Chiral Phase‐Transfer‐Catalyzed Intramolecular aza‐Michael Reactions for the Asymmetric Synthesis of Isoindolinones

Abstract

International audienc

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

“…Though various metal or organic catalysts were used to promote the aza-Michael reaction in different syntheses for the creation of nitrogen–carbon bonds, phase-transfer catalysts were less studied (see reviews [35–38]) in intermolecular [39–43] and intramolecular [44–46] sequences. Among the latter, a short regio- and stereoselective organocatalyzed intramolecular aza-Michael reaction was reported by us for the asymmetric synthesis of several isoindolinones [20,34]. Indeed, we noticed along our studies some intramolecular aza-Michael reactions were effectively catalysed by cinchoninium phase-transfer catalysts (PCT) affording the targeted 3-substituted isoindolinones with promising enantioselectivities (up to 91%) [20].…”

“…First, diastereoselective reactions implying the use of a chiral auxiliary resulted effectively in various optically pure compounds [10,18–20]. Second, enantioselective syntheses of these bicylic lactams were performed by using chiral transition metal- or organocatalysts which control the configuration of the trisubstituted carbon stereocenter alpha to the nitrogen [10,20–34].…”

“…First, diastereoselective reactions implying the use of a chiral auxiliary resulted effectively in various optically pure compounds [10,18–20]. Second, enantioselective syntheses of these bicylic lactams were performed by using chiral transition metal- or organocatalysts which control the configuration of the trisubstituted carbon stereocenter alpha to the nitrogen [10,20–34]. Though various metal or organic catalysts were used to promote the aza-Michael reaction in different syntheses for the creation of nitrogen–carbon bonds, phase-transfer catalysts were less studied (see reviews [35–38]) in intermolecular [39–43] and intramolecular [44–46] sequences.…”

“…Among the latter, a short regio- and stereoselective organocatalyzed intramolecular aza-Michael reaction was reported by us for the asymmetric synthesis of several isoindolinones [20,34]. Indeed, we noticed along our studies some intramolecular aza-Michael reactions were effectively catalysed by cinchoninium phase-transfer catalysts (PCT) affording the targeted 3-substituted isoindolinones with promising enantioselectivities (up to 91%) [20]. However, high enantioselectivities were reached only for specific substitution patterns on the amide nitrogen atom and to a lesser extent on the Michael acceptor.…”

Catalytic Asymmetric Synthesis of Isoindolinones

“…However, the enantioselectivities of the reactions were greatly influenced by the substituents’ patterns on the N atom of amides. For example, when R 1 was phenyl, R 2 was butyl, benzyl, or tert ‐butyl, the desired chiral isoindolinones were obtained in only 2–10 % ee …”