Palladium-Catalyzed Cross-Coupling Reactions of Aryl Chlorides
10.3, 14.3 Hz); 31P NMR (CD2Cl2, 145 MHz) δ 3.63; HRMS
(ESI+) calcd for C26H31N3P (MH+) 416.2256, found 416.2252.
4-Dicyclohexylphosphanyl-1-phenyl-5-(2-methoxyphenyl)-1H-
[1,2,3]triazole (7f). This compound was prepared from triazole
compound 6c and PCy2Cl following the general procedure as a
white solid (64% yield): 1H NMR (360 MHz, CD2Cl2) δ 7.36-
7.42 (m, 6H), 7.30 (dd, J ) 1.3, 7.5 Hz, 1H), 7.05-7.09 (m, 1H),
6.89 (d, J ) 8.4 Hz, 1H), 3.47 (s, 3H), 2.10-2.33 (m, 2H), 1.61-
2.05 (m, 10H), 0.98-1.52 (m, 10H); 13C NMR (90 MHz, CD2Cl2)
δ 157.2, 141.8 (d, J ) 27.4 Hz), 141.5 (d, J ) 15.3 Hz), 137.6,
132.4, 131.1, 128.8, 128.4, 123.8, 120.3, 117.1, 111.1, 55.0, 33.0
(d, J ) 42.4 Hz), 30.3, 29.4 (d, J ) 30.8 Hz), 27.2 (d, J ) 19.5
Hz), 27.1, 26.6; 31P NMR (145 MHz, CD2Cl2) δ -27.99; HRMS
(ESI+) calcd. for C27H35N3OP (MH+) 448.2518, found 448.2510.
4-Di-tert-butylphosphanyl-1-phenyl-5-(2-methoxyphenyl)-1H-
[1,2,3]triazole (7g). This compound was prepared from triazole
compound 6c and PtBu2Cl following the general procedure as a
white solid (76% yield): 1H NMR (CD2Cl2, 360 MHz) δ 7.47-
7.32 (m, 7H), 7.09 (t, J ) 7.2 Hz, 1H), 6.90 (d, J ) 8.2 Hz, 1H),
3.48 (s, 3H), 1.41 (d, J ) 11.8 Hz, 9H), 1.24 (d, J ) 11.8 Hz, 9H);
13C NMR (CDCl3, 90 MHz) δ 157.3, 142.5 (d, J ) 9.3 Hz), 142.2
(d, J ) 24.5 Hz), 137.6, 132.6 (d, J ) 2.6 Hz), 131.1, 128.8, 128.5,
123.9, 120.3, 117.4, 111.0, 54.9, 32.5 (dd, J ) 10.3, 17.0 Hz), 30.2
(dd, J ) 14.1, 44.1 Hz); 31P NMR (CD2Cl2, 145 MHz) δ 3.47;
HRMS (ESI+) calcd for C23H31N3OP (MH+) 396.2205, found
396.2202.
Miyaura coupling to form hindered biaryl compounds (up to
96% yield). A CAChe model for the Pd/7i complex shows that
the likelihood of a Pd-arene interaction might be a rationale
for the its high catalytic reactivity.
Experimental Section
General Procedure for the Preparation of ClickPhos 7a-j.
4-Di-tert-butylphosphanyl-1,5-diphenyl-1H-[1,2,3]triazole (7c).
To a solution of 1,5-diphenyl-1H-[1,2,3]triazole (6a) (0.520 g, 2.35
mmol) in THF (20 mL) was added LDA (2.35 mmol) at 0 °C. The
reaction mixture was stirred at 0 °C for 1.5 h followed by addition
of PtBu2Cl (0.446 mL, 2.35 mmol). The resulting mixture was
slowly warmed to rt and stirred overnight. TLC showed the reaction
was essentially complete after 16 h. The solvent was removed under
vacuum. A degassed mixture of brine/H2O (1:1) was added, and
the resulting mixture was extracted with degassed ether (15 mL ×
3). The combined organic layers were dried over Na2SO4 and
concentrated under vacuum. The residue was purified by flash
column chromatography on silica gel under nitrogen (hexanes/ether,
80:20) to afford 7c as a sticky solid (0.78 g, 91%): 1H NMR (CD2-
Cl2, 360 MHz) δ 7.41-7.23 (m, 10H), 1.27 (d, J ) 12.1 Hz, 18H);
13C NMR (CDCl3, 90 MHz) δ 145.2 (d, J ) 39.0 Hz), 142.2 (d,
J ) 27.9 Hz), 137.2, 131.1 (d, J ) 2.5 Hz), 129.4, 129.3, 129.0,
128.6, 128.5, 125.2, 33.1 (d, J ) 17.0 Hz), 30.6 (d, J ) 14.4 Hz);
31P NMR (CD2Cl2, 145 MHz) δ 3.51; HRMS (ESI+) calcd for
C22H29N3P (MH+) 366.2084, found 366.2099.
