Formaldehyde N,N-dialkylhydrazones as neutral formyl anion equivalents in iridium-catalyzed asymmetric allylic substitution

Abstract

The use of formaldehyde N,N-dialkylhydrazones as neutral C1-nucleophiles in the iridium-catalyzed substitution of allylic carbonates is described for two processes. Kinetic resolution or, alternatively, stereospecific substitution affords configurationally stable α,α-disubstituted aldehyde hydrazones in high enantiomeric excess and yield. This umpolung approach allows for the construction of optically active allylic nitriles and dithiolanes as well as branched α-aryl aldehydes. A catalyst-controlled reaction with Enders' chiral hydrazone derivatives followed by diastereoselective nucleophilic addition to the hydrazone products constitutes a two-step stereodivergent synthesis of chiral amines.