The Journal of Organic Chemistry
NOTE
m (multiplet). Proton-decoupled 13C NMR spectra are recorded at 75
or 125 MHz and are reported relative to the peak for CDCl3 (δ 77).
General Procedure (GP) for Synthesis of Alkynyl Carbonyl
Compounds. Methyl 2-Methyl-4-phenylbut-3-ynoate (3a).
To a drum vial were added PdCl2(MeCN)2 (5 mol %, 0.016 mmol,
4 mg), XPhos (12 mol %, 0.038 mmol, 18 mg), and PhMe (1.0 mL).
Next R-bromo carbonyl compound 1a (0.32 mmol, 53 mg, 1 equiv) and
tributyl(phenylethynyl)stannane (2) (0.64 mmol, 250 mg, 2 equiv)
were added. The reaction mixture was heated at 110 °C for 20 min. The
reaction mixture was then cooled to rt and quenched with a KF solution
(1 M, 1.5 mL). The reaction mixture was passed through a short plug of
Celite, and the layers were separated. The aqueous layer was twice
extracted with Et2O, and the combined organic layers were washed with
brine, dried over MgSO4, filtered, and concentrated under reduced
pressure. Purification was accomplished by flash chromatography to
afford a pale yellow oil of 3a (36 mg, 60%): Rf = 0.3 (hexanes:Et2O =
20:1); IR (film, cmÀ1) 1744, 1199, 758; 1H NMR (300 MHz, CDCl3)
δ 7.44À7.42 (m, 2H), 7.31À7.29 (m, 3H), 3.78 (s, 3H), 3.65 (q, J =
7.1 Hz, 1H), 1.54 (d, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 171.8, 131.7, 128.4, 128.1, 122.9, 86.9, 82.6, 52.6, 32.7, 18.1; HRMS
(ESI) m/z calcd for C12H12O2 [M + H]+ 189.0916, found 189.0918.
Benzyl 2-Methyl-4-phenylbut-3-ynoate (3b). R-Bromo car-
bonyl compound 1b (0.32 mmol, 78 mg, 1.0 equiv) and 2 (0.64 mmol,
250 mg, 2.0 equiv) were treated to the reaction conditions as described
in the GP, affording 3b as a pale yellow oil (51 mg, 60%): Rf = 0.26
(hexanes:Et2O = 20:1); IR (film, cmÀ1) 1744, 1489, 1175, 758, 693; 1H
NMR (300 MHz, CDCl3) δ 7.47À7.29 (m, 10H), 5.26 (s, 2H), 3.73(q,
J = 7.4 Hz, 1H), 1.60 (d, J = 7.0, 3H); 13C NMR (75 MHz, CDCl3) δ
171.2, 135.7, 131.7, 128.6, 128.3, 128.3, 128.2, 128.0, 123.0, 86.9, 82.8,
67.0, 33.0, 18.0; HRMS (ESI) m/z calcd for C18H16O2 [M + H]+
265.1229, found 265.1222.
Methyl 2-(tert-Butyl)-4-phenylbut-3-ynoate (3f). R-Bromo
carbonyl compound 1f (0.32 mmol, 67 mg, 1.0 equiv) and 2 (0.64 mmol,
250 mg, 2.0 equiv) were treated to the reaction conditions as described
in the GP, affording 3f as a pale yellow oil (26 mg, 36%): Rf = 0.32
(hexanes:Et2O = 20:1); IR (film, cmÀ1) 1735, 1146, 755, 687; 1H NMR
(300 MHz, CDCl3) δ 7.46À7.42 (m, 2H), 7.30À7.28 (m, 3H), 3.75
(s, 3H), 3.37 (s, 1H), 1.14(s, 9H); 13C NMR (75 MHz, CDCl3) δ 170.6,
131.7, 128.1, 128.0, 123.2, 85.2, 84.4, 52.0, 50.1, 35.0, 27.7; MS (EI) m/z
calcd for C15H18O2 230.0, found 230.0.
