One-Pot Trimetallic Relay Catalysis: A Unified Approach for the Synthesis of β-Carbolines and Other [c]-Fused Pyridines

Article abstract of DOI:10.1002/anie.201600840

A divergent strategy is presented for the synthesis of 1,3-di- and 1,3,4-trisubstituted β-carbolines through an unprecedented one-pot triple-orthogonal-metal relay catalysis, and 1,3-disubstituted 4-hydroxy-β-carbolines through a one-pot bimetallic relay

Full text of DOI:10.1002/anie.201600840

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201600840
German Edition: DOI: 10.1002/ange.201600840
Heterocycle Synthesis
One-Pot Trimetallic Relay Catalysis: A Unified Approach for the
Synthesis of b-Carbolines and Other [c]-Fused Pyridines
Seema Dhiman, Uttam K. Mishra, and S. S. V. Ramasastry*
Dedicated to Professor N. Sathyamurthy
Abstract: A divergent strategy is presented for the synthesis of
1,3-di- and 1,3,4-trisubstituted b-carbolines through an unpre-
cedented one-pot triple-orthogonal-metal relay catalysis, and
1,3-disubstituted 4-hydroxy-b-carbolines through a one-pot
bimetallic relay catalysis from readily accessible 3-(2-amino-
phenyl)-5-hexenyn-3-ols. These strategies were elaborated to
Orthogonal relay catalytic approaches have received
tremendous attention owing to their potential to create
intricate molecular architectures from simple starting materi-
als in a rapid and efficient manner.[4] However, the develop-
ment of such processes is not always straightforward.
Compatibility issues between the catalytic systems, further
hampered by chemoselectivity aspects, complicate the evolu-
tion of such methods. Significant advances have been made in
the development of novel cascade processes facilitated by two
distinct metal catalysts.[5] However, to the best of our
knowledge, reactions promoted by three orthogonal relay
metal-catalytic systems have not been reported so far. Herein,
we report an example of triple relay catalysis[6] that integrates
silver, bismuth, and palladium catalysts towards the synthesis
of b-carbolines through a one-pot cascade involving intra-
molecular hydroamination, Friedel–Crafts-type dehydrative
azidation, and an unprecedented annulation of the resulting
e,w-unsaturated azide to generate a pyridine ring (Scheme 2).
enable
the
synthesis
of
benzofuro[2,3-c]pyridines,
benzothieno[2,3-c]pyridines, and isoquinolines, which other-
wise require multistep synthesis.
P
yridine-fused indoles, commonly known as carbolines, are
one of the most important and abundant heterocycles. In
particular, the privileged pyrido[3,4-b]indole (b-carboline)
scaffold is a significant substructure prevalent in a variety of
bioactive natural products and druglike molecules
(Scheme 1).[1] Consequently, many protocols have been
developed for the synthesis of b-carboline derivatives.
Among them, approaches based on the Pictet–Spengler (P-
S) and Bischler–Napieralski (B-N) reactions are the most
widely used.[2] A few eminent contributions independent of P-
S or B-N reactions have also emerged.[3]
Scheme 2. Hypothesis based on triple relay catalysis. Pg=protecting
group, M-1, M-2, and M-3 are metal-based catalysts.
Scheme 1. A few representative bioactive b-carboline natural products.
The foremost challenge was to address the synthesis of the
desired indolines B (Scheme 2). We envisioned that an
intramolecular hydroamination of alkynols A promoted by
an appropriate metal catalyst M-1 could provide indolines B.
However, the promotion of a 5-exo-dig cyclization[7] over
other competing cyclization pathways could be a challenge.[8]
A M-2-promoted acid-catalyzed 1,3-allylic alcohol isomer-
ization (1,3-AAI) and dehydrative nucleophilic azidation
cascade of B was considered for the synthesis of e,w-
unsaturated azides C.[9] It was further hypothesized that
a thermal or metal-catalyzed intramolecular azide–alkene
[*] S. Dhiman, U. K. Mishra, Prof. Dr. S. S. V. Ramasastry
Department of Chemical Sciences
Indian Institute of Science Education and Research (IISER) Mohali
Knowledge City, Sector 81, S. A. S. Nagar, Manuali PO
Punjab 140306 (India)
E-mail: ramsastry@iisermohali.ac.in
ramsastrys@gmail.com
Homepage: http://14.139.227.202/faculty/sastry/
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under http://dx.doi.org/10.
