Synlett 2021; 32(17): 1767-1771
DOI: 10.1055/s-0040-1720388
letter

Iron-Catalyzed C(sp3)–H Alkylation through Ligand-to-Metal Charge Transfer

Yi Cheng Kang
,
Sean M. Treacy
,
Tomislav Rovis  ∗
We thank NIGMS for support (GM125206).
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Abstract

We report the FeCl3-catalyzed alkylation of nonactivated C(sp3)–H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates chlorine radicals that then preferentially abstract hydrogen atoms from electron-rich C(sp3)–H bonds distal to electron-withdrawing functional groups. The resultant alkyl radicals are trapped by electron-deficient olefins, and the catalytic cycle is closed by Fe(II) recombination and protodemetalation.

Key words

C(sp3)–H bond activation - photocatalysis - charge transfer - iron catalysis - alkylation - alkenes

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1720388.
  • Supporting Information


Publication History

Received: 17 June 2021

Accepted after revision: 19 July 2021

Article published online:
09 August 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

  • 1 Bergman RG. Nature 2007; 446: 391
    CrossrefPubMedSearch in Google Scholar
  • 2 Hartwig JF, Larsen MA. ACS Cent. Sci. 2016; 2: 281
    CrossrefPubMedSearch in Google Scholar
  • 3 Chu JC. K, Rovis T. Angew. Chem. Int. Ed. 2018; 57: 62
    CrossrefPubMedSearch in Google Scholar
  • 4 Kattamuri PV, West JG. Synlett 2021; 32: 1179
    Thieme ConnectSearch in Google Scholar
  • 5 Hu A, Guo J.-J, Pan H, Zuo Z. Science 2018; 361: 668
    CrossrefPubMedSearch in Google Scholar
  • 6 Perry IB, Brewer TF, Sarver PJ, Schultz DM, DiRocco DA, MacMillan DW. C. Nature 2018; 560: 70
    CrossrefPubMedSearch in Google Scholar
  • 7 Yi H, Zhang G, Wang H, Huang Z, Wang J, Singh AK, Lei A. Chem. Rev. 2017; 117: 9016
    CrossrefPubMedSearch in Google Scholar
  • 8 Ravelli D, Fagnoni M, Fukuyama T, Nishikawa T, Ryu I. ACS Catal. 2018; 8: 701
    CrossrefSearch in Google Scholar
  • 9 Prier CK, Rankic DA, MacMillan DW. C. Chem. Rev. 2013; 113: 5322
    CrossrefPubMedSearch in Google Scholar
  • 10 Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
    CrossrefPubMedSearch in Google Scholar
  • 11 Hu D, Jiang X. Synlett 2021; in press
  • 12 Choi GJ, Zhu Q, Miller DC, Gu CJ, Knowles RR. Nature 2016; 539: 268
    CrossrefPubMedSearch in Google Scholar
  • 13 Chu JC. K, Rovis T. Nature 2016; 539: 272
    CrossrefPubMedSearch in Google Scholar
  • 14 Cuthbertson JD, MacMillan DW. C. Nature 2015; 519: 74
    CrossrefPubMedSearch in Google Scholar
  • 15 Ohkubo K, Fujimoto A, Fukuzumi S. Chem. Commun. 2011; 47: 8515
    CrossrefPubMedSearch in Google Scholar
  • 16 Ohkubo K, Mizushima K, Fukuzumi S. Res. Chem. Intermed. 2013; 39: 205
    CrossrefSearch in Google Scholar
