Asymmetric synthesis of α-(1-oxoisoindolin-3-yl)glycine: synthetic and mechanistic challenges

Abstract

We report herein that the NaOMe-catalyzed reactions between the chiral glycine Schiff base (S)-4 with 2-cyanobenzaldehyde 3a provide for a convenient preparation of the novel α-(1-oxoisoindolin-3-yl)glycine 1 of high pharmaceutical potential. The reactions involve at least eight synthetic steps and can mechanistically be realized only with application of Ni(II) complexes described in this study.

Design of chiral urea-quaternary ammonium salt hybrid catalysts for asymmetric reactions of glycine Schiff bases

“…Nevertheless, a first proof-of-principle for the generality of this reaction was clearly made, thus illustrating the potential of these catalysts for such cascade-reactions and providing a complementary approach to the recently reported analogous auxiliary-based protocol. 8…”

Synthesis and Organocatalytic Asymmetric Nitro-aldol Initiated Cascade Reactions of 2-Acylbenzonitriles Leading to 3,3-Disubstituted Isoindolinones

“…A feature of this sequence of reactions relies on the selectivity of the Wittig reaction of the readily available 2-cyanobenzaldehyde 5 (Scheme 1), in which the cyano group in the 2 position is left non-reacted, while 2-cyanobenzaldehyde is reported to give efficient cascade reactions involving both the aldehyde and the cyano group. This leads to valuable 3-monosubstituted isoindolinones in the presence of a number of carbonand hetero-nucleophiles [21][22][23][24][25][26][27][28][29][30]. The cis/trans olefin mixture 6 was, then, hydrogenated under heterogeneous conditions and, taking advantage from our previous work [8], the obtained 2-alkylbenzonitriles 4 were selectively oxidized at the benzylic position with NBS/AIBN/H 2 O to afford the desired ketones 3 in good yields (Scheme 1).…”

Discrimination of the Chirality of α‐Amino Acids in ZnII Complexes of DPA‐Appended Binaphthyl Imine

“…In the last decade, Soloshonok et al have extensively developed Ni II complexes of amino acids in the form of Schiff bases that lead to deracemization and stereoselective alkylation of the coordinated amino acids under a suitable chiral environment . The complexes developed by Soloshonok et al proved that activation of amino acids by both imine formation and metal binding is an efficient approach for versatile chiral recognition and stereoselective derivatization of the amino acids.…”