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

ABSTRACT

3-Fluorooxindoles and the dibenzo[b,f][1,4]oxazepane scaffolds are important pharmacophores that have important application in medicinal chemistry. An organocatalyzed asymmetric Mannich reaction of 3-fluorooxindoles with dibenzo[b,f][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 Cinchona alkaloid-derived thiourea catalyst afforded a wide range of substrates in moderate to high yields with excellent diastereo- and enantioselectivities (up to 88% yield, >201 dr and >99% ee). A feasible reaction mechanism was also proposed.