1002/anie.201600840.
Angew. Chem. Int. Ed. 2016, 55, 7737 –7741
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7737

Angewandte
Communications
Chemie
[3+2] cycloaddition, or a metal-catalyzed nitrene insertion
into the side-chain olefin in C and subsequent bond reorgan-
ization, could afford b-carbolines D.[10] Since modular access
to enynols A from amino benzaldehydes E is possible in three
simple steps, this method serves as a short and efficient
alternative to existing synthetic approaches to b-carbolines.
We began our investigation towards identifying an
efficient catalytic system to substantiate our hypothesis in
Scheme 2 by evaluating the gold(I)-catalyzed intramolecular
hydroamination conditions reported earlier by our research
group[9d,e] with the enynol 1a as the model substrate.[11]
However, only the 6-exo-trig product 6a was isolated
Notably, the yield could be improved by increasing the
temperature, especially with Pd(OAc)2 as the catalyst
(Table 1, entries 6–8).
Having optimized the reaction conditions, we next
evaluated the scope of the reaction with respect to the
substitution of the substrate and product (Table 2).[15] A wide
Table 2: Synthesis of 1,3-di- and 1,3,4-trisubstituted b-carbolines.[a]
(Table 1, entry 1).[8a,12] Among
a few other variations
Entry
1
5, R1, R2, R3, R4
Yield of 5 [%][b]
Table 1: Optimization of the reaction parameters.[a]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1b
1c
1d
1e
1 f
1g
1h
1i
1j
1k
1l
1m
1n
1o
5b, p-(CH3)C6H4, H, H, H
5c, m-FC6H4, H, H, H
80
78
71
71
65
68
81
76
74
78
79
67
0[c]
0[c]
5d, p-(C6H5)C6H4, H, H, H
5e, p-(OMe)C6H4, H, H, H
5 f, p-OH-m-(OMe)C6H3, H, H, Cl
5g, 2-naphthyl, H, H, OMe
5h, C6H5, H, Me, H
5i, m-FC6H4, H, Me, H
5j, p-(C6H5)C6H4, H, Me, H
5k, p-(OMe)C6H4, H, Me, H
5l, 3-thienyl, H, Me, H
5m, nBu, H, Me, H
5n, C6H5, C4H9, H, H
5o, H, H, H, H
Entry
M-1/M-2
M-3, conditions
Yield of 5a [%][b]
[a] See the Supporting Information for details of the reaction conditions.
[b] Yield of the isolated product after column chromatography. [c] Azide 3
formed but decomposed under the reaction conditions.
[c]
1
2
3
4
5
6
7
8
9
AuCl,K2CO3/–
AgOAc/Yb(OTf)3
AgOAc/BiCl3
AgOAc/BiCl3
AgOAc/BiCl3
AgOAc/BiCl3
AgOAc/BiCl3
AgOAc/BiCl3
AgOAc/BiCl3
AgOAc/FeCl3
AgOAc/Sc(OTf)3
AgOAc/BiCl3
–
–
–
–
54
62
23
47
68
70
78
73
74
63
82
CuCl2, 24 h, 808C
Cu(OTf)2, 24 h, 808C
Pd(OAc)2, RT, 48 h
Pd(OAc)2, 608C, 48 h
Pd(OAc)2, 808C, 4 h
Pd2(dba)3, 808C, 6 h
Pd(OAc)2, 808C, 4 h
Pd(OAc)2, 808C, 16 h
Pd(OAc)2, 808C, 4 h
range of 1,3-disubstituted b-carbolines (Table 2, entries 1–6,
5b–g) and 1,3,4-trisubstituted b-carbolines (entries 7–12, 5h–
m) were assembled in a one-pot process in good to excellent
yield. Thus, the alkyne substituent R1 can be aromatic
(products 5b–k), heteroaromatic (product 5l), and even
10
11
12[d]
aliphatic (product 5m). However,
a slight substitution
dependence was observed. Enynols 1n and 1o did not yield
the respective carbolines 5n and 5o, despite our repeated
attempts. Apparent decomposition of the azide 3n under the
reaction conditions could possibly be due to its inability to
undergo the azide–alkene [3+2] cycloaddition, whereas in the
case of 3o, it is most likely due to instability or insufficient
activation of the primary azide functionality.
