Synthesis of 4-Aminotropones
FULL PAPER
mixture of 22 and 23. The two p-quinamines were isolated separately as
yellow oils with over 70% conversion after column chromatography
(eluent: AcOEt/CH3CN 6:1).
(17), 156 (34), 158 (97), 172 (52), 184 (37), 198 (21), 202 (58), 216 (67),
311 (10), 327 ppm.
N-(tert-Butoxycarbonyl)-4-amino-4-[1’-(phenylsulfinyl)ethyl]-2,5-cyclo-
hexadienone (31): Compound 31 was obtained from N-(tert-butoxycar-
bonyl)-p-benzoquinonimine dimethyl ketal (14) (300 mg, 1.19 mmol,
1 equiv) and EtSOPh 30 (189 mg, 1.18 mmol, 1 equiv) by following a
modified version of method A (the anion was added at 08C and the reac-
tion was stirred at RT). The product was produced as a (80:20) mixture
of diastereoisomers in 40% yield (172 mg). Yellow oil; reaction time:
4 h; eluent: hexane/AcOEt 1:1; 1H NMR (300 MHz, CDCl3): d=0.80 (d,
J=7.1 Hz, 3H), 1.48 (s, 9H), 3.60–3.79 (m, 1H), 5.51 (s, 1H), 6.32 (dd,
J=10.1, 2.0 Hz, 1H), 6.36 (dd, J=10.1, 2.0 Hz, 1H), 7.13 (dd, J=10.1,
3.3 Hz, 1H), 7.29 (dd, J=10.1, 3.3 Hz, 1H), 7.45–7.59 ppm (m, 5H);
13C NMR (75 MHz, CDCl3): d=4.2, 28.3 (3C), 58.1, 63.1, 81.1, 124.1,
129.2, 129.4, 130.7, 130.9, 141.7, 145.4, 146.7, 154.6, 184.6 ppm; MS (EI):
m/z (%): 57 (100), 59 (14), 64 (13), 77 (19), 78 (30), 91 (21), 108 (16), 124
(14), 125 (28), 136 (21), 180 (50), 236 [MÀ125]+ (2); HRMS (EI): m/z:
calcd for C13H18NO5: 236.1287 [MÀSOPh]+; found: 236.1283.
Compound 22: Yield: 37% (20 mg); 1H NMR (300 MHz, CDCl3): d=
2.41 (s, 3H), 2.43 (s, 6H), 2.91–3.08 (AB system, J=14.0 Hz, 2H), 6.38
(dd, J=10.3, 1.8 Hz, 1H), 6.44 (dd, J=10.3, 1.8 Hz, 1H), 6.97 (dd, J=
10.3, 3.3 Hz, 1H), 7.27 (dd, J=10.3, 3.3 Hz, 1H), 7.29–7.53 ppm (AA’BB’
system, J=8.3 Hz, 4H); 13C NMR (125 MHz, CDCl3): d=21.4, 30.7, 58.2,
67.2, 123.9, 130.2, 130.6, 131.5, 140.7, 142.2, 150.6, 150.7, 185.0 ppm; MS
(EI): m/z (%): 165 (28), 166 (27), 167 (22), 175 (13), 179 (15), 191 (10),
219 (20), 214 (10), 257 (10), 272 (10), 288 (34), 289 [M]+ (100).
Compound 23: Yield: 20% (11 mg); 1H NMR (300 MHz, CDCl3): d=
2.30 (s, 3H), 2.41 (s, 3H), 2.69–3.20 (AB system, J=13.3 Hz, 2H), 6.34
(dd, J=10.3, 1.8 Hz, 1H), 6.46 (dd, J=10.3, 1.8 Hz, 1H), 6.88 (dd, J=
10.3, 3.0 Hz, 1H), 7.06 (dd, J=10.3, 3.0 Hz, 1H), 7.27–7.56 ppm (AA’BB’
system J=8.1 Hz, 4H); 13C NMR (125 MHz, CDCl3): d=21.4, 39.7, 60.6,
66.6, 123.9, 130.1, 130.4, 131.8, 141.4, 141.9, 147.3, 150.1, 184.7 ppm; MS
(EI): m/z (%): 164 (12), 165 (14), 166 (12), 219 (27), 272 (11), 275 [M]+
(17).