4-Diphenylphosphanyl-1,5-diphenyl-1H-[1,2,3]triazole (7a).
This compound was prepared from triazole compound 6a and PPh2-
Cl following the general procedure as a white solid (90% yield):
1H NMR (CDCl3, 360 MHz) δ 7.73-7.69 (m, 4H), 7.44-7.36 (m,
14H), 7.26 (d, J ) 7.3 Hz, 2H); 13C NMR (CDCl3, 90 MHz) δ
143.3 (d, J ) 39.5 Hz), 141.1 (d, J ) 14.2 Hz), 136.40, 136.38 (d,
J ) 15.4 Hz), 133.8, 133.5, 130.1 (d, J ) 3.5 Hz), 129.2, 129.0,
128.8, 128.6, 128.35, 128.28, 128.2, 126.5, 124.8; 31P NMR (CDCl3,
145 MHz) δ -35.85; HRMS (ESI+) calcd for C26H21N3P (MH+)
406.1475, found 406.1473.
4-Di-tert-butylphosphanyl-1-phenyl-5-(2-N,N-dimethylphenyl)-
1H-[1,2,3]triazole (7h). This compound was prepared from triazole
compound 6d and PtBu2Cl following the general procedure as a
1
white solid (69% yield). H NMR (360 MHz, CD2Cl2) δ 7.53 (d,
J ) 7.6 Hz, 1H), 7.35-7.40 (m, 4H), 7.26-7.29 (m, 2H), 7.05-
7.10 (m, 1H), 6.88 (d, J ) 8.2 Hz, 1H), 2.16 (s, 6H), 1.38 (d, J )
11.8 Hz, 9H), 1.30 (d, J ) 12.1 Hz, 9H); 13C NMR (90 MHz,
CD2Cl2) δ 151.8, 143.9 (d, J ) 38.2 Hz), 141.5 (d, J ) 28.6 Hz),
138.2, 133.5 (d, J ) 5.0 Hz), 130.4, 128.6, 128.1, 122.8, 120.7,
120.1, 118.8, 41.8, 33.1 (dd, J ) 17.1, 22.3 Hz), 30.6 (dd, J ) 8.7,
14.4 Hz); 31P NMR (145 MHz, CD2Cl2) δ 2.72; HRMS (ESI+)
calcd for C24H34N4P (MH+) 409.2521, found 409.2537.
4-Dicyclohexylphosphanyl-1,5-diphenyl-1H-[1,2,3]triazole (7b).
This compound was prepared from triazole compound 6a and PCy2-
Cl following the general procedure as a white solid (93% yield):
1H NMR (CD2Cl2, 360 MHz) δ 7.41-7.23 (m, 10H), 2.28-2.21
(m, 2H), 1.87-1.67 (m, 10H), 1.38-1.09 (m, 10H); 13C NMR
(CDCl3, 90 MHz) δ 144.7 (d, J ) 34.8 Hz), 141.2 (d, J ) 24.6
Hz), 137.2, 130.9 (d, J ) 2.9 Hz), 129.4, 129.3, 129.1, 128.6, 128.0,
125.3, 33.5 (d, J ) 8.4 Hz), 30.8 (d, J ) 16.3 Hz), 29.8 (d, J ) 7.5
Hz), 27.5 (d, J ) 18.5 Hz), 27.4 (d, J ) 1.6 Hz), 26.8; 31P NMR
(CD2Cl2, 145 MHz) δ -27.76; HRMS (ESI+) calcd for C26H33N3P
(MH+) 418.2419, found 418.2412.
