J.P. Cooksey, O. Saidi, J.M.J. Williams et al.
Tetrahedron 78 (2021) 131785
(1H, d, J ¼ 8.1, C4H), 7.34 (1H, d, J ¼ 8.1, C7H), 7.18 (1H, t, J ¼ 7.5,
C6H), 7.11 (1H, t, J ¼ 7.1, C5H), 7.01 (1H, s, C2H), 2.99 (2H, dd, J ¼ 9.6,
6.6, C50H2), 2.68 (2H, dd, J ¼ 9.6, 6.6, C40H2), 2.60e2.46 (4H, m,
C70H2), 1.66 (4H, quint, J ¼ 5.6, C80H2), 1.52e1.44 (2H, m, C90H2); 13C
4.4. 1,2,3,4,6,7,8,12c-Octahydroindolo[3,2-a]quinolizine (8a)
The title compound 8a was prepared in 61% yield on a 438
scale [along with recovered 6a (35%)] using the general procedure.
Compound 8a was purified by column chromatography [SiO2,
CH2Cl2/MeOH (5:1)] followed by crystallisation from EtOH/H2O as
an off-white solid. mp (EtOH/H2O) 212e213 ꢀC; nmax (solid)
3600e2400 br, s, 2920 s, 2222 br, s, 1901 w, 1869 w, 1840 w, 1793 w,
mmol
NMR (75 MHz, CDCl3)
d
136.4 (C8), 127.6 (C30), 122.0 (C6H), 121.6
(C2H), 119.3 (C5H), 119.0 (C4H), 114.6 (C3), 111.3 (C7H), 60.3 (C40H2),
54.8 (C70H2), 26.1, (2C, C80H2), 24.6 (2C, C90H2), 23.0 (C50H2); m/z
(ESþ) 229 [MHþ, 100%]; HRMS (ESþ): MHþ, found 229.1706.
1653 w, 1621 m, 1579 m, 1505 s, 1455 s cmꢂ1
CDCl3)
;
1H NMR (500 MHz,
7.96 (1H, s, NH), 7.57 (1H, d, J ¼ 7.8, C4H), 7.26e7.23 (1H, m,
C
15H21N2 requires 229.1699.
d
C7H), 7.08 (1H, t, J ¼ 7.3, C6H), 7.04 (1H, t, J ¼ 7.3, C5H), 3.37 (1H, d,
J ¼ 8.4, C110H), 3.14e3.07 (1H, m, C70HAHB), 3.02 (1H, dd, J ¼ 10.7,
6.5, C50HAHB), 3.05e2.98 (1H, m, C40HAHB), 2.70e2.58 (3H, m,
C50HAHB/C70HAHB/C100HAHB), 2.50 (1H, td, J ¼ 11.6, 3.0, C40HAHB),
1.93e1.87 (1H, m, C90HAHB), 1.83e1.71 (2H, m, C8H2), 1.61e1.51 (2H,
4.2. Desbromoarborescidine (3)
A solution of indole 2 (183 mg, 800 mmol, 1.0 equiv) and iridium
complex 5b (1.60 mmol, 2 mol%) in mesitylene (2 mL) was heated
m, C90HAHB/C100HAHB); 13C NMR (75 MHz, CDCl3)
d 136.5 (C8),
132.5 (C30), 126.0 (C2), 120.9 (C6H), 119.4 (C4H), 119.3 (C5H), 112.5
(C3), 110.9 (C7H), 61.4 (C110H), 56.2 (C40H2), 52.6 (C50H2), 31.4
(C100H2), 26.2 (C80H2), 24.9 (C90H2), 24.4 (C70H2); m/z (ESþ) 227
[MHþ, 100%]; HRMS (ESþ): MHþ, found 227.1551. C15H19N2 requires
227.1543.
