4
H. Wang et al. / Tetrahedron xxx (2015) 1e5
McGill University by means of ESI. Column chromatography was
performed with 200e300 mesh silica gel using flash column
techniques. All reagents obtained commercially were used directly
unless otherwise noted.
J¼22.0 Hz), 87.5, 80.5, 42.7, 12.7; HRMS (ESI) calcd for C11H9FONa
(MþþNa): 199.0530; Found: 199.0529.
4.2.8. 5-(4-(Trifluoromethyl)phenyl)pent-4-ynal (3h). Yellow liquid;
1H NMR (400 MHz, CDCl3)
d
9.84 (s, 1H), 7.53 (d, J¼8.0 Hz, 2H), 7.46
4.2. General procedure for the Pd-catalyzed 1,4-addition of
terminal alkynes to acrolein
(d, J¼8.0 Hz, 2H), 2.81e2.71 (m, 4H); 13C NMR (100 MHz, CDCl3)
d
200.1, 131.9, 129.8 (q, J¼32.6 Hz), 127.4, 125.3 (q, J¼3.8 Hz), 124.1
(q, J¼272.0 Hz), 90.7, 80.4, 42.5, 12.7; HRMS (ESI) calcd for C12H9F3O
A mixture of 0.05 mmol Pd(OAc)2 (11.2 mg, 10 mol %) and
0.15 mL of PMe3 solution (0.15 mmol, 1.0 M PMe3 dissolved in tol-
uene, 30 mol %) was stirred at 110 ꢀC under argon for 10 min until
all palladium acetate was dissolved. Then 0.5 mL of water or 1 mL
acetone was added, followed by a mixture of terminal alkyne 1
(0.5 mmol) and acrolein (2) (2.5 mmol). The reaction mixture was
then stirred at 60 ꢀC in an oil bath. After full conversion of the al-
kyne starting material, as shown by TLC, the reaction mixture was
extracted with ethyl ether (3ꢁ10 mL), dried over anhydrous MgSO4,
and concentrated in vacuo. The resulting residue was purified by
flash column chromatography on silica gel (hexane:ethyl
acetate¼95:5 or 50:50) to give the pure product 3.
(MþþNa): 249.0498; Found: 249.0497.
4.2.9. Non-4-ynal (3i). Colorless liquid; 1H NMR (500 MHz, CDCl3)
d
9.78 (s,1H), 2.60 (t, J¼7.0 Hz, 2H), 2.50e2.43 (m, 2H), 2.15e2.08 (m,
2H), 1.49e1.32 (m, 4H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3)
d 201.3, 81.7, 77.9, 43.1, 31.1, 22.0, 18.5, 13.7, 12.3; HRMS (ESI)
calcd for C9H14ONa (MþþNa): 161.0937; Found: 161.0936.
4.2.10. Tridec-4-ynal (3j). Colorless liquid; 1H NMR (500 MHz,
CDCl3)
d
9.79 (s, 1H), 2.61 (t, J¼7.0 Hz, 2H), 2.48 (tt, J¼7.0, 2.2 Hz,
2H), 2.11 (tt, J¼7.0, 2.4 Hz, 2H), 1.50e1.41 (m, 2H), 1.40e1.20 (m,
10H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 201.3, 81.8,
77.9, 43.2, 32.0, 29.3, 29.2, 29.1, 29.0, 22.8, 18.8, 14.2, 12.4; HRMS
4.2.1. 5-Phenylpent-4-ynal (3a).2f,g Colorless liquid; 1H NMR
(ESI) calcd for C13H22ONa (MþþNa): 217.1563; Found: 217.1561.
(500 MHz, CDCl3)
d 9.85 (s, 1H), 7.43e7.35 (m, 2H), 7.33e7.25 (m,
3H), 2.81e2.70 (m, 4H); 13C NMR (125 MHz, CDCl3)
d
200.6, 131.7,
4.2.11. Heptadec-4-ynal (3k). Yellow liquid; 1H NMR (500 MHz,
128.3, 128.0, 123.5, 87.9, 81.6, 42.7, 12.8.
