Download PDF
Synlett 2007(15): 2367-2370  
DOI: 10.1055/s-2007-986626
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Intramolecular Büchner Reaction of α-Diazoketones

Sarah O’Keeffe, Francis Harrington, Anita R. Maguire*
Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland
Fax: +353(21)4274097; e-Mail: a.maguire@ucc.ie;
Further Information

Publication History

Received 30 January 2007
Publication Date:
23 August 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

Enantioselectivities of up to 95% ee have been achieved in the intramolecular Büchner reaction catalysed by copper bis(oxazoline) complexes, the highest asymmetric inductions reported to date for this transformation. Significantly, use of a catalyst derived from a bis(oxazoline) ligand resulted in high enantioselectivities across several substrates, indicating the possibility of developing a catalyst with general applicability.

Key words

intramolecular Büchner reaction - α-diazoketones - carbenes - copper bis(oxazoline) catalysts - asymmetric synthesis

    References and Notes

  • 1 Kennedy M. McKervey MA. Maguire AR. Roos GHP. J. Chem. Soc., Chem. Commun.  1990,  361 
    CrossrefGoogle Scholar
  • 2 Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley; New York: 1998. 
    Google Scholar
  • 3 McCarthy N. McKervey MA. Ye T. Tetrahedron Lett.  1992,  33:  5983 
    CrossrefGoogle Scholar
  • 4 Doyle MP. Ene D. Forbes GDC. Pillow TH. Chem. Commun.  1999,  1691 
    CrossrefGoogle Scholar
  • 6 Hannemann K. Angew. Chem. Int. Ed.  1998,  27:  284 
    Google Scholar
  • 8 Maguire AR. Buckley NR. O’Leary P. Ferguson G. Chem. Commun.  1998,  2696 
    Google Scholar
  • 9 Maguire AR. Buckley NR. O’Leary P. Ferguson G. J. Chem. Soc., Perkin Trans. 1  1996,  4077 
    Google Scholar
5

It is generally accepted that copper(I) rather than copper(II) is the active form of copper in diazo decomposition reactions and although the initial copper species in CuSbF6-based catalyst has an oxidation state of +2, this is reduced during the reaction. See ref. 2.

7

General Experimental Procedure
3,8a-Dihydro-3,3,8a-trimethylazulen-1-(2 H )-one (7)
Diazoketone 6 (100 mg, 0.46 mmol) in CH2Cl2 (75 mL) was added dropwise over 1 h to a refluxing solution of [Cu(MeCN)4]PF6 (8.6 mg, 0.023 mmol) and ligand 2 (2.2 mg, 0.030 mmol) in CH2Cl2 (75 mL). The progress of the reaction was monitored by TLC and was found to be complete upon diazoketone addition. Evaporation of the solvent at reduced pressure gave the crude product as a yellow oil. A 1H NMR spectrum was recorded to determine the efficiency of the cyclisation (99%; percent of azulenone 7 relative to aromatic byproducts). Purification by flash chromatography, using EtOAc-hexane (5%) as eluant, gave the azulenone 7 (84 mg, 97%) as a colourless oil.
IR (film): νmax = 1748 s (CO), 1716 s (CO) cm-1. 1H NMR (300 MHz, CDCl3): δ = 6.21-6.44 [2 H, m, C(4)H, C(5)H, C(6)H], 6.10 [1 H, overlapping dd appears as t, J = 7.6, 7.6 Hz, C(7)H], 4.15 [1 H, d, J = 7.9 Hz, C(8)H], 2.28 [1 H, B of ABq, J AB = 17.3 Hz, one of C(2)H2], 2.20 [1 H, A of ABq, J AB = 17.3 Hz, one of C(2)H2], 1.31, 1.14 [2 × 3 H, 2 × s, C(3)(CH3)2], 0.75 [3 H, s, C(8a)CH3]. 13C NMR (60 MHz, CDCl3): δ = 218.4 [C(1)], 127.2, 126.9, 125.3, 119.7 [C(4)H, C(5)H, C(6)H, C(7)H], 101.6 [C(3a)], 89.1 br [C(8)H], 50.2 [C(2)H2], 41.3 [C(3)], 38.6 [C(8a)], 28.8, 28.7 [C(CH3) 2 ], 11.6 [C(8a)CH3]. HRMS (EI): m/z calcd for C13H16O: 188.1201; found: 188.1187; 76% ee [by 1H NMR analysis using (+)-Eu(hfc)3]; [α]D 20 -35.2 (c 1.0, CHCl3).