The Journal of Organic Chemistry
ARTICLE
Pd(crotyl)(Pt-Bu3)Cl (14). [Pd(crotyl)Cl]2 (276 mg, 0.71 mmol);
Pt-Bu3 (0.29 g, 1.46 mmol); THF (2.8 mL); 30 min. Product obtained as
a yellow solid (384 mg, 68%); 1H NMR (CDCl3, 400 MHz): δ
5.12ꢀ5.04 (m, 1H), 4.45ꢀ4.38 (m, 1H), 3.85 (d, J 5.2, 1H), 2.56 (d,
J 11.2, 1H), 1.68ꢀ1.66 (m, 3H), 1.53 (d, J 12.0, 27H); 13C (CDCl3, 100
MHz): δ 112.7, 103.6, 103.4, 50.9, 39.4, 32.8, 29.1, 17.9; 31P NMR
(CDCl3, 162 MHz): δ 89.7. Anal. Calcd for C16H34ClPPd: C, 48.13; H,
8.58; P, 7.76. Found: C, 48.32; H, 8.62; P, 7.84.
Pd(allyl)P(t-Bu)2(p-NMe2C6H4)Cl (15). [Pd(allyl)Cl]2 (311 mg,
0.85 mmol); P(t-Bu)2(p-NMe2C6H4) (496 mg, 1.87 mmol); THF
(17 mL); 18 h. Product obtained as a yellow solid (727 mg, 96%); 1H
NMR (CDCl3, 400 MHz): δ 7.50 (app t, J 8.8, 2H), 6.65 (d, J 8.0, 2H),
5.50 (heptet, J 7.2, 1H), 4.63 (dt, J 6.8, 2.0, 1H), 3.69 (dd, J 13.2, 9.2,
1H), 3.39 (d, J 6.0, 1H), 3.01 (s, 6H), 2.68 (d, J 12.0, 1H), 1.47 (d,
J 14.0, 9H), 1.39 (d, J 14.0, 9H); 13C (CDCl3, 100 MHz): δ 150.9, 136.7,
136.6, 116.9, 116.6, 115.2, 110.4, 110.3, 80.7, 80.4, 58.8, 39.9, 36.0, 30.6,
29.9; 31P NMR (CDCl3, 162 MHz): δ 61.9. Anal. Calcd for C19H33-
ClNPPd: C, 50.90; H, 7.42; Cl, 7.91; P, 6.91. Found: C, 51.44; H, 7.51; Cl,
7.54; P, 6.94.
Pd(crotyl)P(t-Bu)2(p-NMe2C6H4)Cl (16). [Pd(crotyl)Cl]2 (132
mg, 0.34 mmol); P(t-Bu)2(p-NMe2C6H4) (180 mg, 0.68 mmol); THF
(3.7 mL); 90 min. Product obtained as a yellow solid (263 mg, 85%); 1H
NMR (CDCl3, 400 MHz): δ 7.52 (t, J 8.8, 2H), 6.65 (d, J 8.0, 2H),
5.25ꢀ5.17 (m, 1H), 4.40ꢀ4.29 (m, 1H), 3.21ꢀ3.19 (m, 1H), 3.00 (s,
3H), 2.47 (d, J 11.6, 1H), 1.77 (dd, J 8.4, 6.4, 3H), 1.44 (d, J 13.6, 9H),
1.38 (d, J 13.6, 9H); 13C (CDCl3, 100 MHz): δ 150.9, 149.6, 136.9,
136.7, 117.1, 116.8, 114.1, 110.3, 99.8, 99.6, 53.5, 40.0, 35.8, 30.6, 29.9,
17.4; 31P NMR (CDCl3, 162 MHz): δ 65.5. Anal. Calcd for
C20H35ClNPPd: C, 51.96; H, 7.63; N, 3.03; P, 6.70. Found: C, 51.93;
H, 7.54; N, 2.84; P, 6.58.
Pd(crotyl)(P(t-Bu2)Np)Cl (17). [Pd(crotyl)Cl]2 (451 mg, 1.14
mmol); P(t-Bu2)Np (10 wt % in hexane, used as solvent) (5.0 g, 2.31
mmol); 60 min. Product obtained as a yellow solid (577 mg, 61%);
1H NMR (CDCl3, 400 MHz): δ 5.14ꢀ5.06 (m, 1H), 4.40ꢀ4.33 (m,
1H), 3.66 (d, J 5.6, 1H), 2.53 (d, J 11.6, 1H), 2.18ꢀ2.02 (m, 2H), 1.72 (dd,
J 8.0, 6.4, 3H), 1.38 (dd, J 17.6, 13.6, 18H), 1.22 (s, 9H); 13C (CDCl3,
100 MHz): δ 113.0, 101.2, 101.0, 49.6, 35.5, 35.2, 33.0, 31.1, 30.6, 17.7;
31P NMR (CDCl3, 162 MHz): δ 59.8. Anal. Calcd for C17H36ClPPd: C,
49.40; H, 8.78; P, 7.49. Found: C, 49.40; H, 8.70; P, 7.43.
