Synthesis of 1,2-disubstituted acetylenes via copper-catalyzed Suzuki coupling of organoboronic acids with 1,1-dibromo-1-alkenes

Article abstract of DOI:10.1016/j.tetlet.2012.08.044

An efficient synthesis of 1,2-disubstituted acetylenes has been described. Reactions of organoboronic acids with 1,1-dibromo-1-alkenes in the presence of a catalytic amount of CuI (10 mol %), 8-hydroxyquinoline (10 mol %), and using potassium phosphate as base in C₂H₅OH afforded the desired 1,2-disubstituted acetylenes in good to excellent yields. It is important to note that the formation of 1,3-diynes, which are derived from the homocoupling of 1,1-dibromo-1-alkenes, can be almost completely suppressed under these optimized conditions.

Full text of DOI:10.1016/j.tetlet.2012.08.044

Synthesis of 1,2-disubstituted acetylenes via copper-catalyzed
Suzuki coupling reaction of organoboronic acids with
1,1-dibromo-1-alkenes
Jidan Liu, Fenglin Dai, Zhiyong Yang, Sizhuo Wang, Kai Xie, Anwei Wang, Xiang Chen
and Ze Tan∗
College of Chemistry and Chemical Engineering, State Key Laboratory of Chemo/Biosensing and
Chemometrics, Hunan University, ChangSha 410082, P. R. China
E-mail: ztanze@ gmail.com.
Supporting Information
Content
General Information …………………………………………………...2
Typical procedure for the preparation of 1,1-dibromo-1-alkenes……...2
Characterization data of 1,1-dibromo-1-alkenes……………….............2
Typical procedure for the products……………………………….........3
Characterization data of the products..…………………..……………..4
References……………………………………………………….........27
1

General Information All the solvents and commercially available reagents were
1
13
purchased from commercial sources and used directly. H NMR and C NMR were
recorded in CDCl3 at room temperature on a Varian INOVA-400 spectrometer (400 MHz
1
1H) or Bruker spectrometer (400 MHz H). The chemical-shifts scale is based on TMS.
Products were purified by flash column chromatography on 200-300 mesh silica gel.
Typical procedure for the preparation of 1,1-dibromo-1-alkenes
Typical procedure for the preparation of 1,1-dibromo-1-alkenes: To a solution of
4-methoxybenzaldehyde (2.3 g, 16.5 mmol), carbon tetrabromide (7.1 g, 21.4 mmol) in
dichloromethane (100 mL) at 0 °C was added slowly a solution of PPh3 (10.8 g, 41.2
mmol) in dichloromethane (40 mL). The reaction mixture was stirred until complete
conversion of aldehyde was realized and the mixture was concentrated. The resulting
crude product was purified by flash chromatography over SiO2 with petroleum ether to
afford the title compound 1a as a white solid (4.3 g, 90%).1
Characterization data of 1,1-dibromo-1-alkenes
1-(2,2-dibromovinyl)-4-methoxybenzene (1a)1
White solid, mp 37-38 oC; 1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.8 Hz, 2H), 7.40 (s, 1H), 6.88
(d, J = 8.8 Hz, 2H), 3.81 (s, 3H).
(2,2-dibromovinyl)benzene (1l)1
Pale yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.53-7.51 (m, 2H), 7.47 (s, 1H), 7.36-7.34 (m, 3H).
2-(2,2-dibromovinyl)naphthalene (1m)1
White solid, mp 94-95 oC; 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.86-7.82 (m, 3H), 7.65-7.63
(m, 2H), 7.52-7.49 (m, 2H).
1-(2,2-dibromovinyl)-2,4-dimethoxybenzene (1n)
White solid, mp 45-46 oC; 1H NMR (400 MHz, CDCl3): δ 7.67 (dd, J = 0.4, 8.8 Hz, 1H), 6.49 (dd, J =
2.4, 8.4 Hz, 1H), 7.53 (s, 1H), 6.40 (d, J = 2.4 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H).
2

