Research on transition metals for the multicomponent synthesis of benzo-fused γ-lactams

Abstract

Benzo-fused γ-lactams are fundamental in medicinal chemistry, acting as essential elements for various therapeutic agents due to their structural adaptability and capability to enhance biological activity. In their synthesis, transition metals play a pivotal role as catalysts, offering more efficient alternatives to traditional methods by facilitating C-N bond formation through mechanisms like intramolecular coupling. Recent advances have especially spotlighted transition-metal-catalyzed C-H amination reactions for directly converting C(sp²)-H to C(sp²)-N bonds, streamlining the creation of these compounds. Furthermore, biocatalytic approaches have emerged, providing asymmetric synthesis of lactams with high yield and enantioselectivity. This review examined the transition metal-catalyzed synthesis techniques for producing benzo-fused γ-lactams, marking a significant leap in organic synthesis by proposing more effective, selective, and greener production methods. It serves as a valuable resource for researchers in the fields of transition metal catalysts and those engaged in synthesizing these lactams.

Fig. 1. Several bioactive benzo-fused γ-lactam derivatives.

Scheme 1. Synthesis of isoindolin-1-ones via CuI-catalyzed one-pot three-component reaction of 2-iodobenzoic acids, alkynylcarboxylic acids and ammonium acetate.

Scheme 2. Rational pathway for synthesis of isoindolin-1-ones via CuI-catalyzed one-pot three-component reaction of 2-iodobenzoic acids, alkynylcarboxylic acids and ammonium acetate.

Scheme 3. Synthesis of 3-alkyl/aryl-3-(pyrrole/indole-2/3-yl)-2-phenyl-2,3-dihydro-isoindolinones via Cu₂O-catalyzed multi-component one-pot reaction involving 2-iodo-N-phenylbenzamides, terminal alkyne and substituted indoles/pyrroles.

Scheme 4. Rational pathway for synthesis of 3-alkyl/aryl-3-(pyrrole/indole-2/3-yl)-2-phenyl-2,3-dihydro-isoindolinones via Cu₂O-catalyzed multi-component one-pot reaction involving 2-iodo-N-phenylbenzamides, terminal alkyne and substituted indoles/pyrroles.

Scheme 5. Synthesis of isoindolinones via Cu(OTf)₂-catalyzed one-pot three-component reactions of 2-formylbenzoate, primary amines and terminal alkynes.

Scheme 6. Synthesis of 2,3-diarylisoindolin-1-one derivatives through copper-catalyzed one-pot, three-component annulations of 2-formylbenzonitriles, arenes, and diaryliodonium salts.

Scheme 7. Rational pathway for synthesis of 2,3-diarylisoindolin-1-one derivatives through copper-catalyzed one-pot, three-component annulations of 2-formylbenzonitriles, arenes, and diaryliodonium salts.

Scheme 8. Synthesis of pentacyclic iso-indolinone derivatives through Cu-catalyzed three-component cascade cyclization among 2-formylbenzonitrile, cyclopropyl ketones, and diary liodonium salts.

Scheme 9. Rational mechanism for synthesis of pentacyclic iso-indolinone derivatives through Cu-catalyzed three-component cascade cyclization among 2-formylbenzonitrile, cyclopropyl ketones, and diary liodonium salts.

Scheme 10. Synthesis of dihydroisoindolo[2,1-a]quinolin-11(5H)-ones through Cu(OTf)₂-catalyzed one-pot three-component cascade cyclization among 2-formylbenzonitriles, alkyl aryl ketones/prop-1-en-2-ylbenzene and diaryliodonium salts.

Scheme 11. Rational mechanism for synthesis of dihydroisoindolo[2,1-a]quinolin-11(5H)-ones through Cu(OTf)₂-catalyzed one-pot three-component cascade cyclization among 2-formylbenzonitriles, alkyl aryl ketones/prop-1-en-2-ylbenzene and diaryliodonium salts.

Scheme 12. Synthesis of sulfonated oxindoles through copper-catalyzed one-pot three-component reaction of N-(arylsulfonyl)-acrylamides, DABSO, and aryldiazonium tetrafluoroborates.

Scheme 13. Rational mechanism for synthesis of sulfonated oxindoles through copper-catalyzed one-pot three-component reaction of N-(arylsulfonyl)-acrylamides, DABSO, and aryldiazonium tetrafluoroborates.

Scheme 14. Synthesis of 3-[(dialkylcarbamoyl)methylene]isoindolin-1-ones through PdI₂-catalyzed oxidative carbonylation conditions.

Scheme 15. Rational pathway for synthesis of 3-[(dialkylcarbamoyl)methylene]isoindolin-1-ones through PdI₂-catalyzed oxidative carbonylation conditions.

Scheme 16. Synthesis of 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-diones via palladium-catalyzed one-pot three-component cascade reaction of 2-aminobenzamides with 2-bromobenzaldehydes and carbon monoxide.

Scheme 17. Rational pathway for synthesis of 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-diones via palladium-catalyzed one-pot three-component cascade reaction of 2-aminobenzamides with 2-bromobenzaldehydes and carbon monoxide.

Scheme 18. Synthesis of isoindoles through palladium catalyzed one-pot three-component ligand-free reaction of chloro-quinolinecarbaldehydes with isocyanides and aromatic amines.

Scheme 19. Tentative mechanism for synthesis of isoindoles through palladium catalyzed one-pot three-component ligand-free reaction of chloro-quinolinecarbaldehydes with isocyanides and aromatic amines.

Scheme 20. Synthesis of N-substituted isoindolinones through palladium catalyzed three-component arbonylation–amination–intramolecular Michael addition cascade process.

Scheme 21. Synthesis of 3-aminoisoindolinone derivatives through palladium catalyzed one-pot three-component reactions of chloro-quinolinecarbaldehydes with isocyanides and aromatic amines.

Scheme 22. Synthesis of fluorinated 3-methyleneoxindole derivatives through Pd(PPh₃)₂Cl₂ catalyzed one-pot three-component reactions of 2-ethynylanilines, per-fluoroalkyliodides and carbon monoxide.

Scheme 23. Synthesis of diastereoisomers of oxindole through palladium catalyzed one-pot three-component reaction of acrylamide, CO and 1,4-benzodiazepine.

Scheme 24. Synthesis of 3-(1,3-diarylallylidene)oxindoles through palladium-catalyzed one-pot three-component reaction of N-arylpropiolamides, aryl iodides and boronic acids.

Scheme 25. Synthesis of sulfonated 1-isoindolinones via ruthenium-catalyzed one-pot four-component reaction of 2-vinylbenzoic acids, aryldiazonium tetrafluoroborates, the sulfur dioxide surrogate DABCO-(SO₂)₂, and nitriles.

Scheme 26. Rational mechanism for synthesis of sulfonated 1-isoindolinones via ruthenium-catalyzed one-pot four-component reaction of 2-vinylbenzoic acids, aryldiazonium tetrafluoroborates, the sulfur dioxide surrogate DABCO-(SO₂)₂, and nitriles.

Scheme 27. Synthesis of 3-oxoisoindoline-1-difluoroalkyl derivatives via In(OTf)₃-catalyzed one-pot, three-component Mannich/lactamization cascade reactions.

Scheme 28. Rational pathway for synthesis of 3-oxoisoindoline-1-difluoroalkyl derivatives via In(OTf)₃-catalyzed one-pot, three-component Mannich/lactamization cascade reactions.

Mosstafa Kazemi

Ramin Javahershenas