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Copper (I) Catalysed Conjugate Addition of Grignard Reagents to Enones; Silyl Enol Ethers

SyntheticPage 35 (2001)
Submitted 18th Jul 2001, published 18th Jul 2001

K.Booker-Milburn (k.booker-milburn@bristol.ac.uk),
A contribution from the Booker-Milburn, Bristol


Reaction Scheme

Chemicals Used
2-cyclohexenone; trimethylsilyl chloride; CuI; Mg metal; 4-bromobutene; HMPA; THF

Procedure
Magnesium metal (0.61g, 25.0mmol) was activated by heating (heat gun) for 5 min with a crystal of I2 in dry THF (40cm3) under an Ar atmosphere. To this rapidly stirred suspension was added 4-bromobut-1-ene (2.54cm3, 25.0 mmol) dropwise via syringe. After the initial exotherm had subsided the reaction mixture was stirred for a further 1 h after which HMPA (9cm3) was added and the mixture cooled to -78°C. Anhydrous copper (I) iodide (0.39g, 2.05mmol) was added in one portion and the resulting slurry stirred for a further 10min. To this was added a mixture of 2-cyclohexenone (2.0g, 20.8mmol) and TMSCl (6.2cm3, 48.85 mmol) in 20cm3 dry THF dropwise over 10min. The resulting white suspension was stirred for 1h at -78°C, before the addition of Et3N (5cm3) and allowing to warm to RT. The resulting suspension was poured onto pet. ether (250cm3), washed with water (3 x 200cm3), dried over MgSO4 and the solvent evaporated to give a clear yellow oil. Kugelrohr distillation (130-140° @ 20mmHg) gave the pure product as a clear liquid (4.1g,88%).

Author's Comments
This is a fairly general prep adapted from the literature. Works well for enones as well as unsaturated esters (ketene acetals as products). DMPU can be used as a safer alternative to HMPA but at the expense of a slight drop in yield (10-20%). The enol ether products are labile compounds but as long as petroleum ether is used as the extraction solvent no significant hydrolysis is observed.

Data
1H NMR (300MHz; C6D6) 0.17 (9H,m, SiMe3), 0.79-1.8 (2H,m), 1.9-1.65 (4H,m), 1.96-2.19 (5H,m), 4.88 (1H,bs, 2-H), 4.93-5.05(2H,m, 4'-H), 5.66-5.73 (1H, m, 3'-H); 13C (75.47MHz) 0.44 (SiMe3), 22.04 (CH2), 29.06 (CH2), 30.48 (CH2), 31.67 (CH2), 34.42 (CH), 36.72 (CH2), 108.68 (C-2), 114.47 (C-4'), 139.19 (C-3'), 151.02 (C-1)


Lead Reference
K. I.Booker-Milburn and D. F. Thompson, J. Chem. Soc., Perkin Trans. 1, 1995, 2315.

Other References
S.W. Matsuzawa, Y. Horiguchi, E. Nakamura and I. Kuwajima,Tetrahedron, 1989, 45, 349; K. I. Booker-Milburn and D. F. Thompson, Tetrahedron, 1995, 51, 12955; K.I. Booker-Milburn, A. Barker, W. Brailsford, B. Cox and T.E. Mansley, Tetrahedron , 1998, 54, 15321

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User comments on this page

Stephen Caddick
Thu, 23rd Aug 2001 08:38:56
For another example of conjugate addition using copper chemistry see [SyntheticPage 82]

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