1-(2,2-dibromovinyl)-4-methoxybenzene (1o)2
1
Colorless oil; H NMR (400 MHz, CDCl3): δ 7.44 (s, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0
Hz, 2H), 2.34 (s, 3H).
1-chloro-4-(2,2-dibromovinyl)benzene (1p)1
Light brown liquid; 1H NMR (400 MHz, CDCl3): δ 7.47 (d, J = 8.4 Hz, 2H), 7.43 (s, 1H). 7.34 (d, J =
8.8 Hz, 2H).
1-(2,2-dibromovinyl)-4-nitrobenzene (1q)1
Yellow solid, mp 93-94 oC; 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 8.4
Hz, 2H), 7.26 (s, 1H).
2,2-dibromovinyl-2-pyridine (1r)1
Light green liquid; 1H NMR (400 MHz, CDCl3): δ 8.63 (d, J = 4.4 Hz, 1H), 7.76-7.72 (m, 2H), 7.65 (s,
1H), 7.26-7.23 (m, 1H).
2,2-dibromovinyl-2-furan (1s)1
Pale brown liquid; 1H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 1.6 Hz, 1H), 7.40 (s, 1H), 6.95 (d, J =
4.0 Hz, 1H), 6.47-6.45 (m, 1H).
1,1-dibromo-4-phenylbutene (1t)1
Light yellow liquid; 1H NMR (400 MHz, CDCl3): δ 7.32-7.29 (m, 2H), 7.24-7.19 (m, 3H), 6.40 (t, J =
7.2 Hz, 1H), 2.74 (t, J = 7.7 Hz, 2H), 2.45-2.41 (m, 2H).
Typical procedure for the products
General procedure for the one-pot preparation of 1,2-disubstituted acetylenes from
1,1-dibromo-1-alkenes: Under a nitrogen atmosphere, an over-dried Schlenk tube with a
magnetic stirring bar was charged with 1,1-dibromo-1-alkenes (0.50 mmol), organoboron compound
(1.0 mmol), CuI (0.05 mmol), 8-hydroxyquinoline (0.10 mmol), K3PO4 (2.0 mmol), and ethanol (2.0
o
mL). After the mixture was heated at 100 C for 12 h, the solvent was evaporated under reduced
pressure and the residue was purified by flash column chromatography on a silica gel (petroleum ether
as eluting agent) to give the product.
3

Characterization data of the products
(4-methoxyphenyl)phenylacetylene (3a)3
o
1
White solid; yield: 92%; mp 51-53 C; H NMR (400 MHz, CDCl3): δ 7.52-7.45 (m, 4H), 7.36-7.30
(m, 3H), 6.88 (dd, J = 8.7, 2.1 Hz, 2H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.53, 133.01,
131.40, 128.28, 127.91, 123.50, 115.29, 113.94, 89.30, 88.01, 55.28; IR (KBr): 3053, 2216, 1246,
1028 cm-1; HRMS (EI): [M]+ calcd for C15H12O 208.0888; found 208.0887.
di(4-methoxylphenyl)acetylene (3b)4
o
1
White solid; yield: 96%; mp 145-147 C; H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 8.8 Hz, 4H),
6.87 (d, J = 8.8 Hz, 4H), 3.82 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 158.36, 131.83, 114.61, 112.89,
86.89, 54.25; IR (KBr): 2840, 2254, 1244, 1026 cm-1; LRMS (EI): [M]+ calcd for C16H14O2 238;
found 238.
1-tert-butyl-4-((4-methoxyphenyl)ethynyl)benzene (3c)4
1
White solid; yield: 95%; mp 122-124 oC; HNMR (400 MHz, CDCl3): δ 7.47-7.43 (m, 4H), 7.35 (d, J
= 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H), 1.32 (s, 9H); 13C NMR (100 MHz, CDCl3): δ
159.39, 151.11, 132.96, 131.11, 125.28, 120.46, 115.54, 113.89, 88.60, 88.11, 55.25, 34.73, 31.15; IR
(KBr): 2930, 2310, 2254, 1160 cm-1; LRMS (EI): [M]+ calcd for C19H20O 264; found 264.
4-methyl-4′-methoxyldiphenylacetylene (3d)4
White solid; yield: 94%; mp 126-128 oC; 1H NMR (400 MHz, CDCl3): δ 7.45 (d, J = 9.2 Hz, 2H), 7.40
(d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H), 2.35 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 159.44, 137.97, 132.93, 131.29, 129.04, 120.46, 115.55, 113.93, 88.62,
88.16, 55.24, 21.43; IR (KBr): 2920, 2211, 1246, 1028 cm-1; HRMS (EI): [M]+ calcd for C16H14O
222.1123; found 222.1120.
1-methoxy-4-(3’-tolylethynyl)benzene (3e)5
o
White solid; yield: 92%; mp 43-45 C; 1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 9.0 Hz, 2H), 7.33
(d, J = 8.3 Hz, 2H), 7.22 (t, J = 7.4 Hz, 1H), 7.12 (d, J = 7.9 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 3.82 (s,
3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.53, 137.93, 133.01, 132.01, 128.82, 128.49,
128.18, 123.36, 115.48, 113.96, 88.98, 88.20, 55.28, 21.21; IR (KBr): 2946, 2231, 1203, 1021 cm-1;
HRMS (EI): [M]+ calcd for C16H14O 222.1120; found 222.1121.
1-methoxy-4-(2′-tolylethynyl)benzene (3f)6
4

