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cellent yield. Reaction of thiophen-3-ylacetylene under the op-
timized conditions afforded the tryptamine 4p in 57%, which
is due to the formation of triazole in low yield. Tryptamines (4t
and 4y) containing substitution on the indole moiety were
also achieved in 93 and 89% yields, respectively. However, the
reaction of sterically hindered N-methyl-2-phenylindole gave
the corresponding tryptamine 4ac in moderate yield.
lective functionalization of terminal alkynes. Utility of the syn-
thesized tryptamines was further demonstrated in the synthe-
sis of dihydro-b-carboline, tryptoline, and free tryptamine that
are pivotal scaffolds in drug discovery.
Experimental Section
Synthetic application of the enamide and tryptamine was
demonstrated by converting to dihydro-b-carboline 6 and
tryptoline 7 derivatives, respectively.[30] Thus, the reaction of
enamide 3a with NaH and methoxymethyl chloride (MOMCl)
furnished the MOM-protected enamide, which on cyclization
using TMSOTf through the iminium ion furnished the dihydro-
b-carboline 6 in 47% yield (Scheme 6). Similarly, synthesis of
One-pot synthesis of tryptamine 4a from phenylacetylene
5a
Phenyl acetylene (5a) (67 mg, 0.07 mL, 0.65 mmol), copper(I)-thio-
phene-2-carboxylate (12.4 mg, 0.065 mmol), and toluene (4 mL)
were added under a nitrogen atmosphere to an oven-dried 10 mL
reaction tube equipped with stir bar. Subsequently, a solution of
p-toluenesulfonyl azide (129 mg, 0.1 mL, 0.65 mmol) in toluene
(1 mL) was introduced by syringe. The reaction tube was sealed
and stirred at RT for 3 h. After the TLC analysis, N-methylindole
(1a) (167 mg, 1.3 mmol) and Rh2(OAc)4 (5.6 mg, 0.013 mmol,
2 mol%) was added and then kept at 1008C for 5 h. After the TLC
analysis, it was cooled to room temperature and the solvent was
removed. Next, DCE (5 mL) and NaCNBH3 (122 mg, 1.95 mmol)
were added and then kept at 908C for 8 h. The reaction mixture
was cooled to room temperature, quenched with water, and ex-
tracted with ethyl acetate (210 mL). Evaporation of solvent fol-
lowed by purification of the crude by column chromatography
using hexanes/ethyl acetate mixture as the eluent afforded the
tryptamine 4a in 95% yield. M.p.: 145–1478C; IR (KBr): n˜ =3428,
1
3276, 1323, 1156 cmÀ1; H NMR (400 MHz, CDCl3, 248C): d=7.66 (d,
2H, J=8.3 Hz), 7.28–7.24 (m, 6H), 7.22–7.17 (m, 4H), 7.01–6.97 (m,
1H), 6.77 (s, 1H), 4.39 (t, 1H, J=6.0 Hz), 4.31 (t, 1H, J=7.6 Hz), 3.71
(s, 3H), 3.68–3.62 (m, 1H), 3.57–3.45 (m, 1H), 2.44 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, 248C): d=143.6, 141.3, 137.4, 137.0,
129.9, 128.9, 128.1, 127.3, 127.1, 127.0, 126.9, 122.1, 119.4, 119.3,
114.1, 109.5, 47.6, 42.7, 32.9, 21.7 ppm; HRMS: calcd for
C24H24N2O2S+H: 405.1637; found: 405.1620.
Scheme 6. Synthetic application of enamide 3a and tryptamine 4a.
Acknowledgements
tryptoline derivative 7 was accomplished from tryptamine 4a.
Furthermore, deprotection of the N-sulfonyl moiety was exam-
ined in 4a. The reaction of tryptamine 4a with sodium naph-
thalenide afforded the free tryptamine derivative 8 in 53%
yield.
We thank the Department of Science and Technology (DST),
New Delhi, India (Project No. SR/S1/OC-48/2012) for funding
this work. S.R. thanks the Council of Scientific and Industrial
Research (CSIR) and D.Y. thanks Indian Institute of Technology
Madras (IITM) for fellowships.
Conclusions
Keywords: aminoethylation · indoles · rhodium · triazoles ·
tryptamine
We have demonstrated a general and efficient one-pot amino-
ethylation of substituted indoles/pyrroles for the synthesis of
tryptamine derivatives employing the combination of alkynes
and sulfonyl azides as readily accessible aminoethylating
agent. The reaction was developed through a systematic study
that started with selective insertion of a-imino rhodium car-
benes, generated from N-sulfonyl-1,2,3-triazole and rhodium(II),
onto the C3ÀH bond of indole to enamide derivatives. Subse-
quent integration of the reduction of enamide, in one-pot, al-
lowed the synthesis of various substituted tryptamines in good
to excellent yields. The developed transformation tolerates
well various reactive functional groups. Finally, copper-cata-
lyzed synthesis of triazoles was also successfully integrated to
achieve the one-pot, three-step transformation of alkynes to
tryptamines. The reaction constitutes a one-pot formal regiose-
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Chem. Eur. J. 2015, 21, 17079 – 17084
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