Enantioselective synthesis of isoxazole-containing spirooxindole tetrahydroquinolines via squaramide-catalysed cascade reactions.

A class of o-sulfonylaminostyryl isoxazole synthons were designed and demonstrated to be useful building blocks in asymmetric cascade aza-Michael/Michael reaction with 3-olefinic oxindoles. This squaramide-catalysed cascade reaction afforded structurally complex isoxazole-containing spirooxindole tetrahydroquinolines bearing three contiguous stereocenters in good to excellent yields (up to 99%) with high diastereoselectivities (up to >20 : 1 dr) and enantioselectivities (up to 88% ee). Moreover, the gram-scale synthesis and synthetic transformations were also demonstrated.

Asymmetric synthesis of isoxazole and trifluoromethyl-containing 3,2'-pyrrolidinyl dispirooxindoles via squaramide-catalysed [3 + 2] cycloaddition reactions.

A highly efficient squaramide-catalysed asymmetric domino Michael/Mannich [3 + 2] cycloaddition of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles and N-2,2,2-trifluoroethylisatin ketimines was developed. A new class of complex and diverse-skeleton isoxazole and trifluoromethyl-containing 3,2'-pyrrolidinyl dispirooxindoles bearing four contiguous stereogenic centers including two adjacent spiro quaternary stereocentres were obtained in good to excellent yields (up to 99%) with excellent diastereoselectivities (>20 : 1 dr, in all cases) and enantioselectivities (up to 96% ee). Moreover, the potential utilities of the protocol have been demonstrated by gram-scale synthesis and further transformation experiments.