Download PDF
Synlett 2019; 30(07): 809-812
DOI: 10.1055/s-0037-1612255
letter
© Georg Thieme Verlag Stuttgart · New York

Direct Synthesis of β,γ-Unsaturated α-Keto Esters from Aldehydes and Pyruvates

John Kamanda Mansaray
,
Jiarui Sun
,
Shisheng Huang
,
Weijun Yao  *
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: orgywj@zstu.edu.cn
› Author AffiliationsWe are grateful to the National Natural Science Foundation of China (Grant No. 21702185) and the Science Foundation of Zhejiang Sci-Tech University (Grant No. 16062189-Y).
Further Information

Publication History

Received: 08 December 2018

Accepted after revision: 30 January 2019

Publication Date:
25 February 2019 (online)

    Permissions and Reprints All articles of this category


Abstract

Herein, we describe two practical methods to synthesize β,γ-unsaturated α-keto esters directly from aldehydes and pyruvates promoted by BF3•Et2O in the presence of Ac2O or by Ti(OEt)4 under mild conditions. A variety of aromatic aldehydes was tolerated to afford the desired products in moderate to excellent yield. Moreover, aliphatic aldehydes and Isatin were also employed to give the γ-alkyl β,γ-unsaturated α-keto esters in moderate yield with use of the Ti(OEt)4 system.

Key words

unsaturated α-keto esters - step economy - pyruvates - aldehydes - aldol condensation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1612255.
  • Supporting Information
 

