Catalytic asymmetric mannich-type reactions activated by ZnF2 chiral diamine in aqueous media.
Catalytic asymmetric Mannich-type reactions of an alpha-hydrazono ester with silicon enolates in aqueous media have been developed by using ZnF2 and chiral diamines as catalysts. In these reactions, both Zn2+ and a fluoride anion were necessary to achieve high yields and enantioselectivities, suggesting a double activation mechanism, in which Zn2+ activates the alpha-hydrazono ester and the fluoride anion simultaneously activates the silicon enolate. When chiral diamine ligands bearing methoxy-substituted aromatic rings were employed, the reactions in aqueous THF were markedly accelerated. Furthermore, the use of these diamines facilitated the asymmetric Mannich-type reactions in water without any organic cosolvents. It is noteworthy that either syn or anti adducts were stereospecifically obtained from (E)- or (Z)-silicon enolates, respectively. Interestingly, these reactions proceeded smoothly only in the presence of water. On the basis of several experimental results, it can be concluded that the reaction mechanism is likely to be a fluoride-catalyzed one, in which the ZnF2 chiral diamine complex is regenerated from the Me3SiF formed during the reaction.
Hamada
Tomoaki
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, The HFRE Division, ERATO, Japan Science and Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Manabe
Kei
K
Kobayashi
Shū
S
D002384:Catalysis; D003959:Diamines / Q000737:chemistry*; D005459:Fluorides / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry; D017655:Silicon Compounds / Q000737:chemistry; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry; D017967:Zinc Compounds / Q000737:chemistry*
D003959:Diamines; D008698:Mesylates; D017655:Silicon Compounds; D017967:Zinc Compounds; D014867:Water; C012077:trifluoromethanesulfonic acid; C038904:zinc fluoride; D005459:Fluorides