RhII2-catalyzed synthesis of α-, β-, or δ-carbolines from aryl azides

Article abstract of DOI:10.1002/anie.201201788

Approaching all isomers: A range of α-, β- and δ-carbolinium ions are readily available from ortho-substituted aryl azides using a rhodium(II) carboxylate catalyst (see scheme). The carbolinium ions are readily reduced to afford tryptolines or deprotonated to access pyridoindoles. This [Rh^II₂]-catalyzed C-H bond amination was used in the synthesis of (±)-horsfiline and neocryptolepine. esp=α,α,α',α'- tetramethyl-1,3-benzenedipropionate. Copyright

Full text of DOI:10.1002/anie.201201788

Angewandte
Chemie
DOI: 10.1002/anie.201201788
Synthetic Methods
RhII -Catalyzed Synthesis of a-, b-, or d-Carbolines from Aryl Azides**
2
Ashley L. Pumphrey, Huijun Dong, and Tom G. Driver*
Carbolines and tetrahydrocarbolines are common structural
motifs in pharmaceuticals and natural products.[1] b-Carboline
and its saturated analog, tryptoline, are particularly preva-
lent[2,3] and continue to inspire methods to efficiently access
them.[4,5] In contrast, methods to access the d-[6] or a-isomer[7]
are uncommon despite the important biological properties
exhibited by these carbolines. In addition to antibacterial and
antiplasmodial activities,[8] d-carbolines are potential cancer
therapeutics (SYUIQ-5),[9] and the a-carboline mescengricin
was reported to be a potential neural protective agent
(Figure 1).[10] We anticipated that each structural isomer of
the carboline scaffold would be readily accessible from an
find the optimal conditions for their construction. After
testing a variety of metal complexes,[12] we found that RhII -
2
carboxylates were unique in their ability to catalyze the
conversion of aryl azide 1 into 2,[13] and the highest yield was
attained using 5 mol% of [Rh2(esp)2] complex in dichloro-
ethane [Eq. (1)].[14] Deprotonation of the d-carbolinium ion
using aqueous Na2CO3 produced 3,[15] which was easily
purified using silica gel chromatography.
À
appropriately ortho-substituted aryl azide through a C H
bond amination reaction if a transition metal catalyst was
found that could unlock and control the reactivity embedded
in the azide.
The scope and limitations of d-carbolinium ion generation
was examined by exposing a series of aryl azides 1 to the
optimal reaction conditions. The azides for our study were
synthesized in three steps from commercial 2-bromoanilines
through
a Suzuki cross coupling–azidation–methylation
sequence.[16] We found that our amination reaction tolerated
a range of substituents on the aryl azide portion of the
substrate: azides bearing alkyl- and trifluoromethyl groups as
well as halides were efficiently converted into d-carbolinium
ions (Table 1). The reaction was even tolerant of substitution
adjacent to the azide (entry 8). While a range of groups was
tolerated on the azide portion of the substrate, the reaction
yield was severely attenuated if any additional substituents
were added to the pyridinium ion moiety.
Figure 1. Selected examples of biologically active carbolines.
Table 1: Scope of RhII -catalyzed d-carboline formation.
2
We recently reported that ruthenium trichloride-hydrate
selectively transformed aryl azides into g-carbolinium ions.[11]
Extension of these conditions to the synthesis of the other
carboline isomers, however, was not successful. Because of
the paucity of methods to access d-carbolines,[6] we decided to
Entry
#
Aryl azide 1
Yield [%]
Yield [%]
R1
R2
R3
2[a]
3[b]
1
2
3
4
5
6
7
8
a
b
c
d
e
f
H
Me
F
Cl
F3C
H
H
H
H
H
H
H
H
H
H
H
H
F
quant.
85
quant.
97
97
85
74
71
96
77
78
75
86
66
[*] A. L. Pumphrey, H. Dong, Prof. Dr. T. G. Driver
Department of Chemistry, University of Illinois at Chicago
845 W. Taylor St., Chicago, IL 60607 (USA)
E-mail: tgd@uic.edu
H
Me
F3C
Me
Homepage: http://www.chem.uic.edu/driver
g
h
H
H
98
quant.