  • 17 Rohe S, Morris AO, McCallum T, Barriault L. Angew. Chem. Int. Ed. 2018; 57: 15664
    CrossrefPubMedSearch in Google Scholar
  • 18 Deng H.-P, Zhou Q, Wu J. Angew. Chem. Int. Ed. 2018; 57: 12661
    CrossrefPubMedSearch in Google Scholar
  • 19 Fokin AA, Schreiner PR. Chem. Rev. 2002; 102: 1551
    CrossrefPubMedSearch in Google Scholar
  • 20 Hudzik JM, Bozzelli JW. J. Phys. Chem. A 2012; 116: 5707
    CrossrefPubMedSearch in Google Scholar
  • 21 Walling C. Free Radicals in Solution . Wiley; New York: 1957
    Search in Google Scholar
  • 22 Zavitsas AA, Pinto JA. J. Am. Chem. Soc. 1972; 94: 7390
    CrossrefSearch in Google Scholar
  • 23 Roberts BP, Steel AJ. J. Chem. Soc., Perkin Trans. 2 1994; 2155
    Crossref
  • 24 Zavitsas A. J. Chem. Soc., Perkin Trans. 2 1996; 391
    Crossref
  • 25 Roberts BP. J. Chem. Soc., Perkin Trans. 2 1996; 2719
    Crossref
  • 26 Hu A, Guo J.-J, Pan H, Tang H, Gao Z, Zuo Z. J. Am. Chem. Soc. 2018; 140: 1612
    CrossrefPubMedSearch in Google Scholar
  • 27 An Q, Wang Z, Chen Y, Wang X, Zhang K, Pan H, Liu W, Zuo Z. J. Am. Chem. Soc. 2020; 142: 6216
    CrossrefPubMedSearch in Google Scholar
  • 28 Shields BJ, Doyle AG. J. Am. Chem. Soc. 2016; 138: 12719
    CrossrefPubMedSearch in Google Scholar
  • 29 Ackerman LK. G, Martinez Alvarado JI, Doyle AG. J. Am. Chem. Soc. 2018; 140: 14059
    CrossrefPubMedSearch in Google Scholar
  • 30 Deng H.-P, Fan X.-Z, Chen Z.-H, Xu Q.-H, Wu J. J. Am. Chem. Soc. 2017; 139: 13579
    CrossrefPubMedSearch in Google Scholar
  • 31 Kochi JK. J. Am. Chem. Soc. 1962; 84: 2121
    CrossrefSearch in Google Scholar
  • 32 Shulpin GB, Kats MM. React. Kinet. Catal. Lett. 1990; 41: 239
    CrossrefSearch in Google Scholar
  • 33 Shulpin GB, Kats MM. Pet. Chem. 1991; 31: 647
    Search in Google Scholar
  • 34 Takaki K, Yamamoto J, Matsushita Y, Morii H, Shishido T, Takehira K. Bull. Chem. Soc. Jpn. 2003; 76: 393
    CrossrefSearch in Google Scholar
  • 35 Takaki K, Yamamoto J, Komeyama K, Kawabata T, Takehira K. Bull. Chem. Soc. Jpn. 2004; 77: 2251
    CrossrefSearch in Google Scholar
  • 36 Treacy SM, Rovis T. J. Am. Chem. Soc. 2021; 143: 2729
    CrossrefPubMedSearch in Google Scholar
  • 37 Kang YC, Treacy SM, Rovis T. ACS Catal. 2021; 11: 7442
    CrossrefPubMedSearch in Google Scholar
  • 38 Swanson TB, Laurie VW. J. Phys. Chem. 1965; 69: 244
    CrossrefSearch in Google Scholar
  • 39 Okada M, Fukuyama T, Yamada K, Ryu I, Ravelli D, Fagnoni M. Chem. Sci. 2014; 5: 2893
    CrossrefSearch in Google Scholar
