Molecules 2018, 23, 838
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3.4. N-Methylation of Indolo[3,2-b]quinolines with MeOTf: An Experimental Procedure Exemplified by the
Synthesis of 10fi
Compound 10fi was synthesized based on the modified literature procedure [82], as follows:
A flame-dried 20-mL Schlenk tube was charged with 4fi (28.6 mg, 0.100 mol) and toluene (0.60 mL).
The resulting solution was degassed by three freeze-pump-thaw cycles, and the tube was then filled
with argon. To this solution, MeOTf (31.2 mg, 0.190 mmol) that had been distill◦ed by Kugelrohr
◦
at 90 C/500 Pa prior to use was added, and the mixture was then stirred at 50 C for 24 h. The
resulting mixture, including a solid product, was filtered, and the solid was washed with Et2O
(5 mL). The filtrate was concentrated, and the residue was filtered and then washed with Et2O (5
mL). This concentration–filtration–washing sequence was repeated once again, and the combined
solid was dried in vacuo to give an analytically pure 5-methyl-11-trifluoromethyl-10H-quindolini◦um
1,1,1-trifluoromethanesulfonate (10fi) in 94% yield (42.4 mg) as a yellow solid (mp 281–282 C).
Compound 10fi was characterized by 1H-, 13C- and 19F-NMR spectroscopy and HRMS, as follows:
1H-NMR (500 MHz, dimethyl sulfoxide-d6)
δ 5.13 (s, 3H), 7.62 (ddd, J = 8.3, 7.2, 1.1 Hz, 1H), 7.97 (dt,
J = 8.3, 0.9 Hz, 1H), 8.06 (ddd, J = 8.3, 7.2, 1.1 Hz, 1H), 8.15 (ddd, J = 8.7, 6.8, 0.9 Hz, 1H), 8.28 (ddd,
J = 9.0, 6.9, 1.3 Hz, 1H), 8.51–8.60 (m, 1H), 8.89 (d, J = 8.6 Hz, 1H), 8.97 (d, J = 9.2 Hz, 1H), 12.71 (s, 1H);
13C-NMR (125 MHz, dimethyl sulfoxide-d6)
δ 41.7, 113.5, 113.7, 116.8 (q, J = 32.8 Hz), 119.2, 120.6 (q,
J = 322.2 Hz), 121.5, 122.5, 123.2 (q, J = 275.9 Hz), 124.2 (q, J = 3.0 Hz), 127.1, 129.3, 130.8 (q, J = 1.2 Hz),
132.0, 135.1, 135.9, 142.7, 147.3; 19F-NMR (376 MHz, dimethyl sulfoxide-d6)
Calcd for C17H12F3N2: M+, 301.0947. Found: m/z 301.0936.
δ –77.3, –53.4. HRMS (FD)
Besides a general experimental procedure for the synthesis of compounds 10, details of the
reaction conditions, spectral and analytical data (melting point, NMR, and HRMS), and NMR charts
for all products 10 in Table 6 are provided in Supplementary Materials.
3.5. An Experimental Procedure for the Synthesis of 11fi by Neutralizing 10fi
Compound 11fi was synthesized based on the literature procedure [82], as follows: 10fi (22.5 mg,
0.0500 mmol) was placed in a 15-mL screw-cap vial. To this, a 5 wt % Na2CO3 aqueous solution (2.0
mL) was added, and the resulting mixture was stirred at 30 ◦C for 15 min. The aqueous phase was
extracted with CHCl3 (4 mL
sulfate (Na2SO4). Filtration and evaporation of the solvent followed by column chromatography on
×
4), and the combined organic layer was dried over anhydrous sodium
silica gel (CHCl3/Et3N = 50/1) gave 5-methyl-11-trifluoromethyl-5H-quindoline (11fi) in 99% yield
◦
(14.9 mg) as a dark navy solid [m.p. 251–253 C (decomp.)]. Compound 11fi was characterized by 1H-,
13C- and 19F-NMR spectroscopy and HRMS, as follows: H-NMR (400 MHz, dimethyl sulfoxide-d6)
1
δ
5.02 (s, 3H), 7.12 (ddd, J = 8.4, 6.6, 1.1 Hz, 1H), 7.65 (ddd, J = 8.4, 6.8, 1.1 Hz, 1H), 7.72 (dd, J = 8.6,
0.8 Hz, 1H), 8.86 (ddd, J = 8.6, 6.8, 1.0 Hz, 1H), 7.96 (ddd, J = 8.9, 6.9, 1.1 Hz, 1H), 8.47–8.52 (m, 1H),
8.55 (dd, J = 8.5, 0.7 Hz, 1H), 8.70 (d, J = 8.9 Hz, 1H); 13C-NMR (100 MHz, dimethyl sulfoxide-d6)
δ
40.3, 113.6, 116.1 (q, J = 29.2 Hz), 117.4, 117.9, 119.5, 120.1 (q, J = 1.4 Hz), 124.0 (q, J = 3.8 Hz), 125.0
(q, J = 277.3 Hz), 125.7, 125.9, 127.8, 131.6, 132.7, 142.3, 143.8, 162.9; 19F-NMR (471 MHz, dimethyl
sulfoxide-d6) δ –50.8. HRMS (FD) Calcd for C17H11F3N2: M, 300.0874. Found: m/z 300.0870.
4. Conclusions
We disclosed here that the indium-catalyzed tandem N–C and C–C bond-forming reaction of
o-acylanilines with MeO–heteroarenes is a practical methodology to synthesize a range of HA[b]Qs with
tricyclic and tetracyclic [2,3-b] and [3,2-b] skeletons fused with sulfur-, oxygen-, and nitrogen-based
five-membered heteroaryl rings. Indolo[3,2-b]quinolines, which are also the frameworks constructed
by our method, were readily converted to cryptolepine derivatives that have not yet been prepared.
Mechanistic investigations revealed that the central pyridyl ring is constructed by the sequence of the
intermolecular N–C bond-formation, followed by the C–C bond-forming ring closure.