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I. Tellitu et al. / Tetrahedron 71 (2015) 8251e8255
2.68e2.62 (m, 2H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
NMR (75 MHz, CDCl3) d 173.0, 140.6, 128.4, 128.0, 126.2, 60.4, 36.0,
d
174.7, 168.7, 133.6, 117.9, 61.8, 51.4, 32.8, 14.0; IR (cmꢁ1): 1716.
31.0, 14.2; IR (cmꢁ1): 1731.
4.3.6. 2-(Ethoxycarbonyl)-2-ethylbutanoic acid (2f). Colorless oil,
85% yield. 1H NMR (300 MHz, CDCl3)
11.01 (br s, 1H), 4.16 (q,
J¼7.1 Hz, 2H), 1.88 (m, 4H), 1.21 (t, J¼7.1 Hz, 3H), 0.77 (t, J¼6.2 Hz,
4.4.2. Ethyl propionate (3b). Yellowish oil, 91% yield. 1H NMR
d
(300 MHz, CDCl3)
d
4.16 (q, J¼7.1 Hz, 2H), 2.32 (q, J¼7.6 Hz, 2H), 1.24
(t, J¼7.1 Hz, 3H), 1.14 (t, J¼7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3)
6H); 13C NMR (75 MHz, CDCl3)
d
177.0, 172.5, 61.5, 58.6, 25.8, 13.9,
d 174.8, 60.3, 27.6, 14.2, 9.1.
8.5; IR (cmꢁ1): 3050, 1705; HRMS calculated for C9H16O4$Hþ:
189.1127, found: 189.1110.
4.4.3. Ethyl pentanoate (3c). Yellowish oil, 86% yield. 1H NMR
(300 MHz, CDCl3)
4.15 (q, J¼7.1 Hz, 2H), 2.29 (t, J¼7.4 Hz, 2H),
d
4.3.7. 2-(Ethoxycarbonyl)-2-methyl-4-pentenoic acid (2g). Colorless
1.62e1.56 (m, 2H), 1.33e1.28 (m, 2H), 1.24 (t, J¼7.1 Hz, 2H), 0.91 (t,
oil, 74% yield. 1H NMR (300 MHz, CDCl3)
d
10.60 (br s, 1H),
J¼7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 174.1, 60.2, 34.1, 27.0,
5.80e5.62 (m, 1H), 5.15e5.09 (m, 2H), 4.20 (q, J¼7.2 Hz, 2H),
22.2, 13.9, 13.3.
2.69e2.55 (m, 2H), 1.42 (s, 3H), 1.26 (t, J¼7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3)
d
177.9, 171.6, 132.2, 119.5, 61.7, 53.5, 40.0, 19.8,
4.4.4. Ethyl 4-cyanobutanoate (3d).26 Yellowish oil, 99% yield. 1H
14.0; IR (cmꢁ1): 3100, 1710; HRMS calculated for C9H14O4$Hþ:
NMR (300 MHz, CDCl3)
d
4.15 (q, J¼7.1 Hz, 2H), 2.54e2.31 (m, 4H),
187.0970, found: 187.0954.
2.03e1.95 (m, 2H), 1.27 (t, J¼7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
171.8, 118.6, 60.8, 32.4, 20.8, 16.6, 14.2.
4.3.8. 2-Benzyl-2-(ethoxycarbonyl)propionic acid (2h).24 Yellowish
oil, 79% yield. 1H NMR (300 MHz, CDCl3)
d
11.14 (br s, 1H), 7.24e7.18
4.4.5. Ethyl 4-pentenoate (3e). Yellowish oil, 97% yield. 1H NMR
(m, 5H), 4.24 (q, J¼7.1 Hz, 2H), 3.33 (d, J¼13.6 Hz, 1H), 3.24 (d,
(300 MHz, CDCl3) d 5.85e5.63 (m, 1H), 5.11e4.99 (m, 2H), 4.13 (q,
J¼13.6 Hz, 1H), 1.43 (s, 3H), 1.29 (t, J¼7.1 Hz, 3H); 13C NMR (75 MHz,
J¼7.1 Hz, 2H), 2.38 (m, 4H), 1.25 (t, J¼7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3)
d
178.1, 171.8, 135.8, 130.2, 128.4, 127.1, 61.9, 55.0, 41.2, 19.7,
CDCl3) d 172.8, 137.6, 115.3, 60.2, 33.9, 30.5, 15.8.
