Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

Abstract

SummaryNew bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications.

Cationic Polymers Bearing Quaternary Ammonium Groups-Catalyzed CO2 Fixation with Epoxides

“…To investigate the influence of the counter anion we next tested the corresponding iodide-based polymers (entries [17][18][19][20][21][22][23][24]. These salts were prepared by carrying out a chloride to iodide exchange of the initially used salts (see the supporting information for details).…”

“…On the other hand, those polymers that performed well for the chloride salts already (i.e. C 1,4 and D 1,4 ) performed less satisfactory when using the iodides instead Scheme 1 Cationic polymers A-F used as catalysts for the CO 2 fixation of epoxides 1 (entries 21,22). According to mechanistic studies by others [48,49], the nucleophilic counter anion plays a crucial role in the initial epoxide opening.…”

“…[21,22]), we became interested in elucidating the catalytic potential of ionenes for more challenging reactions. One transformation that has attracted considerable attention over the last years is the incorporation of CO 2 into epoxides to access cyclic carbonates (for selected rather recent reports with different catalyst systems please see Ref.…”

Catalytic Asymmetric Synthesis of Isoindolinones

“…Subsequently, considering their advantages in synthesizing bifunctional group catalysts, Massa and co‐workers reconsidered this cascade reaction. More than twenty ammonium salts bearing various substituents were explored to optimize the reaction conditions . Noticeably, PCT‐4 with the urea group was a prerequisite for obtaining satisfactory enantioselectivity (Scheme ).…”

On the origin of the stereoselectivity in chiral amide-based ammonium ylide-mediated epoxidations

“…However, some limitations were observed: While the use of Cinchona alkaloids as chiral amine leaving groups was found to be a very versatile strategy for enantioselective cyclopropanation reactions [14, 15], these simple naturally occurring chiral amines were not suited for epoxidations and aziridinations [6, 11, 13]. Our group has for years been interested in the development of new catalytic [17, 18] and auxiliary-based methods [8, 11] for the synthesis of chiral heterocycles. Based on this general interest, we recently carried out an extensive screening and optimization of different chiral amines for ammonium ylide-mediated epoxidation reactions.…”