under reflux for 5 d. The reaction mixture was allowed to cool to rt
and MeOH (5 mL) added. NaBH4 (45.5 mg, 1.2 mmol, 1.5 equiv) was
added in one portion to the reaction mixture at 0 ꢀC and the
resulting brown solution stirred at rt for 1 h. The reaction mixture
was quenched with NaHCO3 (saturated aqueous; 10 mL), CH2Cl2
(10 mL) added, the layers separated and the aqueous layer extrac-
ted with CH2Cl2 (3 ꢁ 15 mL). The combined organic layers were
dried (Na2SO4), filtered and concentrated in vacuo to give a brown
oily solid. Purification by column chromatography [SiO2, CH2Cl2/
MeOH (5:1)] gave recovered 2 (38 mg, 21%) along with the title
compound 3 (87 mg, 48%; 61% based on recovered starting mate-
rial) as a yellow/brown solid after crystallisation from EtOH/H2O
mp (EtOH/H2O) 148e149 ꢀC (lit [25]. 147e150 ꢀC). Spectroscopic
data for compound X [1H NMR (500 MHz, CDCl3), 13C NMR (75 MHz,
CDCl3) and IR] are in accordance with those reported [21]. nmax
(solid) 3800e2600 br, s, 2923 s, 2848 s, 2805 s, 2763 s, 1624 m,1569
w, 1464 s, 1449 s, 1392 m, 1371 m, 1350 s, 1318 s, 1274 s, 1249 w
4.5. 10-Methoxy-1,2,3,4,6,7,8,12c-octahydroindolo[3,2-a]
quinolizine (9a)
The title compound 9a was prepared in 61% yield on a 387 mmol
scale [along with recovered 7a (35%)] using the general procedure.
The mixture was purified by column chromatography [SiO2, CH2Cl2/
MeOH (5:1)] followed by crystallisation from EtOH/H2O to give 9a
as an off-white solid. mp (EtOH/H2O) 188e190 ꢀC; nmax (solid)
3700e2500 br, m, 2992 m, 2931 s, 2808 s, 2762 s, 1627 s, 1593 m,
1566 m, 1468 s, 1434 m cmꢂ1; 1H NMR (500 MHz, CDCl3)
d 7.90 (1H,
s, NH), 7.43 (1H, d, J ¼ 8.7, C4H), 6.76 (1H, d, J ¼ 2.0, C7H), 6.70 (1H,
dd, J ¼ 8.7, 2.2, C5H), 3.79 (3H, s, OCH3), 3.32 (1H, d, J ¼ 8.3, C110H),
3.11e3.03 (1H, m, C70HAHB), 3.04e2.97 (2H, m, C40HAHB/C50HAHB),
2.66 (1H, td, J ¼ 11.0, 4.2, C50HAHB), 2.61e2.52 (2H, m, C70HAHB/
C100HAHB), 2.48 (1H, td, J ¼ 11.5, 3.0, C40HAHB), 1.93e1.85 (1H, m,
C90HAHB), 1.85e1.66 (2H, m, C80H2), 1.60e1.49 (2H, m, C90HAHB/
cmꢂ1; 1H NMR (500 MHz, CDCl3)
d 7.71 (1H, broad s, NH), 7.47 (1H,
d, J ¼ 7.7, C4H), 7.29 (1H, d, J ¼ 8.1, C7H), 7.12 (1H, t, J ¼ 7.3, C6H) 7.08
(1H, t, J ¼ 7.3, C5H), 3.24 (1H, br d, J ¼ 10.7, C110H), 3.10e2.97 (3H, m,
C40HAHB/C50HAHB/C70HAHB), 2.74e2.67 (1H, m, C70HAHB), 2.63 (1H,
td, J ¼ 11.1, 4.4, C50HAHB), 2.39 (1H, td, J ¼ 11.1, 3.4, C40HAHB), 2.06
(1H, dd, J ¼ 12.4, 2.1, C100HAHB), 1.90 (1H, broad d, J ¼ 12.4,
C90HAHB), 1.82e1.69 (2H, m, C80HAHB/C90HAHB), 1.60 (1H, qd,
J ¼ 12.4, 3.4, C100HAHB), 1.54e1.43 (1H, m, C80HAHB); 13C NMR
C100HAHB); 13C NMR (75 MHz, CDCl3)
d 155.6 (C6), 137.3 (C8), 131.2
(C30), 120.2 (C6), 119.8 (C4H), 111.8 (C3), 108.6 (C5H), 95.0 (C7H),
61.4 (C110H), 56.1 (C40H2), 55.7 (OCH3), 52.7 (C50H2), 31.3 (C100H2),
26.0 (C80H2), 24.8 (C90H2), 24.1 (C70H2); m/z (ESþ) 257 [MHþ, 100%];
HRMS (ESþ): MHþ, found 257.1651. C16H21N2O [MHþ]: requires
257.1648.
