R. Yamasaki et al. / Tetrahedron 68 (2012) 8450e8456
8455
Anal. Calcd for C20H17NO: C, 83.59; H, 5.96; N, 4.87. Found: C, 83.36;
H, 5.87; N, 4.81.
concentrated in vacuo to give the crude product, which was puri-
fied by silica gel column chromatography.
4.2.4. (4-Bromophenyl)-(40-anilinophenyl)-methanone (10). Yellow
solid; mp 194.0e194.4 ꢀC; 1H NMR (500 MHz, CDCl3) 7.72 (d, 2H,
J¼9.0 Hz), 7.60 (m, 4H), 7.34 (t, 2H, J¼7.5 Hz), 7.18 (d, 2H, J¼7.5 Hz),
7.08 (t, 1H, J¼7.5 Hz), 7.00 (d, 2H, J¼8.5 Hz), 6.07 (br s, 1H); 13C NMR
(126 MHz, DMSO-d6) 192.5, 148.9, 140.9, 137.5, 132.3, 131.3, 131.0,
129.3, 126.2, 125.3, 122.2, 119.7, 113.8; IR (KBr) 3317, 1635, 1582,
1559, 1496, 1340, 1173, 1148, 1069, 1011, 930, 852, 761, 751,
693 cmꢁ1; Anal. Calcd for C19H14BrNO: C, 64.79; H, 4.01; N, 3.98.
Found: C, 64.88; H, 4.10; N, 3.92.
4.3.1. (4-Anilino)-(40-methyl anilino)benzophenone (13). Orange
amorphous; 1H NMR (500 MHz, CDCl3) 7.73 (d, 2H, J¼8.5 Hz), 7.72
(d, 2H, J¼8.5 Hz), 7.32 (t, 2H, J¼8.5 Hz), 7.18 (d, 2H, J¼7.5 Hz), 7.14 (d,
2H, J¼7.5 Hz), 7.08 (d, 2H, J¼7.5 Hz), 7.04 (t, 1H, J¼7.5 Hz), 7.02 (d,
2H, J¼8.5 Hz), 6.95 (d, 2H, J¼7.5 Hz), 2.32 (s, 3H), 1H (NH) was not
observed; 13C NMR (126 MHz, CDCl3) 193.7, 148.2, 147.3, 141.0,
138.2, 133.0, 132.3, 132.2, 130.0, 129.9, 129.5, 129.2, 122.9, 121.2,
120.2, 114.6, 113.9, 20.8; IR (KBr) 3297, 2349, 1634, 1559, 1496, 1286,
1172, 1151, 930, 849, 810, 765, 748, 697, 679 cmꢁ1; Anal. Calcd for
C26H22N2O: C, 82.51; H, 5.86; N, 7.40. Found: C, 82.37; H, 5.93; N,
7.31.
4.2.5. (4-Chlorophenyl)-(40-anilinophenyl)-methanone (12). Yellow
solid; 184.2e184.9 ꢀC; 1H NMR (500 MHz, CDCl3) 7.73 (d, 2H,
J¼8.5 Hz), 7.69 (d, 2H, J¼7.5 Hz), 7.43 (d, 2H, J¼8.5 Hz), 7.34 (t, 2H,
J¼8.5 Hz), 7.19 (d, 2H, J¼7.5 Hz), 7.08 (t, 1H, J¼7.5 Hz), 7.00 (d, 2H,
J¼8.5 Hz); 13C NMR (126 MHz, CDCl3) 193.8, 148.4, 140.4, 137.9,
137.0, 132.6, 131.0, 129.6, 128.4, 128.2, 123.5, 120.8, 114.3; IR (KBr)
