Gold(I)‐Catalyzed Enantioselective Synthesis of Pyrazolidines, Isoxazolidines, and Tetrahydrooxazines

The field of gold(I)-catalyzed addition of heteroatom nucleophiles to allenes has recently expanded to include enantioselective synthesis of heterocyclic products. Despite the growth in this area of research and the biological relevance of heterocycles containing multiple heteroatoms, the asymmetric addition of hydrazine and hydroxylamine nucleophiles to allenes has not yet been reported. In 2007, our group reported the enantioselective hydroamination of allenes catalyzed by gold(I)/bis(p-nitrobenzoate) complexes. We hypothesized that in addition to tosyl amines, gold(I)/bis(pnitrobenzoate) complexes would perform as efficient catalysts for the enantioselective addition of hydroxylamines and hydrazines to allenes. The heterocycles formed from these reactions, vinyl isoxazolidines and pyrazolidines, appear frequently in biologically important molecules. In addition, these heterocycles serve as precursors to unnatural amino acid derivatives such as 5-oxaproline 8] as well as chiral allylic alcohols and 1,3-diamines [Eq. (1)].