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DOI: 10.1055/s-2007-986626
Enantioselective Intramolecular Büchner Reaction of α-Diazoketones
Publication History
Publication Date:
23 August 2007 (online)
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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
- 1
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References and Notes
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).