Highly efficient enantioselective synthesis of bispiro[benzofuran-oxindole/benzofuran-chromanone]s through organocatalytic inter-/intramolecular Michael cycloaddition

A quinine-derived thiourea-catalyzed inter-/intramolecular Michael cycloaddition of chromoneoxindole/benzofuranone synthons with 3-substituted methylenebenzofuranones has been established, which constructed enantiomerically pure bispiro[benzofuran-oxindole/benzofuran-chromanonels bearing five consecutive stereocenters including two spiro quaternary carton centers in good yields (up to 93%) with high diastereoselectivities (up to >20:1 dr) and good enantioselectivities (up to >99% ee). Moreover, this is the first example of bifunctional chromone-benzofuranone synthon directed organocatalytic tandem reaction, and also the first example of the bispiro[benzofuran-oxindole] and bispirobenzofuranone, potentially useful in medicinal chemistry. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.