[a] See the Supporting Information for details of the reaction conditions.
[b] Yield of the isolated product after column chromatography. [c] Prod-
uct 6a formed exclusively. [d] The reaction was carried out with 5 mol%
of BiCl3 at 608C. DCE=1,2-dichloroethane, TMS=trimethylsilyl,
Tf =trifluoromethanesulfonyl, Ts =p-toluenesulfonyl.
We prepared enynols 1p and 1q (Scheme 3) with the
intention to attempt the total synthesis of b-carboline natural
attempted, AgOAc successfully produced the desired 5-exo-
dig product 2a with excellent chemo- and regioselectivity.[9c]
During the screening of different Lewis acids for the cascade
1,3-AAI/nucleophilic azidation, to our surprise, Yb(OTf)3,
BiCl3, and certain other Lewis acids[13] delivered the b-
carboline 5a directly in good yield, plausibly via the azide 3a
and the triazole 4a (Table 1, entries 2 and 3).[14] To improve
the yield, we carried out further optimization studies with
copper- and palladium-based catalysts.[10] Although 5a was
isolated in only moderate yield in the presence of Cu catalysts
(Table 1, entries 4 and 5), our attempts to improve the yield
with Pd catalysts were met with success (entries 6–12).
products
dichotomine A
and
dichotomine B
(see
Scheme 1).[1] However, surprisingly, the reaction of 1p or 1q
under the optimized conditions generated only the b-carbo-
line 5pq. This observation led to the conjecture that
substrates containing propargylic ethers undergo a domino
sequence involving benzylic ether deprotection, benzylic
alcohol oxidation, and retro-Claisen condensation of the
intermediate 5pq’ (see the Supporting Information for further
details). Nevertheless, a new method for the synthesis of
medicinally pertinent 3-substituted b-carbolines was estab-
lished.[16]
7738
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 7737 –7741

Angewandte
Communications
Chemie
Scheme 3. Unusual formation of 3-substituted b-carbolines. TBS=tert-
butyldimethylsilyl.
During our efforts to isolate the azide 3a, we made
a remarkable observation. The isolated sample of the azide 3a
was found to be unstable under ambient conditions[14] and
underwent slow transformation into a crystalline material,
which was characterized to be the 1,3-disubstituted 4-
hydroxy-b-carboline 7a.[17] Prompted by the occurrence of
several bioactive 4-hydroxy-b-carboline natural products (for
representative examples, see Scheme 1),[1,18] we explored the
generality of the observation (Table 3).
Table 3: Synthesis of 1,3-disubstituted 4-hydroxy-b-carbolines.[a]
Scheme 4. Plausible mechanism of formation of the b-carbolines 5a
and 7a.
in Scheme 4a.[21] Thus, silver(I)-catalyzed 5-exo-dig cycliza-
tion and protodemetalation of 1a generates the indoline
intermediate 2a. A bismuth(III)-promoted cascade involving
1,3-allylic alcohol isomerization (1,3-AAI) and nucleophilic
azidation then provides the azide 3a, which undergoes
a Huisgen-type intramolecular azide–alkene [3+2] cyclo-
addition to form 4a. Transformation of the triazole 4a into 8a
and aromatization provides 5a.
On the other hand, the azide 3a is converted into the
aziridine intermediate 9a in the presence of a PdII complex.[20]
Aziridine 9a undergoes deprotonation followed by ring
opening to generate 10a, which upon aromatization delivers
5a. Thus, the PdII complex plays a remarkable role in the
exclusive formation of 5a. This mechanism also explains the
marked yield enhancement in the presence of PdII complexes
(see Table 1).[15] In the absence of a PdII complex, 3a forms
8a, and the reaction takes an interesting detour. Presumably,
8a undergoes an autoxidation and aromatization sequence to
generate the 4-hydroxy-b-carboline 7a (Scheme 4a).