N,N-Diethyl-2-methyl-4-phenylbut-3-ynamide (3g). R-Bromo
carbonyl compound 1g (0.32 mmol, 67 mg, 1.0 equiv) and 2 (0.64 mmol,
250 mg, 2.0 equiv) were treated to the reaction conditions as described in
the GP, affording 3g as a pale yellow oil (31 mg, 42%): Rf = 0.22 (hexanes:
EtOAc = 4:1); IR (film, cmÀ1) 1646, 1024, 758, 690; 1H NMR (300 MHz,
CDCl3) δ 7.43À7.40 (m, 2H), 7.32À7.29 (m, 3H), 3.72 (q, J = 6.0 Hz,
1H), 3.67À3.38 (m, 4H), 1.52 (d, J = 7.2 Hz, 3H), 1.28 (t, J = 6.6 Hz, 3H),
1.17 (t, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.1, 131.8, 128.3,
128.1, 123.5, 88.5, 82.5, 42.1, 40.6, 30.3, 17.9, 14.4, 12.9; HRMS (ESI) m/z
calcd for C15H19NO [M + H]+ 230.1545, found 230.1551.
2-Methyl-4-phenyl-1-(piperidin-1-yl)but-3-yn-1-one (3h).
R-Bromo carbonyl compound 1h (0.32 mmol, 70 mg, 1.0 equiv) and
2 (0.64 mmol, 250 mg, 2.0 equiv) were treated to the reaction conditions
as described in the GP, affording 3h as a pale yellow oil (27 mg, 35%):
Rf = 0.23 (hexanes:EtOAc = 4:1); IR (film, cmÀ1) 1652, 1436, 1003,
758, 687; 1H NMR (300 MHz, CDCl3) δ 7.42À7.40 (m, 2H), 7.32À
7.30 (m, 3H), 3.81À3.73 (m, 2H), 3.71 (q, J = 6.7, 1H), 3.55À3.31
(m, 2H) 1.73À1.56 (m, 6H), 1.52 (d, J = 7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 168.3, 131.8, 128.5, 128.1, 123.4, 88.3, 82.9, 47.2,
43.7, 30.5, 26.3, 25.8, 25.2, 17.8; MS (EI) m/z calcd for C16H19NO
241.0, found 241.0.
2-Methyl-1-morpholino-4-phenylbut-3-yn-1-one (3i). R-Bromo
carbonyl compound 1i (0.32 mmol, 71 mg, 1.0 equiv) and 2 (0.64
mmol, 250 mg, 2.0 equiv) were treated to the reaction conditions as
described in the GP, affording 3i as a pale yellow oil (43 mg, 55%): Rf =
0.4 (hexanes:EtOAc = 1:1); IR (film, cmÀ1) 1649, 1027, 758, 690; 1H
NMR (300 MHz, CDCl3) δ 7.41À7.39 (m, 2H), 7.33À7.31 (m, 3H),
3.89À3.50 (m, 8H), 3.67 (q, J = 6.9, 1H), 1.53 (d, J = 7.6, 3H); 13C
NMR (75 MHz, CDCl3) δ 168.7, 131.8, 128.4, 128.3, 122.9, 87.6, 83.3,
66.9, 66.6, 46.6, 42.8, 30.3, 17.3; HRMS (ESI) m/z calcd for
C15H17NO2 [M + H]+ 244.1338, found 244.1332.
sec-Butyl 2-Methyl-4-phenylbut-3-ynoate (3c). R-Bromo
carbonyl compound 1c (0.32 mmol, 67 mg, 1.0 equiv) and 2 (0.64 mmol,
250 mg, 2.0 equiv) were treated to the reaction conditions as described
in the GP, affording 3c as a pale yellow oil (41 mg, 56%): Rf =
0.4 (hexanes:Et2O = 20:1); IR (film, cmÀ1) 1735, 1190, 864, 755,
1
690; H NMR (300 MHz, CDCl3) δ 7.47À7.43 (m, 2H), 7.34À7.29
(m, 3H), 5.00À4.89 (m, 1H), 3.69 (q, J = 7.3 Hz, 1H), 1.72À1.69
(m, 2H), 1.57À1.53 (m, 3H), 1.29 (d, J= 6.5 Hz, 3H), 1.01À0.94 (m, 3H);
13C NMR (75 MHz, CDCl3) (mixture of diastereoisomer) δ 171.1, 171.0,
131.7, 128.2, 128.0, 123.1, 87.4, 87.3, 82.5, 82.4, 73.4, 33.3, 33.1, 28.8,
28.7, 19.4, 19.3, 18.2, 17.9, 9.7, 9.6; HRMS (ESI) m/z calcd for C15H18O2
[M + H]+ 231.1385, found 231.1389.