[**] We are grateful to the National Institutes of Health NIGMS
(R01GM084945) and the University of Illinois at Chicago for their
generous support. We also thank Profs. L. Anderson (UIC) and D. J.
Wardrop for insightful discussions.
[a] As determined using 1H NMR spectroscopy using CH2Br2 as an
internal standard. [b] Yield of 3 from azide 1 after silica gel chromatog-
raphy. esp=a,a,a’,a’-tetramethyl-1,3-benzenedipropionate; DCE=di-
chloroethane; Tf=trifluoromethanesulfonate.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201201788.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
With the successful synthesis of 1-methyl-d-carbolinium
triflates 2, the conversion of aryl azides bearing 4-substituted
pyridinium ion ortho-substituents into b-carbolinium ions (5)
was next attempted. To our delight, the rhodium(II)-catalyzed
À
C H bond amination conditions proved amenable to the
synthesis of 5 from aryl azides 4 (Table 2). Subsequent
Table 2: Scope of RhII -catalyzed tryptoline formation.
2
Entry
#
Aryl azide 4
Yield [%] Yield [%]
XÀ
R1
H
R2
R3
R4
5[a]
6[b]
1
a
b
c
d
e
f
g
h
i
TfOÀ
BrÀ
H
H
H
H
H
H
H
H
H
Me
F
H
H
H
quant.
90
89
99
60
71
2[c]
3[c]
4
allyl
Bn
H
H
BrÀ
TfOÀ Me
TfOÀ Me
TfOÀ Me
TfOÀ Me
TfOÀ Me
TfOÀ Me
TfOÀ Me
Me
Me
F
Cl
F3CO
H
Me 94
83
Scheme 1. Synthesis of (Æ)-horsfiline and analog.
5
6
7
8
9
10
H
H
H
H
H
H
quant.
94
quant.
91
71
70
[Eq. (2)]. In contrast to azides 1 or 4, this class of substrates
À
contains two C H bonds that potentially could be trans-
quant.
quant.
quant.
88
90
>95
À
formed into C N bonds. Using RuCl3·H2O as the catalyst, the
b
j
Me
À
reaction occurred solely at C H to produce g-carbolinium
ion 9 as the only product.[11] In contrast, exposure of 8 to
[Rh2(esp)2] resulted in the formation of the a-isomer as the
only product.[22] We are actively investigating the mechanistic
implications of this turnover in selectivity.
[a] As determined using 1H NMR spectroscopy using CH2Br2 as an
internal standard. [b] Yield of 6 from azide 4 after silica gel chromatog-
raphy. [c] 1.1 equiv AgOTf added.
reduction of the b-carbolinium ion with NaBH4 produced
tryptoline 6, which was easily purified using silica gel column
chromatography. The alkyl group on the pyridine nitrogen
atom could be varied without attenuating the yield of the
process as long as a stoichiometric amount of AgOTf was
added (entries 2 and 3). The steric environment around azide
could be increased through substitution without preventing
product formation (entry 4). The electronic nature of the aryl
azide could also be modulated without adversely affecting the
reaction (entries 6–10): both electron donating- and electron-
withdrawing groups were tolerated in the method. Impor-
tantly, meta-substituents could be appended to the aryl azide
without compromising the yield of the reaction (entries 9 and
10). The resulting tryptolines 6i and 6j cannot be formed
To further investigate this selectivity trend, a series of
meta-substituted pyridinium ions were submitted to reaction
conditions (Table 3). Basification of the reaction mixture
using Na2CO3 produced 11, which was purified using silica gel
chromatography. Similar to the other isomers, construction of
the a-isomer tolerated both electron-donating and electron-
withdrawing aryl azide substituents (entries 1–7) although the
yield was diminished in the presence of a para-methoxy group
(8b, entry 2). An expanded scope of a-isomer formation was
observed: substitution on the pyridinium ion portion of 8 was
tolerated to allow access to 11h and 11i (entries 8 and 9).
