Sustainable and practical formation of carbon-carbon and carbon-heteroatom bonds employing organo-alkali metal reagents

Abstract

Metal-catalysed cross-coupling reactions are amongst the most widely used methods to directly construct new bonds. In this connection, sustainable and practical protocols, especially transition metal-catalysed cross-coupling reactions, have become the focus in many aspects of synthetic chemistry due to their high efficiency and atom economy. This review summarises recent advances from 2012 to 2022 in the formation of carbon-carbon bonds and carbon-heteroatom bonds by employing organo-alkali metal reagents.

Scheme 1. (a) Stereoselective synthesis of alkenes and alkenyl sulfides from alkenyl halides using Pd and Ru catalysts. (b) Feringa's work: Pd-catalysed cross-coupling with organolithiums.

Scheme 2. (a) Pd-catalysed cross-coupling of (hetero)aryl chlorides with Me₃SiCH₂Li. (b) Pd-catalysed cross-coupling of aryl halides with organolithium reagents under neat conditions. (c) Pd-catalysed fast cross-coupling of (hetero)aryl bromides with organolithium reagents.

Scheme 3. (a) One-pot 1,2-addition/Pd-catalysed cross-coupling of Weinreb amides. (b) Pd-catalysed one-pot approach to functionalised ketones via nucleophilic addition/Buchwald–Hartwig amination strategy. (c) Pd-catalysed one-pot sequential coupling with alkyl- or aryllithium reagents with functionalised nucleophiles.

Scheme 4. Pd-catalysed cross-coupling of (hetero)aryl halides with organolithium reagents on water at room temperature and under air.

Scheme 5. Pd-catalysed direct coupling of aryl chlorides with alkyllithium reagents.

Scheme 6. Pd-catalysed desulfinative cross-couplings with heteroaromatic lithium sulfinates towards the synthesis of bis-heteroaryls.

Scheme 7. (a) Synthesis and functionalisation of allenes by Pd-catalysed cross-coupling with organolithium. (b) Pd-catalysed cross-coupling with lithium acetylides and aryl bromides. (c) Pd-catalysed cross-coupling of benzyl bromides with lithium acetylides.

Scheme 8. Pd-catalysed intermolecular arylation and alkynylation with organolithiums and terminal alkynes.

Scheme 9. Ni-catalysed dealkoxylative C_aryl–Csp³ cross-coupling reaction.

Scheme 10. Ni-catalysed dealkoxylation of enol ether silylation.

Scheme 11. Ni-catalysed cross-coupling of (hetero)aryl electrophiles with organolithium reagents.

Scheme 12. Ni-catalysed cross-coupling of ethers or aryl ammonium salts with organolithiums via C–O or C–N bond cleavage.

Scheme 13. Ni-catalysed anionic cross-coupling reaction of lithium sulfonimidoyl alkylidene carbenoids with organolithiums. (a) Ni-catalysed anionic cross-coupling reaction (ACCR). (b) Proposed mechanism for ACCR (Solid lines depicted the proposed reaction pathway of the Ni-catalysed ACCR. Dashed lines depicted the oxidative addition pathway, which induced the opposite stereoselectivity).

Scheme 14. Proposed mechanism (anionic and dianionic) of Ni-catalysed cross-coupling of aryl ethers.

Scheme 15. Fe-catalysed homo-coupling with aryllithium reagents.

Scheme 16. Fe-catalysed Csp²–Csp² cross-coupling with aryllithium.

Scheme 17. Co/Ti catalysed cooperative couplings of aryl halides with organometallics.

Scheme 18. Polymer-supported silicon-transfer agents for cross-coupling reactions with organolithium reagents.

Scheme 19. Ni-catalysed synthesis of diaryl sulfones from aryl halides and sodium sulfinates.

Scheme 20. Mn(OAc)₃ mediated C–H sulfonylation of 1,4-dimethoxybenzenes with sodium and lithium sulfinates (HFIP = hexafluoroisopropanol).

Scheme 21. Visible-light mediated photoredox/nickel dual catalysis for the cross-coupling of aryl iodides with sulfonic acid salts.

Scheme 22. (a) Pd-catalysed Negishi or Suzuki–Miyaura cross-coupling reactions with arylsodiums. (b) Pd-catalysed cross-coupling reactions with arylsodiums directly. (c) Pd-catalysed Negishi cross-coupling reactions with arylsodiums. (d) Pd-catalysed Suzuki–Miyaura cross-coupling reactions with aryl- and alkenylsodiums. (e) Pd-catalysed cross-coupling reactions of arylsodiums and 2-chloronaphthalene directly.

Scheme 23. (a) Multisodiation through bromine–sodium exchange. (b) Pd-catalysed Negishi cross-coupling reactions using arylsodiums. (c) Pd-catalysed Suzuki–Miyaura cross-coupling reactions using aryl- and alkenylsodiums. (d) Pd-catalysed direct cross-coupling reactions of arylsodiums and 2-chloronaphthalene (MCH = methylcyclohexane).

Scheme 24. Fe-catalysed substrate-directed Suzuki–Miyaura coupling reaction.

Scheme 25. Conjunctive cross-coupling enabled by metal-induced metallate rearrangement in the combination of organoboronates and organolithium.

Scheme 26. (a) Sodium magnesiate catalysed hydroamination of isocyanates. (b) Synthesis of potassium magnesiate and donor-induced redistribution processes to form higher-order species (PMDETA = pentamethyldiethylenetriamine).

Scheme 27. (a) Sodium-mediated ferration of 1,3-difluorobenzene with [(dioxane)_0.5NaFe{N(SiMe₃)₂}₃]. (b) Sodium-mediated regioselective ferration of fluoroarenes via C–H and C–F bond activation. (c) Two-fold C–H/three-fold C–F activation of 1,3,5-trifluorobenzenes.

Scheme 28. Selected examples of s-block bimetallic cooperation in zinc chemistry for transition metal-free C–C bond-forming processes (DDQ = dichlorodicyanoquinone).

Scheme 29. Nucleophilic addition of tetraorganozincates to nitroolefins.

Scheme 30. (a) Synthesis of isoquinolines via nucleophilic addition between o-cyanoalkenes and organolithiums. (b) Continuous flow process to access ketones from organolithiums and CO₂. (c) Unsymmetrical synthesis of ketones with a pyrrole-bearing formal carbonyl dication linchpin reagent.

Scheme 31. (a) In situ generation of lithium phosphides and one-pot chemoselective addition to aldehydes and epoxides. (b) Nucleophilic addition of amides by organolithium compounds in air (CPME = cyclopentyl methyl ether).

Scheme 32. (a) Synthetic application of the Pd-catalysed one-pot 1,2 addition/cross-coupling of Weinreb amides. (b) Synthetic application of Pd-catalysed cross-coupling of aryl halides with organolithium reagents under neat conditions. (c) Synthesis of radiolabeled celecoxib via Pd-catalysed ultrafast cross-coupling with organolithium reagents.

Scheme 33. (a) Synthesis of axially asymmetric structures by Ni-catalysed polycondensation. (b) Visible-light photoredox/nickel dual catalysis cross-coupling of sulfinic acid salts with aryl iodides for late-stage modification of small molecular drugs. (c) Pd-catalysed nucleophilic addition/Buchwald–Hartwig amination for the synthesis of AMA37.

Scheme 34. Potential applications of Pd-catalysed cross-coupling of benzyl bromides with lithium acetylides.

Scheme 35. Potential applications of the Pd-catalysed cross-coupling of benzyl bromides with lithium acetylides.