To establish the role of atmospheric oxygen during the
conversion of 8a into 7a, we conducted an isotopic labeling
experiment with 18O2 (Scheme 4b). The HRMS spectrum of
the product showed a distinct [M+H] peak for 18O-containing
7a.[21]
Entry
1
7, R1, R2
Yield of 7 [%][b]
1
2
3
4
5
6
7
8
9
1a
1c
1d
1e
1r
1s
1t
1u
1v
1p
7a, C6H5, H (X-ray crystal structure)
7b, m-FC6H4, H
7c, p-(C6H5)C6H4, H
7d, p-(OMe)C6H4, H
7e, p-iPrC6H4, H
7 f, 2-naphthyl, H
7g, 3-thienyl, H
7h, C6H5, Cl
89
81
79
78
86
81
87
84
78
76
7i, nBu, H
7j, CH3CH(OTBS), H
10
[a] See the Supporting Information for details of the reaction conditions.
[b] Yield of the isolated product after column chromatography.
It can be inferred from Table 3 that the scope of this
procedure is significant.[19] All 4-hydroxy-b-carbolines 7a–j
were obtained in consistent turnaround times and excellent
yields. Notably, electronically diverse substituents R1 and R2,
both aromatic and aliphatic, were tolerated well under the
reaction conditions. As a substantial advancement, the enynol
1p with a propargylic tert-butyldimethylsilyl ether moiety was
converted into the expected product 7j (in contrast to the
reaction of 1p in Scheme 3). Compound 7j possesses the
complete carbon framework present in the b-carboline
natural products dichotomide IX and tunicoidine D (see
Scheme 1).[1]
In an attempt to interrupt and detect the proposed
autoxidation of 8a to 11a, we designed the enynol 1w with
a methyl group positioned at the allylic position (Scheme 4c).
The role of the methyl group is to restrict the formation of the
ketone. Indeed, we were able to isolate and characterize the
tertiary alcohol 12w.[21] Besides supporting an autoxidation
On the basis of our experimental observations and in
conjunction with previous reports,[10,20] a plausible mechanism
that explains the formation of 5a and 7a from 1a is proposed
Angew. Chem. Int. Ed. 2016, 55, 7737 –7741
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7739

Angewandte
Communications
Chemie
process, this result also provides valuable information about
the triazole decomposition pathway.
tial and will stimulate further research in the synthesis of new
heterocycles.
After successfully establishing one-pot relay processes for
the facile synthesis of unusual b-carbolines by effectively
accommodating orthogonal metal-catalytic cycles, we
extended this strategy to the synthesis of other important
[c]-fused pyridines. Accordingly, a variety of e,w-unsaturated
azides were prepared and subjected to the optimized con-
ditions to demonstrate the versatility of the current approach
(Scheme 5). An interesting array of 1,3-disubstituted and
1,3,4-trisubstituted benzofuro[2,3-c]pyridines (products 15a–
c) and benzothieno[2,3-c]pyridines (products 18a–d) were
efficiently assembled. Benzofuro- and benzothienopyridines
are the primary molecular architectures of many biologically
active compounds and drug candidates,[22] and find applica-
tion in materials science as well.[23]
Acknowledgements
We thank the DST, Government of India for funding (SR/FT/
CS-156/2011). IISER Mohali is acknowledged for financial
support and for the NMR spectroscopic, mass spectrometric,
and X-ray crystallographic (both central and departmental)
facilities. We thank Dr. R. Vijaya Anand for the generous
donation of 18O2 and Dr. B. Prashant for his help with the X-
ray crystal structures. S.D. and U.K.M. thank IISER Mohali
for research fellowships.
Keywords: azides · b-carbolines · Lewis acids · relay catalysis ·
The versatility of this method was furthered by setting up
new approaches to isoquinolines (product 21a), 2-(isoquino-
lin-1-yl)quinolones (product 21b),[24] and 4-hydroxyisoquino-
lines (product 21c), which otherwise require multistep syn-
thesis. Isoquinolines are the key structural scaffolds of several
naturally occurring alkaloids; they are also the principal
components of numerous therapeutics and can provide the
backbone for chiral ligands.[25]
In conclusion, we have presented unprecedented exam-
ples of relay catalysis through the sequential use of silver,
bismuth, and palladium catalysts to access an array of distinct
b-carbolines. The method was subsequently extended to the
synthesis of intriguing [c]-fused pyridines, such as benzofuro-
and benzothieno[2,3-c]pyridines, and isoquinolines. Intrigu-
ing mechanistic details governing these processes were
elucidated. This methodology has demonstrated great poten-
transition metals
How to cite: Angew. Chem. Int. Ed. 2016, 55, 7737–7741
Angew. Chem. 2016, 128, 7868–7872
[1] For dichotomines, see: a) S. Tagawa, T. Choshi, A. Okamoto, T.
