From racemic precursors to fully stereocontrolled products: one-pot synthesis of chiral α-amino lactones and lactams

Abstract

Substituted racemic lactols or cyclic hemiaminals were directly used as nucleophiles in enamine-based asymmetric amination reactions to access enantioenriched α-amino lactones or lactams via a one-pot sequence. The desired products, which are very important building blocks in organic synthesis but difficult to be prepared in the optically enriched form, could be afforded with two stereogenic centers in high yields with excellent enantioselectivities. Moreover, starting from the racemic precursors and catalyzed by the enantiomeric pair of the catalyst, all possible stereoisomeric products were discretely provided only after simple column chromatography. Additionally, this protocol provides facile access to several novel bicyclic carbamates, and such drug-like heterocyclic compounds should be potentially useful in medicinal chemistry.

Organocatalytic Enantioselective Functionalization of Cyclic α-Hydroxyamides: Access to Chiral Cyclic Imides and Azapolycyclic Compounds

“…Undoubtedly, it would be highly desirable to develop a convenient and general approach to the efficient synthesis of chiral cyclic α-hydroxyamides. As a continuation of our previous work on the application of cyclic N , O -hemiaminals in enantioselective organocatalysis, we report herein a concise approach, where unfunctionalized cyclic α-hydroxyamides were directly converted to chiral cyclic α-hydroxyamides by enantioselective enamine catalysis (Scheme c, enamine catalysis).…”

Synthesis of Enantiopure γ‐Lactones via a RuPHOX‐Ru Catalyzed Asymmetric Hydrogenation of γ‐Keto Acids

“…(Figure 1, up). [5] Many methodologies have been reported for the synthesis of enantiopure g-lactones, including asymmetric oxidation, [6] hydroboration, [7] hydrosilylation, [8] transfer hydrogenation, [9] and enzyme catalysis, [10] etc. For example, it can be transferred to several norepinephrine reuptakes inhibiting antidepressants which treat psychiatric disorders (Figure1, down).…”

“…For example, it can be transferred to several norepinephrine reuptakes inhibiting antidepressants which treat psychiatric disorders (Figure1, down). [5] Many methodologies have been reported for the synthesis of enantiopure g-lactones, including asymmetric oxidation, [6] hydroboration, [7] hydrosilylation, [8] transfer hydrogenation, [9] and enzyme catalysis, [10] etc. Generally, asymmetric hydrogenation is undoubtedly an efficient pathway for the construction of enantiopure g-lactones because of its high efficiency, environmental friendliness, and low economic cost (Scheme 1).…”