The Chemistry of Enamine Derivatives via an Umpolung Chemistry

Umpolung strategies are of considerable interest to oragnic chemists because they provided alternative synthetic routes to those imposed by the natural polarity of classic synthons. In recent years, umpolung of enamines has received much attention as a novel strategy to access α-substituted ketones. We focused on the synergistic effect of N-alkoxyenamines and organoaluminum reagents and found that the N-O bond cleavage and introduction of nucleophiles at the β-position of N-alkoxyenamine can be achieved in a SN2′-type reaction manner. This approach is amenable to the synthesis of α-substituted ketones by incorporating various C (sp3) and C (sp2) units, such as alkyl, aryl, heteroaryl, and alkenyl groups. We applied this method to aldehydes, vicinal functionalization to double bond of enamines is possible, allowing the double introduction of nucleophiles at both the α- and β-positions of the enamine. Moreover, this method can also be applied to O-silyl-N,O-keteneacetals derived from isoxazolidine amides, affording α-substituted amides via nucleophilic β-phenylation of O-silyl-N,O-keteneacetals. Furthermore, polarity inversion of amides was achieved, enabling the introduction of nucleophiles at the α-position as well as the γ-position. In this review, we want to describe the details of our endevours to develop the novel enamine chemistry through an umpolung startegy.