Nishiyama, S. Watanabe, N. Hatae, M. Ishikura, S. Hibino, Eur. J.
Org. Chem. 2013, 1805; for dehydrocrenatine, see: b) B. S. Joshi,
V. N. Kamat, D. H. Gawad, Heterocycles 1977, 7, 193; for
dichotomides, see: c) Y.-F. Chen, P. -C. Kuo, H.-H. Chan, I.-J.
Kuo, F.-W. Lin, C.-R. Su, M.-L. Yang, D.-T. Li, T.-S. Wu, J. Nat.
Prod. 2010, 73, 1993; for tunicoidines, see: d) J. Tian, Y. Shen, H.
Li, R. Liu, L. Shan, J. Gao, W. Zhang, Planta Med. 2012, 78, 625;
for lavendamycin and nitramarine, see: e) S. Ramesh, R.
Nagarajan, J. Org. Chem. 2013, 78, 545; for tabernines, see:
f) T. A. Mansoor, C. Ramalhete, J. Molnar, S. Mulhovo, M. J. U.
Ferreira, J. Nat. Prod. 2009, 72, 1147; g) P. Ashok, S. Ganguly, S.
Murugesan, Mini-Rev. Med. Chem. 2013, 13, 1778; h) M. Zhang,
D. Sun, Anticancer Agents Med. Chem. 2015, 15, 537; i) A.
Kamlah, F. Lirk, F. Bracher, Tetrahedron 2016, 72, 837.
[2] a) Y. Torisawa, A. Hashimoto, M. Nakagawa, H. Seki, R.
Hara, T. Hino, Tetrahedron 1991, 47, 8067; b) K. Pulka, Curr.
Opin. Drug Discovery Dev. 2010, 13, 669; c) G. Domínguez, J.
PØrez-Castells, Eur. J. Org. Chem. 2011, 7243; d) Y.-P. Zhu,
M.-C. Liu, Q. Cai, F.-C. Jia, A.-X. Wu, Chem. Eur. J. 2013, 19,
10132; e) G. C. Condie, J. Bergman, Eur. J. Org. Chem. 2004,
1286.
[3] a) H. Zhang, R. C. Larock, J. Org. Chem. 2002, 67, 7048;
b) D. B. England, A. Padwa, Org. Lett. 2008, 10, 3631; c) S.
Ding, Z. Shi, N. Jiao, Org. Lett. 2010, 12, 1540; d) Z. Shi, Y.
Cui, N. Jiao, Org. Lett. 2010, 12, 2908; e) F. Nissen, V.
Richard, C. Alayrac, B. Witulski, Chem. Commun. 2011, 47,
6656; f) A. L. Pumphrey, H. Dong, T. G. Driver, Angew.
Chem. Int. Ed. 2012, 51, 5920; Angew. Chem. 2012, 124, 6022;
g) J. D. Panarese, S. P. Waters, Org. Biomol. Chem. 2013, 11,
3428; h) A. K. Verma, S. K. R. Kotla, D. Choudhary, M.
Patel, R. K. Tiwari, J. Org. Chem. 2013, 78, 4386;
i) V. V. N. P. B. Tiruveedhula, K. R. Methuku, J. R.
Deschamps, J. M. Cook, Org. Biomol. Chem. 2015, 13,
10705; j) A. Kamal, Y. Tangella, K. L. Manasa, M. Sathish,
V. Srinivasulu, J. Chetna, A. Alarifi, Org. Biomol. Chem.
2015, 13, 8652.
[4] For selected articles on relay catalysis, see: a) A. Ajamian,
J. L. Gleason, Angew. Chem. Int. Ed. 2004, 43, 3754; Angew.
Chem. 2004, 116, 3842; b) A. De Meijere, P. von Zezschwitz,
S. Brase, Acc. Chem. Res. 2005, 38, 413; c) J.-C. Wasilke, S. J.
Obrey, R. T. Baker, G. C. Bazan, Chem. Rev. 2005, 105, 1001;
d) D. B. Ramachary, R. Sakthidevi, Org. Biomol. Chem.
2008, 6, 2488; e) A. Grossmann, D. Enders, Angew. Chem.