Because our reaction tolerated substitution on the pyr-
idinium moiety, we anticipated that our method might
facilitate access to neocryptolepine.[23,24] This indoloquinoline
alkaloid exhibits promising cytotoxicity toward cancer cells as
well as strong antiplasmodial activity toward chloroquinine-
selectively from a Fischer indole synthesis.[17]
II
À
To illustrate the synthetic utility of this Rh -catalyzed C
2
H bond amination method, (Æ)-horsfiline[18,19] was synthe-
sized (Scheme 1). The aryl azide substrate (4k) for our
amination reaction was synthesized in three steps (Suzuki-,
azidation-, and methylation reactions, 67%) from commer-
cially available 2-bromo-4-methoxyaniline and 4-pyridinyl-
boronic acid. Exposure of azide 4k to our amination-
reduction sequence produced tryptoline 6k in 91%. Oxida-
tion of 6k using N-bromosuccinimide[20] in aqueous acetic
acid afforded (Æ)-horsfiline.[21] Using the same oxidative
conditions, tryptoline 6g was converted into spirocyclic
oxindole 7 in 71%. Our overall yield for (Æ)-horsfiline and
7 for the six steps from the 2-bromo-4-substituted-anilines
was 53% and 42%, respectively.
resistant strains.[24f,25] Exposure of azide 8j to [Rh2(esp)2]
a
À
resulted in amination of only the C H bond to produce
Finally, aryl azides with meta-substituted pyridinium ion
ortho-substituents were examined as potential substrates
neocryptolepine (11j) as a single regioisomer in 68%
(entry 10).
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Table 3: Scope of RhII -catalyzed a-carboline formation.
[3] cf; a) Marinacarboline A: H. Huang, Y. Yao, Z. He, T. Yang, J.
2
Ma, X. Tian, Y. Li, C. Huang, X. Chen, W. Li, S. Zhang, C.
Zhang, J. Ju, J. Nat. Prod. 2011, 74, 2122; b) hyrtiocarboline:
W. D. Inman, W. M. Bray, N. C. Gassner, R. S. Lokey, K. Tenney,
Y. Y. Shen, K. TenDyke, T. Suh, P. Crews, J. Nat. Prod. 2010, 73,
255; c) tadalafil: A. Daugan, P. Grondin, C. Ruault, A.-C.
Le Monnier de Gouville, H. Coste, J. M. Linget, J. Kirilovsky, F.
Hyafil, R. Labaudiniꢁre, J. Med. Chem. 2003, 46, 4533.
Entry
#
Aryl azide 8
Yield [%]
R1
R2
R3
R4
11[a]
[4] Recent Pictet–Spengler reports, see: a) M. S. Taylor, E. N.
Jacobsen, J. Am. Chem. Soc. 2004, 126, 10558; b) J. Seayad,
A. M. Seayad, B. List, J. Am. Chem. Soc. 2006, 128, 1086; c) M. J.
Wanner, R. N. S. van der Haas, K. R. de Cuba, J. H. van Maar-
seveen, H. Hiemstra, Angew. Chem. 2007, 119, 7629; Angew.
Chem. Int. Ed. 2007, 46, 7485; d) R. S. Klausen, E. N. Jacobsen,
Org. Lett. 2009, 11, 887.
1
2
3
4
5
6
7
8
9
a
b
c
d
e
f
g
h
i
Me
MeO
H
F
Cl
F3C
Me
H
H
H
H
H
H
H
H
H
F
H
H
H
H
H
H
H
H
H
H
Me
Cl
=
H
H
H
H
H
H
H
H
H
83
63
80
83
67
78
64
77
77
68
´
[5] Non-Pictet–Spengler reports, see: a) B. P. Bondzic, P. Eilbracht,
Org. Lett. 2008, 10, 3433; b) M. Movassaghi, M. D. Hill, Org.
Lett. 2008, 10, 3485; c) D. B. England, A. Padwa, Org. Lett. 2008,
10, 3631; d) Y. Ohta, S. Oishi, N. Fujii, H. Ohno, Org. Lett. 2009,
11, 1979; e) J. K. Laha, S. M. Barolo, R. A. Rossi, G. D. Cuny, J.
Org. Chem. 2011, 76, 6421.
À
=
10
j
HC CH CH CH
[a] Yield of 11 from azide 8 after silica gel chromatography.
[6] a) H. Zhang, R. C. Larock, Org. Lett. 2001, 3, 3083; b) H. Zhang,
R. C. Larock, J. Org. Chem. 2002, 67, 7048; c) S. Chiba, Y.-J. Xu,
Y.-F. Wang, J. Am. Chem. Soc. 2009, 131, 12886; d) S. Ding, Z.
