M.A. Amin et al. / Tetrahedron 75 (2019) 130591
5
4.1.3. (S,S) and (S,R)-1-(9H-Fluoren-9-yl)ethyl-2-methyl-3,4-
dihydroquinoline-1(2H)-carboxylate 7
To a solution of carbamate (S,S)-7 (40 mg, 0.10 mmol) in MeOH
(1.0 M) was added piperidine (0.05 mL) and DBU (0.05 mL). The
mixture was stirred at RT for 2 h. The solvent was removed in vacuo
and the residue was purified by column chromatography (0e15%
EtOAc in petroleum benzine) to give the title compound (S)-6 as a
pale yellow oil (13 mg, 85%). TLC: Rf (10% EtOAc in petroleum
benzine) ¼ 0.80. Analytical RP-HPLC: tR ¼ 3.80 min, >99% purity.
ESI-HRMS (m/z): calcd for C10H14Nþ [MþH]þ, 148.1121; found,
148.1122. 1H NMR (400 MHz, CDCl3)
d 6.99e6.92 (m, 2H, ArH),
6.63e6.58 (m, 1H, ArH), 6.50e6.44 (m, 1H, ArH), 3.88e3.48 (br, 1H,
NH), 3.49e3.29 (m, 1H, CH), 2.91e2.65 (m, 2H, CH2), 2.00e1.85 (m,
1H, CH2), 1.65e1.59 (m, 1H, CH2) and 1.23e1.18 (d, J ¼ 6.3 Hz, 3H,
To
a solution of racemic tetrahydroquinaldine (THQ) (6)
(352 mg, 2.4 mmol) in CH2Cl2 (12 mL) at 0 ꢁC was added (S)-4
(980 mg, 3.6 mmol) and TEA (290 mg, 2.80 mmol). The mixture was
stirred overnight at RT, the solvent was evaporated in vacuo and the
residue was taken up in EtOAc and washed with 1 M aqueous HCl
(3 ꢂ 40 mL) and brine (1 ꢂ 40 mL). The organic layer was dried
(Na2SO4), concentrated in vacuo and the residue was purified by
silica gel column chromatography (3e60% EtOAc in petroleum
benzine) to afford 7 (750 mg, 81%, <1% de) as a white solid. The
diastereomers were resolved by RP-HPLC (35e80% ACN in 0.1% aq.
TFA) to give (S,S)-7 (80 mg, 11%, 99% de) and (S,R)-7 (150 mg, 21%,
94% de).
CH3) ppm. 13C NMR (101 MHz, CDCl3)
d 144.9 (C), 129.4 (CH), 126.8
(CH), 121.2 (C), 117.1 (CH), 114.1 (CH), 47.3 (CH), 30.3 (CH2), 26.7
(CH2) and 22.8 (CH3) ppm.
4.1.5. (R)-2-Methyl-1,2,3,4-tetrahydroquinoline (R)-6 [21]
(S,S)-7: Mp 57e59 ꢁC. TLC: Rf (10% EtOAc in petroleum
benzine) ¼ 0.34. Analytical RP-HPLC: 20e80% solvent B, 5 min,
tR ¼ 3.83 min (S/S), purity >99% (de). ESI-HRMS (m/z): calcd for
To a solution of carbamate (S,R)-7 (40 mg, 0.10 mmol) in MeOH
(1.0 M) was treated as for (S,S)-7a above to give (R)-6 as an oil
(12 mg, 81%). TLC: Rf (10% EtOAc in petroleum benzine) ¼ 0.8.
Analytical RP-HPLC: tR ¼ 3.81 min, purity >99%. The data matched
that previously reported for (S)-6 above.
C
26H26NOþ2 [MþH]þ, 384.1958; found, 384.1966. 1H NMR (400 MHz,
CDCl3)
d
7.76 (d, J ¼ 7.6 Hz, 2H, ArH), 7.59 (t, J ¼ 8.7 Hz, 2H, ArH), 7.50
(d, J ¼ 7.5 Hz, 1H, ArH), 7.43e7.29 (m, 3H, ArH), 7.26e7.02 (m, 4H,
ArH), 5.81e5.66 (m, 1H, CHCHCO), 4.72e4.54 (m, 1H, NCH), 4.38 (d,
J ¼ 3.1 Hz, 1H, CHCHCO), 2.78e2.59 (m, 2H, CCH2), 2.27 (td, J ¼ 12.9,
6.6 Hz,1H, CCH2CH2),1.55 (td, J ¼ 13.3, 6.9 Hz,1H, CCH2CH2),1.20 (d,
J ¼ 6.5 Hz, 3H, OCHCH3) and 0.83 (d, J ¼ 6.3 Hz, 3H, NCHCH3) ppm.