3316, 1635, 1496, 1343, 1173, 1148, 1091, 1013, 930, 854, 763, 753,
741, 693, 674 cmꢁ1; Anal. Calcd for C19H14ClNO: C, 74.15; H, 4.58; N,
4.55. Found: C, 74.12; H, 4.62; N, 4.54.
4.4. Competitive reduction of a mixture of phenylogous
amides
To an oven-dried side-armed flask, equipped with a magnetic
stirrer and condenser, was added a solution of 1a (0.273 g, 1 mmol),
2a (0.273 g, 1 mmol), and 3a (0.273 g, 1 mmol) in a mixture of THF
(3.0 mL) and H2O (0.1 mL). NaBH4 (0.038 g, 1 mmol) was then
added in a single portion and the resulting mixture was heated to
gentle reflux. Upon completion of the reaction, distilled water
(3 mL) was added and the reaction mixture was stirred for an ad-
ditional 5 min. The mixture was then extracted with CH2Cl2
(3ꢂ8 mL), dried over anhydrous Na2SO4, and evaporated in vacuo to
give the crude product as a residue, which was purified by silica gel
column chromatography to obtain 20 (216 mg, 79%), 1a (228 mg,
84%), and 2a (202 mg, 74%). The compound data of 2122 and 2223
were consistent with those reported elsewhere.
4.2.6. (2-Methyl-phenyl)-((20-methyl)phenyl)-phenyl-methanone
(16). Yellow solid; mp 146.2e147.0 ꢀC; 1H NMR (500 MHz, CDCl3)
7.68 (d, 2H, J¼6.7 Hz), 7.32 (t, 1H, J¼7.7 Hz), 7.29e7.17 (m, 6H), 7.08
(t,1H, J¼7.4 Hz), 6.76 (d, 2H, J¼9.0 Hz), 5.80 (s,1H), 2.29 (s, 3H), 2.24
(s, 3H); 13C NMR (126 MHz, CDCl3) 196.9, 150.0, 139.6, 138.3, 135.7,
132.5, 132.2, 131.1, 130.5, 129.3, 128.0, 127.5, 126.8, 124.98, 124.97,
123.7, 113.5, 19.6, 17.8; IR (KBr) 3341, 3262, 3019, 3020, 2760, 2604,
1934, 1635, 1578, 1552, 1523, 1424, 1379, 1336, 1314, 1295, 1277,
1182, 1150, 1112, 1039, 997, 953, 927, 843, 800, 776, 750, 732, 702,
680, 644, 631, 610, 532, 498, 445, 419, 410; Anal. Calcd for
C21H19NO: C, 83.69; H, 6.35; N, 4.65. Found: C, 83.94; H, 6.01; N,
4.62.
4.4.1. 1-Phenyl-1-(3-anilino)-methanol (20). Colorless solid; mp
109.6e110.1 ꢀC; 1H NMR (500 MHz, CDCl3) 7.39e7.27 (m, 6H),
7.22e7.18 (m, 3H), 7.10 (d, 1H, J¼7.5 Hz), 6.92 (d, 2H, J¼7.5 Hz),
6.90e6.86 (m, 2H), 6.37 (br s, 1H) 5.95 (s, 1H), 2.50 (br s, 1H); 13C
NMR (126 MHz, CDCl3) 143.2, 142.0, 141.8, 131.9, 129.2, 128.8, 128.7,
128.5, 127.7, 126.6, 121.0, 120.7, 118.6, 118.0, 74.6; IR (KBr) 3410,
3170, 3039, 2877, 2800, 2615, 2337, 1921, 1589, 1504, 1419, 1304,
1165, 1080, 987, 856, 748, 663, 494 cmꢁ1; Anal. Calcd for C19H17NO:
C, 82.88; H, 6.22; N, 5.08. Found: C, 83.09; H, 6.22; N, 5.08.