o
White solid; yield: 90%; mp 75-77 C; 1H NMR (400 MHz, CDCl3): δ 7.48-7.46 (m, 3H), 7.23-7.15
(m, 3H), 6.87 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.53,
139.92, 132.90, 131.62, 129.38, 127.94, 125.52, 123.30, 115.65, 113.97, 93.30, 86.98, 55.27, 20.73;
IR (KBr): 2931, 2224, 1594, 1245, 1029 cm-1; HRMS (EI): [M]+ calcd for C16H14O 222.1124; found
222.1123.
(p-fluorophenyl)(p-anisyl)acetylene (3g)7
White solid; yield: 86%; mp 83-85 oC; 1H NMR (400 MHz, CDCl3): δ 7.47-7.45 (m, 4H), 7.36 (d, J =
8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H,) 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.48, 161.00,
159.60, 133.20 (d, J=8.3 Hz), 119.63, 115.55 (d, J = 22.1 Hz), 115.09, 113.97, 88.94, 86.93, 55.27; IR
(KBr): 2923, 2217, 1287, 1029 cm-1; HRMS (EI): [M]+ calcd for C15H11FO 226.0870; found
226.0872.
1-(4-methoxyphenyl)-2-[4-(trifluoromethyl)-phenyl]ethyne (3h)8
White solid; yield: 83%; mp 120-122 oC; 1H NMR (400 MHz, CDCl3): δ 7.60-7.54 (m, 4H), 7.49 (d, J
= 8.4 Hz, 2H,), 6.89 (d, J = 8.4 Hz, 2H,)
3.84 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.97,
133.24, 131.56, 129.50 (q, J = 33 Hz, C), 125.30 (d, J = 3 Hz, CH), 125.21(q, J = 272 Hz, CF3),
114.53, 114.06, 91.87, 86.81, 55.31; IR (KBr): 2946, 2230, 1195, 1012 cm-1; HRMS (EI): [M]+ calcd
for C16H11F3O 276.2560; found 276.2562.
(p-chlorophenyl)(p-anisyl)acetylene (3i)9
White solid; yield: 88%; mp 115-116 oC; 1H NMR (400 MHz, CDCl3): δ 7.47-7.42 (m, 4H), 7.31 (d, J
= 7.5 Hz, 2H), 6.88 (d, J = 8.2 Hz, 2H)
3.83 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.70,
132.81, 132.03, 131.59, 127.60, 121.03, 113.91, 112.99, 89.28, 85.93, 54.28; IR (KBr): 2937, 2217,
1176, 1012 cm-1; HRMS (EI): [M]+ calcd for C15H11ClO 242.0498; found 242.0496.
1-bromo-4-((4-methoxyphenyl)ethynyl)benzene (3j)4
White solid; yield: 90%; mp 235-237 oC; 1H NMR (400 MHz, CDCl3): δ 7.47-7.45 (m, 4H), 7.03 (t, J
= 8.6 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H)
3.83 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.76,
133.04, 132.82, 131.53, 122.55, 122.03, 114.95, 114.02, 90.52, 87.02, 55.28; IR (KBr): 2925, 2217,
1164, 1036 cm-1; HRMS (EI): [M]+ calcd for C15H11BrO 286.0072; found 286.0073.
1-(2-(4-methoxyphenyl)ethynyl)naphthalene (3k)6
Yellow solid; yield: 91%; mp 60-62 oC; 1H NMR (400 MHz, CDCl3): δ 8.43 (d, J = 8.2 Hz, 1H), 7.85
(d, J = 8.2 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1H), 7.73 (dd, J = 7.2, 1.1 Hz, 1H), 7.61-7.55 (m, 3H), 7.52
5