CDCl3)
d
9.77 (s, 1H), 2.59 (t, J¼7.0 Hz, 2H), 2.46 (tt, J¼7.0, 2.3 Hz,
2H), 2.10 (tt, J¼7.0, 2.4 Hz, 2H), 1.48e1.40 (m, 2H), 1.36e1.16 (m,
4.2.2. 5-(p-Tolyl)pent-4-ynal (3b). Colorless liquid; 1H NMR
20H), 0.86 (t, J¼7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 201.1, 81.7,
(500 MHz, CDCl3)
d
9.85 (s, 1H), 7.27 (d, J¼8.0 Hz, 2H), 7.09 (d,
77.8, 43.1, 32.0, 29.79, 29.74, 29.76, 29.7, 29.5, 29.3, 29.05, 28.97,
22.8, 18.8, 14.2, 12.3; HRMS (ESI) calcd for C17H29O (MþꢂH):
249.2224; Found: 249.2223.
J¼8.0 Hz, 3H), 2.81e2.66 (m, 4H), 2.33 (s, 3H); 13C NMR (125 MHz,
CDCl3)
d 200.8, 138.1, 131.7, 129.2, 120.5, 87.1, 81.8, 42.9, 21.6, 13.0;
HRMS (ESI) calcd for C12H12ONa (MþþNa): 195.0780; Found:
195.0779.
4.2.12. 8-Methylnon-4-ynal (3l). Colorless liquid; 1H NMR
(500 MHz, CDCl3)
d
9.78 (t, J¼1.4 Hz, 1H), 2.60 (t, J¼7.0 Hz, 2H),
4.2.3. 5-(4-Butylphenyl)pent-4-ynal (3c). Yellow liquid; 1H NMR
2.51e2.42 (m, 2H), 2.17e2.08 (m, 2H), 1.69e1.57 (m, 1H), 1.41e1.30
(500 MHz, CDCl3)
d
9.83 (t, J¼1.0 Hz, 1H), 7.30 (d, J¼8.0 Hz, 2H), 7.09
(m, 2H), 0.87 (d, J¼6.7 Hz, 6H); 13C NMR (125 MHz, CDCl3)
d 201.2,
(d, J¼8.0 Hz, 2H), 2.78e2.65 (m, 4H), 2.58 (t, J¼7.7 Hz, 2H),
1.61e1.53 (m, 2H), 1.34 (qt, J¼7.4, 7.4 Hz, 2H), 0.92 (t, J¼7.4 Hz, 3H);
81.8, 77.7, 43.1, 38.0, 27.3, 22.3, 16.8, 12.3; HRMS (ESI) calcd for
C
10H16ONa (MþþNa): 175.1093; Found: 175.1093.
13C NMR (125 MHz, CDCl3)
d 200.8, 143.0, 131.5, 128.4, 120.6, 87.0,
81.7, 42.8, 35.6, 33.5, 22.4, 14.0, 12.8; HRMS (ESI) calcd for
4.2.13. Tetradeca-4,10-diynedial (3m). Colorless liquid; 1H NMR
(500 MHz, CDCl3)
9.78 (t, J¼1.4 Hz, 2H), 2.66e2.55 (m, 4H),
2.52e2.41 (m, 4H), 2.20e2.04 (m, 4H), 1.61e1.43 (m, 4H); 13C NMR
C
15H18ONa (MþþNa): 237.1250; Found: 237.1248.
d
4.2.4. 5-(4-Methoxyphenyl)pent-4-ynal (3d). Colorless liquid; 1H
(125 MHz, CDCl3) d 201.2, 81.2, 78.3, 43.1, 28.1, 18.3, 12.3; HRMS
NMR (500 MHz, CDCl3)
d
9.81 (t, J¼1.0 Hz, 1H), 7.30 (d, J¼8.0 Hz,
(ESI) calcd for C14H18O2Na (MþþNa): 241.1199; Found: 241.1197.
2H), 6.79 (d, J¼8.0 Hz, 2H), 3.77 (s, 3H), 2.75e2.67 (m, 4H); 13C NMR
(125 MHz, CDCl3)
d 200.8, 159.4, 133.1, 115.6, 114.0, 86.3, 81.4, 55.4,
4.2.14. Undeca-4,10-diynal (3m0). Colorless liquid; 1H NMR
42.8, 12.8; HRMS (ESI) calcd for C12H12O2Na (MþþNa): 211.0730;
(500 MHz, CDCl3)
d
9.79 (s, 1H), 2.61 (t, J¼7.9 Hz, 2H), 2.47 (tt, J¼7.0,
Found: 211.0728.
