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Practical Access to Benzylic-Substituted Chiral Oxazoline P,N-Ligands (BSPHOX) Enabled by an Iodonium-Claisen
Lei Zhang1, Ao Cui1, Dingming Zheng1
1Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University, Jinhua 321004, China.
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Phosphinooxazoline (PHOX) ligands bearing a benzylic stereocenter (BSPHOX) remain underexplored within the PHOX family, largely due to their lengthy and demanding synthetic routes. Consequently, an efficient, stereocontrolled, and practically scalable route to BSPHOX ligands is highly desirable. Herein, we disclose a concise two-step strategy featuring an asymmetric iodonium-promoted Claisen rearrangement to establish the chiral scaffold, followed by a palladium-catalyzed C-P coupling with diphenylphosphine. The sequence is operationally simple, proceeds under mild conditions, and is readily scalable to 7 g quantities. Preliminary evaluation of the resulting BSPHOX ligands in several asymmetric transformations─including hydroamination, the Heck reaction, and 1,3-dipolar cycloaddition─demonstrates their promising potential in enantioselective catalysis.
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