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Synlett 2010(19): 2839-2842  
DOI: 10.1055/s-0030-1259024
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Highly Substituted Symmetrical 1,3-Dienes via Tandem Carbocupration and Organocuprate Oxidation

Sarah J. Avesa, Kurt G. Pikeb, David R. Spring*a
a Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
Fax: +44(1223)336362; e-Mail: spring@ch.cam.ac.uk;
b AstraZeneca R&D, Alderley Park, Macclesfield, Cheshire, SK10 4TF, UK
Further Information

Publication History

Received 2 September 2010
Publication Date:
03 November 2010 (online)

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Abstract

A ‘one-pot’ tandem carbocupration/organocuprate oxidation allows the formation of highly substituted symmetrical 1,3-dienes from alkynyl esters and alkyl organolithium or Grignard reagents with three C-C bonds being formed in one step.

Key words

cuprates - oxidation - carbocupration - 1,3-diene - tandem reaction

    References and Notes

  • 1a Tarnchompoo B. Thebtaranonth C. Thebtaranonth Y. Tetrahedron Lett.  1987,  28:  6671 
    Search in Google Scholar
  • 1b Tarnchompoo B. Thebtaranonth C. Thebtaranonth Y. Tetrahedron Lett.  1987,  28:  6675 
    Search in Google Scholar
  • 1c Kotera M. Lehn J.-M. Vigneron J.-P. Tetrahedron  1995,  51:  1953 
    Search in Google Scholar
  • For recent examples of the synthesis of 2,3-bis(alkylidene)succinate compounds, see:
  • 2a Kiji J. Okano T. Fujii E. Tsuji J. Synthesis  1997,  869 
  • 2b Béji F. Lebreton J. Villiéras J. Amri H. Tetrahedron  2001,  57:  9959 
    Search in Google Scholar
  • 2c Béji F. Lebreton J. Villiéras J. Amri H. Synth. Commun.  2002,  32:  3273 
    Search in Google Scholar
  • 2d Patel RM. Argade NP. J. Org. Chem.  2007,  72:  4900 
    Search in Google Scholar
  • 3a Surry DS. Su X. Fox DJ. Franckevicius V. Macdonald SJF. Spring DR. Angew. Chem. Int. Ed.  2005,  44:  1870 
    Search in Google Scholar
  • 3b Surry DS. Fox DJ. Macdonald SJF. Spring DR. Chem. Commun.  2005,  2589 
  • 3c Su X. Fox DJ. Blackwell DT. Tanaka K. Spring DR. Chem. Commun.  2006,  3883 
  • 3d Su X. Surry DS. Spandl RJ. Spring DR. Org. Lett.  2008,  10:  2593 
    Search in Google Scholar
  • 3e Su X. Thomas GL. Galloway WRJD. Surry DS. Spandl RJ. Spring DR. Synthesis  2009,  3880 
  • For reviews, see:
  • 4a Surry DS. Spring DR. Chem. Soc. Rev.  2006,  35:  218 
    Search in Google Scholar
  • 4b Aves SJ. Spring DR. In The Chemistry of Organocopper Compounds   Rappoport Z. Marek I. Wiley; Chichester: 2009.  p.585 
  • 5 Corey EJ. Katzenellenbogen JA. J. Am. Chem. Soc.  1969,  91:  1851 
    CrossrefSearch in Google Scholar
  • 6 Marino JP. Linderman RJ. J. Org. Chem.  1983,  48:  4621 
    CrossrefSearch in Google Scholar
  • 7 Ito Y. Konoike T. Harada T. Saegusa T. J. Am. Chem. Soc.  1977,  99:  1487 
    CrossrefSearch in Google Scholar
  • For examples of carbonyl enolate couplings, see:
  • 8a Baran PS. Guerrero CA. Ambhaikar NB. Hafensteiner BD. Angew. Chem. Int. Ed.  2005,  44:  606 
    Search in Google Scholar
  • 8b Baran PS. DeMartino MP. Angew. Chem. Int. Ed.  2006,  45:  7083 
    Search in Google Scholar
  • 9a Siddall JB. Biskup M. Fried JH. J. Am. Chem. Soc.  1969,  91:  1853 
    Search in Google Scholar
  • 9b Klein J. Turkel RM. J. Am. Chem. Soc.  1969,  91:  6186 
    Search in Google Scholar
  • 10 Nilsson K. Andersson T. Ullenius C. Gerold A. Krause N. Chem. Eur. J.  1998,  4:  2051 
    CrossrefSearch in Google Scholar
  • 11a Normant JF. Cahiez G. Chuit C. Villieras J.
    J. Organomet. Chem.  1974,  77:  269 
    Search in Google Scholar
  • 11b For a different oxidation pathway following carbocupration, see: Zhang DH. Ready JM. Org. Lett.  2005,  7:  5681 
    Search in Google Scholar
  • 13 Taylor RJK. In Organocopper Reagents: A Practical Approach   Taylor RJK. Oxford University Press; Oxford: 1994.  p.13 
  • 14 Lipshutz BH. In Organometallics in Synthesis: A Manual   Schlosser M. Wiley; Chichester: 2002.  2nd ed.. p.665 
  • 15 van Koten G. James SL. Jastrzebski JTBH. In Comprehensive Organometallic Chemistry II   Vol. 3:  Abel EW. Stone FGA. Wilkinson G. Wardell JL. Pergamon; Oxford: 1995.  p.57 
    Search in Google Scholar
  • For recent reviews on DOS, see:
  • 17a Schreiber SL. Nature (London)  2009,  457:  153 
    Search in Google Scholar
  • 17b Galloway WRJD. Spring DR. Expert Opin. Drug Discovery  2009,  4:  467 
    Search in Google Scholar
  • 17c Nielsen E. Schreiber SL. Angew. Chem. Int. Ed.  2008,  47:  48 
    Search in Google Scholar
  • 17d Spandl R. Bender A. Spring DR. Org. Biomol. Chem.  2008,  6:  1149 
    Search in Google Scholar
  • 17e Spandl R. Diaz-Gavilan M. O’Connell KMG. Thomas GL. Spring DR. Chem. Rec.  2008,  8:  129 
    Search in Google Scholar
  • 18 Maercker A. van de Flierdt J. Girreser U. Tetrahedron  2000,  56:  3373 
    CrossrefSearch in Google Scholar
12

