Catalytic Asymmetric Reductive Amination of α‐Branched Ketones

Abstract

Branching out: An organocatalytic reductive amination of α‐branched ketones using dynamic kinetic resolution is reported. The cis‐2‐substituted cyclohexyl amines were obtained in high diastereoselectivity and enantioselectivity from the corresponding ketones.

Disulfonimide‐Catalyzed Asymmetric Reduction of N‐Alkyl Imines

“…(entry 4). Electron-withdrawing para substituents such as fluorine,chlorine,bromine,ortrifluoromethyl groups have no significant influence on enantioselectivity or reactivity (entries [5][6][7][8]. However,t he p-cyano group in imine 1i decreased the reactivity and also required al onger reaction time to achieve full conversion with an e.r.…”

“…[2] Recently,w ed eveloped aB r ønsted acid catalyzed asymmetric imine reduction and reductive amination of ketones using Hantzsch esters as hydrogen source, [3] and independent variations and applications have appeared. [4][5][6][7][8] Despite these advances,h owever, such reductions have been limited to Naryl imines.W en ow report ah ighly enantioselective chiral disulfonimide (DSI)-catalyzed Hantzsch ester mediated reduction of N-alkyl imines.N-Alkyl imines are highly attractive substrates for asymmetric reductions since they would directly furnish the Nalkyl amine pharmacophore.Chiral phosphoric acids typically fail in the corresponding Hantzsch ester mediated imine reductions and alternative approaches have only rarely been investigated and remain am ajor challenge. [3b,6,9,10] At the onset of our work, we hypothesized that owing to the high basicity of the desired N-alkyl amine products,astronger Brønsted acid catalyst may be required for Hantzsch ester reductions to achieve high turnover and enantioselectivity.…”

Disulfonimid‐katalysierte asymmetrische Reduktion von N‐Alkyliminen

“…[4][5][6][7][8] Tr otz all dieser Fortschritte waren solche Reduktionen jedoch auf N-Arylimine beschränkt. Im Folgenden berichten wir nun über eine durch Hantzsch-Ester unterstützte Reduktion von N-Alkyliminen, die von einem chiralen Disulfonimid katalysiert wird.…”

Organocatalysis

“…35 List has reported the formal asymmetric synthesis of (+)-grandisol through desymmetrization of a meso-anhydride. 32 Arseniyadis and Cossy have applied enamine organocatalysis in their elegant total syntheses of (-)-bitungolide F. 4 Hong and co-workers have applied cascade enamine/iminium ion catalysis in the synthesis of (+)-conicol and didehydroconicol. 6 MacMillan has also reported the asymmetric synthesis of the angiogenesis inhibitor 18.…”