Stereodivergent Synthesis of 3‑Aminooxindole Derivatives Containing Vicinal Tetrasubstituted Stereocenters via the Mannich Reaction

A highly
enantioselective stereodivergent synthesis of 3-aminooxindole
derivatives was accomplished via asymmetric Mannich reaction between
2-substituted benzofuran-3-one and isatin-derived ketimines. Both anti and syn-selective chiral 3,3-disubstituted
amino oxindoles bearing two adjacent tetrasubstituted stereogenic
centers with high yield and excellent enantioselectivities were obtained
using readily available cinchona-alkaloid derived organocatalysts.
The control experiment revealed that oxygen atom present in the benzofuran
ring played an important role in switching diastereodivergence. The
obtained Mannich product was further transformed into a biologically
important 2,3-dihydrobenzofuran derivative having three contiguous
stereocenters with no loss of enantioselectivity.