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Synlett 2009(1): 51-54  
DOI: 10.1055/s-0028-1087481
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Rapid 1,4-Alkynylation of Acyclic Enones Using K[F3BCCR]

Ferruccio Bertolini, Simon Woodward*
School of Chemistry, The University of Nottingham, Nottingham NG7 2RD, UK
e-Mail: simon.woodward@nottingham.ac.uk;
Further Information

Publication History

Received 12 September 2008
Publication Date:
12 December 2008 (online)

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Abstract

Conjugate alkynylation of acyclic enones using sp-hybridised potassium organotrifluoroborates in the presence of BF3˙OEt2 is rapidly attained. The simplicity of the processes is suitable for the preparation of small compound libraries.

Key words

conjugated alkynylation - enones - potassium organotrifluoroborates

    References and Notes

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3

Based on a survey of the SciFinder Scholar (ACS), CAPLUS and MEDLINE databases, September 2008.

15

α,β-Unsaturated esters were unreactive under the present conditions.

16

Typical Procedure for the Conjugated Alkynylation of Acyclic Enones (Entry 4, Table 2)
Under an argon atmosphere, BF3˙OEt2 (0.45 mmol, 63.9 mg), was added at r.t. to a stirred suspension of potassium organotrifluoroborate 1b (0.6 mmol, 124.8 mg) in CH2Cl2 (3.0 mL). To the resulting mixture was added a solution of enone 2b (0.3 mmol, 62.6 mg), and the reaction was allowed to react for 25 min at r.t. The reaction was then quenched with brine (2.0 mL) and then diluted with CH2Cl2 (6 mL). Evaporation of the dried (MgSO4) organic solution afforded a crude reaction mixture which was purified by silica gel column chromatography eluting with light petroleum-Et2O (9:1) to give pure 1,3,5-triphenylpent-4-yn-1-one (4bb; 87%) as a white solid, mp 89-90 ˚C. IR (CHCl3): ν = 3009, 1687, 1601, 1491, 1449, 1351, 1239 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 3.47 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.0 Hz), 3.71 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 8.0 Hz), 4.66-4.73 (m, 1 H), 7.28-7.32 (m, 4 H), 7.38-7.43 (m, 4 H), 7.48-7.52 (m, 2 H), 7.57-7.61 (m, 3 H), 7.98-8.04 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 33.8, 47.3, 83.4, 90.8, 123.4, 127.1, 127.6, 127.9, 128.2, 128.7, 128.8, 131.7, 133.3, 136.9, 141.3, 197.15. ESI-MS (+): m/z = 333.12 [M + Na]+.
5-Methyl-7-phenylhept-6-yn-3-one (4ab, Entry 1, Table 2)
Yield 70%. Yellow liquid. IR (CHCl3): ν = 3011, 2979, 2937, 1713, 1599, 1489, 1459, 1410, 1359, 1239, 1116 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.12 (t, 3 H, J = 7.2 Hz), 1.30 (d, 3 H, J = 7.2 Hz), 2.48-2.55 (m, 2 H), 2.58 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 7.2 Hz), 2.76 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.8 Hz), 3.19-3.26 (m, 1 H), 7.27-7.32 (m, 3 H), 7.37-7.41 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 7.7, 21.0, 22.4, 36.7, 49.1, 80.9, 93.2, 123.6, 127.4, 128.2, 131.6, 209.4. ESI-MS (+): m/z = 223.11 [M + Na]+.
5,8-Dimethylnon-8-en-6-yn-3-one (4ac, Entry 2, Table 2)
Yield 57%; pale yellow liquid. ¹H NMR (400 MHz, CDCl3): δ = 1.09 (t, 3 H, J = 7.2 Hz), 1.22 (d, 3 H, J = 6.8 Hz), 1.89 (s, 3 H), 2.41-2.53 (m, 3 H), 2.69 (dd, 1 H, J 1 = 16.0 Hz, J 2 = 7.2 Hz), 3.08-3.14 (m, 1 H), 5.15-5.20 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 7.7, 20.9, 22.3, 23.8, 36.6, 49.1, 82.1, 92.2, 120.8, 127.0, 209.4.
1,3-Diphenyldec-4-yn-1-one (4ba, Entry 3, Table 2)
Yield 75%; colorless oil. IR (CHCl3): ν = 3008, 2933, 2861, 1686, 1600, 1494, 1449, 1351, 1255, 1181, 1024, 977 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.89 (t, 3 H, J = 6.0 Hz), 1.22-1.39 (m, 4 H), 1.41-1.50 (m, 2 H), 2.19 (dt, 2 H, J 1 = 7.2 Hz, J 2 = 2.4 Hz), 3.30 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 7.2 Hz), 3.57 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 8.0 Hz), 4.40-4.46 (m, 1 H), 7.23-7.30 (m, 1 H), 7.32-7.38 (m, 2 H), 7.43-7.51 (m, 4 H), 7.54-7.61 (m, 1 H), 7.95-8.00 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.0, 18.8, 22.2, 28.6, 31.1, 33.4, 47.7, 81.0, 83.7, 126.9, 127.5, 128.2, 128.3, 128.6, 133.1, 137.0, 142.0, 197.6. ESI-MS (+): m/z = 327.17 [M + Na]+.
6-Methyl-1,3-diphenylhept-6-en-4-yn-1-one (4bc, Entry 5, Table 2)