Oxidant-derived by-products can easily be removed by an acidic wash during workup or by filtration through a pad of silica gel.

16

General Procedure for Tandem Carbocupration/Oxidation Reaction: A solution of the requisite organometallic reagent (2.10 mmol) was added to a suspension of CuBr˙SMe2 (216 mg, 1.05 mmol) in THF
(4 mL) at -78 ˚C and stirred for 30 min. Alkyne (2.00 mmol) was added dropwise and the reaction was stirred for 3 h at
-78 ˚C. A solution of oxidant 5 (589 mg, 2.00 mmol) in THF (4 mL) was added, the reaction was allowed to stir at -78 ˚C for 30 min and then allowed to warm to r.t. over 1 h. The resulting solution was filtered through a plug of silica, eluting with either PE-Et2O (1:1) or i-hexane-Et2O (1:1) and the solvent was removed in vacuo. The residue was purified by flash column chromatography.
(2 E ,3 E )-Diethyl 2,3-dipentylidenesuccinate (8a): colourless oil; R f 0.25 (PE-EtOAc, 10:1). IR (Neat): 2957, 2932, 2871, 1712 (C=O), 1631 (C=C), 1464, 1363, 1231, 1206 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.01 (t, 2 H, J = 7.6 Hz), 4.16 (q, 4 H, J = 7.1 Hz), 2.02 (app q, 4 H, J = 7.2 Hz), 1.36-1.46 (m, 4 H), 1.26-1.36 (m, 4 H), 1.24 (t, 6 H, J = 7.1 Hz), 0.90 (t, 6 H, J = 7.2 Hz). ¹³C NMR (125 MHz, CDCl3): δ = 166.5 (C), 146.3 (CH), 127.6 (C), 60.5 (CH2), 30.3 (CH2), 29.3 (CH2), 22.4 (CH2), 14.2 (Me), 13.8 (Me). HRMS (ESI): m/z [M + H]+ calcd for C18H31O4: 311.2217; found: 311.2217.
(2 Z ,3 Z )-Dimethyl 2,3-bis(1-phenylpentylidene)succinate (8b): colourless crystals; mp 60-64 ˚C (i-hexane-EtOAc); R f 0.13 (PE-EtOAc, 10:1). IR (CDCl3): 2957, 2871, 1717 (C=O), 1429, 1305, 1219, 1166, 1022 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.28-7.39 (m, 6 H), 7.18-7.23 (m, 4 H), 3.45 (s, 6 H), 2.53 (m, 4 H), 1.18-1.32 (m, 8 H), 0.83 (t, 6 H, J = 6.7 Hz). ¹³C NMR (125 MHz, CDCl3): δ = 168.0 (C), 154.0 (C), 141.2 (C), 128.0 (CH), 127.3 (CH), 127.1 (CH), 126.5 (C), 51.5 (Me), 36.1 (CH2), 29.1 (CH2), 22.9 (CH2), 13.9 (Me). HRMS (ESI): m/z [M + Na]+ calcd for C28H34O4Na: 457.2349; found: 457.2368.