  • References and Notes


      • For reviews see:
    • 1a Desimoni G, Faita G, Quadrell P. Chem. Rev. 2013; 113: 5924-5988
      CrossrefPubMed
    • 1b Eftekhari-Sis B, Zirak M. Chem. Rev. 2015; 115: 151-264
      CrossrefPubMed
  • 2 Dou X, Hayashi T. Adv. Synth. Catal. 2016; 358: 1054-1058
    Crossref
    • 3a Zhang Q, Lv J, Li S, Luo S. Org. Lett. 2018; 20: 2269-2272
      CrossrefPubMed
    • 3b Ouyang B, Yu T, Luo R, Lu G. Org. Biomol. Chem. 2014; 12: 4172-4176
      CrossrefPubMed
    • 4a Sinha D, Perera S, Zhao JC.-G. Chem. Eur. J. 2013; 19: 6976-6979
      CrossrefPubMed
    • 4b Lv J, Zhang L, Luo S, Cheng J.-P. Angew. Chem. Int. Ed. 2013; 52: 9786-9790
      CrossrefPubMed
    • 4c Wang L, Lv J, Zhang L, Luo S. Angew. Chem. Int. Ed. 2017; 56: 10867-10871
      CrossrefPubMed
    • 4d Kano T, Maruyama H, Hommaa C, Maruoka K. Chem. Commun. 2018; 54: 3496-3499
      CrossrefPubMed
    • 4e Liu Q.-J, Wang L, Kang Q.-K, Zhang XP, Tang Y. Angew. Chem. Int. Ed. 2016; 55: 9220-9223
      CrossrefPubMed
    • 5a Hao X, Lin L, Tan F, Ge S, Liu X, Feng X. Org. Chem. Front. 2017; 4: 1647-1650
      Crossref
    • 5b Zhang Y, Yang N, Liu X, Guo J, Zhang X, Lin L, Hua C, Feng X. Chem. Commun. 2015; 51: 8432-8435
      CrossrefPubMed
    • 5c Chen X, Jiang H, Hou B, Gong W, Liu Y, Cui Y. J. Am. Chem. Soc. 2017; 139: 13476-13482
      CrossrefPubMed
    • 6a Li Y, Huang Y, Gui Y, Sun J, Li J, Zha Z, Wang Z. Org. Lett. 2017; 19: 6416-6419
      CrossrefPubMed
    • 6b Deng Y.-H, Chen J.-Q, He L, Kang T. -R, Liu Q.-Z, Luo S.-W, Yuan W.-C. Chem. Eur. J. 2013; 19: 7143-7150
      CrossrefPubMed
    • 6c Konda S, Guo Q.-S, Abe M, Huang H, Arman H, Zhao JC.-G. J. Org. Chem. 2015; 80: 806-815
      CrossrefPubMed
    • 6d Wei A.-J, Nie J, Zheng Y, Ma J.-A. J. Org. Chem. 2015; 80: 3766-3776
      CrossrefPubMed
    • 7a Kuang Y, Shen B, Dai L, Yao Q, Liu X, Lin L, Feng X. Chem. Sci. 2018; 9: 688-692
      CrossrefPubMed
    • 7b Konda S, Zhao JC.-G. Tetrahedron Lett. 2014; 55: 5216-5218
      Crossref
    • 7c Chew R, Teo K, Huang Y, Li B.-B, Li Y, Pullarkat SA, Leung P.-H. Chem. Commun. 2014; 50: 8768-8770
      CrossrefPubMed
    • 7d Chen S, Wang Y, Zhou Z. J. Org. Chem. 2016; 81: 11432-11438
      CrossrefPubMed
    • 8a Zhu C, Bi B, Ding Y, Zhang T, Chen Q.-Y. Org. Biomol. Chem. 2015; 13: 6278-6285
      CrossrefPubMed
    • 8b Jiang L, Jin W, Hu W. ACS Catal. 2016; 6: 6146-6150
      Crossref
    • 9a Yao Q, Yu H, Zhang H, Dong S, Chang F, Lin L, Liu X, Feng X. Chem. Commun. 2018; 54: 3375-3378
      CrossrefPubMed
    • 9b Jin H, Lee J, Shi H, Lee J, Yoo E, Song C, Ryu D. Org. Lett. 2018; 20: 1584-1588
      CrossrefPubMed
    • 9c Sadeghzadeh S. RSC. Adv. 2016; 6: 99586-99594
      Crossref
    • 9d Cheng Y, Han Y, Li P. Org. Lett. 2017; 19: 4774-4777
      CrossrefPubMed
    • 9e Wang S, Radosevich AT. Org. Lett. 2013; 15: 1926-1929
      CrossrefPubMed
    • 9f Li E, Huang Y. Chem. Eur. J. 2014; 20: 3520-3527
      CrossrefPubMed
    • 9g Duan J, Cao F, Wang X, Ma C. Chem. Commun. 2013; 49: 1124-1126
      CrossrefPubMed
  • 10 Stecher ED, Ryder HF. J. Am. Chem. Soc. 1952; 74: 4392-4395
    Crossref
  • 11 Sugimura H, Yoshida K. Bull. Chem. Soc. Jpn. 1992; 65: 3209-3211
    Crossref
  • 12 Meijer LH, Pandit UK. Tetrahedron 1985; 41: 467-472
    Crossref
  • 13 Trost BM. Angew. Chem., Int. Ed. Engl. 1995; 34: 259-281
    Crossref
  • 14 Wender PA, Verma VA, Paxton TJ, Pillow TH. Acc. Chem. Res. 2008; 41: 40-49
    CrossrefPubMed
  • 15 Dujardin G, Leconte S, Bénard A, Brown E. Synlett 2001; 147-149
    • 16a Yao W, Dou X, Lu Y. J. Am. Chem. Soc. 2015; 137: 54-57
      CrossrefPubMed
    • 16b Yao W, Pan L, Wu Y, Ma C. Org. Lett. 2010; 12: 2422-2425
      CrossrefPubMed
    • 16c Yao W, Wu Y, Wang G, Zhang Y, Ma C. Angew. Chem. Int. Ed. 2009; 48: 9713-9716
      CrossrefPubMed
  • 17 β,γ-Unsaturated α-Keto Esters (1a–u); General Procedure A To the solution of aldehyde (2 mmol) and pyruvate (2.4 mmol) in toluene (10 mL) were added BF3•Et2O (1 mmol) and Ac2O (3 mmol). After stirring for 48 h at 40 °C, the mixture was poured into saturated NaHCO3 (aq) solution (20 mL). The separated aqueous phase was extracted with ethyl acetate (20 mL) and the combined organic phases were washed by brine (20 mL), dried with Na2SO4, filtered, and concentrated in vacuum. The residue was filtered through a short pad of silica gel with petroleum ether/ethyl acetate (10:1) as the eluent to obtain a crude product, which was analyzed by 1H NMR spectroscopy to calculate the E/Z ratio. Further purification was carried out by column chromatography on silica gel with petroleum ether/ethyl acetate (20:1) as the eluent to afford the products 1. Ethyl (E)-4-Cyclohexyl-2-oxobut-3-enoate (1t) Pale yellow oil; yield: 176 mg (42%). 1H NMR spectrum of the crude product shows an E/Z ratio of >19:1. 1H NMR (400 MHz CDCl3): δ = 7.09 (dd, J = 16.0, 6.8 Hz, 1 H), 6.57 (dd, J = 16.0, 1.1 Hz, 1 H), 4.31 (q, J = 7.1 Hz, 2 H), 2.29–2.13 (m, 1 H), 1.78–1.64 (m, 5 H), 1.35 (t, J = 7.1 Hz, 3 H), 1.31–1.08 (m, 5 H). 13C NMR (101 MHz, CDCl3): δ = 183.8, 162.5, 159.6, 122.7, 62.2, 41.2, 31.4, 25.8, 25.6, 14.0.
  • 18 Collados JF, Toledano E, Guijarro D, Yus M. J. Org. Chem. 2012; 77: 5744-5750
    CrossrefPubMed
  • 19 Ti(OEt)4 System; General Procedure B To the solution of aldehyde (2 mmol) and pyruvate (2.4 mmol) in toluene (10 mL) was added Ti(OEt)4 (2.4 mmol). After stirring for 72 h at 40 °C, the mixture was diluted with ethyl acetate (40 mL) and quenched with water (1 mL). After stirring for 0.5 h at rt, the mixture was dried with Na2SO4, filtered, and concentrated in vacuum. The residue was filtered through a short pad of silica gel with petroleum ether/ethyl acetate (10:1) as the eluent to obtain a crude product, which was analyzed by 1H NMR spectroscopy to calculate the E/Z ratio. Further purification was carried out by column chromatography on silica gel with petroleum ether/ethyl acetate (20:1) as the eluent to afford the products 1. Ethyl (E)-2-Oxohept-3-enoate (1s) Pale yellow oil; yield: 122 mg (36%). 1H NMR spectrum of the crude product shows an E/Z ratio of >19:1. 1H NMR (400 MHz, CDCl3): δ = 7.18 (dt, J = 15.8, 6.9 Hz, 1 H), 6.64 (d, J = 15.9 Hz, 1 H), 6.64 (d, J = 15.9 Hz, 1 H), 4.34 (q, J = 7.1 Hz, 2 H), 2.29 (td, J = 8.0, 1.0 Hz, 2 H), 1.59–1.47 (m, 2 H), 1.37 (t, J = 7.1 Hz, 3 H), 0.95 (t, J = 7.4 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 183.5, 162.4, 154.9, 125.3, 62.30, 35.1, 21.1, 14.0, 13.7.
  • 20 Yang C, Chen X, Tang T, He Z. Org. Lett. 2016; 18: 1486-1489
    CrossrefPubMed