Dinuclear Zn-Catalytic System as Brønsted Base and Lewis Acid for Enantioselectivity in Same Chiral Environment

Abstract

Zinc (Zn) is a crucial element with remarkable significance in organic transformations. The profusion of harmless zinc salts in the Earth's outer layer qualifies zinc as a noteworthy contender for inexpensive and eco-friendly reagents and catalysts. Recently, widely recognized uses of organo-Zn compounds in the field of organic synthesis have undergone extensive expansion toward asymmetric transformations. The ProPhenol ligand, a member of the chiral nitrogenous-crown family, exhibits the spontaneous formation of a dual-metal complex when reacted with alkyl metal (R-M) reagents, e.g., ZnEt₂. The afforded Zn complex possesses two active sites, one Lewis acid and the other Brønsted base, thereby facilitating the activation of nucleophiles and electrophiles simultaneously within the same chiral pocket. In this comprehensive analysis, we provide a thorough account of the advancement and synthetic potential of these diverse catalysts in organic synthesis, while emphasizing the reactivity and selectivities, i.e., dr and ee due to the design/structure of the ligands employed.

Scheme 1. Synthesis and Structure of the Bimetallic Zn-ProPhenol Complex

Scheme 2. Synthesis of the Spiro[cyclohexanone-oxindole] Related Compounds Employing a Dinuclear Zinc Catalytic System

Scheme 3. Synthesis of the α,β-Dihydroxy γ-Keto Ester Derivatives by the Asymmetric Aldol Addition Reaction

Scheme 4. Asymmetrical Zn-Catalyzed Cycle for the Aldol Addition Reaction

Scheme 5. Synthesis of the β-Amino Ketones Using Zn-ProPhenol Ligand

Scheme 6. Mannich Reaction between Butenolides and Imines

Scheme 7. Catalytic Cycle of the Mannich Transformation between Butenolides and Imines by Employing Binuclear Complex of (L3)

Scheme 8. Mannich Synthesis between Unsaturated α-Branched Ketone Derivatives and N-Carbamoyl Imines

Scheme 9. Effect of Unsaturation Added Adjacent to the Carbonyl in α,β-Branched Ketone Derivatives on the Reactivity of Zn-Catalyst

Scheme 10. α-Selective Addition between β,γ-Unsaturated Ketone Derivatives and Benzoxazinone Cyclic α-Imino Esters

Scheme 11. Synthesis of 3-Indolylglycine Derivatives by Asymmetric Friedel–Crafts Alkylation Using Zn-catalyst

Scheme 12. Catalytic Mechanism of the Reaction Involving Indole Derivatives and Ethyl Glyoxylate Imine

Scheme 13. Synthesis of β-Pyrrole-Substituted Dihydrochalcone Derivatives by Asymmetric Friedel–Crafts Alkylation using Zn-Catalyst.

Scheme 14. Synthesis of Organophosphate Compounds with the Skeleton of 1-Tetralones or 1-Indanones Using Zn-Catalyzed Phospha-Michael Reaction

Scheme 15. Zn-Catalyzed Cycle for the Synthesis of Organophosphate Compounds with the Skeleton of 1-Tetralones or 1-Indanones

Scheme 16. Synthesis of the β,γ-Unsaturated α-Keto Ester Derivatives via Asymmetric Conjugated Addition

Scheme 17. Synthesis of N-Alkylated Indole Derivatives Using Zn-ProPhenol Dinuclear Complex

Scheme 18. Binuclear Zn-Catalyzed Mechanism for N-Alkylation

Scheme 19. Synthesis of β,β-Diaryl-α-hydroxy Ketone Derivatives via 1,6-Conjugated Addition Reaction Using Zn-Catalyst

Scheme 20. Catalytic Asymmetric C–F Alkylation Reaction of Indoles and Trifluoromethyl Pyruvate

Scheme 21. Synthesis of Tetrasubstituted C–F Stereogenic Centers via Aldol Addition Reaction

Scheme 22. Synthesis of Nitroamines by an Asymmetric Nitro-Mannich Reaction by Employing Dinuclear Zn-Catalytic System

Scheme 23. Cyclic Mechanism of Nitro-Mannich Reaction Catalyzed by Dinuclear Zn-AzePhenol System

Scheme 24. Synthesis of α-Tertiary Amines via Amination of Vinyl Ketone Derivatives

Scheme 25. Synthesis of α-Tertiary Amines via Amination of Vinyl Ketone Derivatives

Scheme 26. Synthesis of Tetrahydrofuran Spiro Oxindoles via One-Pot Reaction Using Dinuclear Zn-Catalyst and TFA

Scheme 27. Mechanistic Cycle Synthesizing the Tetrahydrofuran Spiro Oxindole Derivatives Using Dinuclear Zn-Complex and TFA

Scheme 28. Synthesis of γ-Butyrolactones via Zn-Catalyzed Michael 1,4-Addition Reaction

Scheme 29. Synthesis of Spiro[indanone-2,3′-isochromane-1-one] Derivatives via Transesterification/Cascade Michael Reaction

Scheme 30. Catalytic Cycle for the Transesterification/Cascade Michael Reaction

Scheme 31. Synthesis of 3,3′-Dihydrofuran Spirooxindole Derivatives by Domino Reaction

Scheme 32. Catalytic Cycle of Three-Component Domino Reaction

Scheme 33. Synthesis of Spiro[indoline-3,40-thiopyrano[2,3-b]indole] Derivatives by Catalytic Asymmetric Cascade [3 + 3] Cyclization Reaction

Scheme 34. Synthesis of 2,5-Pyrrolidinyl Di-spirooxindoles Using Semi-aza Crown Ether Ligand via Tandem Reaction

Scheme 35. Synthesis of 1,2,3-Tri-substituted Indanes via Michael Tandem/Phospha-Michael Reaction

Scheme 36. Mechanism for the Michael Tandem/Phospha-Michael Reaction

Scheme 37. Synthesis of Oxindoles Bispiro[3,2′-tetrahydrofuran-5′,2″-indanone] via Catalytic One-Pot Reaction

Scheme 38. Asymmetric 1,4-Addition of Butanolide Derivatives to the Chromone Nucleus

Scheme 39. Synthesis Involving Hemiacetals As α-Carbon Nucleophiles

Scheme 40. Catalytic Cycle Involving Umpolung of Hemiacetal