toluene (2.0 mL). The general procedure afforded the title compound in
96% yield (434 mg; X = Br) and 95% yield (429 mg; X = Cl); 1H NMR
(CDCl3, 400 MHz): δ 7.29ꢀ7.19 (m, 3H), 6.73 (d, J 6.8, 2H), 6.44 (d,
J 6.8, 2H), 4.95 (br s, 1H), 3.73 (s, 3H), 3.19 (heptet, J 6.8, 2H), 1.14 (d,
J 7.2, 12H); 13C (CDCl3, 100 MHz): δ 152.2, 147.1, 142.2, 136.0, 126.7,
123.8, 115.0, 114.2, 55.7, 28.0, 23.8. Anal. Calcd for C19H25NO: C,
80.52; H, 8.89; N, 4.94. Found: C, 80.95; H, 9.05; N, 5.03.
N-(4-Methoxyphenyl)morpholine (18c):27 4-Bromoanisole
(200 μL, 1.6 mmol) or 4-chloroanisole (196 μL, 1.6 mmol); morpholine
(175 μL, 2.0 mmol); NaOt-Bu (230 mg, 2.4 mmol); Pd(crotyl)Q-
PhosCl (7.2 mg, 0.008 mmol, 0.5 mol %); toluene (2.0 mL). The general
procedure afforded the title compound in 98% yield (302 mg; X = Br)
1
and 96% yield (297 mg; X = Cl); H NMR (CDCl3, 400 MHz): δ
6.91ꢀ6.84 (m, 4H), 3.86 (t, J 4.4, 4H), 3.77 (s, 3H), 3.05 (t, J 4.8, 4H).
N-(4-Methoxyphenyl)diphenylamine (18d):28,29 4-Bromo-
anisole (200 μL, 1.6 mmol) or 4-chloroanisole (196 μL, 1.6 mmol);
diphenylaniline (338 mg, 2.0 mmol); NaOt-Bu (230 mg, 2.4 mmol);
Pd(crotyl)Q-PhosCl (7.2 mg, 0.008 mmol, 0.5 mol %); toluene
(2.0 mL). The general procedure afforded the title compound in 84%
1
yield (370 mg; X = Br) and 68% yield (298 mg; X = Cl); H NMR
(CDCl3, 400 MHz): δ 7.22ꢀ7.18 (m, 4H), 7.08ꢀ7.02 (m, 6H),
6.95ꢀ6.92 (m, 2H), 6.85ꢀ6.81 (m, 2H), 3.80 (s, 3H).
4-Methoxydiphenylamine (18e):30 4-Bromoanisole (200 μL,
1.6 mmol); aniline (182 μL, 2.0 mmol); NaOt-Bu (230 mg, 2.4 mmol);
Pd(crotyl)Q-PhosCl (7.2 mg, 0.008 mmol, 0.5 mol %); toluene
(2.0 mL). The general procedure afforded the title compound in 91%
yield (288 mg); 1H NMR (CDCl3, 400 MHz): δ 7.24ꢀ7.19 (m, 2H),
7.08ꢀ7.06 (m, 2H), 6.91ꢀ6.81 (m, 5H), 5.48 (s, 1H), 3.79 (s, 3H).
N-(4-Methoxyphenyl)-N-methylaniline (18f):28 4-Bromo-
anisole (200 μL, 1.6 mmol), 4-chloroanisole (196 μL, 1.6 mmol), or
4-iodoanisole (374 mg, 1.6 mmol); N-methylaniline (217 μL, 2.0
mmol); NaOt-Bu (230 mg, 2.4 mmol); Pd(crotyl)Q-PhosCl (7.2 mg,
0.008 mmol, 0.5 mol %); toluene (2.0 mL). The general procedure
afforded the title compound in 93% yield (315 mg; X = Br), 98% yield
(335 mg; X = Cl) and 95% yield (325 mg; X = I); 1H NMR (CDCl3, 400
MHz): δ 7.17 (dd, J 8.4, 2H), 7.09ꢀ7.05 (m, 2H), 6.88ꢀ6.84 (m, 2H),
6.78ꢀ6.74 (m, 3H), 3.77 (s, 3H), 3.22 (s, 3H).
4-Chloro-2-methyldiphenyl-methylamine (18g). 2-Bromo-
5-chlorotoluene (213 μL, 1.6 mmol); N-methylaniline (217 μL, 2.0
mmol); NaOt-Bu (230 mg, 2.4 mmol); Pd(crotyl)Q-PhosCl (7.2 mg,
0.008 mmol, 0.5 mol %); toluene (2.0 mL). The general procedure
afforded the title compound in 88% yield (324 mg); 1H NMR (CDCl3,
400 MHz): δ 7.27 (d, J 2.0, 1H), 7.21ꢀ7.16 (m, 3H), 7.07 (d, J 8.4, 1H),
6.73 (t, J 7.2, 1H), 6.53 (d, J 8.0, 2H), 3.19 (s, 3H), 2.11 (s, 3H); 13C
(CDCl3, 100 MHz) δ 146.5, 143.1, 136.4, 129.1, 128.9, 127.2, 126.7,
125.3, 114.9, 110.7, 36.8, 15.5. Anal. Calcd for C14H14ClN: C, 72.57; H,
6.09; N, 6.04. Found: C, 72.31; H, 6.13; N, 6.05.