2.4 Hz, 2H), 2.25e2.12 (m, 4H), 1.94 (t, J¼2.7 Hz, 1H), 1.70e1.51 (m,
4H); 13C NMR (125 MHz, CDCl3)
d 201.1, 84.3, 81.0, 78.4, 68.6, 43.1,
4.2.5. 5-(3-Hydroxyphenyl)pent-4-ynal (3e). Colorless liquid; 1H
27.9, 27.6, 18.3,18.1, 12.3; HRMS (ESI) calcd for C11H14ONa (MþþNa):
NMR (400 MHz, CDCl3)
J¼7.9 Hz, 1H), 6.88e6.84 (m, 1H), 6.81e6.76 (m, 1H), 5.67 (br, 1H),
2.81e2.67 (m, 4H); 13C NMR (100 MHz, CDCl3)
201.5, 155.5, 129.7,
d
9.83 (s, 1H), 7.13 (t, J¼7.9 Hz, 1H), 6.94 (d,
185.0937; Found: 185.0937.
d
4.2.15. 5-(Triisopropylsilyl)pent-4-ynal (3n). Colorless liquid; 1H
124.6, 124.3, 118.4, 115.6, 87.8, 81.3, 42.7, 12.8; HRMS (ESI) calcd for
C
NMR (500 MHz, CDCl3)
d
9.79 (t, J¼1.3 Hz,1H), 2.65 (t, J¼7.0 Hz, 2H),
11H9O2 (MþꢂH): 173.0603; Found: 173.0608.
2.56 (t, J¼7.0 Hz, 2H), 1.07e0.99 (m, 21H); 13C NMR (125 MHz,
CDCl3) d 200.6, 106.5, 81.9, 42.9, 18.7, 13.4, 11.3; HRMS (ESI) calcd for
4.2.6. 5-(4-(Hydroxymethyl)phenyl)pent-4-ynal (3f). Colorless liq-
C
14H26OSiNa (MþþNa): 261.1645; Found: 261.1643.
uid; 1H NMR (400 MHz, CDCl3)
d
9.86 (s, 1H), 7.39 (d, J¼8.0 Hz, 2H),
7.29 (d, J¼8.0 Hz, 2H), 4.68 (s, 2H), 2.82e2.72 (m, 4H); 13C NMR
4.2.16. 6-Oxohex-2-yn-1-yl propionate (3o). Colorless liquid; 1H
NMR (500 MHz, CDCl3)
9.77 (s, 1H), 4.63 (t, J¼2.2 Hz, 2H), 2.67 (t,
(100 MHz, CDCl3)
d
200.6, 140.8, 131.9, 126.9, 122.7, 87.9, 81.4, 65.0,
d
42.7, 12.8; HRMS (ESI) calcd for C13H16O3Na (MþþNaþMeOH):
J¼7.0 Hz, 2H), 2.54 (tt, J¼7.0, 2.2 Hz, 2H), 2.35 (q, J¼7.6 Hz, 2H), 1.14
243.0992; Found: 243.0987.
(t, J¼7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 200.2, 173.9, 85.2,
75.3, 52.5, 42.4, 27.5, 12.1, 9.1; HRMS (ESI) calcd for C9H12O3Na
4.2.7. 5-(4-Fluorophenyl)pent-4-ynal (3g). Yellow liquid; 1H NMR
(MþþNa): 191.0679; Found: 191.0675.
(400 MHz, CDCl3)
2H), 2.82e2.63 (m, 4H); 13C NMR (100 MHz, CDCl3)
(d, J¼248.7 Hz), 133.5 (d, J¼8.2 Hz), 119.6 (d, J¼3.4 Hz), 115.6 (d,
d
9.83 (s, 1H), 7.39e7.30 (m, 2H), 7.00e6.90 (m,
d
200.6, 162.4
4.2.17. tert-Butyl (6-oxohex-2-yn-1-yl)carbamate (3p). Yellow liq-
uid; 1H NMR (400 MHz, CDCl3)
d
9.75 (t, J¼1.2 Hz, 1H), 4.69 (br, 1H),