  • 40 Benzyl 6-Oxooctanoate (3); Typical Procedure An oven-dried 1.5 dram vial was charged with FeCl3 (25 mol%). (Any solid reactants were also added at this stage.) A magnetic stirrer bar was added, and the vial was transferred to a glovebox. Anhyd MeCN (1 mL, 0.3 M) was then added, followed by pentan-3-one (5 equiv) and benzyl acrylate (1 equiv, 0.3 mmol). The vial was sealed and then placed on a stirrer plate 2 in. (5 cm) from a 390 nm Kessil lamp. Ambient temperature was maintained by the use of a fan above the setup. After 36 h, the mixture was concentrated in vacuo and purified by flash column chromatography [silica gel, EtOAc–hexanes (1:5)]. to give a colorless oil; yield: 40.4 mg (54%). IR (film): 2939, 1732, 1712, 1497, 1455, 1414, 1377, 1211, 1113, 1084, 976, 739, 697 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.62–7.12 (m, 5 H), 5.11 (s, 2 H), 2.54–2.25 (m, 6 H), 1.72–1.51 (m, 4 H), 1.04 (t, J =7.4 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 211.12, 173.26, 136.14, 128.63, 128.38, 128.28, 66.24, 41.92, 35.95, 34.13, 24.56, 23.34, 7.90. LRMS (EI): m/z [M+] calcd for C15H20O3; 248.14; found: 248.1.
  • 41 Ethyl 3-(3-Oxocyclobutyl)propanoate (10) Prepared by following the typical procedure from cyclobutanone and ethyl acrylate as a yellow oil; yield: 20.1 mg (39%). IR (film): 2979, 1780, 1728, 1448, 1374, 1342, 1251, 1179, 1099, 1028 cm–1. 1H NMR (500 MHz, CDCl3) δ = 4.13 (q, J = 7.1 Hz, 2 H), 3.23–3.02 (m, 2 H), 2.79–2.61 (m, 2 H), 2.47–2.35 (m, 1 H), 2.34 (t, J = 7.5 Hz, 2 H), 1.92 (q, J = 7.6 Hz, 2 H), 1.26 (t, J = 7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 207.51, 173.06, 60.64, 52.48, 33.18, 31.45, 23.58, 14.34. HRMS (ASAP): m/z [M + H]+calcd for C9H15O3: 171.1021; found: 171.1012. Benzyl 3-(1,1-Dioxidotetrahydro-3-thienyl)propanoate (16) Prepared by following the typical procedure from sulfolane and benzyl acrylate as a viscous colorless oil; yield: 49.3 mg (58%). IR (film): 2940, 1728, 1497, 1454, 1414, 1388, 1354, 1301, 1268, 1168, 1117, 749, 698, 570, 460 cm–1. 1H NMR (500 MHz, CDCl3) δ = 7.41–7.30 (m, 5 H), 5.12 (s, 2 H), 3.19 (tdd, J = 13.2, 7.8, 2.1 Hz, 2 H), 2.99 (ddd, J = 13.2, 11.3, 7.7 Hz, 1 H), 2.64 (dd, J = 13.0, 10.8 Hz, 1 H), 2.47–2.35 (m, 3 H), 2.31 (dddd, J = 14.9, 7.7, 3.5, 1.6 Hz, 1 H), 1.92–1.72 (m, 3 H). 13C NMR (126 MHz, CDCl3) δ = 172.31, 135.67, 128.73, 128.54, 128.46, 66.69, 56.61, 52.26, 36.16, 31.99, 29.50, 28.94. LRMS (EI): m/z [M+] calculated for C14H18O4S; 282.09; found: 282.1. 1-Methyl-3-(3-Oxopentyl)pyrrolidine-2,5-dione (22) Prepared by following the typical procedure from pentan-3-one and N-methylmaleimide as a yellow oil; yield: 33.9 mg (57%). IR (film): 2938, 1774, 1691, 1434, 1379, 1278, 1117, 954, 698 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.94 (s, 3 H), 2.89–2.75 (m, 2 H), 2.71–2.55 (m, 2 H), 2.43 (q, J =7.3 Hz, 2 H), 2.33 (dd, J =17.3, 3.7 Hz, 1 H), 2.05–1.95 (m, 1 H), 1.93–1.83 (m, 1 H), 1.04 (t, J =7.3 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 210.16, 179.70, 176.39, 39.04, 38.84, 36.11, 34.86, 25.64, 24.85, 7.84. HRMS (ASAP): m/z [M + H]+ calcd for C10H16NO3: 198.1130; found: 198.1127.