Enantioselective Synthesis of Difluoroalkylated Isoindolinones via Chiral Spirocyclic Phosphoric Acid Catalyzed Mannich-Type Reaction

Abstract

An enantioselective Mannich-type reaction of in situ generated cyclic ketimines with difluoroenoxysilanes catalyzed by chiral spirocyclic phosphoric acid has been developed. This methodology provides a facile route to difluoroalkyl-substituted chiral isoindolinones bearing a quaternary stereogenic center in high yields and up to 96% enantioselectivity.

Three‐Component Reactions of Quinoxalin‐2(1H)‐ones: Recent Advances

“…3‐trifluoroalkylquinoxalin‐2(1 H )‐ones bearing various functional groups were formed via a radical pathway, which was basically consistent with that of Wei, Li group. Subsequently, Lin and coworkers [24] developed a H 2 O 2 ‐mediated hydrocarbylation reaction of quinoxaline‐2(1 H )‐ones and styrene, exhibiting good product yields (26 examples, 43 %‐84 % yields) and good functional group tolerance (alkyl, aryl, halogen, etc .) (Scheme 7).…”

Efficient synthesis of bioactive isoindolinone derivatives containing continuous quaternary carbons by intermolecular OH transfer

“…Isoindolinones represent an important class of biologically active small molecules and have seen increasing applications in medicinal chemistry. 1,2 It has been reported that isoindolinones exhibit widespread biological activity, 2 including antitumor, anti-inflammatory, antiviral, and anti-addictive effects. Many synthetic pharmaceutical molecules contain isoindolinones, such as MDM2-p53 inhibitors, 3 PI3Kγ inhibitors, 4 RSV inhibitors, 5 HIV-1 reverse transcriptase inhibitors, 6 muscarinic acetylcholine receptor modulators 7 and anticancer agents 8 (Scheme 1).…”