Scheme 5. Benzofuro[2,3-c]pyridines, benzothieno[2,3-c]pyridines, and iso-
quinolines prepared by this approach.
7740 www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 7737 –7741

Angewandte
Communications
Chemie
Int. Ed. 2012, 51, 314; Angew. Chem. 2012, 124, 320; f) N. T. Patil,
[15] Pd(OAc)2 was crucial for the synthesis of the products in good
V. S. Shinde, B. Gajula, Org. Biomol. Chem. 2012, 10, 211; g) S.
Fustero, E. Rodriguez, R. Lazaro, L. Herrera, S. Catalan, P.
Barrio, Adv. Synth. Catal. 2013, 355, 1058; h) S. Zhang, F. Wei, C.
Song, J. Jia, Z. Xu, Chin. J. Chem. 2014, 32, 937.
yield. Use of the AgI/BiIII/PdII system rather than the AgI/BiIII
system alone led to a yield enhancement of at least 20–30%.
[16] a) M. Nielsen, C. Braestrup, Nature 1980, 286, 606; b) P. Venault,
G. Chapouthier, L. P. De Carvalho, J. Simiand, M. Morre, R. H.
Dodd, J. Rossier, Nature 1986, 321, 864; c) D. B. Pritchett, H.
Lueddens, P. H. Seeburg, Science 1989, 245, 1389; d) A. K.
Evans, C. A. Lowry, CNS Drug Rev. 2007, 13, 475.
[5] See, for example: a) P. C. Too, S. H. Chua, S. H. Wong, S. Chiba,
J. Org. Chem. 2011, 76, 6159; b) Y.-F. Wang, K. K. Toh, J.-Y. Lee,
S. Chiba, Angew. Chem. Int. Ed. 2011, 50, 5927; Angew. Chem.
2011, 123, 6049; c) S. Zhang, Z. Xu, J. Jia, C.-H. Tung, Z. Xu,
Chem. Commun. 2014, 50, 12084; d) X. Wang, S. Dong, Z. Yao,
L. Feng, P. Daka, H. Wang, Z. Xu, Org. Lett. 2014, 16, 22; e) Q.
Gao, P. Zhou, F. Liu, W. J. Hao, C. Yao, B. Jiang, S.-J. Tu, Chem.
Commun. 2015, 51, 9519.
[17] CCDC 1449095 (4a), 1447120 (5a), and 1447093 (7a) contain
the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre. See the Supporting Information
for details.
[6] a) G. Dong, P. Teo, Z. K. Wickens, R. H. Grubbs, Science 2011,
333, 1609; b) N. T. Patil, V. S. Raut, R. B. Tella, Chem. Commun.
2013, 49, 570; c) X.-P. Yin, X.-P. Zeng, Y.-L. Liu, F.-M. Liao, J.-S.
Yu, F. Zhou, J. Zhou, Angew. Chem. Int. Ed. 2014, 53, 13740;
Angew. Chem. 2014, 126, 13960.
[7] 3-(2-Aminophenyl)-5-hexenyn-3-ols A are underexplored sub-
strates, and their 5-exo-dig cyclization has not been reported so
far.
[8] Piperidines are obtained from similar substrates under Pd and
Cu catalysis; see: a) W. Rao, P. Kothandaraman, C. B. Koh,
P. W. H. Chan, Adv. Synth. Catal. 2010, 352, 2521; b) N.
Thirupathi, S. Puri, T. J. Reddy, B. Sridhar, M. S. Reddy, Adv.
Synth. Catal. 2016, 358, 303.
[18] No general methodology for the synthesis of 4-hydroxy-b-
carbolines has been reported previously. Only multistep syn-
thetic sequences are known; see: a) N. Fukada, M. L. Trudell, B.
Johnson, J. M. Cook, Tetrahedron Lett. 1985, 26, 2139; b) W.
Schlecker, A. Huth, E. Ottow, J. Mulzer, Synthesis 1995, 1225;
c) H. Suzuki, C. Iwata, K. Sakurai, K. Tokumoto, H. Takahashi,
M. Hanada, Y. Yokoyama, Y. Murakami, Tetrahedron 1997, 53,
1593; d) C. A. Busacca, M. C. Eriksson, Y. Dong, A. S. Proko-
powicz, A. M. Salvagno, M. A. Tschantz, J. Org. Chem. 1999, 64,
4564.
