Download PDF
Synthesis 2012; 44(13): 1964-1973
DOI: 10.1055/s-0031-1291142
feature article
© Georg Thieme Verlag Stuttgart · New York

Investigation of the Origins of Regiochemical Control in [4+2] Cycloadditions of 2-Pyrones and Alkynylboronates

James D. Kirkham
a   Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK, Fax: +44(114)2229346   Email: j.harrity@sheffield.ac.uk
,
Andrew G. Leach
b   AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
,
Eleanor C. Row
c   Department of Isotope Chemistry and Metabolite Synthesis, sanofi-aventis, Willowburn Avenue, Alnwick, NE66 2JH, UK
,
Joseph P. A. Harrity*
a   Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK, Fax: +44(114)2229346   Email: j.harrity@sheffield.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 23 March 2012

Accepted after revision: 10 April 2012

Publication Date:
31 May 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

The [4+2] cycloaddition of 2-pyrones with substituted alkynylboronates has been studied. In general, the highest yielding cycloadditions were obtained in reactions that employed a trimethylsilyl-substituted alkynylboronate. The highest regioselectivities were obtained using the corresponding phenyl-substituted alkyne, which provided a single regioisomer irrespective of the 2-pyrone used. Mechanistic studies suggest that the high regioselectivity observed is due to stabilization of a zwitterionic transition state.

Key words

cycloaddition - Diels–Alder reaction - alkynes - boron - regioselectivity

Supporting Information

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

  • References

  • 1 Hall DG. Boronic Acids . Wiley-VCH; Weinheim: 2005
    CrossrefSearch in Google Scholar
    • 3a Davies MW, Johnson CN, Harrity JP. A. Chem. Commun. 1999; 2107
    • 3b Ester C, Maderna A, Pritzkow H, Siebert W. Eur. J. Inorg. Chem. 2000; 1177
    • 3c Davies MW, Johnson CN, Harrity JP. A. J. Org. Chem. 2001; 66: 3525
      CrossrefSearch in Google Scholar
    • 3d Moore JE, York M, Harrity JP. A. Synlett 2005; 860
    • 3e Gandon V, Leboeuf D, Amslinger S, Vollhardt KP. C, Malacria M, Aubert C. Angew. Chem. Int. Ed. 2005; 44: 7114
      CrossrefSearch in Google Scholar
    • 3f Yamamoto Y, Ishii J.-i, Nishiyama H, Itoh K. J. Am. Chem. Soc. 2005; 127: 9625
      CrossrefPubMedSearch in Google Scholar
    • 3g Auvinet A.-L, Harrity JP. A, Hilt G. J. Org. Chem. 2010; 75: 3893
      CrossrefSearch in Google Scholar
    • 3h Auvinet A.-L, Harrity JP. A. Angew. Chem. Int. Ed. 2011; 50: 2769
      Search in Google Scholar
    • 3i Iannazzo L, Vollhardt KP. C, Malacria M, Aubert C, Gandon V. Eur. J. Org. Chem. 2011; 3283
  • 5 Afarinkia K, Vinader V, Nelson TD, Posner GH. Tetrahedron 1992; 48: 9111
    CrossrefSearch in Google Scholar
  • 6 Afarinkia K, Bearpark MJ Ndibwami J. Org. Chem. 2005; 70: 1122
    CrossrefSearch in Google Scholar
  • 9 The regiochemistry of compound 3a was elucidated by NOE NMR spectroscopy, and that of compound 3b/4b was carried out by chemical derivatization to the corresponding p- and m-chlorophenols
  • 10 The regiochemistry of 5a was assigned by inference in comparison to the analogous cycloaddition reaction of 3,5-dibromopyran-2-one.4a The regiochemistry of compound 5c was elucidated by NOE NMR spectroscopy, but that of compounds 5b/6b, 5d/6d, and 5e/6e was not established due to the low levels of selectivity observed in these cases
  • 11 The regiochemistry of compounds 7a, 7c/8c, 7d, and 7e/8e was elucidated by NOE NMR spectroscopy
  • 13 Guner V, Khuong KS, Leach AG, Lee PS, Bartberger MD, Houk KN. J. Phys. Chem. A 2003; 107: 11445
    CrossrefSearch in Google Scholar
  • 15 R2 values computed including the out of range values corresponding to >49:1 are 0.68 for B3LYP, 0.58 for RHF and 0.35 for M06-2X and RMSEs are 0.82, 0.93 and 1.16 respectively. When the out-of-range values are excluded, the R2 values are 0.59 (B3LYP), 0.49 (RHF), and 0.08 (M06) with RMSEs of 0.59, 0.65, and 0.88, respectively
  • 16 Štefane B, Perdih A, Pevec A, Šolmajer T, Kočevar M. Eur. J. Org. Chem. 2010; 5870
  • 17 Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
    Search in Google Scholar
  • 18 The cycloaddition of hex-1-yne derived alkyne 2c and methyl coumalate (1g) provides a 3:1 regioselectivity for the same major boronate isomer; see ref. 4b
  • 19 The regiochemistry of compounds 9/10 was elucidated by NOE NMR spectroscopy
  • 21 Brown HC, Bhat NG, Srebnik M. Tetrahedron Lett. 1988; 29: 2631
    CrossrefSearch in Google Scholar
  • 22 The carbon attached to boron is not visible in the 13C NMR spectrum because of the quadrupole effect at boron: Brown C, Cragg RH, Miller T, Smith DON, Steltner A. J. Organomet. Chem. 1978; 149: C34
    Search in Google Scholar