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

James D. Kirkham; Andrew G. Leach; Eleanor C. Row; Joseph P. A. Harrity

doi:10.1055/s-0031-1291142

Synthesis, Inhaltsverzeichnis

Synthesis 2012; 44(13): 1964-1973
DOI: 10.1055/s-0031-1291142

feature article

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

James D. Kirkham

^aDepartment of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK, Fax: +44(114)2229346 eMail: j.harrity@sheffield.ac.uk

,

Andrew G. Leach

^bAstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK

,

Eleanor C. Row

^cDepartment of Isotope Chemistry and Metabolite Synthesis, sanofi-aventis, Willowburn Avenue, Alnwick, NE66 2JH, UK

,

Joseph P. A. Harrity*

^aDepartment of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK, Fax: +44(114)2229346 eMail: j.harrity@sheffield.ac.uk

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

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

Volltext

Referenzen

References
1 Hall DG. Boronic Acids . Wiley-VCH; Weinheim: 2005

2a Gilman H, Moore LO. J. Am. Chem. Soc. 1958; 80: 3609
2b Ishiyama T, Murata M, Miyaura N. J. Org. Chem. 1995; 60: 7508
2c Mkhalid IA. I, Barnard JH, Marder TB, Murphy JM, Hartwig JF. Chem. Rev. 2010; 110: 890
2d Del Grosso A, Singleton PJ, Muryn CA, Ingleson MJ. Angew. Chem. Int. Ed. 2011; 50: 2102

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
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
3f Yamamoto Y, Ishii J.-i, Nishiyama H, Itoh K. J. Am. Chem. Soc. 2005; 127: 9625
3g Auvinet A.-L, Harrity JP. A, Hilt G. J. Org. Chem. 2010; 75: 3893
3h Auvinet A.-L, Harrity JP. A. Angew. Chem. Int. Ed. 2011; 50: 2769
3i Iannazzo L, Vollhardt KP. C, Malacria M, Aubert C, Gandon V. Eur. J. Org. Chem. 2011; 3283

4a Delaney PM, Moore JE, Harrity JP. A. Chem. Commun. 2006; 3323
4b Delaney PM, Browne DL, Adams H, Plant A, Harrity JP. A. Tetrahedron 2008; 64: 866
4c Kirkham JD, Delaney PM, Ellames GJ, Row EC, Harrity JP. A. Chem. Commun. 2010; 46: 5154

5 Afarinkia K, Vinader V, Nelson TD, Posner GH. Tetrahedron 1992; 48: 9111
6 Afarinkia K, Bearpark MJ Ndibwami J. Org. Chem. 2005; 70: 1122

7a Kranjc K, Štefane B, Polanc S, Kočevar M. J. Org. Chem. 2004; 69: 3190
7b Kranjc K, Kočevar M. New J. Chem. 2005; 29: 1027

8a Gomez-Bengoa E, Helm MD, Plant A, Harrity JP. A. J. Am. Chem. Soc. 2007; 129: 2691
8b Browne DL, Vivat JF, Plant A, Gomez-Bengoa E, Harrity JP. A. J. Am. Chem. Soc. 2009; 131: 7762

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

12a Becke AD. J. Chem. Phys. 1993; 98: 5648
12b Lee C, Yang W, Parr RG. Phys. Rev. B: Condens. Matter 1988; 37: 785

13 Guner V, Khuong KS, Leach AG, Lee PS, Bartberger MD, Houk KN. J. Phys. Chem. A 2003; 107: 11445

14a Zhao Y, Truhlar DG. Theor. Chem. Acc. 2008; 120: 215
14b Zhao Y, Truhlar DG. Acc. Chem. Res. 2008; 41: 157
14c Xu X, Alecu IM, Truhlar DG. J. Chem. Theory Comput. 2011; 7: 1667

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
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

20a Cho CG, Kim YW, Lim YW, Park JS, Lee H, Koo S. J. Org. Chem. 2002; 67: 290
20b Kvita V, Sauter H. Helv. Chim. Acta 1990; 73: 883
20c Ashworth IW, Bowden MC, Dembofsky B, Levin D, Moss W, Robinson E, Szczur N, Virica J. Org. Process Res. Dev. 2003; 7: 74

21 Brown HC, Bhat NG, Srebnik M. Tetrahedron Lett. 1988; 29: 2631
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

Zusatzmaterial

Supporting Information