Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Dec 21;14(6):1342-1362.
doi: 10.1039/d2sc05475b. eCollection 2023 Feb 8.

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

Lu-Qiong Huo  1 , Xin-Hao Wang  1 , Zhenguo Zhang  2 , Zhenhua Jia  2 , Xiao-Shui Peng  1   3 , Henry N C Wong  1   3
Affiliations
Review

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

Lu-Qiong Huo et al. Chem Sci. .

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.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
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
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
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
Scheme 4. Pd-catalysed cross-coupling of (hetero)aryl halides with organolithium reagents on water at room temperature and under air.
Scheme 5
Scheme 5. Pd-catalysed direct coupling of aryl chlorides with alkyllithium reagents.
Scheme 6
Scheme 6. Pd-catalysed desulfinative cross-couplings with heteroaromatic lithium sulfinates towards the synthesis of bis-heteroaryls.
Scheme 7
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
Scheme 8. Pd-catalysed intermolecular arylation and alkynylation with organolithiums and terminal alkynes.
Scheme 9
Scheme 9. Ni-catalysed dealkoxylative Caryl–Csp3 cross-coupling reaction.
Scheme 10
Scheme 10. Ni-catalysed dealkoxylation of enol ether silylation.
Scheme 11
Scheme 11. Ni-catalysed cross-coupling of (hetero)aryl electrophiles with organolithium reagents.
Scheme 12
Scheme 12. Ni-catalysed cross-coupling of ethers or aryl ammonium salts with organolithiums via C–O or C–N bond cleavage.
Scheme 13
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
Scheme 14. Proposed mechanism (anionic and dianionic) of Ni-catalysed cross-coupling of aryl ethers.
Scheme 15
Scheme 15. Fe-catalysed homo-coupling with aryllithium reagents.
Scheme 16
Scheme 16. Fe-catalysed Csp2–Csp2 cross-coupling with aryllithium.
Scheme 17
Scheme 17. Co/Ti catalysed cooperative couplings of aryl halides with organometallics.
Scheme 18
Scheme 18. Polymer-supported silicon-transfer agents for cross-coupling reactions with organolithium reagents.
Scheme 19
Scheme 19. Ni-catalysed synthesis of diaryl sulfones from aryl halides and sodium sulfinates.
Scheme 20
Scheme 20. Mn(OAc)3 mediated C–H sulfonylation of 1,4-dimethoxybenzenes with sodium and lithium sulfinates (HFIP = hexafluoroisopropanol).
Scheme 21
Scheme 21. Visible-light mediated photoredox/nickel dual catalysis for the cross-coupling of aryl iodides with sulfonic acid salts.
Scheme 22
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
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
Scheme 24. Fe-catalysed substrate-directed Suzuki–Miyaura coupling reaction.
Scheme 25
Scheme 25. Conjunctive cross-coupling enabled by metal-induced metallate rearrangement in the combination of organoboronates and organolithium.
Scheme 26
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
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
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
Scheme 29. Nucleophilic addition of tetraorganozincates to nitroolefins.
Scheme 30
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
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
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
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
Scheme 34. Potential applications of Pd-catalysed cross-coupling of benzyl bromides with lithium acetylides.
Scheme 35
Scheme 35. Potential applications of the Pd-catalysed cross-coupling of benzyl bromides with lithium acetylides.
See this image and copyright information in PMC

References

    1. For recent reviews, see:

    2. Fricke C. Sperger T. Mendel M. Schoenebeck F. Angew. Chem., Int. Ed. 2021;60:3355–3366. doi: 10.1002/anie.202011825. - DOI - PMC - PubMed
    3. Shaughnessy K. H. Isr. J. Chem. 2020;60:180–194. doi: 10.1002/ijch.201900067. - DOI
    4. Gildner P. G. Colacot T. J. Organometallics. 2015;34:5497–5508. doi: 10.1021/acs.organomet.5b00567. - DOI
    5. Johansson Seechurn C. C. C. Kitching M. O. Colacot T. J. Snieckus V. Angew. Chem., Int. Ed. 2012;51:5062–5085. doi: 10.1002/anie.201107017. - DOI - PubMed
    1. Johansson Seechurn C. C. C. Kitching O. M. Colacot T. J. Snieckus V. Angew. Chem., Int. Ed. 2012;51:5062–5085. doi: 10.1002/anie.201107017. - DOI - PubMed
    2. Biffis A. Centomo P. Del Zotto A. Zecca M. Chem. Rev. 2018;118:2249–2295. doi: 10.1021/acs.chemrev.7b00443. - DOI - PubMed
    3. Christoffel F. Ward T. R. Catal. Lett. 2018;148:489–511. doi: 10.1007/s10562-017-2285-0. - DOI
    4. Roy D. Uzomi Y. Adv. Synth. Catal. 2018;360:602–605. doi: 10.1002/adsc.201700810. - DOI
    5. Ruiz-Castillo P. Buchwald S. L. Chem. Rev. 2016;116:12564–12649. doi: 10.1021/acs.chemrev.6b00512. - DOI - PMC - PubMed
    1. Schlosser M., Organometallics in Synthesis: A Manual, Wiley, 2nd edn, 2002
    2. Seyferth D. Organometallics. 2009;28:2–33. doi: 10.1021/om801047n. - DOI
    3. Nobis J. F. Moormeier L. F. Robinson R. E. Adv. Chem. 1959;23:63–68.
    4. Seyferth D. Organometallics. 2001;20:2940–2955. doi: 10.1021/om010439f. - DOI
    5. Gentner T. X. Mulvey R. E. Angew. Chem., Int. Ed. 2021;60:9247–9262. doi: 10.1002/anie.202010963. - DOI - PMC - PubMed
    6. https://www.rsc.org/periodic-table/, accessed 10 November 2022
    7. Chen Z. Yang H. Kang Z. Driess M. Menezes P. W. Adv. Mater. 2022;34:2108432. doi: 10.1002/adma.202108432. - DOI - PubMed

    1. For recent reviews, see:

    2. Heravi M. M. Zadsirjan V. Hajiabbasi P. Habidi H. Chem. Mon. 2019;150:535–591. doi: 10.1007/s00706-019-2364-6. - DOI
    3. Qureshi Z. Toker C. Lautens M. Synthesis. 2017;49:1–16.
    4. Jana R. Pathak T. P. Sigman M. S. Chem. Rev. 2011;111:1417–1492. doi: 10.1021/cr100327p. - DOI - PMC - PubMed
    1. Yamamura M. Moritani I. Murahashi S. J. Organomet. Chem. 1975;91:39–42. doi: 10.1016/S0022-328X(00)89636-9. - DOI
    2. Murahashi S. Yamamura M. Yanagisawa K. Mita N. Kondo K. J. Org. Chem. 1979;44:2408–2417. doi: 10.1021/jo01328a016. - DOI