14.0; IR (cmꢁ1): 3085, 1710.
4.4.6. Ethyl 2-ethylbutanoate (3f).27 Yellowish oil, 98% yield. 1H
4.3.9. 2-(2-Bromo-5-methoxybenzyl)-2-(ethoxycarbonyl)-propionic
NMR (300 MHz, CDCl3)
d
4.14 (q, J¼7.1 Hz, 2H), 2.18 (m, 1H), 1.54 (m,
acid (2i). White solid, 77% yield, mp 64e65 ꢀC (hexanes). 1H NMR
4H), 1.25 (t, J¼7.1 Hz, 3H), 0.88 (t, J¼7.4 Hz, 6H); 13C NMR (75 MHz,
(300 MHz, CDCl3)
d
11.20 (br s, 1H), 7.42 (d, J¼8.9 Hz, 1H), 6.78 (d,
CDCl3) d 176.4, 59.9, 49.0, 25.1, 14.3, 11.8.
J¼3.0 Hz,1H), 6.66 (dd, J¼8.9, 3.0 Hz,1H), 4.25 (q, J¼7.1 Hz, 2H), 3.75
(s, 3H), 3.53 (d, J¼3.0 Hz,1H), 3.49 (d, J¼3.0 Hz,1H),1.45 (s, 3H),1.28
4.4.7. Ethyl 2-methyl-4-pentenoate (3g). Yellowish oil, 100% yield.
1H NMR (300 MHz, CDCl3)
5.82e5.61 (m, 1H), 5.08e5.00 (m, 2H),
(t, J¼7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
178.0, 171.5, 158.7,
d
136.8, 133.6, 116.7, 116.6, 114.7, 62.0, 55.2, 39.5, 19.2, 13.9; IR (cmꢁ1):
4.12 (q, J¼7.1 Hz, 2H), 2.59e2.28 (m, 2H), 2.23e2.17 (m, 1H), 1.24 (t,
1713; HRMS calculated for
345.0343.
C
14H18BrO5$Hþ: 345.0338, found:
J¼7.1 Hz, 3H), 1.14 (d, J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
176.2, 135.5, 116.8, 60.2, 39.2, 37.8, 16.5, 14.2; IR (cmꢁ1): 1730.
4.3.10. 2-(Ethoxycarbonyl)-2-propyl-4-pentenoic
acid
8.67 (br s,
4.4.8. Ethyl 2-methyl-3-phenylpropionate (3h).28 Yellowish oil,
100% yield. 1H NMR (300 MHz, CDCl3)
7.30e7.10 (m, 5H), 4.11 (q,
J¼7.1 Hz, 2H), 3.08e2.96 (m, 1H), 2.82e2.60 (m, 2H), 1.25e1.18 (m,
(2j). Yellowish oil, 45% yield. 1H NMR (300 MHz, CDCl3)
d
d
1H), 5.68e5.53 (m, 1H), 5.13e5.09 (m, 2H), 4.21 (q, J¼7.1 Hz, 2H),
2.72e2.57 (m, 2H), 1.84e1.75 (m, 2H), 1.23 (m, 5H), 0.9 (t, J¼7.3 Hz,
6H); 13C NMR (75 MHz, CDCl3)
d 176.1, 139.4, 129.0, 128.3, 126.3,
3H); 13C NMR (75 MHz, CDCl3)
d
176.1, 172.5, 132.1, 119.1, 61.8, 57.7,
60.2, 41.5, 39.8, 16.8, 14.2; IR (cmꢁ1): 1730.
38.2, 35.8, 17.6, 14.2, 14.1; IR (cmꢁ1): 3100, 1710; HRMS calculated
for C11H18O4$Hþ: 215.1283, found: 215.1272.