Yield 77%; solid; mp 44-46 ˚C. IR (CHCl3): ν = 3009, 1687, 1600, 1494, 1450, 1351, 1255, 1023, 976, 900 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.86 (m, 3 H), 3.38 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.4 Hz), 3.61 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 7.6 Hz), 4.57 (dd, 1 H, J 1 = 7.6 Hz, J 2 = 6.4 Hz), 5.17-5.23 (m, 2 H), 7.24-7.30 (m, 1 H), 7.33-7.39 (m, 2 H), 7.44-7.51 (m, 4 H), 7.57-7.62 (m, 1 H), 7.94-8.01 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 23.6, 33.6, 47.3, 84.6, 89.7, 121.2, 126.9, 127.1, 127.6, 128.2, 128.6, 128.7, 133.2, 136.9, 141.3, 197.2. ESI-MS (+): m/z = 297.12 [M + Na]+.
4,6-Diphenylhex-5-yn-2-one (4cb, Entry 6, Table 2)
Yield 65%; pale yellow liquid. IR (CHCl3): ν = 3011, 1717, 1601, 1491, 1453, 1405, 1360, 1240, 1160, 1070, 1027 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 2.21 (s, 3 H), 2.93 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.0 Hz), 3.11 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 8.0 Hz), 4.44-4.48 (m, 1 H), 7.22-7.50 (m, 10 H). ¹³C NMR (100 MHz, CDCl3): δ = 30.7, 33.6, 51.9, 83.3, 90.4, 123.3, 127.2, 127.5, 128.0, 128.3, 128.8, 131.7, 141.0, 205.8. ESI-MS (+): m/z = 271.10 [M + Na]+.
7-Methyl-4-phenyloct-7-en-5-yn-2-one (4cc, Entry 7, Table 2)
Yield 54%; pale yellow liquid. IR (CHCl3): ν = 3011, 1715, 1602, 1494, 1453, 1359, 1240, 1160, 900 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.91 (s, 3 H), 2.18 (s, 3 H), 2.85 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.4 Hz), 3.01 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 8.0 Hz), 4.33 (dd, 1 H, J 1 = 8.0 Hz, J 2 = 6.4 Hz), 5.21-5.28 (m, 2 H), 7.25-7.43 (m, 5 H). ¹³C NMR (100 MHz, CDCl3): δ = 23.7, 30.7, 33.5, 52.0, 84.5, 89.3, 121.3, 126.8, 127.1, 127.4, 128.7, 141.0, 205.8. ESI-MS (+): m/z = 235.11 [M + Na]+.
4-(Phenylethynyl)heptan-2-one (4db, Entry 8, Table 2)
Yield 55%; light yellow liquid.IR (CHCl3): ν = 3010, 2961, 2933, 2874, 1713, 1600, 1490, 1442, 1362, 1239, 1163, 909 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.98 (t, 3 H, J = 6.0 Hz), 1.45-1.62 (m, 4 H), 2.25 (s, 3 H), 2.62 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.4 Hz), 2.78 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 7.6 Hz), 3.09-3.15 (m, 1 H), 7.28-7.31 (m, 3 H), 7.39-7.42 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.9, 20.5, 27.6, 30.6, 37.0, 49.0, 81.9, 92.0, 123.6, 127.7, 128.2, 131.6, 207.0. ESI-MS (+): m/z = 237.12 [M + Na]+.
4-Pentylundec-5-yn-2-one (4ea, Entry 9, Table 2)
Yield 40% (conversion 75%); colorless liquid. IR (CHCl3): ν = 3007, 2958, 2932, 2860, 1713, 1602, 1466, 1361, 1239, 1163 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.82-0.93 (m, 6 H), 1.18-1.55 (m, 14 H), 2.15 (dt, 2 H, J 1 = 6.8 Hz, J 2 = 2.4 Hz), 2.20 (s, 3 H), 2.48 (dd, 1 H, J 1 = 16.0 Hz, J 2 = 6.0 Hz), 2.61 (dd, 1 H, J 1 = 16.0 Hz, J 2 = 8.0 Hz), 2.78-2.90 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.0 (2 C), 18.7, 22.2, 22.6, 26.9, 27.5, 28.7, 30.6, 31.0, 31.5, 35.2, 49.5, 81.9, 82.1, 207.4.
4-Hexylundec-5-yn-2-one (4fa, Entry 10, Table 2)
Yield 57%; pale yellow liquid. IR (CHCl3): ν = 3010, 2958, 2931, 2859, 1713, 1602, 1466, 1361, 1239, 1162 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.81-0.92 (m, 6 H), 1.21-1.52 (m, 16 H), 2.15 (dt, 2 H, J 1 = 7.2 Hz, J 2 = 2.0 Hz), 2.20 (s, 3 H), 2.48 (dd, 1 H, J 1 = 15.6 Hz, J 2 = 6.4 Hz), 2.61 (dd, 1 H, J 1 = 15.6 Hz, J 2 = 8.0 Hz), 2.78-2.87 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.0, 14.1, 18.7, 22.2, 22.6, 27.2, 27.5, 28.8, 29.0, 30.6, 31.0, 31.8, 35.2, 49.5, 81.9, 82.1, 207.5. ESI-MS (+): m/z = 273.21 [M + Na]+.
4-(Phenylethynyl)decan-2-one (4fb, Entry 11, Table 2)
Yield 48%; light yellow liquid. IR (CHCl3): 3011, 2930, 2858, 1714, 1601, 1490, 1466, 1362, 1161, 913 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 0.86-0.94 (m, 3 H), 1.25-1.41 (m, 6 H), 1.43-1.62 (m, 4 H), 2.20 (s, 3 H), 2.62 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 6.4 Hz), 2.78 (dd, 1 H, J 1 = 16.4 Hz, J 2 = 7.6 Hz), 3.06-3.13 (m, 1 H), 7.28-7.33 (m, 3 H), 7.39-7.43 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.1, 22.7, 27.3, 27.9, 29.0, 30.6, 31.8, 34.9, 49.0, 81.9, 92.1, 123.7, 127.7, 128.2, 131.6, 206.9. ESI-MS (+): m/z = 279.17 [M + Na]+.