Organocatalytic Asymmetric Mannich Addition of 3-Fluorooxindoles to Dibenzo[,][1,4]oxazepines: Highly Enantioselective Construction of Tetrasubstituted C-F Stereocenters.

3-Fluorooxindoles and the dibenzo[,][1,4]oxazepane scaffolds are important pharmacophores that have important application in medicinal chemistry. An organocatalyzed asymmetric Mannich reaction of 3-fluorooxindoles with dibenzo[,][1,4]oxazepines affording various seven-member cyclic amines containing chiral tetrasubstituted C-F stereocenters was developed. These reactions which were catalyzed by a bifunctional alkaloid-derived thiourea catalyst afforded a wide range of substrates in moderate to high yields with excellent diastereo- and enantioselectivities (up to 88% yield, >20:1 dr and >99% ee). A feasible reaction mechanism was also proposed.