Metal-free tandem reaction in water: An efficient and regioselective synthesis of 3-hydroxyisoindolin-1-ones

Abstract

A mild and effective method was developed for the construction of heterocyclic building blocks 3-hydroxyisoindolin-1-ones via a metal-free tandem transformation with excellent regioselectivity. Significantly, the strategy presents an atom-economical and environmentally friendly transformation, in which two new C-N bonds and one C-O bond are formed in water from two simple starting materials. Moreover, a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields.

Synthesis of 3‐Benzylated Isoindolinones by Photoredox Decarboxylation of Arylacetates in the Presence of N‐Benzylphthalimide: Conductivity as a Kinetic Tool

“…2,3-Dibenzyl-3-hydroxyisoindolin-1-one (3 a) [21] Colorless crystals, 66 %, m.p. 164 8C; 1 146.3, 138.6, 134.9, 131.8, 131.0, 130.6, 129.6, 128.6, 128.5, 128.0, 127.4, 127.1, 131.7, 131.7, 91.5, 44.1, 42.5 1, 147.0, 138.9, 135.3, 132.0, 131.5, 131.2, 129.8, 129.0, 128.1, 128.0, 128.0, 126.6, 123.1, 122.0, 91.1, 42.8, 42.3, 54.8 23 H 21 NO 2 :C ,8 0.44;H ,6 .16;N ,4.08.…”

“…8,138.8,131.7 ( 3 J F,C = 7.70 Hz),131.6,131.4,131.2,129.1,128.0,128.0 126.6,123.1,122.0,114.2 ( 2 1, 146.7, 138.8, 134.2, 131.7, 131.7, 131.2, 131.2, 129.2, 128.0, 128.0, 127.4, 126.6, 123.1, 122.1, 90.8, 42.4, 42.2 1, 146.7, 138.8, 134.6, 132.1, 131.6, 131.1, 130.3, 129.2, 128.0, 128.0, 126.6, 123.1, 122.1, 119.7, 90.7, 42.4, 42.2 ,4 .44;N ,3 .43. Found:C ,6 4.82;H ,4 .45;N ,3.40. 2-Benzyl-3-(4-methoxybenzyl)-3-hydroxyisoindolin-1-one (3 f) [21] Colorless crystals, 73 %, m.p. 160 8C; 1 HNMR (300 MHz, CDCl 3 ) d 2, 157.7, 147.1, 138.8, 131.5, 131.3, 131.0, 129.0, 128.0, 128.0, 127.0, 126.6, 123.2, 122.1, 112.9, 91.1, 54.8, 42.4, 42.3 23 H 21 NO 3 :C ,7 6.86;H ,5.89;N ,3.90.…”

A Catalyst‐Free Cascade Reaction for the Selective Assembly of 3‐Hydroxyisoindolinones on Water

“…In 2010, Zhou and coworkers reported a promising method which realized the construction of 3-hydroxyisoindolinones from 2-(phenylethynyl)benzoic acids and alkyl amines catalyzed by Bu 4 N + OAc À . [17] Recently, transition-metal-catalyzed tandem reactions of acetophenones [18] or benzamides [19] offer an efficient access to 3-hydroxyisoindolinones. However, their values are reduced by the employment of expensive metal catalysts, which causes metal contamination of the products as well.…”

“…Among the reported methods for the synthesis of 3hydroxyisoindolinones, what seems particularly interesting is the Bu 4 N + OAc À catalyzed two-step one-pot protocol developed by Zhou and coworkers (Scheme 1a). [17] They revealed that the alkyne moiety of 2-alkynylbenzoic acids I could be activated by a catalytic amount of Bu 4 N + OAc À to be attacked by the carboxyl group to form the enol lactone II at 100°C under microwave irradiation in the first step. Then the amines, which are added in the second step, could attack the enol lactone II to give the 3-hydroxyisoindolinones III in good to high yields.…”

Microwave dielectric heating in modern organic synthesis and drug discovery

“…Under microwave heating, a mild and effective method for the construction of 3-hydroxyisoindolin-1-ones via a metal-free tandem transformation using a phase transfer catalyst proceeded in good yields with excellent regioselectivity (Scheme 21). The strategy presents an atom-economical and environmentally friendly transformation, in which one C-O bond and two new C-N bonds are formed in water from two simple starting materials (Zhou, Y. et al, 2010).…”