolated yield with 95% ee (S) after acidic hydrolysis. This result, together with other representative examples, clearly demonstrates the effectiveness of the present method for the hitherto difficult asymmetric synthesis of acyloins. Furthermore, we found that the treatment of the in situ generated A with DIBAH afforded the corresponding anti amino alcohol exclusively without loss of enantiomeric excess. Our approach casts light on the previously unexplored yet potential utility of α-amino aldehydes as synthetic building blocks and also provides a new entry to optically active α-hydroxy ketones and 1,2-amino alcohols.