Shi, N. Jiao, Org. Lett. 2010, 12, 1540.
[7] a) A. S. Kumar, R. Nagarajan, Org. Lett. 2011, 13, 1398; b) S.
Gupta, B. Kumar, B. Kundu, J. Org. Chem. 2011, 76, 10154.
[8] cf; a) L. C. Meurer, R. N. Guthikonda, J. L. Huber, F. DiNinno,
Bioorg. Med. Chem. Lett. 1995, 5, 767; b) E. Arzel, P. Rocca, P.
Grellier, M. Labaeꢂd, F. Frappier, F. Guꢃritte, C. Gaspard, F.
Marsais, A. Godard, G. Quꢃguiner, J. Med. Chem. 2001, 44, 949;
c) I. El Sayed et al., J. Med. Chem. 2009, 52, 2979; d) T. K. Mazu,
J. R. Etukala, M. R. Jacob, S. I. Khan, L. A. Walker, S. Y.
Ablordeppey, Eur. J. Med. Chem. 2011, 46, 2378.
[9] SYUIQ-5: a) Y. Takeuchi, T. Oda, M.-r. Chang, Y. Okamoto, J.
Ono, Y. Oda, K. Harada, K. Hashigaki, M. Yamato, Chem.
Pharm. Bull. 1997, 45, 406; b) J.-M. Zhou, X.-F. Zhu, Y.-J. Lu, R.
Deng, Z.-S. Huang, Y.-P. Mei, Y. Wang, W.-L. Huang, Z.-C. Liu,
L.-Q. Gu, Y.-X. Zeng, Oncogene 2005, 25, 503; c) J.-N. Liu, R.
Deng, J.-F. Guo, J.-M. Zhou, G.-K. Feng, Z.-S. Huang, L.-Q. Gu,
Y.-X. Zeng, X.-F. Zhu, Leukemia 2007, 21, 1300.
In conclusion, we have developed a method to access a-,
b-, or d-carbolinium ions from aryl azides with ortho-
pyridinium ion substituents using 1–5 mol% of [Rh2(esp)2].
In combination with our previous report using RuCl3 to access
g-carbolinium ions, we believe our work demonstrates that
À
metal-catalyzed C H bond amination is a simple, efficient
strategy to access all possible carbolinium ion isomers from
readily accessible aryl azides. The synthetic utility of our
method was illustrated in a four-flask synthesis of cytotoxic
and antiplasmodial agent, neocryptolepine and the analgesic
oxindole (Æ)-horsfiline. By synthesizing a chlorinated analog
of horsfiline—one not readily accessible through previously
reported syntheses—we demonstrated that the modular
nature of our method facilitates the construction of natural
and non-natural alkaloids.
Received: March 6, 2012
Revised: April 10, 2012
Published online: && &&, &&&&
[10] Mescengricin: a) J.-S. Kim, K. Shin-ya, K. Furihata, Y. Hay-
akawa, H. Seto, Tetrahedron Lett. 1997, 38, 3431; b) K. Shin-ya,
J.-S. Kim, K. Furihata, Y. Hayakawa, H. Seto, J. Asian Nat. Prod.
Res. 2000, 2, 121.
[11] H. Dong, R. T. Latka, T. G. Driver, Org. Lett. 2011, 13, 2726.
[12] Refer to the Supporting Information for the conditions sur-
veyed.
[13] a) B. J. Stokes, H. Dong, B. E. Leslie, A. L. Pumphrey, T. G.
Driver, J. Am. Chem. Soc. 2007, 129, 7500; b) M. Shen, B. E.
Leslie, T. G. Driver, Angew. Chem. 2008, 120, 5134; Angew.
Keywords: azides · carbolines · horsfiline · neocryptolepine ·
rhodium
.
[1] a) E. D. Cox, J. M. Cook, Chem. Rev. 1995, 95, 1797; b) K. M.
Czarwinski, J. M. Cook, Advances in Heterocyclic Natural
Products Synthesis Vol. III (Ed.: W. Pearson), JAI, Greenwich,
1996, p. 217; c) J. J. Maresh, L.-A. Giddings, A. Friedrich, E. A.
Loris, S. Panjikar, B. L. Trout, J. Stockigt, B. Peters, S. E.
