Development of Efficient Synthetic Reactions Using Enamines and Enamides Carrying Oxygen Atom Substituent on Nitrogen Atom

We have developed efficient synthetic reactions using enamines and enamides carrying oxygen atom substituent on nitrogen, such as N-alkoxyenamines, N,α-dialkoxyenamines, N-alkoxyanamides, and N-(benzoyloxy)enamides. The umpolung reaction by polarity inversion at the β-position of N-alkoxyenamines afforded α-alkyl-, α-aryl-, α-alkenyl-, and α-heteroarylketones by using aluminum reagent as nucleophiles. Furthermore, one-pot umpolung α-phenylation of ketones has been also developed. We applied this method to umpolung reaction of N,α-dialkoxyenamine, generated from N-alkoxyamide to afford α-arylamides. The vicinal functionalization of N-alkoxyenamines has been achieved with the formation of two new carbon-carbon bonds by using an organo-aluminum reagent and subsequent allyl magnesium bromide or tributyltin cyanide. A sequential retro-ene arylation has been developed for the conversion of N-alkoxyenamides to the corresponding tert-alkylamines. The [3,3]-sigmatropic rearrangement of N-(benzoyloxy)enamides followed by arylation afforded cyclic β-aryl-β-amino alcohols bearing a tetrasubstituted carbon center. The resulting products were converted into the corresponding sterically congested cyclic β-amino alcohols, as well as the dissociative anesthetic agent Tiletamine.