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DOI: 10.1055/s-2004-829095
An Efficient Synthesis of α-Branched Enones
Publication History
Publication Date:
22 June 2004 (online)
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Abstract
A new method for preparing α-branched enones from carboxylic acid derivatives is reported. The procedure commenced by the reaction of N,O-dimethylamides with a masked acyl anion equivalent, followed by the addition of (trimethylsilyl-methyl)cerium dichloride to give intermediates that undergo Lewis acid mediated olefination to produce enol ethers that are then hydrolyzed to afford simple α-branched enones in high overall yields.
Key words
enones - Peterson olefination - titanium - acyl anion equivalents - homologation
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References
All new compounds were purified (>95%) by flash chromatography or distillation and were characterized by 1H NMR and 13C NMR, IR, and HRMS.
12Characterization data for new enones 4b, 4f, and 4h. Enone 4b: 1H NMR (400 MHz, CDCl3): δ = 7.34-6.86 (comp, 4 H), 6.04 (d, J = 1.2 Hz, 1 H), 5.65 (d, J = 1.2 Hz, 1 H), 3.76 (s, 3 H), 2.26 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 200.3, 156.8, 148.4, 130.5, 130.1, 128.0, 124. 0, 121.2, 111.0, 55.7, 27.4. MS (CI): m/z = 177 [M + H+]. IR (neat): 2939, 1698, 1600, 1491, 1243, 1170, 1026 cm-1. Enone 4f: 1H NMR (400 MHz, CDCl3): δ = 5.65 (s, 1 H), 5.23 (s, 1 H), 2.23 (s, 3 H), 2.00-1.96 (comp, 3 H), 1.80 (d, J = 2.9 Hz, 6 H), 1.73-1.64 (comp, 6 H). 13C NMR (100 MHz, CDCl3): δ = 203.4, 159.1, 120.1, 40.9, 37.7, 37.0, 30.3, 28.8. MS (CI): m/z = 205 [M + H+]. IR (neat): 2906, 1676, 1265, 1135 cm-1. Enone 4h: 1H NMR (400 MHz, CDCl3): δ = 7.37-7.25 (comp, 5 H), 6.00 (s, 1 H), 5.77-5.76 (m, 1 H), 4.50 (s, 2 H), 3.48 (t, J = 6.5 Hz, 2 H), 2.33 (s, 3 H), 2.30-2.25 (comp, 2 H), 1.67-1.58 (comp, 2 H), 1.55-1.45 (comp, 2 H). 13C NMR (100 MHz, CDCl3): δ = 200.1, 149.2, 138.8, 128.6, 127.9, 127.7, 125.3, 73.1, 70.4, 30.5, 29.7, 26.2, 25.2. MS (CI): m/z = 233 [M + H+]. IR (neat): 2937, 2860, 1678, 1454, 1365, 1104 cm-1.
14The 4g produced from enantiomerically pure (>99% ee) proline had an enantiomeric ratio of >97:3; Chiralcel OD column, flowrate = 1.0 mL/min, gradient elution (1 to 3% i-PrOH/hexanes over 60 min).
15Enone 4d was most conveniently purified by distillation at 90-93 °C (10 mm Hg).