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J.-L. Zhang et al. / Tetrahedron: Asymmetry 24 (2013) 492–498
4.7. General procedure for the synthesis of imidazo[1,5-a]tetra-
hydroquinolinium salts 12
128.0, 130.0, 131.0, 131.7, 141.5, 145.0, 145.1; HRMS (ESI) calcd
for [C26H33N2]+ (MꢀCl)+: 373.2644; found: 373.2650.
According to the modified procedure reported by Aron et al.,8b
to a solution of aldehyde 11 (1.0 equiv) in EtOH (0.5 M) were added
aniline (1.0 equiv), formalin (1.5 equiv), and 3 M HCl in EtOH
(1.5 equiv). The reaction mixture was stirred at room temperature
until aldehyde 11 was consumed as determined by TLC. Next, the
reaction mixture was concentrated and purified by flash chroma-
tography on silica gel (eluting with 10% CH3OH/CH2Cl2) to afford
the imidazo[1,5-a]tetrahydroquinolinium salts 12.
4.7.4. Synthesis of (7R,9R)-2-(4-methoxyphenyl)-8,8-dimethyl-
6,7,8,9-tetrahydro-7,9-methanoimidazo[1,5-a]quinolin-2-ium
chloride 12d
Treatment of aldehyde 11 (113 mg, 0.56 mmol) in EtOH
(1.1 mL) with p-anisidine (69.1 mg, 0.56 mmol), formalin
(0.068 mL, 0.84 mmol), and 3 M HCl in EtOH (0.28 mL) at room
temperature for 1 h afforded imidazo[1,5-a]tetrahydroquinolinium
salt 12d (188.8 mg, 95%) as a yellow solid. Mp 142–143 °C;
½
a 2D0
ꢃ
¼ þ68:8 (c 0.8, CHCl3); IR (film): 2968, 2918, 1648, 1546,
4.7.1. Synthesis of (7R,9R)-8,8-dimethyl-2-phenyl-6,7,8,9-tetra-
hydro-7,9-methanoimidazo[1,5-a]quinolin-2-ium chloride 12a
Treatment of aldehyde 11 (70 mg, 0.35 mmol) in EtOH (0.7 mL)
with aniline (0.032 mL, 0.35 mmol), formalin (0.042 mL,
0.52 mmol), and 3 M HCl in EtOH (0.17 mL) at room temperature
for 3 h afforded imidazo[1,5-a]tetrahydroquinolinium salt 12a
1370, 1265, 1244, 749 cmꢀ1 1H NMR (400 MHz, CDCl3) d 0.73 (s,
;
3H), 1.37 (d, J = 9.7 Hz, 1H), 1.55 (s, 3H), 2.35–2.39 (m, 1H), 2.86–
2.99 (m, 3H), 3.76 (s, 3H), 4.45 (t, J = 5.4 Hz, 1H), 6.98 (d,
J = 9.1 Hz, 2H), 7.04 (d, J = 9.3 Hz, 1H), 7.55 (d, J = 9.3 Hz, 1H),
8.08 (d, J = 9.1 Hz, 2H), 8.20 (s, 1H), 11.65 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 21.1, 25.5, 30.9, 31.8, 39.8, 40.2, 42.3, 55.7,
110.2, 114.4, 115.3 (2C), 122.4, 123.4, 123.9 (2C), 127.4, 127.9,
130.2 141.4, 160.7; HRMS (ESI) calcd for [C21H23N2O]+ (MꢀCl)+:
319.1810; found: 319.1809.
(105 mg, 93%) as colorless crystals. Mp 121–122 °C; ½a D20
¼ þ60:6
ꢃ
(c 1.1, CH3OH); IR (KBr): 2956, 2940, 2909, 2888, 1652, 1259,
1030, 814, 755, 681 cmꢀ1 1H NMR (400 MHz, DMSO-d6) d 0.73
;
(s, 3H), 1.38 (d, J = 9.4 Hz, 1H), 1.50 (s, 3H), 2.38–2.40 (m, 1H),
2.81–2.86 (m, 1H), 2.90–3.06 (m, 2H), 3.74 (t, J = 5.3 Hz, 1H), 7.28
(d, J = 9.3 Hz, 1H), 7.63–7.74 (m, 3H), 7.78 (d, J = 9.3 Hz, 1H), 8.00
(d, J = 7.8 Hz, 2H), 8.79 (s, 1H), 10.49 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) d 21.4, 25.9, 30.7, 31.5, 39.5, 40.1 41.8, 112.4, 115.5,
122.5, 123.2, 127.7, 130.2, 130.7, 130.8, 135.7, 139.7; HRMS (ESI)
calcd for [C20H21N2]+ (MꢀCl)+: 289.1705; found: 289.1706.
4.7.5. Synthesis of (7R,9R)-2-(3,5-bis(trifluoromethyl)phenyl)-
8,8-dimethyl-6,7,8,9-tetrahydro-7,9-methanoimidazo[1,5-a]
quinolin-2-ium chloride 12e
Treatment of aldehyde 11 (113 mg, 0.56 mmol) in EtOH
(1.1 mL)
with
3,5-bis(trifluoromethyl)aniline
(0.090 mL,
0.56 mmol), formalin (0.068 mL, 0.84 mmol), and 3 M HCl in EtOH
(0.18 mL) at room temperature for 12 h afforded imidazo[1,5-a]tet-
rahydroquinolinium salt 12e (221.9 mg, 86%) as a yellow solid. Mp
4.7.2. Synthesis of (7R,9R)-2-mesityl-8,8-dimethyl-6,7,8,9-tet-
rahydro-7,9-methanoimidazo[1,5-a]quinolin-2-ium chloride
12b
129–130 °C; ½a 2D0
ꢃ
¼ þ34:4 (c 1.0, CHCl3); IR (film): 2965, 2925,
2869, 1652, 1546, 1463, 1367, 752 cmꢀ1
;
1H NMR (400 MHz,
Treatment of aldehyde 11 (100 mg, 0.50 mmol) in EtOH
(1.0 mL) with 2,4,6-trimethylaniline (0.070 mL, 0.50 mmol), forma-
lin (0.061 mL, 0.75 mmol), and 3 M HCl in EtOH (0.25 mL) at room
temperature for 12 h afforded the product imidazo[1,5-a]tetrahy-
droquinolinium salt 12b (152.3 mg, 83%) as colorless crystals. Mp
CDCl3) d 0.74 (s, 3H), 1.38 (d, J = 9.7 Hz, 1H), 1.50 (s, 3H), 2.38–
2.40 (m, 1H), 2.84–3.03 (m, 3H), 4.38 (t, J = 5.4 Hz, 1H), 7.12 (d,
J = 9.4 Hz, 1H), 7.84 (d, J = 9.4 Hz, 1H), 7.91 (s, 1H), 8.94 (s, 2H),
9.16 (s, 1H), 12.2 (s, 1H); 13C NMR (100 MHz, CDCl3) d 21.0, 25.4,
30.8, 31.8, 39.8, 40.1, 42.3, 112.0, 115.5, 121.0, 123.6, 123.7,
262–263 °C; ½a 2D0
¼ þ38:4 (c 1.3, CHCl3); IR (film): 2934, 1553,
ꢃ
1
1386, 1284, 1185, 1138, 755, 681 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 0.73 (s, 3H), 1.42 (d, J = 9.6 Hz, 1H), 1.50 (s, 3H), 2.02 (s, 3H), 2.05
(s, 3H), 2,37–2.39 (m, 4H), 2,79–2.84 (m, 1H), 2.92–3.03 (m, 2H),
3.67 (t, J = 5.2 Hz, 1H), 7.19 (s, 2H), 7.31 (d, J = 9.6 Hz, 1H), 7.82
(d, J = 9.6 Hz, 1H), 8.44 (s, 1H), 10.33 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) d 17.4, 17.5, 21.1, 21.2, 25.8, 30.7, 31.6, 39.5, 40.1,
42.0, 115.1, 115.7, 122.4, 125.2, 127.6, 129.6, 129.7, 130.1, 132.2,
134.6, 134.7, 139.9, 140.9; HRMS (ESI) calcd for [C23H27N2]+
(MꢀCl)+: 331.2174; found: 331.2172.
123.9, 124.2, 127.9, 130.9, 133.7 (q, JCF = 34.0 Hz), 136.5, 141.1;
HRMS (ESI) calcd for [C22H19F6N2]+ (MꢀCl)+: 425.1452; found:
425.1449.
4.8. General procedure for the synthesis of NHC–CuCl complex
13
A
solution of imidazo[1,5-a]tetrahydroquinolinium salt 12
(1.0 equiv) and Ag2O (0.6 equiv) in CH2Cl2 (0.2 M) was stirred for
12 h at room temperature under N2 and then filtered through a
pad of Celite. The filtrate was concentrated under reduced pressure
to afford the crude silver–carbene complex, which was used imme-
diately in the next step without further purification.
4.7.3. Synthesis of (7R,9R)-2-(2,6-diisopropylphenyl)-8,8-dimeth-
yl-6,7,8,9-tetrahydro-7,9-methanoimidazo[1,5-a] quinolin-2-
ium chloride 12c
A solution of the crude silver–carbene complex and CuCl
(1.0 equiv) in CH2Cl2 (0.2 M) was stirred for 4 h at room tempera-
ture under N2 and then filtered through a pad of Celite. The filtrate
was concentrated under reduced pressure to give the copper com-
plex 13.
Treatment of aldehyde 11 (100 mg, 0.50 mmol) in EtOH
(1.0 mL) with 2,6-diisopropylaniline (0.11 mL, 0.50 mmol), forma-
lin (0.061 mL, 0.75 mmol), and 3 M HCl in EtOH (0.25 mL) at room
temperature for 12 h afforded the product imidazo[1,5-a]tetrahy-
droquinolinium salt 12c (182 mg, 89%) as colorless crystals. Mp
289–290 °C; ½a 2D0
ꢃ
¼ þ26:0 (c 1.0, CHCl3); IR (film): 3431, 3067,
2971, 2931, 1550, 1516, 1259, 1188, 1021, 814 cmꢀ1
;
1H NMR
4.8.1. Synthesis of ((7R,9R)-8,8-dimethyl-2-phenyl-1,2,6,7,8,9-
hexahydro-7,9-methanoimidazo[1,5-a]quinolin-1-yl)copper(I)
chloride 13a
(400 MHz, CDCl3) d 0.79 (s, 3H), 1.13 (d, J = 6.8 Hz, 3H), 1.15 (d,
J = 6.8 Hz, 3H), 1.25 (d, J = 6.8 Hz, 3H), 1.28 (d, J = 6.8 Hz, 3H),
1.48 (d, J = 9.7 Hz, 1H), 1.57 (s, 3H), 2.05–2.12 (m, 1H), 2.18–2.24
(m, 1H), 2.41–2.44 (m, 1H), 2.91–3.08 (m, 3H), 4.43 (t, J = 5.4 Hz,
1H), 7.21 (d, J = 9.3 Hz, 1H), 7.31–7.33 (m, 2H), 7.54 (t, J = 7.8 Hz,
1H), 7.71 (s, 1H), 7.75 (d, J = 9.3 Hz, 1H), 11.3 (s 1H); 13C NMR
(100 MHz, CDCl3) d 21.0, 24.3, 24.4, 24.7, 25.4, 28.6, 28.7, 31.0,
31.9, 39.7, 40.1, 42.5, 114.6, 114.8, 122.9, 124.4, 124.5, 126.7,
1H NMR (400 MHz, CDCl3) d 0.81 (s, 3H), 1.40 (d, J = 9.5 Hz, 1H),
1.55 (s, 3H), 2.37–2.40 (m, 1H), 2.81–2.95 (m, 3H), 5.08 (t,
J = 5.6 Hz, 1H), 6.82 (d, J = 9.2 Hz, 1H), 7.27 (d, J = 9.2 Hz, 1H),
7.45–7.54 (m, 4H), 7.72 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 21.2, 25.8, 31.1, 32.0, 39.9, 40.2, 43.9, 111.1, 114.1,
118.3, 124.6 (2C), 125.6, 129.2, 129.8 (2C), 131.8, 140.8, 143.3.