N-(tert-Butoxycarbonyl)-4-amino-4-[1’-(phenylsulfonyl)ethyl]-2,5-cyclo-
hexadienone (33): Compound 33 was obtained pure by following meth-
od B from N-(tert-butoxycarbonyl)-4-amino-4-[1’-(phenylsulfinyl)ethyl]-
2,5-cyclohexadienone (31) (32 mg, 0.09 mmol, 1.0 equiv) as a yellow oil in
99% yield (33 mg). 1H NMR (300 MHz, CDCl3): d=1.10 (d, J=7.1 Hz,
3H), 1.48 (s, 9H), 3.77–3.89 (m, 1H), 6.35 (dd, J=9.9, 2.0 Hz, 1H), 6.45
(dd, J=9.9, 2.0 Hz, 1H), 6.51 (s, 1H), 7.01 (dd, J=10.1, 3.3 Hz, 1H), 7.27
(dd, J=10.1, 3.3 Hz, 1H), 7.51–7.73 (m, 1H), 7.63 (d, J=8.1 Hz, 2H),
7.92 ppm (d, J=7.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=11.5, 28.2
(3C), 57.8, 62.1, 80.9, 128.6 (2C), 129.4 (2C), 129.5, 130.8, 134.3, 138.5,
145.0, 147.5, 154.3, 184.7 ppm; MS (EI): m/z (%): 55 (100), 59 (10), 77
(32), 78 (19), 91 (16), 105 (10), 108 (321), 109 (12), 136 (21), 151 (11), 161
(10), 169 (40), 180 (42), 321 ([MÀ56]+, 1); HRMS (EI): m/z: calcd for
C15H15NO5S: 321.0671 [MÀtBu]+; found: 321.0683.
N-Benzyl-4-amino-4-[(p-tolylsulfinyl)methyl]-2,5-cyclohexadienone (24):
BnBr (53 mL, 0.44 mmol, 2 equiv) was added to a solution of 1 (58 mg,
0.22 mmol, 1 equiv) in CH3CN (3 mL), under an argon atmosphere at
RT. The resulting solution was stirred at RT for 3 d, then the solvent was
removed at reduced pressure. The reaction crude was then purified by
column chromatography to give 24 as a yellow solid in a 61% yield
(47 mg). Eluent: hexane/AcOEt 4:1; m.p. 94–968C; 1H NMR (300 MHz,
CDCl3): d=2.36 (s, 3H), 2.70–3.18 (AB system, J=13.3 Hz, 2H), 3.51–
3.69 (AB system, J=12.9 Hz, 2H), 6.28 (dd, J=10.1, 2.0 Hz, 1H), 6.39
(dd, J=10.1, 2.0 Hz, 1H), 6.92 (dd, J=10.1, 3.2 Hz, 1H), 7.07 (dd, J=
10.1, 3.2 Hz, 1H), 7.17–7.32 (m, 5H), 7.28–7.53 ppm (AA’BB’ system, J=
8.3 Hz, 4H); 13C NMR (75 MHz, CDCl3): d=21.4, 48.5, 57.9, 67.3, 123.9,
127.3, 128.0, 128.5, 130.1, 130.2, 131.0, 139.6, 140.6, 142.2, 150.9, 151.0,
185.0 ppm; MS (EI): m/z (%): 165 (28), 166 (25), 167 (20), 175 (38), 177
(20), 211 (10), 121 (36), 219 (21), 220 (16), 258 (12), 260 [MÀ91]+ (5);
HRMS (FAB+): m/z: calcd for C14H14NO2S: 260.0745 [MÀBn]+; found:
260.0675.
