Synlett 2024; 35(10): 1190-1194
DOI: 10.1055/a-2268-4386
cluster
Thieme Chemistry Journals Awardees 2023

Are β-Lactones Involved in Carbon-Based Olefination Reactions?

Jan Nowak
,
Michał Tryniszewski
,
Michał Barbasiewicz  ∗
This work was financed by the OPUS 16 program (Grant No. DEC-2018/31/B/ST5/01118) of the National Science Centre, Poland.
› Further Information
    Permissions and Reprints All articles of this category


Abstract

Heteroatom-based olefinating reagents (e.g., organic phosphonates, sulfonates, etc.) are used to transform carbonyl compounds into alkenes, and their mechanism of action involves aldol-type addition, cyclization, and fragmentation of four-membered ring intermediates. We have developed an analogous process using ethyl 1,1,1,3,3,3-hexafluoroisopropyl methylmalonate, which converts electrophilic aryl aldehydes into α-methylcinnamates in up to 70% yield. The reaction plausibly proceeds through the formation of β-lactone that spontaneously decarboxylates under the reaction conditions. The results shed light on the Knoevenagel–Doebner olefination, for which decarboxylative anti-fragmentation of aldol-type adducts is usually considered.

Key words

olefination - carbonyl compounds - reaction mechanism - lactones - malonates - Knoevenagel–Doebner reaction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2268-4386.
  • Supporting Information