[19] The transformation of 3 into 7 takes place even at room
temperature. To expedite the formation of 7, we heated the
azides 3 in toluene at 808C.
[9] For similar transformations, see: a) B. Gabriele, R. Mancuso, G.
Salerno, J. Org. Chem. 2008, 73, 7336; b) P. Kothandaraman, W.
Rao, S. J. Foo, P. W. H. Chan, Angew. Chem. Int. Ed. 2010, 49,
4619; Angew. Chem. 2010, 122, 4723; c) D. Susanti, F. Koh, J. A.
Kusuma, P. Kothandaraman, P. W. H. Chan, J. Org. Chem. 2012,
77, 7166; d) S. Dhiman, S. S. V. Ramasastry, Chem. Commun.
2015, 51, 557; e) S. Dhiman, S. S. V. Ramasastry, Org. Lett. 2015,
17, 5116.
[10] The synthesis of pyridines from e,w-unsaturated azides has not
been reported previously. For the formation of piperidines, see:
a) Y. Zhou, P. V. Murphy, Org. Lett. 2008, 10, 3777; b) B. W.-Q.
Hui, S. Chiba, Org. Lett. 2009, 11, 729; c) D. Janreddy, V. Kavala,
C.-W. Kuo, W.-C. Chen, C. Ramesh, T. Kotipalli, T.-S. Kuo, M.-L.
Chen, C.-H. He, C. F. Yao, Adv. Synth. Catal. 2013, 355, 2918;
d) L. Moynihan, R. Chadda, P. McArdle, P. V. Murphy, Org. Lett.
2015, 17, 6226.
[20] a) T. Migita, K. Hongoh, H. Naka, S. Nakaido, M. Kosugi, Bull.
Chem. Soc. Jpn. 1988, 61, 931; b) T. Katsuki, Chem. Lett. 2005,
34, 1304; c) H.-Y. Thu, W.-Y. Yu, C.-M. Che, J. Am. Chem. Soc.
2006, 128, 9048; d) S. Chiba, Y.-J. Xu, Y.-F. Wang, J. Am. Chem.
Soc. 2009, 131, 12886; e) T. G. Driver, Org. Biomol. Chem. 2010,
8, 3831; f) L. Zhang, J.-Y. Lee, N. Yamazaki, S. Chiba, Synlett
2011, 2167; g) Y. Wang, J. Li, Y. He, Y. Xie, H. Wang, Y. Pana,
Adv. Synth. Catal. 2015, 357, 3229; h) J.-L. Li, Y.-C. Wang, W.-Z.
Li, H.-S. Wang, D.-L. Mo, Y. M. Pan, Chem. Commun. 2015, 51,
17772.
[21] See the Supporting Information for further details.
[22] a) Y. Rao, Z. Li, G. Yin, Green Chem. 2014, 16, 2213; b) W. S.
Yue, J. J. Li, Org. Lett. 2002, 4, 2201; J. Hu, Z. Deng, X. Zhang, F.
Zhang, H. Zheng, Org. Biomol. Chem. 2014, 12, 4885.
[23] J.-A. Seo, M.-S. Gong, J. Y. Lee, Org. Electron. 2014, 15, 2068.
[24] a) R. Hrdina, I. Valterova, J. Hodacova, I. Cisarova, M. Kotora,
Adv. Synth. Catal. 2007, 349, 822; b) C. T. Carver, B. N. Williams,
K. R. Ogilby, P. L. Diaconescu, Organometallics 2010, 29, 835.
[25] T. J. Donohoe, B. S. Pilgrim, G. R. Jones, J. A. Bassuto, Proc.
Natl. Acad. Sci. USA 2012, 109, 11605, and references therein.
[11] See the Supporting Information for the synthesis of enynols
1 employed in this study.
[12] This result establishes a new gold(I)-catalyzed approach for the
synthesis of 1,2-dihydroquinolines of the type 6a.
[13] See Supporting Information for detailed screening results.
[14] The intermediates 2a and 3a are isolable (but have short
lifetimes), and preliminary screening was performed with the
isolated samples.
Received: January 27, 2016
Published online: March 8, 2016
Angew. Chem. Int. Ed. 2016, 55, 7737 –7741
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
7741