4-Amino-4-[1’-(phenylsulfonyl)ethyl]-2,5-cyclohexadienone (34): Com-
pound 34 was obtained from N-(tert-butoxycarbonyl)-4-amino-4-[1’-(phe-
nylsulfonyl)ethyl]-2,5-cyclohexadienone
(33)
(42 mg,
0.11 mmol,
1.0 equiv) by following method C. The product was isolated as a white
solid in 52% yield (16 mg) as a (80:20) mixture of epimers. Reaction
time: 24 h; eluent: hexane/AcOEt 3:1; m.p. 128–1308C (hexane/AcOEt);
1H NMR (300 MHz, CDCl3): d=1.10 (d, J=7.1 Hz, 3H), 2.27 (s, 2H),
3.42 (q, J=7.1 Hz, 1H), 6.25 (dd, J=10.1, 1.8 Hz, 1H), 6.30 (dd, J=10.1,
1.8 Hz, 1H), 6.64 (dd, J=10.2, 3.2 Hz, 1H), 7.43 (dd, J=10.2, 3.2 Hz,
1H), 7.60 (d, J=7.9 Hz, 2H), 7.65–7.73 (m, 1H), 7.93 ppm (d, J=8.5 Hz,
2H); 13C NMR (75 MHz, CDCl3): d=12.2, 56.8, 65.9, 128.3, 128.5, 129.2,
129.4 (2C), 134.2, 138.9, 149.1, 150.0, 184.8 ppm; MS (EI): m/z (%): 57
(100), 65 (20), 67 (21), 69 (58), 71 (42), 77 (77), 78 (41), 79 (23), 81 (28),
83 (33), 85 (23), 91 (36), 95 (22), 97 (27), 105 (19), 107 (21), 121 (23), 135
(34), 136 (90), 148 (25), 208 (18), 277 [M]+ (4); HRMS (EI): m/z: calcd
for C14H15NO5S: 277.0773 [M]+; found: 277.0765.
N-(tert-Butoxycarbonyl)-4-amino-4-[p-(tolylsulfinyl)methyl]-4H-naphtha-
len-1-one (27): Compound 27 was obtained from N-(tert-butoxycarbon-
yl)-1,4-naphthoquinonimine dimethyl ketal (26) (435 mg, 1.45 mmol,
1 equiv), MeSOTol 16 (223 mg, 1.45 mmol, 1 equiv) and HMPA (1.7 mL,
8.70 mmol, 6 equiv) in THF (5 mL) by following method A. After 5 h
stirring, the mixture was treated with Et3N (36 mL, 0.25 mmol, 1 equiv),
DMAP (12 mg, 0.1 mmol, 0.5 equiv) and di-tert-butyldicarbonate
(270 mg, 1.23 mmol, 5 equiv) in refluxing CH3CN (4 mL) for 5 d at RT,
to reprotect the unprotected NH2 residues. Compound 27 was finally iso-
lated as a yellow oil in 31% yield as a (66:33) mixture of diastereoiso-
mers. Eluent: hexanes/AcOEt 3:1; 1H NMR (300 MHz, CDCl3): d=2.38
(s, 3H), 2.58–3.31 (AB system, J=13.5 Hz, 2H), 6.37 (d, J=10.1 Hz,
1H), 7.09 (d, J=10.1 Hz, 1H), 7.24–7.65 (m, 5H), 7.72 (t, J=6.7 Hz,
1H), 8.01 (d, J=7.9 Hz, 1H), 8.20 ppm (d, J=7.9 Hz, 1H); MS (EI): m/z
(%): 57 (100), 59 (52), 63 (18), 65 (23), 75 (12), 77 (25), 91 (51), 92 (31),
102 (20), 127 (27), 128 (90), 139 (48), 140 (47), 156 (50), 172 [MÀ139]+
(45); HRMS (EI): m/z: calcd for C11H10NO: 172.0762 [MÀSOpTol]+;
found: 172.0766.