Publication History

Received: 19 December 2023

Accepted after revision: 14 February 2024

Accepted Manuscript online:
14 February 2024

Article published online:
02 April 2024

© 2024. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

  • 2 Edmonds M, Abell A. In Modern Carbonyl Olefination, Chap. 1. Takeda T. Wiley-VCH; Weinheim: 2004. 1; and references cited therein
    Search in Google Scholar
  • 3 Korotchenko VN, Nenajdenko VG, Balenkova ES, Shastin AV. Russ. Chem. Rev. 2004; 73: 957
    CrossrefSearch in Google Scholar
  • 5 For a demonstration of mechanistic switch between anti-elimination, and cyclization–syn-fragmentation of trifluoroethyl β-hydroxysulfonates, see: Górski B, Basiak D, Grzesiński Ł, Barbasiewicz M. Org. Biomol. Chem. 2019; 17: 7660
    CrossrefPubMedSearch in Google Scholar
  • 7 Xavier T, Condon S, Pichon C, Le Gall E, Presset M. Org. Lett. 2019; 21: 6135
    CrossrefPubMedSearch in Google Scholar
  • 8 Baudoux J, Lefebvre P, Legay R, Lasne M.-C, Rouden J. Green Chem. 2010; 12: 252
    CrossrefSearch in Google Scholar
  • 10 Adam W, Baeza J, Liu J.-C. J. Am. Chem. Soc. 1972; 94: 2000
    CrossrefSearch in Google Scholar
  • 11 Mulzer J, Pointner A, Chucholowski A, Brüntrup G. J. Chem. Soc., Chem. Commun. 1979; 52
    Crossref
  • 12 McLaughlin C, Smith AD. Chem. Eur. J. 2021; 27: 1533
    CrossrefPubMedSearch in Google Scholar
  • 14 For a subsequent decarboxylation of a tricyclic β-lactone formed by a nucleophile-catalyzed aldol lactonization process, see: Kong W, Romo D. J. Org. Chem. 2017; 82: 13161
    CrossrefPubMedSearch in Google Scholar
  • 15 Danheiser RL, Nowick JS. J. Org. Chem. 1991; 56: 1176
    CrossrefSearch in Google Scholar
  • 16 Wedler C, Kunath A, Schick H. J. Org. Chem. 1995; 60: 758
    CrossrefSearch in Google Scholar
  • 17 Wedler C, Kleiner K, Kunath A, Schick H. Liebigs Ann. 1996; 881
    Crossref
  • 20 For an analogous process involving α,α-disubstituted aldehydes, see: Dixon GJ, Rodriguez MR, Chong TG, Kim KY, Downey CW. J. Org. Chem. 2022; 87: 14846
    CrossrefPubMedSearch in Google Scholar
  • 21 For an aldol-Grob mechanism of the carbonyl–olefin metathesis between vinyl ethers and aldehydes, see: Rivero-Crespo M. Á, Tejeda-Serrano M, Pérez-Sánchez H, Cerón-Carrasco JP, Leyva-Pérez A. Angew. Chem. Int. Ed. 2020; 59: 3846
    CrossrefPubMedSearch in Google Scholar
  • 22 Brady WT, Glang YF. J. Org. Chem. 1986; 51: 2145
    CrossrefSearch in Google Scholar
  • 23 For an analogous synthesis of dihydrothiophenes and dihydrothiopyrans by elimination of carbon oxysulfide (O=C=S), see: Cromwell S, Sutio R, Zhang C, Such GK, Lupton DW. Angew. Chem. Int. Ed. 2022; 61: e202206647
    CrossrefPubMedSearch in Google Scholar
  • 24 Compare: Tryniszewski M, Barbasiewicz M. Synthesis 2022; 54: 1446
    Thieme ConnectSearch in Google Scholar
  • 25 The pK a data for fluorinated alcohols were taken from: Zhu Z, Boger DL. J. Org. Chem. 2022; 87: 14657
    CrossrefPubMedSearch in Google Scholar
  • 26 For a review of DBU opening processes, see: Muzart J. ChemistrySelect 2020; 5: 11608
    CrossrefSearch in Google Scholar
  • 27 Under similar conditions (LiHMDS/THF), aryl hexafluoroisopropyl ethers eliminate HF to form aryl perfluoroisopropenyl ethers; see: Su J, Chen K, Kang Q.-K, Shi H. Angew. Chem. Int. Ed. 2023; 62: e202302908
    CrossrefPubMedSearch in Google Scholar
  • 28 Compare: Adam W, Encarnación LA. A. Chem. Ber. 1982; 115: 2592
    CrossrefSearch in Google Scholar
  • 29 See the Supporting Information for details
  • 30 α-Methylcinnamates 12a–m; General Procedure A 30 mL Schlenk flask was charged with diester 5b (2.2 mmol) and the appropriate aldehyde (2.0 mmol), and the mixture was purged with argon. Anhyd THF (8 mL) was added, followed by dropwise addition of DBU (0.6 mL; 4.0 mmol) over ~90 s with stirring. The flask was then immersed in an oil bath at 40 °C for 16 h. The mixture was cooled to rt, poured into 5% aq NaHCO3 (50 mL), and extracted with EtOAc (3 × 50 mL). The combined organic phases were washed with H2O (50 mL) and brine (50 mL), then dried (MgSO4), filtered, and concentrated. The residue was purified by column chromatography [silica gel (d = 20 cm; ø = 3 cm)]. Ethyl (2E)-2-Methyl-3-phenylacrylate (12a) Eluent: cyclohexane–toluene (2:1). Colorless oil; yield: 91 mg (0.48 mmol, 23%). 1H NMR (400 MHz, CDCl3): δ = 7.67 (d, J = 1.5 Hz, 1 H), 7.42–7.26 (m, 5 H), 4.26 (q, J = 7.1 Hz, 2 H), 2.10 (d, J = 1.5 Hz, 3 H), 1.34 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 168.7, 138.6, 136.0, 129.6, 128.6, 128.3, 128.2, 60.8, 14.3, 14.0. The NMR spectra were consistent with those reported in the literature.33 Ethyl (2E)-3-(2-Bromophenyl)-2-methylacrylate (12b) Eluent: cyclohexane–toluene (2:1). Colorless oil; yield: 170 mg (0.64 mmol, 32%). 1H NMR (400 MHz, CDCl3): δ = 7.69–7.66 (m, 1 H), 7.57 (dd, J = 8.0, 1.1 Hz, 1 H), 7.32–7.23 (m, 2 H), 7.17–7.10 (m, 1 H), 4.26 (q, J = 7.1 Hz, 2 H), 1.94 (d, J = 1.6 Hz, 3 H), 1.32 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.9, 137.9, 136.2, 132.6, 130.4, 130.3, 129.4, 126.9, 124.1, 60.9, 14.2, 13.9. The NMR spectra were consistent with those reported in the literature.33
  • 31 Ramachandran PV, Otoo B. Chem. Commun. 2015; 51: 12388
    CrossrefPubMedSearch in Google Scholar
  • 32 Distinction between open-chain aldol-type adduct and cyclized β-lactone is difficult, when analyzing mixture of components with NMR spectroscopy. Therefore, we remain cautious with definite statements, concerning the structure of intermediate I.
  • 33 Leung PS.-W, Teng Y, Toy PH. Org. Lett. 2010; 12: 4996
    CrossrefPubMedSearch in Google Scholar
  • 34 For a biosynthesis of olefinic hydrocarbons via β-lactones, see: Christenson, J. K.; Richman, J. E.; Jensen, M. R.; Neufeld, J. Y.; Wilmot, C. M.; Wackett, L. P. Biochemistry 2017, 56, 348; and references cited therein.