4.2.7. (2-Pyridiyl)-(20-pyridiyl)phenyl-methanone
(19). Yellow
solid; mp 158.9e160.1 ꢀC; 1H NMR (500 MHz, CDCl3) 8.70 (d, 1H,
J¼4.3 Hz), 8.27 (d, 1H, J¼4.3 Hz), 8.11 (d, 2H, J¼8.6 Hz), 7.98 (d, 1H,
J¼7.6 Hz), 7.87 (t, 1H, J¼6.4 Hz), 7.57 (t, 1H, J¼7.1 Hz), 7.45 (d, 3H,
J¼8.5 Hz), 6.98 (d, 1H, J¼8.3 Hz), 6.84 (t, 1H, J¼7.1 Hz), 6.80 (s, 1H);
13C NMR (126 MHz, CDCl3) 192.0, 155.9, 154.3, 148.3, 148.2, 145.3,
138.0, 137.0, 133.2, 129.4, 125.8, 124.5, 117.0, 116.5, 110.3; IR (KBr)
3356, 3211, 3117, 3049, 2595, 2306, 1637, 1620, 1579, 1524, 1498,
1481,1428,1411,1354, 1323, 1283, 1238, 1194, 1164,1146, 1092,1013,
990, 940, 899, 845, 822, 803, 750, 730, 722, 692, 673, 642, 617, 607,
571, 520, 502, 459, 403; Anal. Calcd for C17H13N3O: C, 74.17; H, 4.76;
N, 15.26. Found: C, 74.09; H, 4.79; N, 15.10.
4.5. X-ray crystallography
Single crystal X-ray diffraction data of the crystals were col-
lected on a CCD diffractometer with graphite monochromated Mo
ꢀ
Ka
(l
¼0.71073 A) radiation. The crystal structure was solved by
direct methods SHELXS-97 and refined by full-matrix least-squares
SHELXL-97.24 All non-hydrogen atoms were refined anisotropically.
Some hydrogen atoms of amino groups (for 1a and 3b) were refined
isotropically. Other hydrogen atoms were included at their calcu-
lated positions.
4.3. General procedure of the double coupling reaction
An oven-dried side-armed flask was charged with Pd2(dba)3
(23 mg, 0.025 mmol), Xantphos (58 mg, 0.10 mmol), NaOtBu
(106 mg, 1.1 mmol) and 9. The flask was then evacuated and back-
filled with argon. Toluene (2.5 mL) and aniline (0.09 mL, 1.0 mmol)
were then added to the flask via a syringe and the resulting mixture
was heated with stirring to 80 ꢀC. The reaction was monitored by
TLC. Upon complete consumption of 9, p-toluidine (107 mg,
1.0 mmol), Pd2(dba)3 (23 mg, 0.025 mmol), Xantphos (58 mg,
0.10 mmol), and NaOtBu (106 mg, 1.1 mmol) were added to the
reaction and the flask was flushed with argon. Additional toluene
(2.5 mL) was then added and the resulting mixture was heated at
80 ꢀC with stirring until the aryl halide intermediate could no
longer be detected. The mixture was cooled to ambient tempera-
ture, diluted with CH2Cl2 (30 mL), filtered through Celite, and
4.5.1. Crystal data for 1a. C19H15NO, Mr¼273.32, orthorhombic,
3
ꢀ
ꢀ
Pbcn, a¼31.221(5), b¼12.696(2), c¼7.2579(12) A, V¼2876.9(8) A ,
Z¼8, Dcalcd¼1.262 Mg mꢁ3, 2qmax¼54.12ꢀ, T¼150 K,
m
¼0.078 mmꢁ1
,
13,116 reflections measured, 3005 unique (Rint¼0.0281). The final
R1 and wR2 were 0.0386 and 0.0920 (I>2s(I)), 0.0568 and 0.1020 (all
data). CCDC 877867.
4.5.2. Crystal data for 2b. C20H17NO$CH2Cl2, Mr¼372.27, ortho-
ꢀ
rhombic, Pca21, a¼10.401(2), b¼21.779(4), c¼8.1491(16) A,
3
V¼1845.9(6) A , Z¼4, Dcalcd¼1.262 Mg mꢁ3
,
2
qmax¼54.36ꢀ,
ꢀ
T¼243 K,
m
¼0.360 mmꢁ1, 8748 reflections measured, 3703 unique
(Rint¼0.0173). The final R1 and wR2 were 0.0327 and 0.0835