N-(tert-Butoxycarbonyl)-4-amino-4-[1’-(p-tolylsulfinyl)propyl]-2,5-cyclo-
hexadienone (36): Compound 36 was obtained from 14 (276 mg,
1.09 mmol, 1 equiv) and PrSOpTol (35) (200 mg, 1.09 mmol, 1 equiv) by
following a modified version of method A (the anion was formed with
2 equiv of nBuLi and 1 equiv of PrSOpTol, and the addition was carried
out at 08C). The product was formed as a single diastereoisomer and as a
white solid in 30% yield (130 mg). Reaction time: 2 h; eluent hexane/
AcOEt 2:1; m.p. 128–1308C (hexane/AcOEt); 1H NMR (300 MHz,
CDCl3): d=0.28 (t, J=7.4 Hz, 3H), 0.92–1.11 (m, 1H), 1.46 (s, 9H), 1.84
(dq, J=7.1, 7.1 Hz, 1H), 2.40 (s, 3H), 3.40–3.52 (m, 1H), 5.60 (brs, 1H),
6.34 (d, J=9.0 Hz, 1H), 6.37 (d, J=9.0 Hz, 1H), 7.11, 7.34 (dd, J=10.5,
2.4 Hz, 2H), 7.22–7.47 ppm (AA’BB’ system, J=8.1 Hz, 4H); 13C NMR
(75 MHz, CDCl3): d=13.4, 14.9, 21.3, 28.2 (3C), 58.4, 70.2, 81.0, 124.0,
129.4, 129.9, 131.0, 138.0, 141.2, 145.7, 146.9, 154.5, 184.6 ppm; MS (EI):
m/z (%): 57 (100), 59 (11), 65 (22), 77 (15), 79 (19), 91 (55), 92 (49), 105
(13), 121 (13), 123 (17), 133 (35), 134 (32), 139 (28), 140 (46), 149 (46),
193 (30), 194 (31), 205 (60), 249 (98), 279 (10), 316 (20), 330 [MÀ58]+,
159.
N-(tert-Butoxycarbonyl)-4-amino-4-[p-(tolylsulfonyl)methyl]-4H-naph-
thalen-1-one (28): Compound 28 was obtained from 26 (300 mg,
0.99 mmol, 1 equiv) and MeSO2pTol 29 (168 mg, 1.0 mmol, 1 equiv) as an
orange oil in 18% yield (77 mg) by following a modified version of meth-
od A (the anion was formed at 08C, and the reaction was stirred at RT).
Reaction time: 5 h; eluent: hexane/AcOEt 4:1; 1H NMR (300 MHz,
CDCl3): d=1.50 (s, 9H), 2.42 (s, 3H), 3.16–3.66 (AB system, J=14.1 Hz,
2H), 6.45 (d, J=10.5 Hz, 1H), 6.77 (brs, 1H), 7.28–7.74 (AA’BB’ system,
J=10.5 Hz, 4H), 7.41 (dd, J=14.9, 1.4 Hz, 1H), 7.53 (dd, J=7.8, 1.4 Hz,
1H), 7.59 (td, J=7.1, 1.4 Hz, 1H), 7.72 (dd, J=7.9, 1.4 Hz, 1H),
8.10 ppm (dd, J=7.9, 1.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=21.6,
28.0 (3C), 60.3, 66.5, 80.8, 125.0, 127.2 (2C), 127.9, 128.3, 128.4, 130.2,
130.5, 133.2 (2C), 136.4, 145.8, 149.9, 153.7, 183.4 ppm; MS (EI): m/z
(%): 57 (100), 65 (26), 77 (18), 91 (69), 115 (17), 127 (18), 128 (57), 143
N-(tert-Butoxycarbonyl)-4-amino-4-[1’-(p-tolylsulfonyl)propyl]-2,5-cyclo-
hexadienone (38): Compound 38 was obtained from 14 (253 mg,
Chem. Eur. J. 2008, 14, 621 – 636
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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