Chiral Phosphoric Acid-catalyzed Asymmetric Synthesis of Acyclic N,N'-Ketals
Chiral N,N'-ketal is one of the most important core structures of drug molecules and biologi-cally active compounds,as well as important catalyst or ligand in organic synthesis,accordingly the asymmetric synthesis of N,N'-ketal is of great significance.Screening of chiral phosphoric acid,sol-vent,catalyst loading,and ratio,the optimal reaction condition was determined,that is,under the ca-talysis of chiral phosphoric acid,with 1,4-dioxane as solvent,the asymmetric N—H alkylations of isoxazoles were achieved by regioselective aza-Mannich reactions of 5-amino-isoxazoles with β,γ-alky-nyl-α-ketimino esters to synthesize the acyclic N,N'-ketals in moderate to good yield(46％～83％yield)and good enantioselectivity(82％～92％ee).The structures of all the products were confirmed by 1H NMR,13C NMR and HR-MS(ESI)and the absolute configuration was determined by X-ray crystal structure analysis.
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