4.1.6. (S)-1-(2-Methyl-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one
(S)-8
13C NMR (101 MHz, CDCl3)
d 154.7 (CO), 143.6 (C), 143.5 (C),
142.2(C), 141.7 (C), 136.7 (C), 132.3 (C), 127.8 (CH), 127.7 (CH), 127.6
(CH), 127.2 (CH), 127.0 (CH), 126.3 (CH), 126.0 (CH), 125.7 (CH), 124.8
(CH), 124.3 (CH), 120.0 (CH), 119.9 (CH), 74.3 (CH), 52.2 (CH), 49.9
(CH), 31.5 (CH2), 25.5 (CH2), 19.8 (CH3) and 14.9 (CH3) ppm.
(S,R)-7: Mp: 103e105 ꢁC. TLC: Rf (10% EtOAc in petroleum
benzine) ¼ 0.28. . Analytical RP-HPLC: 20e80% solvent B, 5 min,
tR ¼ 3.95 min (S/R) > 99% purity, 94% (de). ESI-HRMS (m/z): calcd for
To a solution of (S)-1-(2-Methyl-3,4-dihydroquinolin-1(2H)-yl)
ethan-1-one (S)-6 (30 mg, 0.20 mmol) (1.0 equiv.) in dichloro-
methane (CH2Cl2) (0.1 M) at 0 ꢁC was added acetic anhydride (4.0
equiv.) and the mixture was allowed to stir at room temperature
(RT) for 16 h. The mixture was poured into ice-water and acidified
with 1 M aqueous HCl to pH~ 4. The aqueous layer was extracted
with CH2Cl2 (3 ꢂ 100 mL). The combined organic layers were dried
(Na2SO4), and concentrated in vacuo to give (S)-8 (35 mg, 90%) as a
colourless crystalline solid. Mp: 50e51 ꢁC. TLC: Rf (15% EtOAc in
petroleum benzine) ¼ 0.3. Analytical RP-HPLC: 6.62 min, >99%
purity. ESI-HRMS (m/z): calcd for C12H16NOþ [MþH]þ, 190.1226;
found, 190.1227. Analytical CHPLC: Lux Amylose-2, tR ¼ 5.07 min (S)
C
26H26NOþ2 [MþH]þ, 384.1958; found, 384.1965. 1H NMR (400 MHz,
CDCl3)
d
7.72 (dd, J ¼ 7.5, 2.9 Hz, 2H, ArH), 7.53 (dd, J ¼ 12.4, 7.8 Hz,
2H, ArH), 7.41e7.27 (m, 3H, ArH), 7.25e7.06 (m, 5H, ArH), 5.80e5.71
(m, 1H, CHCHCO), 4.77e4.65 (m, 1H, NCH), 4.29 (d, J ¼ 3.8 Hz, 1H,
CHCHCO), 2.79e2.64 (m, 2H, CCH2), 2.36e2.24 (m, 1H, CCH2CH2),
1.56 (td, J ¼ 13.4, 6.8, Hz, 1H, CCH2CH2), 1.24 (d, J ¼ 6.5 Hz, 3H,
OCHCH3) and 0.78 (d, J ¼ 6.4 Hz, 3H, NCHCH3) ppm. 13C NMR
(101 MHz, CDCl3)
d 154.6 (CO), 143.5 (C), 143.4 (C), 142.2 (C), 141.7
(C), 136.7 (C), 132.7 (C), 127.8 (CH), 127.7 (CH), 127.5 (CH),127.2 (CH),
126.9 (CH), 126.4 (CH), 126.19 (CH), 126.17 (CH), 124.7 (CH), 124.4
(CH), 120.0 (CH), 119.8 (CH), 74.0 (CH), 51.9 (CH), 49.9 (CH), 31.5
(CH2), 25.5 (CH2), 19.8 (CH3) and 14.9 (CH3) ppm.
97% (ee). 1H NMR (400 MHz, CDCl3)
d 7.24e7.03 (m, 4H, ArH), 4.78
(br.s, 1H, CHCH3), 2.67e2.44 (m, 2H, CCH2), 2.41e2.28 (m, 1H,
CH3CHCH2), 2.14 (s, 3H, C(O)CH3), 1.41e1.23 (m, 1H, CH3CHCH2) and
4.1.4. (S)-2-Methyl-1,2,3,4-tetrahydroquinoline, (S)-6 [15]
1.12 (d, J ¼ 6.5 Hz, 3H, CH3) ppm. 13C NMR (101 MHz, CDCl3)
d 169.7
(CO), 166.3 (C), 137.7 (C), 127.4 (CH), 126.2 (CH), 125.9 (CH), 125.6
(CH), 48.4 (CH), 32.7 (CH2), 26.2 (CH2), 23.0 (CH3) and 20.3 (CH3)
ppm. The product was identical to a sample obtained by acetylation
of (S)-6 from diastereomeric resolution [15].