(75 MHz, CDCl3)
d
136.1 (C8), 135.3 (C30), 127.6 (C2), 121.3 (C6H),
119.4 (C5H), 118.2 (C4H), 110.9 (C7H), 108.2 (C3), 60.4 (C110H), 55.9
(C40H2), 53.7 (C70H2), 30.1 (C50H2), 25.8 (C100H2), 24.4 (C80H2), 21.7
(C90H2); m/z (ESþ) 228 (15%), 227 [MHþ, 100%]. HRMS (ESþ): MHþ,
found 227.1550. C15H19N2 requires 227.1543.
4.6. 3,4,6,7,8,12c-hexahydro-1H- [1,4]oxazino[40,3’:1,2]-pyrido[4,3-
b]indole (8b)
The title compound 8b was prepared in 35% yield on a 400 mmol
4.3. General procedure for catalytic dehydrogenative iso-Pictet-
scale [along with recovered 6b (39%)] using the general procedure.
The mixture was purified by column chromatography [SiO2, CH2Cl2/
MeOH (10:1)] followed by crystallisation from PhH/petrol to give
the title compound 8b as an off-white solid. mp (PhH/petrol)
153e156 ꢀC; nmax (solid) 3400e2500 br, s, 2920 s, 2949 s, 2847 s,
A solution of indole 6a-f/7a-d (462
mmol, 1.0 equiv) and iridium
catalyst 5b (5.24 mg, 9.34 mol, 2 mol%) in xylenes (1 mL) was
m
heated under reflux for 2 d. The reaction mixture was allowed to
cool to rt and MeOH (5 mL) added. NaBH4 (70.0 mg, 1.85 mmol, 4.0
equiv) was added in one portion to the reaction mixture at 0 ꢀC and
the resulting brown solution stirred at rt for 1 h. The reaction
mixture was quenched with NaHCO3 (saturated aqueous; 10 mL),
CH2Cl2 (10 mL) added, the layers separated and the aqueous layer
extracted with CH2Cl2 (3 ꢁ 10 mL). The combined organic layers
were dried (Na2SO4), filtered and concentrated in vacuo to give the
crude product 8a-d/9a-d and recovered starting material that was
purified by column chromatography/recrystallisation using the
solvents specified.
2789 s, 1622 w, 1588 w, 1565 w, 1502 m, 1455 s cmꢂ1
;
1H NMR
8.19 (1H, s, NH), 7.44 (1H, d, J ¼ 7.7, C4H), 7.20
(500 MHz, CDCl3)
d
(1H, d, J ¼ 7.8, C7H), 7.09 (1H, td, J ¼ 7.6, 1.1, C6H), 7.05 (1H, td,
J ¼ 7.6, 1.1, C5H), 4.68 (1H, dd, J ¼ 11.0, 2.7, C100H), 3.93 (1H, d,
J ¼ 10.6, C80HAHB), 3.84 (1H, td, J ¼ 10.6, 4.0, C80HAHB), 3.67 (1H, dd,
J ¼ 10.1, 1.9, C90HAHB), 3.53 (1H, t, J ¼ 10.6, C90HAHB), 3.00e3.08 (2H,
m, C50HAHB/C40HAHB), 2.79e2.85 (2H, m, C70HAHB), 2.70e2.75 (1H,
m, C50 HAHB), 2.57 (1H, dd, J ¼ 14.7, 4.9, C40HAHB); 13C NMR
(75 MHz, CDCl3)
119.6 (C5H), 118.9 (C4H), 111.0 (C7H), 107.6 (C3), 70.5 (C100H), 67.2
d
136.2 (C8), 133.3 (C30), 125.3 (C2), 121.2 (C6H),
4