Relay PHOS: Ligands with Fluxional Chirality in Asymmetric Palladium-Catalyzed Allylic Alkylation
Regina C So1, Hariharaputhiran Subramanian1, Carter R Kuehn1
1Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108-6050, United States.
Abstract:
A modular route toward the synthesis of P,N ligands containing a fluxional group along the pyrazoline ring core is described. The racemic ligands were accessed in three steps from commercially available fluoroacetophenone in overall yields ranging from 18 to 76%. The enantiopure ligands were obtained using semi-preparative chiral high-performance liquid chromatography and chiral enantioselective phase-transfer catalysis. The effectiveness of the new ligands was assessed in palladium-catalyzed allylic alkylation with diphenylpropenyl acetate and dimethylpropenyl acetate. Under optimized conditions, diphenylpropenyl acetate underwent alkylation with dimethyl malonate in 98% yield and 94% ee. In general, the enantioselectivity for the product correlates with the size of the ligand fluxional group; the larger the fluxional group, the higher the selectivity.
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