Highly Efficient and Practical N-Heterocyclic Carbene Organocatalyzed Chemoselective N₁/C₃-Functionalization of Isatins with Green Chemistry Principles.

ABSTRACT: Ecofriendly N-heterocyclic carbene (NHC) organocatalysis can control the N₁-functionalization (aza-Michael addition) and C₃-functionalization (Morita-Baylis-Hillman reaction, MBH) of isatins in the absence of (1) a protecting group, (2) a stoichiometric reagent, and (3) heat energy. The challengeable N₁-functionalization of N-unsubstituted isatins into N-substituted (NS) isatins was realized through 10 mol % NHC and 10 mol % 1,8-diazabicyclo[5.4.0]undec-7-ene catalysts within 10 min with up to 98% isolation yield. The subsequent MBH adducts of as-synthesized NS-isatins (N₁/C₃-functionalization) was perfectly acquired in 10 mol % NHC and 10 mol % 1,4-diazabicyclo[2.2.2]octane catalysis within 30 min with superiority to C₃/N₁-functionalization (MBH/aza-Michael). For guiding the application to a versatile druggable isatin library, the NHC catalysis was compared with reported functionalization of isatins in view of green chemistry principles including solvent scoring of ACS GCI pharmaceutical roundtable, E-factor, atom economy, and so on.

SUBMITTER: Mudithanapelli C 

PROVIDER: S-EPMC6643579 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature