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A. P. Dhondge et al. / Tetrahedron: Asymmetry 23 (2012) 723–733
39.8, 34.5, 26.7, 23.2. IR (KBr, thin film): 3434, 2934, 1739, 1585,
1363, 1229, 1105, 765 cmꢀ1. MS-EI (m/z): 264 (M+, 13), 246 (17),
206 (42), 195 (100), 128 (14), 77 (19). HRMS-EI (m/z): [M]+ calcd
for C18H20N2, 264.1626; found 264.1620.
(c 3.25, CHCl3). {lit.10, ½a D25
ꢃ
¼ þ117:9 (c 1.1, CHCl3}. 1H NMR
(400 MHz, CDCl3): d 8.03 (d, J = 7.6 Hz, 2H), 7.46 (m, 3H), 7.37 (t,
J = 7.1 Hz, 1H), 7.28 (t, J = 7.7 Hz, 1H), 4.23 (d, J = 2.2 Hz, 1H), 2.77
(m, 2H), 2.62 (br s, 2H), 2.53 (m, 1H), 1.46 (s, 3H), 1.42 (t,
J = 5.0 Hz, 1H), 0.78 (s, 3H). 13C NMR (100.6 MHz, CDCl3): d 159.7,
154.9, 139.5, 139.0, 133.4, 128.6, 128.6, 128.4, 127.4, 126.5,
117.9, 58.0, 47.2, 46.9, 39.8, 34.5, 26.7, 23.2. IR (KBr, thin film):
3434, 2934, 1739, 1585, 1363, 1229, 1105, 765 cmꢀ1. MS-EI (m/
z): 264 (M+, 13), 246 (17), 206 (42), 195 (100), 128 (14), 77 (19).
HRMS-EI (m/z): [M]+ calcd. for C18H20N2, 264.1626; found
264.1620. A solution of crude amine 7 (38.0 mg, 0.14 mmol) and
aldehyde 12 (0.03 g, 0.14 mmol) in dry MeOH (100 mL) was heated
at reflux overnight. Excess MeOH was evaporated under reduced
pressure; the resulting crude product was recrystallized by MeOH
to afford 10 as a pale yellow solid (52.0 mg, 0.36 mmol). Yield: 75%.
Compound 7a: ½a 2D5
ꢃ
¼ þ22:0 (c 1.0, CHCl3). {lit.10, ½a D25
¼ þ23:3
ꢃ
(c 1.1, CHCl3}. 1H NMR (400 MHz, CDCl3): d 8.02 (d, J = 8.0 Hz, 2H),
7.46 (m, 3H), 7.38 (t, J = 7.1 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 4.20 (d,
J = 2.7 Hz, 1H), 2.81 (t, J = 5.6 Hz, 1H), 2.62 (m, 1H), 2.39 (m, 1H),
2.10 (bs, 1H), 1.46 (s, 3H), 1.42 (d, J = 8.0 Hz, 1H), 0.69 (s, 3H). 13C
NMR (100.6 MHz, CDCl3): d 159.2, 154.8, 139.5, 139.4, 133.5, 128.6,
128.4, 126.5, 118.0, 54.1, 46.7, 46.5, 43.5, 29.0, 26.4, 20.8. IR (KBr,
thin film): 3434, 2931, 1740, 1575, 1374, 1233, 938, 764 cmꢀ1
.
MS-EI (m/z): 264 (M+, 13), 246 (17), 206 (42), 195 (100), 128
(14), 77 (19). HRMS-EI (m/z): [M]+ calcd for C18H20N2, 264.1626;
found 264.1620.
Mp: 177–178 °C.
½
a 2D6
ꢃ
¼ þ177:1 (c 0.21, CH2Cl2). 1H NMR
4.1.2. 2,4-Di-tert-butyl-6-[(10,10-dimethyl-5-phenyl-6-aza-
tricyclo[7.1.1.02,7]undeca-2(7),3,5-trien-8-ylimino)-methyl]-
phenol 10 and 10a
(400 MHz, CDCl3): d 13.70 (br s, 1H), 8.92 (s, 1H), 7.99, (s, 2H),
7.55 (d, J = 7.7 Hz, 1H), 7.38 (m, 6H), 4.85 (s, 1H), 2.90 (s, 2H),
2.65 (s, 1H), 1.55 (s, 4H), 1.48 (s, 9H), 1.40 (s, 9H), 1.01 (s, 3H).
13C NMR (100.6 MHz, CDCl3): d 167.5, 158.2, 155.1, 154.8, 139.8,
139.7, 139.4, 136.5, 133.9, 128.6, 128.5, 126.7, 126.7, 126.4,
118.4, 73.5, 47.4, 46.8, 40.5, 35.1, 34.2, 33.9, 31.6, 29.5, 26.8,
A solution of amine 7 (50.0 mg, 0.18 mmol) and aldehyde 12
(0.04 g, 0.18 mmol) in dry MeOH (100 mL) was heated at reflux
overnight. Excess MeOH was evaporated under reduced pressure;
the resulting crude product was recrystallized by MeOH to afford
10 as a pale yellow solid (68.0 mg, 0.14 mmol). Yield: 75%. Mp:
23.8. IR (KBr): 3396, 2952, 1738, 1626, 1438, 1383, 1216 cmꢀ1
.
MS-EI (m/z): 480 (M+, 100), 465 (38), 249 (40), 234 (36), 220
(15). HRMS-EI (m/z): [M]+ calcd for C33H40N2O, 480.3141; found
480.3129.
177–178 °C. ½a 2D6
ꢃ
¼ þ177:1 (c 0.21, CH2Cl2). 1H NMR (400 MHz,
CDCl3): d 13.70 (br s, 1H), 8.92 (s, 1H), 7.99, (s, 2H), 7.55 (d,
J = 7.7 Hz, 1H), 7.38 (m, 6H), 4.85 (s, 1H), 2.90 (s, 2H), 2.65 (s,
1H), 1.55 (s, 4H), 1.48 (s, 9H), 1.40 (s, 9H), 1.01 (s, 3H). 13C NMR
(100.6 MHz, CDCl3): d 167.5, 158.2, 155.1, 154.8, 139.8, 139.7,
139.4, 136.5, 133.9, 128.6, 128.5, 126.7, 126.7, 126.4, 118.4, 73.5,
47.4, 46.8, 40.5, 35.1, 34.2, 33.9, 31.6, 29.5, 26.8, 23.8. IR (KBr):
3396, 2952, 1738, 1626, 1438, 1383, 1216 cmꢀ1. MS-EI (m/z):
480 (M+, 100), 465 (38), 249 (40), 234 (36), 220 (15). HRMS-EI
(m/z): [M]+ calcd for C33H40N2O, 480.3141; found 480.3129.
A solution of amine 7a (30.0 mg, 0.11 mmol) and aldehyde 12
(0.02 g, 0.11 mmol) in dry MeOH (100 mL) was heated at reflux
overnight. Excess MeOH was evaporated under reduced pressure;
the resulting crude product was recrystallized by MeOH to afford
10a as pale yellow solid (39.0 mg, 0.08 mmol). Yield: 73%. Mp:
4.1.4. 2,4-Di-tert-butyl-6-[(10,10-dimethyl-5-pyridin-2-yl-6-
aza-tricyclo[7.1.1.02,7]undeca-2(7),3,5-trien-8-ylimino)-
methyl]-phenol 11
To a solution of ketone 6 (1.02 g, 3.86 mmol) in MeOH (150 mL)
was added NH4OH (aq) (100 mL). This reaction mixture was stirred
at room temperature for 2 days and then ammonium formate
(2.43 g, 38.6 mmol), and Pd/C (0.44 g, 10%) were sequentially
added. The reaction mixture was stirred at the same temperature
for 1 day. The reaction was worked-up by filtration through a short
pad of Celite, evaporation of MeOH, extraction with dichlorometh-
ane, drying over anhydrous Na2SO4 and concentration gave crude
amine 8. To a solution of crude amine 8 (1.02 g, 3.85 mmol) in
dry MeOH (100 mL) was added aldehyde 12 (0.89 g, 3.82 mmol),
and the reaction was heated at reflux overnight. Excess MeOH
was evaporated under reduced pressure, resulting crude product
was recrystallized by MeOH to afford product 10 as a pale yellow
solid product (0.65 g, 1.34 mmol). Yield: 35%. Mp: 98–99 °C.
174–175 °C. ½a 2D6
ꢃ
¼ ꢀ163:1 (c 0.5, CH2Cl2). 1H NMR (400 MHz,
CDCl3): d 13.77 (br s, 1H), 8.89 (s, 1H), 7.92, (m, 2H), 7.51 (d,
J = 7.7 Hz, 1H), 7.37 (m, 5H), 7.24 (d, J = 2.4 Hz, 1H), 4.77 (s, 1H),
2.90 (m, 1H), 2.73 (m, 1H), 2.51 (m, 1H), 1.87(d, J = 9.8 Hz, 1H),
1.54 (s, 4H), 1.41 (s, 9H), 1.33 (s, 9H), 0.76 (s, 3H). 13C NMR
(100.6 MHz, CDCl3): d 167.3, 158.4, 155.3, 152.9, 140.2, 136.9,
134.2, 130.6, 128.9, 128.8, 127.0, 126.6, 120.3, 118.8, 118.7, 70.8,
47.2, 46.8, 43.6, 35.3, 34.5, 31.9, 30.2, 29.8, 26.7, 21.4. IR (KBr):
3421, 2955, 1738, 1625, 1446, 1389, 1248 cmꢀ1. MS-EI (m/z):
480 (M+, 100), 465 (38), 249 (40), 234 (36), 220 (15). HRMS-EI
(m/z): [M]+ calcd for C33H40N2O, 480.3141; found 480.3129.
½
a 2D3
ꢃ
¼ þ126:0 (c 0.27, CH2Cl2). 1H NMR (400 MHz, CDCl3): d
13.61 (s, 1H), 8.85 (s, 1H), 8.61 (d, J = 3.9 Hz, 1H), 8.33 (d,
J = 8.0 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H), 7.71 (m, 1H), 7.42 (m, 2H),
7.26 (m, 2H), 4.80 (s, 1H), 2.90 (m, 2H), 2.62 (m, 1H), 1.57 (d,
J = 9.1 Hz, 1H), 1.52 (s, 3H), 1.42 (s, 9H), 1.36 (s, 9H), 0.97 (s, 3H).
13C NMR (100.6 MHz, CDCl3): d 167.3, 158.2, 156.4, 154.7, 153.7,
148.9, 141.5, 139.8, 136.7, 136.6, 134.0, 126.8, 126.2, 123.2,
121.0, 119.2, 118.3, 73.7, 47.5, 47.0, 40.5, 35.0, 34.1, 33.8, 31.6,
29.4, 26.7, 23.7. IR (KBr): 3560, 2953, 1738, 1626, 1433, 1384,
1216, 787 cmꢀ1. MS-EI (m/z): 481 (M+, 100), 466 (29), 250 (35),
235 (38), 221 (15), 208 (14), 207 (52). HRMS-EI (m/z): [M]+ calcd
for C32H39N3O, 481.3093; found 481.3090.
4.1.3. 2,4-Di-tert-butyl-6-[(10,10-dimethyl-5-phenyl-6-aza-
tricyclo[7.1.1.02,7]undeca-2(7),3,5-trien-8-ylimino)-methyl]-
phenol 10
To a solution of ketone 5 (0.05 g, 0.18 mmol) in MeOH (5 mL)
was added NH4OH (aq) (3 mL). This reaction mixture was stirred
at room temperature for 3 days and then ammonium formate
(0.12 g, 1.89 mmol), and Pd/C (39.0 mg, 10%) were sequentially
added. The reaction mixture was stirred at the same temperature
for 2 days, and then one more portion of ammonium formate
(0.12 g, 1.89 mmol) and Pd/C (39.0 mg, 10%) was added and stirred
for one additional day. The reaction was worked-up by filtration
through a short pad of Celite, evaporation of MeOH, extraction
with methylene chloride, drying over anhydrous Na2SO4, and con-
centration gave crude amine 7 (38.0 mg, 0.14 mmol) without fur-
4.1.5. 2-Methoxyphenyl methyl ketone 14
A
solution of 1-(2-hydroxy-phenyl)-ethanone 13 (35.2 mL,
300 mmol) and LiOHꢂH2O (24.8 g, 590 mmol) in THF (400 mL)
was stirred at room temperature for 1 h, and then dimethyl sulfate
(42 mL, 293 mmol) was added. After completion of the reaction
(TLC, 60 h), the solvent was removed under reduced pressure.
The residue was dissolved in 2 M NaOH, and the resulting solution
was extracted with diethyl ether. The combined extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
ther purification for the next step. Compound 7: ½a D25:7
¼ þ102:8
ꢃ