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.
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.
Key Laboratory of Polyoxometalate Chemistry of Henan Province, Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004, P. R. China.
Xiao-Yu
XY
Cui
Key Laboratory of Polyoxometalate Chemistry of Henan Province, Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004, P. R. China.
Hui-Xin
HX
Duan
Key Laboratory of Polyoxometalate Chemistry of Henan Province, Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004, P. R. China.
Yongna
Y
Zhang
Key Laboratory of Polyoxometalate Chemistry of Henan Province, Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004, P. R. China.
You-Qing
http://orcid.org/0000-0001-8697-9165
YQ
Wang
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013843:Thiazines / Q000737:chemistry*; D014269:Trifluoroacetic Acid / Q000737:chemistry
D000588:Amines; D002930:Cinchona Alkaloids; D007097:Imines; D007659:Ketones; D013843:Thiazines; D014269:Trifluoroacetic Acid
Mannich reaction; asymmetric catalysis; ketones; nitrogen heterocycles; organocatalysis