(2 E ,3 E )-Diethyl 2,3-di(hexan-2-ylidene)succinate (8c): colourless oil; R f 0.37 (PE-EtOAc, 10:1). IR (CDCl3): 2957, 2927, 2867, 1709 (C=O), 1613 (C=C), 1459, 1206, 1092, 1039 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 4.11 (q, 4 H, J = 7.1 Hz), 2.13 (s, 6 H), 2.04 (br s, 4 H), 1.32-1.40 (m, 4 H), 1.22-1.29 (m, 4 H), 1.21 (t, 6 H, J = 7.1 Hz), 0.86 (t, 6 H, J = 7.3 Hz). ¹³C NMR (125 MHz, CDCl3): δ = 167.6 (C), 152.7 (C), 125.2 (C), 59.8 (CH2), 37.0 (CH2), 29.1 (CH2), 22.8 (CH2), 19.7 (Me), 14.2 (Me), 13.9 (Me). HRMS (ESI): m/z [M + Na]+ calcd for C20H34O4Na: 361.2349; found: 361.2348.
(2 E ,3 E )-Diethyl 2,3-bis(2-methylpropylidene)succinate (8d): yellow oil; R f 0.28 (PE-EtOAc, 10:1). IR (CDCl3): 2963, 2872, 1712 (C=O), 1231, 1038, 731 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.77 (d, 2 H, J = 10.7 Hz), 4.15 (q, 4 H, J = 7.1 Hz), 2.35 (m, 2 H), 1.22 (t, 6 H, J = 7.1 Hz), 0.96 (m, 12 H). ¹³C NMR (125 MHz, CDCl3): δ = 166.6 (C), 151.9 (CH), 125.2 (C), 60.6 (CH2), 29.0 (CH), 21.4 (Me), 14.2 (Me). HRMS (ESI): m/z [M + Na]+ calcd for C16H26O4Na: 305.1723; found: 305.1708.
(2 Z ,3 Z )-Dimethyl 2,3-bis(1-phenylethylidene)succinate (8e): white amorphous solid; R f 0.04 (PE-EtOAc, 10:1). IR (CDCl3): 2950, 1712 (C=O), 1433, 1221, 1199, 1043, 907, 720, 699 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.15-7.29 (m, 10 H), 3.37 (s, 6 H), 2.10 (s, 6 H). ¹³C NMR (125 MHz, CDCl3): δ = 167.6 (C), 149.8 (C), 142.5 (C), 128.0 (CH), 127.5 (CH), 127.1 (C), 126.5 (CH), 51.4 (Me), 23.0 (Me). HRMS (ESI): m/z [M + H]+ calcd for C22H23O4: 351.1596; found: 351.1601.
Diethyl 2,3-di(propan-2-ylidene)succinate (8f): colourless oil; R f 0.31 (PE-EtOAc, 10:1). IR (CDCl3): 2982, 2911, 1709 (C=O), 1625 (C=C), 1444, 1220, 1076 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 4.12 (q, 4 H, J = 7.1 Hz), 2.16 (s,
6 H), 1.72 (s, 6 H), 1.22 (t, 6 H, J = 7.1 Hz). ¹³C NMR (125 MHz, CDCl3): δ = 167.4 (C), 149.1 (C), 125.7 (C), 59.9 (CH2), 23.7 (Me), 22.1 (Me), 14.2 (Me). LCMS (ES+): m/z = 255 [M + H]+. Spectroscopic data were consistent with the literature values.¹8