N,N-Diethyl-2-isopropyl-4-phenylbut-3-ynamide (3j). R-Bromo
carbonyl compound 1j (0.32 mmol, 76 mg, 1.0 equiv) and 2 (0.64
mmol, 250 mg, 2.0 equiv) were treated to the reaction conditions as
described in the GP, affording 3j as a pale yellow oil (33 mg, 40%): Rf =
0.32 (hexanes:EtOAc = 4:1); IR (film, cmÀ1) 1652, 1030, 755, 690; 1H
NMR (300 MHz, CDCl3) δ 7.45À7.42 (m, 2H), 7.32À7.30 (m, 3H),
3.65À3.39 (m, 4H), 3.31 (d, J = 9.0, 1H), 2.43À2.33 (m, 1H), 1.29
(t, J = 7.3 Hz, 3H), 1.18 (t, J = 7.3 Hz, 6H), 1.01 (d, J = 6.9 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 169.1, 131.8, 128.2, 128.0, 123.5, 87.0, 83.7,
43.8, 42.3, 40.8, 31.0, 21.3, 20.6, 14.8, 13.0; HRMS (ESI) m/z calcd for
C17H23NO 258.1858, found 258.1863.
Methyl 2-Isopropyl-4-phenylbut-3-ynoate (3d). R-Bromo
carbonyl compound 1d (0.32 mmol, 62 mg, 1.0 equiv) and 2 (0.64 mmol,
250 mg, 2.0 equiv) were treated to the reaction conditions as described
in the GP, affording 3d as a pale yellow oil (38 mg, 55%): Rf =
0.3 (hexanes:Et2O = 20:1); IR (film, cmÀ1) 1744, 1492, 1018, 752,
1
690; H NMR (300 MHz, CDCl3) δ 7.47À7.41 (m, 2H), 7.31À7.25
(m, 3H), 3.76 (s, 3H), 3.41(d, J = 6.5 Hz, 1H), 2.33À2.26 (m, 1H), 1.09
(dd, J = 5.3, 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 171.2, 131.7,
128.1, 128.0, 123.1, 84.5, 52.3, 46.0, 31.2, 20.8, 19.2; HRMS (ESI) m/z
calcd for C14H16O2 [M + H]+ 217.1229, found 217.1234.
2-Isopropyl-1-morpholino-4-phenylbut-3-yn-1-one (3k).
R-Bromo carbonyl compound 1k (0.32 mmol, 80 mg, 1.0 equiv) and
2 (0.64 mmol, 250 mg, 2.0 equiv) were treated to the reaction conditions
as described in the GP, affording 3k as a pale yellow solid (43 mg, 50%):
Rf = 0.5 (hexanes:EtOAc = 1:1); IR (film, cmÀ1) 1649, 1430, 971, 758,
Benzyl 2-Isopropyl-4-phenylbut-3-ynoate (3e). R-Bromo
carbonyl compound 1e (0.32 mmol, 87 mg, 1.0 equiv) and 2 (0.64 mmol,
250 mg, 2.0 equiv) were treated to the reaction conditions as described
in the GP, affording 3e as a pale yellow oil (56 mg, ca. 85% pure by 1H
and 13C NMR): Rf = 0.23 (hexanes:Et2O = 20:1); IR (film, cmÀ1) 1741,
1486, 1166, 755, 693; 1H NMR (300 MHz, CDCl3) δ 7.49À7.29
(m, 10H), 5.14 (s, 2H), 3.48 (d, J = 6.3 Hz, 1H), 2.40À2.30 (m, 1H),
1.11 (t, J = 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 170.5, 135.7,
131.7, 128.5, 128.2, 128.2, 128.1, 128.0, 123.2, 84.7, 84.6, 66.9, 46.2, 31.3,
20.9, 19.2; HRMS (ESI) m/z calcd for C20H20O2 [M + H]+ 293.1542,
found 293.1535.
1
690; H NMR (300 MHz, CDCl3) δ 7.41À7.37 (m, 2H), 7.31À7.26
(m, 3H), 3.85À3.50 (m, 8H), 3.31 (d, J = 8.2 Hz, 1H), 2.37À2.25
(m, 1H), 1.19 (d, J = 7.1 Hz, 3H), 1.03 (d, J = 7.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 168.3, 131.7, 128.4, 128.2, 123.1, 86.0, 85.0, 67.2,
66.9, 47.2, 44.2, 43.0, 30.6, 21.7, 20.6; HRMS (ESI) m/z calcd for
C17H21NO2 [M + H]+ 272.1651, found 272.1656. The structure assign-
ment was confirmed by X-ray crystallography.
6858
dx.doi.org/10.1021/jo200939u |J. Org. Chem. 2011, 76, 6856–6859