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Synthesis of isoindolinones

Recent Literature

The use of a simple undivided cell with carbon electrodes enables an efficient and practical electrochemical reduction of cyclic imides at room temperature to provide hydroxylactams and lactams in a controllable manner, tuned by electric current and reaction time. The reaction exhibits broad substrate scope and high functional group tolerance.
Y. Bai, L. Shi, L. Zheng, S. Ning, X. Che, Z. Zhang, J. Xiang, Org. Lett., 2021, 23, 2298-2302.

Various N-substituted isoindolinones can be synthesized in excellent yields through the reductive C-N coupling and intramolecular amidation of 2-carboxybenzaldehyde with amines in the presence of ultrathin Pt nanowires as catalysts under 1 bar of hydrogen. These unsupported catalysts can also be used for the synthesis of phthalazinones in high yield when hydrazine or phenyl hydrazine is used instead of amines.
L. Shi, L. Hu, J. Wang, X. Cao, H. Gu, Org. Lett., 2012, 14, 1876-1879.

A copper-catalyzed sp³ C-H functionalization of 2-alkyl-N-substituted benzamides provides an efficient approach to various functionalized isoindolinones without preparation of halogenated substitutes, use of expensive transition metals, or toxic Sn or CO gas.
K. Nozawa-Kumada, J. Kadokawa, T. Kameyama, Y. Kondo, Org. Lett., 2015, 17, 4479-4481.

A palladium-catalyzed C-H carbonylation of readily available free primary benzylamines, in which NH₂ acts as a chelating group, provides benzolactams under an atmospheric pressure of CO. Application of this new method is exemplified in the concise syntheses of two bioactive molecules.
C. Zhang, Y. Ding, Y. Gao, S. Li, G. Li, Org. Lett., 2018, 20, 2595-2598.

A palladium-catalyzed C-H carbonylation of benzylamines provides isoindolinone scaffolds in good yields under gas-free conditions by using benzene-1,3,5-triyl triformate (TFBen) as a convenient CO surrogate.
L-Y. Fu, J. Ying, X. Qi, J.-B. Peng, X.-F. Wu, J. Org. Chem., 2019, 84, 1238-1246.

The merger of strain-release of 1,2-oxazetidines with carboxylic acid directed C-H activation enables a catalytic synthesis of a range of structurally diverse isoindolinones from readily available benzoic acids.
X.-Q. Hu, Z.-K. Liu, Y.-X. Hou, J.-H. Xu, Y. Gao, Org. Lett., 2021, 23, 6332-6336.

2-Benzyl-N-tosylbenzamides and related substrates undergo copper-catalyzed intramolecular benzylic sulfamidation to provide N-arylsuflonyl-1-arylisoindolinones.
R. B. Bedford, J. G. Bowen, C. Méndez-Gálvez, J. Org. Chem., 2017, 82, 1719-1725.

A new type of C₂-symmetric chiral diene ligand was applied successfully in the Rh-catalyzed asymmetric arylation of N-tosylarylimines with arylboronic acids to give a broad range of highly enantiomerically enriched diarylmethylamines as well as 3-aryl substituted phthalimidines.
Z.-Q. Wang, C.-G. Feng, M.-H. Xu, G.-Q. Lin, J. Am. Chem. Soc., 2007, 129, 5336-5337.

Electronically tunable cyclopentadienyl ligands enable a unprecedented Rh-catalyzed enantioselective [4+1] annulation reaction of benzamides and alkenes with a broad substrate scope under mild reaction conditions, providing a variety of isoindolinones with excellent regio- and enantioselectivity.
W.-J. Cui, Z.-J. Wu, Q. Gu, S.-L. You, J. Am. Chem. Soc., 2020, 142, 7379-7385.

Addition of o-iodobenzoyl chlorides to imines affords N-acyliminium ions as adducts. Subsequent reaction of these adducts with phenyllithium at -78˚C followed by warming to ambient temperature induces an intramolecular Wurtz-Fittig coupling to afford 2,3-dihydroisoindolones in excellent yields.
J. B. Campbell, R. F. Dedinas, S. Trumbower-Walsh, Synlett, 2010, 3008-3010.

N-Heterocyclic nitrenium (NHN) salts, the analogues of N-heterocyclic carbenes, can serve as catalytic electron acceptors for charge transfer complex photoactivations. Under blue light irradiation, NHN salts catalyze the generation of aryl radicals from aryl halides.
K.-Q. Chen, B.-B. Zhang, Z.-X. Wang, X.-Y. Chen, Org. Lett., 2022, 24, 4598-4602.

An acylation/arylation reaction of α-aminoboronate salts with 2-bromobenzoyl chlorides provides isoindolinones in very good yields under mild conditions via an intramolecular, Cu-catalyzed sp³-sp² coupling.
A. M. Dumas, A. J. Sieradzki, L. J. Donnelly, Org. Lett., 2016, 18, 1848-1851.

