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Asymmetric Mannich Reaction of Aryl Methyl Ketones with Cyclic Imines Benzo[ e ][1,2,3]oxathiazine 2,2‐Dioxides Catalyzed by Cinchona Alkaloid‐based Primary Amines
Author(s) -
Cui XiaoYu,
Duan HuiXin,
Zhang Yongna,
Wang YouQing
Publication year - 2016
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201601149
Subject(s) - chemistry , aryl , imine , cinchona , beckmann rearrangement , steric effects , mannich reaction , enantioselective synthesis , trifluoroacetic acid , amide , organic chemistry , catalysis , medicinal chemistry , combinatorial chemistry , alkyl
Aryl ketones represent problematic substrates for asymmetric Mannich reactions due to a large steric hindrance exhibited by such compound species. A highly enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imine benzo[ e ][1,2,3]oxathiazine 2,2‐dioxides could be successfully carried out utilizing a combination of cinchona alkaloid‐derived primary amines with trifluoroacetic acid (TFA); the primary amines feature a superior catalytic efficacy over secondary amines with a variety of sterically hindered carbonyl compounds as substrates. The reaction proceeded well with various cyclic imines in 89–97 % ee and with various aryl methyl ketones in 85–98 % ee . Moreover, the aryl carbonyl of a Mannich product could be transformed to ketoxime, which further undergoes a Beckmann rearrangement to produce an amide compound while maintaining enantioselectivity.