Chiral Ligands for Palladium-Catalyzed Coordination-Assisted Enantioselective C(sp3)—H Functionalization Reactions

doi:10.6023/cjoc202406002

Abstract

Abstract Enantioselective C(sp³)—H functionalization reactions have emerged as a powerful and straightforward strategy in the construction of chiral molecules. Palladium, highlighted by its remarkable reactivity, versatility, and functional group tolerance, stands out among transition metal catalysts and is one of the most prevalently employed in enantioselective C(sp³)—H functionalization reactions. In these reactions, chiral ligands play a pivotal role, serving as a decisive factor in controlling both reactivity and stereoselectivity. Focusing on chiral ligands, the latest progress in palladium-catalyzed coordination-assisted enantioselective C(sp³)—H bond functionalization reactions in recent years is summarized, emphasizing the design concept, reaction mechanism, and stereocontrol model of chiral ligands.

Key words: palladium catalysis, C(sp³)—H functionalization, chiral ligands, enantioselectivity

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Chen-Hui Yuan, Lei Jiao. Chiral Ligands for Palladium-Catalyzed Coordination-Assisted Enantioselective C(sp³)—H Functionalization Reactions[J]. Chinese Journal of Organic Chemistry, 2025, 45(2): 602-619.

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Fig. & Tab. 34

Scheme 1. Three modes of Pd-catalyzed enantioselective C(sp3)—H functionalization reactions

Scheme 2. Structure of MPAA ligands and the catalytic cycle of Pd/MPAA-catalyzed C—H functionalization

Scheme 3. MPAA ligand-controlled desymmetrical alkylation of 2-isopropylpyridine

Scheme 4. MPAA ligand-controlled desymmetrization of N-(4- cyanoperfluorophenyl)cyclopropanecarboxamide

Scheme 5. MPAA ligand-controlled cyclopropyl desymmetrical arylation of trifluoromethanesulfonamide

Scheme 6. MPAA ligand-controlled carboxylic acid-directed cyclopropyl desymmetrization

Scheme 7. MPAA ligand-controlled secondary amine-directed gem-dimethyl desymmetrization

Scheme 8. MPAA ligand-controlled tertiary amine-directed de- symmetrization

Scheme 9. Structural changes of MPAA ligands to protected amino-N-block ligands

Scheme 10. MPAHA ligand-controlled desymmetrization of cyclobutyl and gem-dimethyl groups

Scheme 11. APAQ ligand-controlled desymmetrization of methylene and cyclohexyl groups

Scheme 12. APAO ligand-controlled desymmetrical borylation

Scheme 13. APAO ligand-controlled desymmetrization of isopropyl and gem-dimethyl groups

Scheme 14. APAO ligand-controlled desymmetrization and kinetic resolution of trifluoromethanesulfonamide

Scheme 15. MPAAM ligand-controlled desymmetrization of carboxylic acids

Scheme 16. Structural changes of MPAA ligands to protected amino-S-block ligands

Scheme 17. APASO ligand-controlled desymmetrization of N-(perfluorophenyl)cyclopropanecarboxamide

Scheme 18. APAThio ligand-controlled desymmetrization of cyclopropylmethylamine

Scheme 19. APAThio ligand-controlled desymmetrization of cyclopropyl carboxylic acids

Scheme 20. Structural changes of N-acyl ligands to chiral hydroxypyridine ligands

Scheme 21. SOHP ligand-controlled enantioselective β-arylation of tertiary aliphatic amides

Scheme 22. SOHP ligand-controlled enantioselective γ-arylation of primary aliphatic amines

Scheme 23. TZ ligand-controlled enantioselective remote arylation of cycloalkane carboxylic acids

Scheme 24. CPA ligand-controlled 8-aminoquinoline-directed desymmetrization

Scheme 25. CPA ligand-controlled pyridine-2-carboxamide-directed desymmetrization

Scheme 26. CPA ligand-controlled PIP-directed desymmetrization

Scheme 27. CPA ligand-controlled thioamide-directed desymmetrization and kinetic resolution

Scheme 28. CPA ligand-controlled secondary amine-directed desymmetrization

Scheme 29. BINOL ligand-controlled PIP-directed enantioselective functionalization

Scheme 30. BINOL ligand-controlled 8-aminoquinoline-dire- cted desymmetrization

Scheme 31. BINOL ligand-controlled PIP-directed P-stereogenic center construction

Scheme 32. Chiral phosphoramidite ligand-controlled 8-aminoquinoline-directed desymmetrization

Scheme 33. Chiral phosphoramidite ligand-controlled thioamide-directed desymmetrization

Scheme 34. Preparation and transformation of palladacycle with SOHP ligand-induced-chirality

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手性配体在钯催化配位辅助对映选择性C(sp³)—H键官能团化反应中的应用

Chiral Ligands for Palladium-Catalyzed Coordination-Assisted Enantioselective C(sp³)—H Functionalization Reactions

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手性配体在钯催化配位辅助对映选择性C(sp3)—H键官能团化反应中的应用