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Synthesis 2021; 53(23): 4461-4476
DOI: 10.1055/a-1551-4093
paper

Preparation of Functionalized Diorganomagnesium Reagents in Toluene via Bromine or Iodine/Magnesium-Exchange Reactions

Alexandre Desaintjean‡
,
Fanny Danton‡
,
Paul Knochel  ∗
We thank the Deutsche Forschungsgemeinschaft (DFG) and Ludwig-Maximilians-Universität München for financial support.
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Abstract

A wide range of polyfunctionalized di(hetero)aryl- and dialkenyl-magnesium reagents are prepared in toluene within 10 to 120 minutes between –78 °C and 25 °C via an I/Mg- or Br/Mg-exchange reaction using reagents of the general formula R2Mg (R = sBu, Mes). Highly sensitive functional groups, such as triazene or nitro, are tolerated in these exchange reactions, enabling the synthesis of various functionalized (hetero)arene and alkene derivatives after quenching with several electrophiles including allyl bromides, acyl chlorides, aldehydes, ketones, and aryl iodides.

Key words

alkenes - apolar solvents - arenes - Grignard reaction - halogen/magnesium-exchange - heterocycles - magnesium

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1551-4093.
  • Supporting Information


Publication History

Received: 01 July 2021

Accepted after revision: 15 July 2021

Accepted Manuscript online:
15 July 2021

Article published online:
04 August 2021

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  • References

    • 1a McGrath NA, Brichacek M, Njardarson JT. J. Chem. Educ. 2010; 87: 1348
      Crossref
    • 1b Brown DG, Boström J. J. Med. Chem. 2016; 59: 4443
      CrossrefPubMed
    • 1c Nishimura RH. V, Weidmann N, Knochel P. Synthesis 2020; 52: 3036
      CrossrefPubMed
    • 1d Tüllmann CP, Steiner S, Knochel P. Synthesis 2020; 52: 2357
      Article in Thieme Connect
    • 1e Skotnitzki J, Kremsmair A, Kicin B, Saeb R, Ruf V, Knochel P. Synthesis 2020; 52: 873
      Crossref
    • 1f Skotnitzki J, Kremsmair A, Knochel P. Synthesis 2020; 52: 189
      CrossrefPubMed
    • 1g Weidmann N, Nishimura RH. V, Harenberg JH, Knochel P. Synthesis 2021; 53: 557
      CrossrefPubMed
    • 1h Kremsmair A, Graßl S, Seifert CJ. B, Godineau E, Knochel P. Synthesis 2021; 53 in press; DOI: DOI: 10.1055/a-1534-0624.
      CrossrefPubMed
  • 2 Handbook of Functionalized Organometallics . Knochel P. Wiley-VCH; Weinheim: 2008
    CrossrefGoogle Scholar
    • 3a Kremsmair A, Harenberg JH, Schwärzer K, Hess A, Knochel P. Chem. Sci. 2021; 12: 6011
      CrossrefPubMed
    • 3b Lutter FH, Hofmayer MS, Hammann JM, Malakhov V, Knochel P. Org. React. 2019; 100: 63
    • 4a Krasovskiy A, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 3333 ; Angew. Chem. 2004, 116, 3396
      CrossrefPubMed
    • 4b Krasovskiy A, Straub BF, Knochel P. Angew. Chem. Int. Ed. 2006; 45: 159 ; Angew. Chem. 2005, 118, 165
      CrossrefPubMed
    • 4c Schnegelsberg C, Bachmann S, Kolter M, Auth T, John M, Stalke D, Koszinowski K. Chem. Eur. J. 2016; 22: 7752
      CrossrefPubMed
    • 5a Ziegler DS, Karaghiosoff K, Knochel P. Angew. Chem. Int. Ed. 2018; 57: 6701 ; Angew. Chem. 2018, 130, 6811
      CrossrefPubMed
    • 5b Ziegler DS, Wei B, Knochel P. Chem. Eur. J. 2019; 25: 2695
      CrossrefPubMed
    • 5c Desaintjean A, Haupt T, Bole LJ, Judge NR, Hevia E, Knochel P. Angew. Chem. Int. Ed. 2021; 60: 1513 ; Angew. Chem. 2021, 133, 1536
      CrossrefPubMed
    • 5d Bole LJ, Judge NR, Hevia E. Angew. Chem. Int. Ed. 2021; 60: 7626 ; Angew. Chem. 2021, 133, 7704
      CrossrefPubMed
  • 6 Balkenhohl M, Ziegler DS, Desaintjean A, Bole LJ, Kennedy AR, Hevia E, Knochel P. Angew. Chem. Int. Ed. 2019; 58: 12898 ; Angew. Chem. 2019, 131, 13030 features a related halogen/zinc exchange
    CrossrefPubMed
    • 7a Solvent Recovery Handbook . Smallwood IM. Blackwell Science; Oxford: 2002
      Google Scholar
    • 7b Delhaye L, Ceccato A, Jacobs P, Köttgen C, Merschaert A. Org. Process Res. Dev. 2007; 11: 160
      Crossref
  • 8 This reagent still contained 0.5 equivalents of Et2O, having the formula sBu2Mg·0.5Et2O (determined by 1H NMR analysis) that we have abbreviated as sBu2Mg for the sake of clarity: Hess A, Prohaska JP, Doerrich SB, Trauner F, Lutter FH, Lemaire S, Wagschal S, Karaghiosoff K, Knochel P. Chem. Sci. 2021; 12: 8424
    CrossrefPubMed
  • 9 The same reactivity was observed after 5 days of storage of the sBu2Mg toluene solution at –20 °C.
  • 10 Knochel P, Yeh MC. P, Berk SC, Talbert J. J. Org. Chem. 1988; 53: 2390
    Crossref
  • 11 Metzger A, Piller FM, Knochel P. Chem. Commun. 2008; 5824
    PubMed
  • 12 Negishi E, Huang Z, Wang G, Mohan S, Wang C, Hattori H. Acc. Chem. Res. 2008; 41: 1474
    CrossrefPubMed

      • When used in association with R2Mg (1c, R = sBu; 1d, R = Mes), DMPU increases the exchange rate, thus improving conversions and diminishing side reactions:
    • 13a Mukhopadhyay T, Seebach D. Helv. Chim. Acta 1982; 65: 385
      Crossref
    • 13b Benischke AD, Le Corre G, Knochel P. Chem. Eur. J. 2017; 23: 778
      CrossrefPubMed
    • 13c Bengtsson M, Liljefors T. Synthesis 1988; 250
    • 13d Riguet E, Klement I, Reddy CK, Cahiez G, Knochel P. Tetrahedron Lett. 1996; 37: 5865
      Crossref
    • 13e Ellwart M, Makarov IS, Achrainer F, Zipse H, Knochel P. Angew. Chem. Int. Ed. 2016; 55: 10502 ; Angew. Chem. 2016, 128, 10658
      CrossrefPubMed
  • 14 Arylmetal reagents tolerate more functional groups than their alkyl counterparts: Benischke AD, Anthore-Dalion L, Kohl F, Knochel P. Chem. Eur. J. 2018; 24: 11103
    CrossrefPubMed
  • 15 The syntheses of all starting materials and the corresponding literature references are given in the Supporting Information.