3-Chloro-4-methyldiphenyl-methylamine (18h). 4-Bromo-
2-chlorotoluene (217 μL, 1.6 mmol); N-methylaniline (217 μL, 2.0
mmol); NaOt-Bu (230 mg, 2.4 mmol); Pd(crotyl)Q-PhosCl (7.2 mg,
0.008 mmol, 0.5 mol %); toluene (2.0 mL). The general procedure
afforded the title compound in 97% yield (358 mg); 1H NMR (CDCl3,
400 MHz): δ 7.30ꢀ7.26 (m, 2H), 7.08 (d, J 8.4, 1H), 7.02ꢀ6.96 (m,
4H), 6.79 (dd, J 8.4, 2.4, 1H), 3.27 (s, 3H), 2.30 (s, 3H); 13C (CDCl3,
100 MHz): δ 148.7, 148.1, 134.7, 131.2, 129.4, 128.2, 121.9, 121.0,
120.3, 118.5, 40.4, 19.2. Anal. Calcd for C14H14ClN: C, 72.57; H, 6.09;
N, 6.04. Found: C, 72.01; H, 6.04; N, 5.98.
General Procedure for the BuchwaldꢀHartwig Coupling
Reaction. A Schlenk flask was charged with the catalyst, NaOt-Bu, and
aryl halide, if solid, and the flask was evacuated and backfilled with
nitrogen three times. Subsequently, a solution of the aryl halide, if liquid,
and the amine in toluene was added. The resulting reaction mixture was
stirred under nitrogen at the indicated temperature and time (see
Table 4). The crude reaction mixture was absorbed onto silica gel and
purified by flash column chromatography (MTBE/40ꢀ60 petroleum
ether eluent).
2-CO2Me-30,40,50-trimethoxy-diphenylamine (18a). Methyl
anthranilate (390 μL, 3.0 mmol); 5-bromo-1,2,3-trimethoxybenzene
(594 mg, 2.3 mmol); NaOt-Bu (345 mg, 3.6 mmol); Pd(crotyl)-
Q-PhosCl (43.5 mg, 0.06 mmol, 2.0 mol %); toluene (5.0 mL). The
general procedure afforded the title compound as an off-white solid (462
mg, 65%); 1H NMR (CDCl3, 400 MHz): δ 9.39 (br s, 1H), 7.96 (dd,
J 4.4, 1.6, 1H), 7.33 (dd, J 6.8, 1.6, 1H), 7.21 (d, J 8.4, 1H), 6.73 (dd, J 8.0,
0.8, 1H), 6.49 (s, 2H), 3.91 (s, 3H), 3.85 (s, 3H), 3.83 (s, 6H); 13C
(CDCl3, 100 MHz): δ 169.0, 153.8, 148.4, 136.6, 134.6, 134.2, 131.6,
116.9, 114.1, 111.6, 100.7, 61.0, 56.1, 51.8. Anal. Calcd for C17H19NO5:
C, 64.34; H, 6.03; N, 4.41. Found: C, 64.30; H, 6.06; N, 4.41.
N-(2,6-Diisopropylphenyl)-N-(p-methoxy)amine (18b). 4-
bromoanisole (200 μL, 1.6 mmol) or 4-chloroanisole (196 μL, 1.6
mmol); 2,6-diisopropylaniline (377 μL, 2.0 mmol); NaOt-Bu (230 mg,
2.4 mmol); Pd(crotyl)Q-PhosCl (X = Br; 14.4 mg, 0.016 mmol, 1.0 mol %)
or Pd(crotyl)Q-PhosCl (X = Cl; 7.2 mg, 0.008 mmol, 0.5 mol %)
N-(2,6-Diisopropylphenyl)-N-(o-tolyl)amine (18i):31 2-Bro-
motoluene (274 mg, 1.6 mmol) or 2-chlorotoluene (168 μL, 1.6 mmol);
2,6-diisopropylaniline (377 μL, 2.0 mmol); NaOt-Bu (230 mg, 2.4
mmol); Pd(crotyl)Q-PhosCl (7.2 mg, 0.008 mmol, 0.5 mol %); toluene
(2.0 mL). The general procedure afforded the title compound in 96%
yield (410 mg; X = Br) and 87% conversion (X = Cl); 1H NMR (CDCl3,
400 MHz): δ 7.31ꢀ7.21 (m, 3H), 7.12 (d, J 7.2, 1H), 6.94 (t, J 7.6, 1H),
7929
dx.doi.org/10.1021/jo2013324 |J. Org. Chem. 2011, 76, 7918–7932