Subtle Structural Tuning Enables Bifunctional Cinchona Alkaloid Thiourea and Chiral Pyridine-Oxazoline Ligands To
Qianmao Zhang1,2, Guo Cheng1,2, Jingliang Yu1,2
1Key Laboratory of Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China.
Abstract:
A new series of bifunctional chiral ligands integrated with cinchona alkaloid thiourea and pyridine-oxazoline scaffolds were designed and synthesized, and it was found that the connecting position between cinchona alkaloid thiourea and pyridine-oxazoline is crucial, any separate part of the multifunctional ligand is inactive for catalysis, and only the two scaffolds synergistically work with the central metal to enable α-aminomaleimides and para-quinone methides to occur effectively and selectively. By subtle structural tuning, the new chiral ligands synergistically worked with Tp*Cu to effectively catalyze this enantioselective Micheal addition in excellent enantioselectivities (up to 96%ee) under mild conditions even in a scale-up preparation, in which α-aminomaleimide was used as a nucleophile for the first time. The multifunctional chiral product molecules may find potential in new pharmaceutical entities and further transformations.
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