Asymmetric Organic Catalytic [4+2] Cycloaddition And Michael Addition Reaction Of 5H-thiazole/Oxazole-4-ones

Versatile synthetic strategies that access diverse chemical substrates in a highly chemo- and stereo-selective manner are crucial but demanding. Construction of chiral molecules with multiple(hetero)-quaternary carbon stereocenters in a single fashion is a particularly significant challenge, with important applications in the synthesis of a range of bioactive compounds containing the 1,4-oxa and sulfur bridged piperidinone structural motifs. The asymmetric synthesis of these entities is complicated due to building at least two hetero-quaternary stereocenters concurrently. In order to achieve this, we have developed an efficient organocatalytic [4+2] cycloaddition reaction between 5H-oxazol-4-ones and N-malemides to allow easy access to valuable chiral oxo-bridged piperidone-fused succinimides. Furthermore, a highly enantio- and diasteoselective [4+2] cycloaddition reaction of 5H-thiazole-4-ones with electron-deficient alkenes has been established. This protocol could be applied to a series of alkenes such as nitroalkenes, N-itaconimides, and methyleneindolinones.1 Asymmetric [4 + 2] cycloaddition reaction and Michael addition of 5H-oxazol-4-ones with N-MaleimidesBased on the history research in our group, herein, 5H-Oxazol-4-ones was applied again in Michael addition and [4 + 2] cycloaddition reaction with another substrate N-Maleimides. With different catalyst(I and II) in use, excellent results involving yields and stereoselectivities have been successfully obtained(for Michael products: up to 90% yield, > 99% ee and >19:1 dr; for cycloaddition products:up to >70% yield, 94% ee and >19:1 dr).2 Asymmetric [4 + 2] cycloaddition reaction based on 5H–thiazole–4–onesThrough developing a new type of dipeptide Br?nsted base catalyst, the first [4+2] cycloaddition reactions of 5H-thiazole-4-ones with N-itaconimides, methyleneindolinones and nitroolefins have been developed, providing an efficient approach to valuable chiral 1,4-sulfur bridged piperidinones and their derivatives with multiple hetereo-quaternary stereogenic centers in high yields and enantioselectivities.