Cross-Coupling of Aryl and Acyl Halides with Zinc Reagents
6.8 Hz, 3H), 2.66 (sept, J ) 6.8 Hz, 1H), 7.06-7.46 (m, 13H). 13
C
2-Bromo-2′-methylbenzophenone, 53.24 Purification by flash
chromatography (hexanes/ethyl acetate 10:1) gave 253.1 mg of a
colorless oil (0.92 mmol, 92%). 1H NMR: δ 2.58 (s, 3H), 7.12-7.18
(m, 1H), 7.26-7.41 (m, 6H), 7.56-7.60 (m, 1H). 13C NMR: δ 21.9,
120.6, 126.1, 127.8, 130.3, 132.0, 132.2, 132.5, 132.7, 133.9, 136.9,
140.4, 142.1, 198.4.
NMR: δ 22.4, 25.6, 30.0, 125.3, 125.5, 126.7, 127.3, 127.8, 127.9,
128.0, 130.0, 131.1, 140.3, 140.6 141.3, 141.6, 146.7.
4-Cyano-2,2′-dimethylbiphenyl, 40. Purification by flash chro-
matography (hexanes/ethyl acetate 10:1) gave 182.4 mg of a
1
colorless oil (0.88 mmol, 88%). H NMR: δ 2.03(s, 3H), 2.08 (s,
3-Chloro-2′-methylbenzophenone, 55.10 Purification by flash
chromatography (hexanes/ethyl acetate 10:1) gave 219.2 mg of a
colorless oil (0.95 mmol, 95%). 1H NMR: δ 2.33 (s, 3H), 7.19-7.40
(m, 5H), 7.48-7.51 (m, 1H), 7.80 (dd, J ) 2.1 Hz, 1.6 Hz, 1H).
13C NMR: δ 20.5, 125.8, 128.8, 129.1, 130.3, 131.2, 131.7, 132.5,
133.4, 135.2, 137.5, 138.2, 139.9, 197.4.
3H), 7.03 (d, J ) 7.3 Hz, 1H), 7.19 (d, J ) 7.8 Hz, 1H), 7.21-7.31
(m, 3H), 7.48-7.52 (m, 1H), 7.55 (dd, J ) 1.2 Hz, 0.8 Hz, 1H).
13C NMR: δ 20.2, 111.6, 119.6, 126.4, 128.6, 129.1, 129.9, 130.7,
133.8, 133.9, 135.7, 138.1, 140.2, 147.2. Anal. Calcd for C15H13N:
C, 86.92; H, 6.32; N, 6.76. Found: C, 86.61; H, 6.38; N, 6.83.
4-Acetyl-2′-methylbiphenyl, 42.19 Purification by flash chro-
matography (hexanes/ethyl acetate 10:1) gave 182.9 mg of a
colorless oil (0.87 mmol, 87%). 1H NMR: δ 2.25 (s, 3H), 2.62 (s,
3H), 7.18-7.28 (m, 4H), 7.40 (d, J ) 8.5 Hz, 2H), 7.99 (d, J )
8.5 Hz, 2H). 13C NMR: δ 20.9, 27.2, 126.5, 128.5, 128.8, 130.0,
130.1, 131.1, 135.7, 136.1, 141.3, 147.5, 198.5.
4-Cyanobenzophenone, 58.25 Purification by flash chromatog-
raphy (hexanes/ethyl acetate 10:1) gave 188.6 mg of colorless
crystals (0.91 mmol, 91%). 1H NMR: δ 7.48-7.54 (m, 2H),
7.61-7.67 (m, 1H), 7.77-7.80 (m, 4H), 7.85-7.89 (m, 2H). 13C
NMR: δ 116.0, 118.4, 129.0, 130.4, 130.6, 132.6, 133.7, 136.7,
141.5, 195.3.
3-Nitro-2′-methylbiphenyl, 45.20 Purification by flash chroma-
tography (hexanes/ethyl acetate 9:1) gave 191.9 mg of a yellow
Piperonyloylbenzene, 60.26 Purification by flash chromatography
(hexanes/ethyl acetate 10:1) gave 201.3 mg of a colorless oil (0.89
1
oil (0.90 mmol, 90%). H NMR: δ 2.26 (s, 3H), 7.18-7.31 (m,
1
mmol, 89%). H NMR: δ 6.00 (s, 2H), 6.81 (d, J ) 8.3 Hz, 1H),
4H), 7.53-7.66 (m, 2H), 8.16-8.19 (m, 2H). 13C NMR: δ 20.9,
122.4, 124.6, 126.7, 128.9, 129.6, 130.1, 131.2, 135.7, 135.9, 139.9,
144.1, 148.6.
7.32-7.35 (m, 2H), 7.40-7.46 (m, 2H), 7.49-7.55 (m, 1H),
7.70-7.74 (m, 2H). 13C NMR: δ 102.2, 107.9, 110.1, 127.1, 128.4,
129.9, 132.0, 132.2, 138.4, 148.2, 151.8, 195.2.
4-Methoxy-2′-methylbenzophenone, 62.27 Purification by flash
chromatography (hexanes/ethyl acetate 10:1) gave 217.2 mg of a
colorless oil (0.96 mmol, 96%). 1H NMR: δ 2.29 (s, 3H), 3.84 (m,
3H), 6.89-6.93 (m, 2H), 7.19-7.38 (m, 4H), 7.76-7.80 (m, 2H).
13C NMR: δ 20.3, 56.1, 114.3, 125.7, 128.5, 130.3, 131.1, 131.4,
133.0, 136.7, 139.8, 164.3, 197.9.