4-Dicyclohexylphosphanyl-1-phenyl-5-(1-naphthyl)-1H-[1,2,3]-
triazole(7d). This compound was prepared from triazole compound
6b and PCy2Cl following the general procedure as a white solid
(81% yield): 1H NMR (300 MHz, CD2Cl2) δ 7.93 (dd, J ) 8.3,
18.7 Hz, 2H), 7.24-7.53 (m, 10H), 2.36 (t, J ) 11.3 Hz, 1H),
2.09 (t, J ) 11.2 Hz, 1H), 1.52-1.98 (m, 10H), 0.97-1.48 (m,
10H); 13C NMR (75 MHz, CD2Cl2) δ 143.5 (d, J ) 27.4 Hz), 143.2,
143.0, 137.2, 133.7, 132.4, 130.3, 129.3, 128.9, 128.8, 127.1, 126.7,
125.9, 125.5, 125.3, 124.2, 33.6 (d, J ) 9.2 Hz), 30.9 (d, J ) 16.3
Hz), 30.0 (d, J ) 8.8 Hz), 27.4 (d, J ) 10.3 Hz), 27.2 (d, J ) 3.7
Hz), 26.8; 31P NMR (145 MHz, CD2Cl2) δ -28.31; HRMS (ESI+)
calcd for C30H35N3P (MH+) 468.2569, found 468.2571.
4-Di-tert-butylphosphanyl-1-phenyl-5-(2,6-dimethoxyphenyl)-
1H-[1,2,3]triazole (7i). This compound was prepared from triazole
compound 6e and PtBu2Cl following the general procedure as a
1
white solid (79% yield): H NMR (360 MHz, CD2Cl2) δ 7.37-
7.42 (m, 6H), 6.58 (d, J ) 8.4 Hz, 2H), 3.63 (s, 6H), 1.28 (d, J )
12.0 Hz, 18 H); 13C NMR (90 MHz, CD2Cl2) δ 158.5, 143.0, 139.5,
137.4, 131.5, 128.7, 128.5, 124.1, 105.7, 103.3, 55.2, 32.3 (d, J )
16.2 Hz), 30.2 (d, J ) 14.4 Hz); 31P NMR (145 MHz, CD2Cl2) δ
4.73; HRMS (ESI+) calcd for C24H33N3O2P (MH+) 426.2310,
found 426.2307.
4-Dicyclohexylphosphanyl-1-phenyl-5-(2,6-dimethoxyphenyl)-
1H-[1,2,3]triazole (7j). This compound was prepared from triazole
compound 6e and PCy2Cl following the general procedure as a
1
white solid (76% yield): H NMR (360 MHz, CD2Cl2) δ 7.38-
7.42 (m, 6H), 6.59 (d, J ) 8.4 Hz, 2H), 3.65 (s, 6H), 2.16-2.22
(m, 2H), 1.69-1.77 (m, 10H), 1.13-1.39 (m, 10H); 13C NMR (90
MHz, CD2Cl2) δ 158.9, 142.6 (d, J ) 20.4 Hz), 139.0 (d, J ) 40.6
Hz), 137.7, 131.9, 129.1, 128.8, 124.2, 105.9, 103.8, 55.7, 33.2 (d,
J ) 7.8 Hz), 30.5 (d, J ) 16.3 Hz), 29.7 (d, J ) 7.9 Hz), 27.5 (d,
J ) 10.5 Hz), 27.4 (d, J ) 6.0 Hz), 26.9; 31P NMR (145 MHz,
CD2Cl2) δ -27.36; HRMS (ESI+) calcd for C28H37N3O2P (MH+)
478.2623, found 478.2599.
General Procedure for Amination of Aryl Chlorides. To a
Schlenk tube, which was flame-dried under vacuum and backfilled
with nitrogen, NaOtBu (1.2 mmol), were subsequently added toluene
(3 mL), a stock solution of ligand 7 in toluene (0.01 mmol), a stock
solution of Pd(dba)2 (0.005 mmol) in toluene, aryl chloride 8 (1.0
mmol) and amine 9 (1.2 mmol). The flask was sealed, and the
reaction mixture was heated at 110 °C with vigorous stirring for
20 h. After the mixture was cooled to rt, 15 mL of EtOAc was
added and the mixture was washed with 5 mL of brine. The organic
4-Di-tert-butylphosphanyl-1-phenyl-5-(1-naphthyl)-1H-[1,2,3]-
triazole (7e). This compound was prepared from triazole compound
6b and PtBu2Cl following the general procedure as a white solid
(75% yield): 1H NMR (CD2Cl2, 300 MHz) δ 7.98-7.88 (m, 2H),
7.55-7.21 (m, 10H), 1.34-1.24 (m, 18H); 13C NMR (CDCl3, 75
MHz) δ 144.1 (d, J ) 14.9 Hz), 143.7 (d, J ) 28.6 Hz), 137.3,
133.7, 132.4, 130.6, 130.3, 129.3, 129.0, 128.8, 127.0, 126.6, 126.1,
125.6, 125.3, 124.2, 32.9 (dd, J ) 17.0, 21.7 Hz), 30.8 (dd, J )
J. Org. Chem, Vol. 71, No. 10, 2006 3933