Copper(II) trifluoromethanesulfonate efficiently catalyzes the C-C coupling of 3-hydoxyisoindolinones with various aryl-, heteroaryl-, and alkenylboronic acids to furnish C(3)-substituted isoindolinones in 1,2-dicholoroethane (DCE) at reflux. The photolabile 2-nitrobenzyl protecting group is most appropriate for promotion of the coupling reaction and for deprotection.
H. S. P. Rao, A. V. B. Rao, J. Org. Chem., 2015, 80, 1506-1516.

A nickel-catalyzed reductive dicarbofunctionalization of 1,1-disubstituted enamides with unactivated alkyl iodides provides 3,3-dialkyl-substituted isoindolinones. This tandem cyclization/reductive tolerates a broad range of functional groups. The use of a chiral Bn-Biox ligand induces excellent enantioselectivities.
K. Fang, W. Huang, C. Shan, J. Qu, Y. Chen, Org. Lett., 2021, 23, 5523-5527.

A highly efficient palladium-catalyzed asymmetric tandem aza-Heck/Sonogashira coupling reaction of O-phenyl hydroxamic ethers with terminal alkynes provides challenging chiral isoindolinone derivatives bearing a quaternary stereogenic center with excellent enantioselectivity under mild conditions. This Pd-catalyzed aminoalkynylation reaction shows broad functional group tolerance.
L. Wang, Y. Wang, S. Wu, C.-G. Yan, C. Zhang, J. Zhang, Y. Han, J. Am. Chem. Soc., 2024, 146, 4320-4026.

A metal-free tandem cyclization reaction for the synthesis of 3-methyleneisoindolin-1-ones starting from ester-functionalized aziridines is effectively promoted by DBU and carboxylic acids. Mechanistically, it involves sequential ring opening of aziridines with carboxylic acids, lactamization, and elimination of carboxylic acids.
S. Xing, C. Jin, P. Zhang, J. Yang, Y. Liang, X. Ao, W. Pi, K. Wang, B. Zhu, J. Org. Chem., 2024, 89, 5153-5158.

An efficient palladium-catalyzed intramolecular cyclization of 2-iodobenzamides with a 2-oxoethyl function group on the nitrogen atom moiety provides 3-acyl isoindolin-1-ones and 3-hydroxy-3-acylisoindolin-1-ones under mild conditions in good yields.
W. Chen, L. Jin, Y. Zhu, X. Cao, L. Zheng, W. Mo, Synlett, 2013, 24, 1856-1860.

An iridium-catalyzed oxidative annulation of benzamides with cyclopropanols as C1 synthon provides structurally diverse isoindolin-1-ones via sequential C-H/C-C cleavage and C-C/C-N bond formation.
S. Xu, C. Luo, K. Yan, J. Li, R. Lai, L. Hai, M. Guan, Y. Wu, Synthesis, 2022, 54, 3015-3024.

A N-heterocyclic carbene (NHC)-catalyzed synthesis of N-substituted isoindolinone acetates proceeds through a tandem imine umpolung-intramolecular aza-Michael addition followed by oxidation with molecular oxygen in air as the sole oxidant. This method offers atom efficiency, operational simplicity, large-scale syntheses, and mild reaction conditions.
J. Ramarao, P. C. Behera, M. S. Reddy, S. Suresh, J. Org. Chem., 2024, 89, 414-424.

A regioselective visible-light-mediated denitrogenative alkene insertion of 1,2,3-benzotriazin-4(3H)-ones provides 3-substituted isoindolinones. The photocatalytic reaction is compatible with activated terminal alkenes and cyclic α,β-unsaturated esters and ketones, with wide functional group tolerance for N-substitution of the 1,2,3-benzotriazin-4(3H)-ones.
F. R. B. Bokosi, O. J. Shiels, C. Richardson, A. J. Trevitt, S. T. Keaveney, J. Org. Chem., 2024, 89, 1777-1783.

A cascade reaction enables a regiospecific synthesis of substituted 3-hydroxyisoindolinones under transition-metal-free conditions via base-mediated C-C bond coupling and N-α-sp³C-H bond hydroxylation. The procedure offers high regioselectivity, efficiency, and environmental friendliness. Various substituted 3-hydroxyisoindolinones, including some bioactive molecules, were provided in very good yields.
J. Shen, Q. You, Q. Fu, C. Kuai, H. Huang, L. Zhao, Z. Zhuang, Org. Lett., 2017, 19, 5170-5173.

A metal-free photoredox catalyzed amidyl N-centered radical addition to the C-C triple bond of o-alkynylated benzamides provides isoquinoline-1,3,4(2H)-triones, 3-hydroxyisoindolin-1-ones, and phthalimides via a proton-coupled electron transfer (PCET) process under mild reaction conditions.
M. B. Reddy, K. Prasanth, R. Anandhan, Org. Lett., 2022, 24, 3674-3679.

Pd-Catalyzed Aminocarbonylation of the Blaise Reaction Intermediate: One-Pot Synthesis of (Z)-3-Methyleneisoindolin-1-ones from Nitriles
Z. Xuan, D. J. Jung, H. J. Jeon, S.-g. Lee, J. Org. Chem., 2016, 81, 10094-10098.