General Procedure for the POPd-Catalyzed Cross-Coupling
of Acyl Chlorides and Organozinc Reagents. Anhydrous ZnCl2 (1.6
mmol) and 3.0 mL of anhydrous N-methylpyrrolidinone (NMP)
were placed in a 50 mL round-bottom flask under nitrogen. Then,
o-tolylmagnesium chloride (2.0 M solution in diethyl ether; 0.75
mL, 1.5 mmol) was added dropwise to the colorless solution. The
resulting mixture was heated to 60 °C and purged with nitrogen
for 20 min to remove the ether. The mixture was cooled to room
temperature and stirred for 1 h. After addition of benzoyl chloride
(1.0 mmol) and POPd (0.05 mmol) in NMP (1.0 mL), the reaction
mixture was stirred at room temperature for 30 min, quenched with
water, extracted with diethyl ether, and dried over anhydrous
MgSO4. The solvents were removed under vacuum, and the crude
products were purified by flash chromatography on silica gel as
described below.
3-Methoxybenzophenone, 64.8 Purification by flash chroma-
tography (hexanes/ethyl acetate 10:1) gave 197.3 mg of a colorless
1
oil (0.93 mmol, 93%). H NMR: δ 3.80 (m, 3H), 7.08-7.12 (m,
1H), 7.30-7.37 (m, 3H), 7.40-7.46 (m, 2H), 7.51-7.57 (m, 1H),
7.77-7.80 (m, 2H). 13C NMR: δ 55.8, 114.8, 119.2, 123.3, 128.7,
129.7, 130.5, 132.9, 138.0, 139.3, 160.0, 196.8.
3-Cyanobenzophenone, 66.28 Purification by flash chromatog-
raphy (hexanes/ethyl acetate 10:1) gave 188.6 mg of colorless
crystals (0.91 mmol, 91%). 1H NMR: δ 7.48-7.54 (m, 2H),
7.61-7.67 (m, 2H), 7.76-7.79 (m, 2H), 7.85-7.88 (m, 1H),
8.00-8.06 (m, 2H). 13C NMR: δ 113.2, 118.4, 129.1, 129.8, 130.4,
133.7, 133.8, 134.3, 135.8, 136.7, 139.0, 194.8.
2-Methylbenzophenone, 47.21 Purification by flash chromatog-
raphy (hexanes/ethyl acetate 10:1) gave 192.3 mg of a colorless
1
oil (0.98 mmol, 98%). H NMR: δ 2.32 (s, 3H), 7.18-7.30 (m,
3H), 7.34 (dd, J ) 7.1 Hz, 1.6 Hz, 1H), 7.38-7.44 (m, 2H),
7.50-7.56 (m, 1H), 7.78 (d, J ) 7.1 Hz, 2H). 13C NMR: δ 20.5,
125.7, 128.9, 129.0, 130.6, 130.8, 131.5, 133.6, 137.2, 138.2, 139.1,
199.0.
Ethyl 3-benzoylbenzoate, 68.29 Purification by flash chroma-
tography (hexanes/ethyl acetate 10:1) gave 244.1 mg of a colorless
1
oil (0.96 mmol, 96%). H NMR: δ 1.38 (t, J ) 7.1 Hz, 3H), 4.39
(q, J ) 7.1 Hz, 2H), 7.45-7.62 (m, 4H), 7.78-7.81 (m, 2H),
7.94-7.98 (m, 1H), 8.23-8.27 (m, 1H), 8.46 (t, J ) 1.7 Hz, 1H).
13C NMR: δ 14.7, 61.8, 128.9, 130.4, 131.3, 133.2, 133.5, 134.4,
137.4, 138.3, 166.1, 196.0.
2-(1-Naphthoyl)toluene, 49.22 Purification by flash chromatog-
raphy (hexanes/ethyl acetate 10:1) gave 238.9 mg of a colorless
1
oil (0.97 mmol, 97%). H NMR: δ 2.44 (s, 3H), 7.07-7.15 (m,
Acetophenone, 70.30 Purification by flash chromatography
(hexanes/ethyl acetate 10:1) gave 108.1 mg of a colorless oil (0.90
mmol, 90%). 1H NMR: δ 2.57 (s, 3H), 7.40-7.46 (m, 2H),
7.50-7.57 (m, 1H), 7.92-7.96 (m, 2H). 13C NMR: δ 27.0, 128.7,
129.0, 133.5, 137.5, 198.6.
1H), 7.23 (d, J ) 6.8 Hz, 1H), 7.30-7.35 (m, 3H), 7.43-7.54 (m,
3H), 7.82 (d, J ) 8.1 Hz, 1H), 7.90 (d, J ) 8.1 Hz, 1H), 8.56 (d,
J ) 8.1 Hz, 1H). 13C NMR: δ 21.2, 124.8, 125.9, 126.3, 127.0,
128.3, 129.0, 130.7, 130.9, 131.5, 131.6, 131.9, 133.0, 134.4, 136.9,
138.6, 140.0, 200.7.
5-Bromo-1-phenylpentan-1-one, 72.31 Purification by flash
chromatography (hexanes/ethyl acetate 10:1) gave 202.5 mg of
2,3′-Dimethylbenzophenone, 51.23 Purification by flash chro-
matography (hexanes/ethyl acetate 10:1) gave 199.8 mg of a
colorless oil (0.95 mmol, 95%). 1H NMR: δ 2.32 (s, 3H), 2.35 (s,
3H), 7.18-7.38 (m, 6H), 7.53-7.57 (m, 1H), 7.65 (dd, J ) 1.2
Hz, 0.7 Hz, 1H). 13C NMR: δ 20.5, 21.8, 125.7, 128.1, 128.8, 129.0,
130.7, 130.9, 131.5, 134.4, 137.1, 138.3, 138.8, 139.3, 199.2.
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