Download PDF
Synlett 2012; 23(19): 2785-2788
DOI: 10.1055/s-0032-1317496
letter
© Georg Thieme Verlag Stuttgart · New York

Base-Promoted Michael Reaction Concomitant with Alkylation of Cyclic-1,3-diones, an Efficient Approach to 2-Substituted Vinylogous Esters

Subhadip De
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, ITI (Gas Rahat) Building, Govindpura, Bhopal, MP 462 023, India   Fax: +91(755)4092392   Email: alakesh@iiserb.ac.in
,
Lakshmana K. Kinthada
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, ITI (Gas Rahat) Building, Govindpura, Bhopal, MP 462 023, India   Fax: +91(755)4092392   Email: alakesh@iiserb.ac.in
,
Alakesh Bisai*
Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, ITI (Gas Rahat) Building, Govindpura, Bhopal, MP 462 023, India   Fax: +91(755)4092392   Email: alakesh@iiserb.ac.in
› Author Affiliations
Further Information

Publication History

Received: 15 August 2012

Accepted after revision: 28 September 2012

Publication Date:
31 October 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

Vinylogous esters can be synthesized by a base-promoted Michael reaction concomitant with alkylation of the cyclic 1,3-dione substrate. The methodology provides a wide range of 2-substituted vinylogous esters in good to excellent yields.

Key words

vinylogous esters - cyclohexenones - Michael reaction - alkylation - diones

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

    • 2a Smith AB. III. Evolution of a Synthetic Strategy: Total Synthesis of (±)-Jatrophone. In Strategies and Tactics in Organic Synthesis. Lindberg T. Academic; New York: 1984: 224-254 , Chap. 9
      Search in Google Scholar
    • 2b For numerous examples, see: Nicolaou KC, Sorensen EJ. Classics in Total Synthesis . 1st ed Wiley-VCH; New York: 1996
      Search in Google Scholar
    • 2c Nicolaou KC, Snyder SA. Classics in Total Synthesis II . 1st ed Wiley-VCH; Weinheim: 2003
      Search in Google Scholar
    • 2d Nicolaou KC, Chen JS. Classics in Total Synthesis III . 1st ed Wiley-VCH; Weinheim: 2011
      Search in Google Scholar
    • 2e Mohr PJ, Halcomb RL. J. Am. Chem. Soc. 2003; 125: 1712
      CrossrefPubMedSearch in Google Scholar
  • 5 Staben ST, Kennedy-Smith JJ, Huang D, Corkey BK, LaLonde RL, Toste FD. Angew. Chem. Int. Ed. 2006; 45: 5991
    Search in Google Scholar
  • 6 Shigeyama T, Katakawa K, Kogure N, Kitajima M, Katayama H. Org. Lett. 2007; 9: 4069
    CrossrefSearch in Google Scholar
    • 7a Harayama T, Takatani M, Inubushi Y. Tetrahedron Lett. 1979; 4307
    • 7b Harayama T, Takatani M, Inubushui Y. Chem. Pharm. Bull. 1979; 27: 726
      CrossrefSearch in Google Scholar
  • 8 For isolation of huperzine W, see: Tan CH, Ma XQ, Chen GF, Jiang SH, Zhu DY. Chin. Chem. Lett. 2002; 13: 331
    Search in Google Scholar
    • 9a For synthesis of (R)-5-methyl-2-alkylcyclohexen-2-ones 2 from (R)-pulegone, see: Caine D, Procter K, Cassel RA. J. Org. Chem. 1984; 49: 2647
      CrossrefSearch in Google Scholar
    • 9b For the use of 2-iodo-2-cyclohexenones of the type 4c in cross-coupling, see: Pandey G, Balakrishnan M. J. Org. Chem. 2008; 73: 8128
      CrossrefSearch in Google Scholar
    • 10a Carlone A, Marigo M, North C, Landa A, Jørgensen KA. Chem. Commun. 2006; 4928
    • 10b Marigo M, Wabnitz TC, Fielenbach D, Jørgensen KA. Angew. Chem. Int. Ed. 2005; 44: 794
      CrossrefPubMedSearch in Google Scholar
  • 14 Under base-catalyzed conditions it has been reported that cyclohexane-1,3-dione can follow double Michael reactions with acrylates, for example, see: Konno M, Nakae T, Sakuyama S, Imaki K, Nakai H, Hamanaka N. Synlett 1997; 1472
    Thieme Connect
  • 17 Synthesis of Vinylogous Esters; General Procedure: A flame-dried, round-bottomed flask was charged with cyclic 1,3-dione (1 mmol) and ethyl acrylate (1.3 mmol) in DMSO (5 mL). To this solution was added NaH or Cs2CO3 (1.2 mmol) and the reaction mixture was stirred at 80 °C for the indicated time. Upon completion of the Michael reaction (typically, TLC showed complete conversion of starting materials after 3 h of reaction), alkyl halide (1.2 mmol) was added and the reaction mixture was heated at 80 °C for the indicated time (typically 1 h). Upon completion of the alkylation (TLC), the reaction mixture was acidified with 2 M HCl. The resulting mixture was extracted with EtOAc (4 × 20 mL) and the combined organic layers were dried over MgSO4 and concentrated under vacuum. The crude product was purified by flash chromatography (petroleum ether–EtOAc) to give the pure product. Ethyl 3-{2-[(2-Bromoallyl)oxy]-6-oxocyclohex-1-en-1-yl}propanoate (5a): Rf = 0.54 (EtOAc–hexane, 50%); 1H NMR (400 MHz, CDCl3): δ = 5.95 (m, 1 H), 5.69 (m, 1 H), 4.63 (t, J = 1.44 Hz, 2 H), 4.10 (q, J = 7.12 Hz, 2 H), 2.65 (m, 2 H), 2.55 (t, J = 6.2 Hz, 2 H), 2.34–2.38 (m, 4 H), 1.99 (m, 2 H), 1.24 (t, J = 7.16 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 197.9, 173.4, 170.2, 126.5, 119.0, 117.9, 70.4, 60.1, 36.3, 33.0, 25.1, 20.9, 18.0, 14.2; IR (film): 2939, 1728, 1628, 1589, 1446, 1385, 1354, 1277, 1169, 1072, 1041, 856 cm–1; HRMS (ESI): m/z [M + Na]+ calcd for [C14H19BrO4+Na]+: 353.0359; found: 353.0342. Ethyl 3-[2-(Allyloxy)-6-oxocyclohex-1-en-1-yl]propanoate (5b): Rf = 0.59 (EtOAc–hexane, 50%); 1H NMR (400 MHz, CDCl3): δ = 5.88–5.98 (m, 1 H), 5.31–5.36 (m, 1 H), 5.24–5.28 (m, 1 H), 4.55 (m, 2 H), 4.08 (q, J = 7.12 Hz, 2 H), 2.59–2.64 (m, 2 H), 2.55 (t, J = 6.24 Hz, 2 H), 2.33 (m, 4 H), 1.95 (m, 2 H), 1.22 (t, J = 7.16 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 198.0, 173.6, 171.8, 132.8, 118.2, 117.5, 68.1, 60.1, 36.3, 33.1, 25.3, 20.9, 17.9, 14.2 cm–1; IR (film): 2931, 1724, 1597, 1438, 1385, 1265, 1184, 1076, 1030, 930, 860 cm–1; HRMS (ESI): m/z [M + H]+ calcd for [C19H21O4+Na]+: 313.1434; found: 313.1273.