(dt, J = 7.6, 1.3 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 6.91 (d, J = 8.9 Hz, 2H), 3.82 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 159.65, 133.15, 133.07, 130.01, 128.36, 128.24, 126.62, 126.32, 126.22, 125.26,
121.16, 115.41, 114.01, 94.31, 86.16, 55.27; IR (KBr): 2942, 2225, 1235, 1042 cm-1; LRMS (EI):
[M]+ calcd for C19H14O 258; found 258.
diphenylacetylene (3l)3
o
White solid; yield: 90%; mp 59-61 C; 1H NMR (400 MHz, CDCl3): δ 7.55-7.52 (m, 4H), 7.35-7.33
(m, 6H); 13C NMR (100 MHz, CDCl3): δ 131.56, 128.31, 128.22, 123.18, 89.31; IR (KBr): 2913, 2219,
1213, 1026 cm-1; LRMS (EI): [M]+ calcd for C14H10 178; found 178.
2-(phenylethynyl)naphthalene (3m)4
o
White solid; yield: 88%; mp 105-106 C; 1H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.82-7.79 (m,
3H), 7.59-7.57 (m, 3H), 7.50-7.47 (m, 2H), 7.37-7.35 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 132.96,
132.75, 131.63, 131.40, 128.36, 128.34, 128.26, 127.98, 127.75, 127.74, 126.64, 126.52, 123.22,
120.51, 89.76, 89.70; IR (KBr): 2923, 2218, 1493, 1023, 965 cm-1; HRMS (EI): [M]+ calcd for C18H12
228.0939; found 228.0935.
(2,4-dimethoxyphenyl)phenylacetylene (3n)4
Yellow oil; yield: 93%; 1H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.4 Hz,
1H), 7.32-7.30 (m, 3H), 6.48-6.45 (m, 2H), 3.88 (s, 3H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
161.13, 161.04, 134.26, 131.43, 128.14, 127.73, 123.75, 104.85, 104.73, 98.34, 91.97, 85.69, 55.78,
55.38; IR (neat): 2926, 2227, 1493, 749 cm-1; LRMS (EI): [M]+ calcd for C16H14O2 238; found 238.
phenyl-p-tolyacetylene (3o)3
Colorless solid; yield: 91%; mp 69-71 oC; 1H NMR (400 MHz, CDCl3): δ 7.53-7.51 (m, 2H), 7.43 (d,
J = 8.0 Hz, 2H), 7.33-7.31 (m, 3H), 7.14(d, J = 8.0 Hz, 2H), 2.35 (s, 3H); 13C NMR (400 MHz,
CDCl3): δ 138.35, 131.50, 131.44, 129.08, 128.28, 128.04, 123.38, 120.08, 89.50, 88.67, 21.49; IR
(KBr): 2923, 2216, 1493, 1023, 965 cm-1; LRMS (EI): [M]+ calcd for C15H12 192; found 192.
(4-chlorophenyl)phenylacetylene (3p)4
White solid; yield: 86%; mp 80-82 oC; 1H NMR (400 MHz, CDCl3): δ 7.53-7.51 (m, 2H), 7.46 (d, J =
8.4 Hz, 2H), 7.36-7.34 (m, 3H), 7.32(d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 134.20,
132.77, 131.56, 128.66, 128.46, 128.37, 122.85, 121.71, 90.26, 88.20; IR (KBr): 3048, 2228, 1486,
1024, 973 cm-1; HRMS (EI): [M]+ calcd for C14H9Cl 212.6705; found 212.6707.
6

1-nitro-4-(phenylethynyl)benzene (3q)10
Colorless solid; yield: 75%; mp 121-123 oC; 1H NMR (400 MHz, CDCl3): δ 8.22 (d, J = 8.8 Hz, 2 H),
7.67 (d, J = 9.2 Hz, 2 H), 7.57-7.55 (m, 2 H), 7.40-7.38 (m, 3 H); 13C NMR (100 MHz, CDCl3): δ
146.91, 132.24, 131.82, 130.23, 129.26, 128.52, 123.62, 122.04, 94.67, 87.52; IR (KBr): 2916, 2215,
1357, 1035, 931 cm-1; HRMS (EI): [M]+ calcd for C14H9NO2 223.2379; found 223.2380.
2-(2-phenylethynyl)pyridine (3r)11
Oil; yield: 90%; 1H NMR (400 MHz, CDCl3): δ 8.78 (s, 1 H), 7.70-7.66 (m, 1 H), 7.62-7.54 (m, 2 H),
7.53 (d, J = 8.0 Hz, 1H), 7.38-7.35 (m, 3 H), 7.27-7.23 (m, 1H); 13C NMR (100 MHz, CDCl3): 150.01,
143.37, 136.14, 131.98, 128.93, 128.34, 127.12, 122.72, 122.16, 89.15, 88.52; IR (neat): 3055, 2223,
1357, 1035, 931 cm-1; HRMS (EI): [M]+ calcd for C13H9N 179.0731; found 179.0734.
2-(2-phenylethynyl)furan (3s)12
Colorless oil; yield: 91%; 1H NMR (400 MHz, CDCl3): δ 7.53 (dd, J = 6.1, 3.1 Hz, 2H), 7.43 (s, 1H),
7.34 (t, J = 3.7 Hz, 3H), 6.66 (d, J = 3.2 Hz, 1H), 6.44 (dd, J = 3.2, 1.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) : δ 143.62, 137.06, 131.38, 128.67, 128.36, 122.20, 115.22, 111.05, 93.20, 79.32; IR (neat):
3060, 2208, 1291, 1034, 929 cm-1; HRMS (EI): [M]+ calcd for C12H8O 168.0575; found 168.0578.
7