4.4.9. Ethyl 3-(2-bromo-5-methoxyphenyl)-2-methylpropionate
(3i). Yellowish oil, 72% yield. 1H NMR (300 MHz, CDCl3)
d 7.35 (d,
4.3.11. 2-Benzyl-2-(ethoxycarbonyl)pentanoic acid (2k). Colorless
J¼8.7 Hz,1H), 6.72(d, J¼3.1 Hz,1H), 6.59(dd, J¼8.7, 3.1 Hz,1H), 4.05(q,
oil, 70% yield. 1H NMR (300 MHz, CDCl3)
d 9.97 (br s, 1H), 7.30e7.00
J¼7.0 Hz, 2H), 3.70 (s, 3H), 3.12e3.00 (m, 1H), 2.80e2.69 (m, 1H), 1.15
(m, 5H), 4.24 (q, J¼7.1 Hz, 2H), 3.37 (d, J¼13.8 Hz, 1H), 3.16 (d,
(t, J¼7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 175.7, 158.7, 139.8, 133.3,
J¼13.8 Hz, 1H), 2.02e1.93 (m, 2H), 1.40e1.29 (m, 5H), 0.94 (t,
115.1, 116.8, 113.7, 60.3, 55.3, 40.0, 39.7, 17.0, 14.1; IR (cmꢁ1): 1730;
J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
174.9, 174.4, 135.8, 129.5,
HRMS calculated for C13H17BrO3$Hþ: 301.0441, found: 301.0439.
128.5, 127.3, 62.3, 59.3, 41.3, 37.5, 18.3, 14.0, 13.9; IR (cmꢁ1): 3100,
1709; HRMS calculated for
265.1429.
C
15H20O4$Hþ: 265.1440, found:
4.4.10. Ethyl 2-propyl-4-pentenoate (3j). Yellowish oil, 88% yield. 1H
NMR (300 MHz, CDCl3) d 5.83e5.60 (m, 1H), 5.11e5.05 (m, 2H), 4.13
(q, J¼7.1 Hz, 2H), 2.50e2.15 (m, 3H), 1.68e1.25 (m, 4H), 1.24 (t,
4.4. General procedure for the microwave assisted de-
carboxylation of 2aek. Synthesis of ester 3a
J¼7.1 Hz, 3H), 0.90 (t, J¼7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 175.1, 135.6, 116.5, 61.1, 53.4, 36.5, 34.0, 20.5, 14.3, 14.0.
A cap closed-vessel that has been charged with monoacid 2a
(52 mg, 0.23 mmol) and imidazole (28 mg, 0.23 mmol) was irra-
diated for the programmed time and temperature (see Table 2). For
the work-up, the residue was diluted with CH2Cl2 and washed with
water (to remove imidazole), the organic layer was dried over
Na2SO4, and the solvent evaporated under vacuum to render
chromatographically pure ester 3a as a colorless oil (82% yield).25
4.4.11. Ethyl 2-benzylpentanoate (3k).29 Yellowish oil, 82% yield. 1H
NMR (300 MHz, CDCl3)
d
7.33e7.18 (m, 5H), 4.06 (q, J¼7.1 Hz, 2H),
2.97e2.86 (m, 1H), 2.70e2.60 (m, 2H), 1.62e1.18 (m, 4H), 1.15 (t,
J¼7.0 Hz, 3H), 0.90 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
175.7, 139.5, 128.9, 128.3, 126.2, 60.1, 47.5, 38.6, 34.3, 20.5, 14.1,
13.9; IR (cmꢁ1): 1731.
Acknowledgements
4.4.1. Ethyl 3-phenylpropionate (3a). Colorless oil, 82% yield. 1H
NMR (300 MHz, CDCl3)
d
7.42e7.30 (m, 5H), 4.13 (q, J¼7.1 Hz, 2H),
This research was supported by the Basque Government (IT-
774-13), the Spanish Ministry of Economy and Competitiveness
2.96 (t, J¼7.8 Hz, 2H), 2.62 (t, J¼7.8 Hz, 2H), 1.24 (t, J¼7.1 Hz, 3H); 13
C