1H NMR spectrum of the product 3a
13C NMR spectrum of the product 3a
8

1H NMR spectrum of the product 3b
13C NMR spectrum of the product 3b
9

1H NMR spectrum of the product 3c
13C NMR spectrum of the product 3c
10

1H NMR spectrum of the product 3d
13C NMR spectrum of the product 3d
11

1H NMR spectrum of the product 3e
13C NMR spectrum of the product 3e
12

1H NMR spectrum of the product 3f
13C NMR spectrum of the product 3f
13

1H NMR spectrum of the product 3g
13C NMR spectrum of the product 3g
14

1H NMR spectrum of the product 3h
13C NMR spectrum of the product 3h
15

1H NMR spectrum of the product 3i
13C NMR spectrum of the product 3i
16

1H NMR spectrum of the product 3j
13C NMR spectrum of the product 3j
17

1H NMR spectrum of the product 3k
13C NMR spectrum of the product 3k
18

1H NMR spectrum of the product 3l
13C NMR spectrum of the product 3l
19

1H NMR spectrum of the product 3m
13C NMR spectrum of the product 3m
20

1H NMR spectrum of the product 3n
13C NMR spectrum of the product 3n
21

1H NMR spectrum of the product 3o
13C NMR spectrum of the product 3o
22

1H NMR spectrum of the product 3p
13C NMR spectrum of the product 3p
23

1H NMR spectrum of the product 3q
13C NMR spectrum of the product 3q
24

1H NMR spectrum of the product 3r
13C NMR spectrum of the product 3r
25

1H NMR spectrum of the product 3s
13C NMR spectrum of the product 3s
26

1. Rao, M. L. N.; Jadhav, D. N.; Dasgupta, P. Org. Lett. 2010, 12, 2048-2051.
2. Huh, D. H.; Jeong, J. S.; Lee, H. B.; Ryu, H.; Kim, Y. G. Tetrahedron 2002, 58, 9925-9932.
3. Huang, H.; Liu, H.; Jiang, H. L; Chen, K. X. J. Org. Chem. 2008, 73, 6037-6040.
4. Wang, S. H.; Wang, M.; Wang, L.; Wang, B.; Li, P. H.; Yang, J. Tetrahedron 2011, 67,
4800-4806.
5. Komáromi, A.; Tolnai, G. L.; Novák, Z. Tetrahedron Lett. 2008, 49, 7294-7298.
6. Lee, D.-H.; Kwon, Y.-J.; Jin, M.-J. Adv. Synth. Catal. 2011, 353, 3090-3094.
7. Liu, N.; Liu, C.; Xu, Q.; Jin, Z. L. Eur. J. Org. Chem. 2011, 4422-4428.
8. Shirakawa, E.; Kitabata, T.; Otsuka, H.; Tsuchimoto, T. Tetrahedron 2005, 61, 9878-9885.
9. Kabalka, G. W.; Al-Masum, M.; Mereddy, A. R.; Dadush, E. Tetrahedron Lett. 2006, 47,
1133-1136.
10. Pan, D. L.; Zhang, C.; Ding, S. T.; Jiao, N. Eur. J. Org. Chem. 2011, 4751-4755.
11. Li, T. Y.; Qu, X. M.; Zhu, Y.; Sun, P.; Yang, H. L.; Shan, Y. Q.; Zhang, H. X.; Liu, D. F.; Zhang,
X.; Mao, J. C. Adv. Synth. Catal. 2011, 353, 2731-2738.
12. Chelucci, G.; Capitta, F.; Baldino, S. Tetrahedron 2008, 64, 10250-10257.
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