OꢀConnor, J. Am. Chem. Soc. 2008, 130, 710; d) L. Y. P. Luk, S.
Bunn, D. K. Liscombe, P. J. Facchini, M. E. Tanner, Biochemistry
2007, 46, 10153, and references therein.
[2] a) Z. Czarnocki, A. Siwicka, J. Szawkalo, Curr. Org. Synth. 2005,
2, 301; b) S. W. Youn, Org. Prep. Proced. Int. 2006, 38, 505; c) G.
Zeni, R. C. Larock, Chem. Rev. 2006, 106, 4644; d) C. R.
Edwankar, R. V. Edwankar, O. A. Namjoshi, S. K. Rallapappi,
J. Yang, J. M. Cook, Curr. Opin. Drug Discovery Dev. 2009, 12,
752; e) R. S. Alekseyev, A. V. Kurkin, M. A. Yurovskaya, Chem.
Heterocycl. Compd. 2009, 45, 889; f) M. Bandini, A. Eichholzer,
Angew. Chem. 2009, 121, 9786; Angew. Chem. Int. Ed. 2009, 48,
9608.
´
Chem. Int. Ed. 2008, 47, 5056; c) B. J. Stokes, B. Jovanovic, H.
Dong, K. J. Richert, R. D. Riell, T. G. Driver, J. Org. Chem. 2009,
74, 3225.
[14] a) C. G. Espino, K. W. Fiori, M. Kim, J. Du Bois, J. Am. Chem.
Soc. 2004, 126, 15378; b) D. N. Zalatan, J. Du Bois, J. Am. Chem.
Soc. 2009, 131, 7558.
[15] Attempts to reduce carbolinium ion 2 (or 10) using NaBH4 (or
any other hydride reducing agent) resulted in only decomposi-
tion.
[16] See Scheme 1 for more details as well as the Supporting
Information for the experimental conditions for the three-step
substrate synthesis.
[17] cf. E. S. Lee, S. I. Kim, S. H. Lee, T. C. Jeong, T. C. Moon, H. W.
Chang, Y. Jahng, Bull. Korean Chem. Soc. 2005, 26, 1975.
[18] A. Jossang, P. Jossang, H. A. Hadi, T. Sevenet, B. Bodo, J. Org.
Chem. 1991, 56, 6527.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
[19] For previous total syntheses of horsfiline, see: a) S.-I. Bascop, J.
Sapi, J.-Y. Laronze, J. Lꢃvy, Heterocycles 1994, 38, 725; b) C.
Pellegrini, C. Strꢄssler, M. Weber, H.-J. Borschberg, Tetrahe-
dron: Asymmetry 1994, 5, 1979; c) G. Lakshmaiah, T. Kawabata,
M. Shang, K. Fuji, J. Org. Chem. 1999, 64, 1699; d) G. Cravotto,
G. B. Giovenzana, T. Pilati, M. Sisti, G. Palmisano, J. Org. Chem.
2001, 66, 8447; e) U. K. Syam Kumar, H. Ila, H. Junjappa, Org.
Lett. 2001, 3, 4193; f) D. E. Lizos, J. A. Murphy, Org. Biomol.
Chem. 2003, 1, 117; g) J. A. Murphy, R. Tripoli, T. A. Khan,
U. W. Mali, Org. Lett. 2005, 7, 3287; h) B. M. Trost, M. K.
Brennan, Org. Lett. 2006, 8, 2027; i) M. G. Kulkarni, A. P.
Dhondge, S. W. Chavhan, A. S. Borhade, Y. B. Shaikh, D. R.
Birhade, M. P. Desai, N. R. Dhatrak, Beilstein J. Org. Chem.
2010, 6, 876; j) J. D. White, Y. Li, D. C. Ihle, J. Org. Chem. 2010,
75, 3569; k) N. Deppermann, H. Thomanek, A. H. G. P. Prenzel,
W. Maison, J. Org. Chem. 2010, 75, 5994.
[24] For previous syntheses of neocryptolepine, see: a) Ł. Kacz-
´
marek, R. Balicki, P. Nantka-Namirski, W. Peczynska-Czoch, M.
Mordarski, Arch. Pharm. 1988, 321, 463; b) W. Peczynska-
Czoch, F. Pognan, L. Kaczmarek, J. Boratynski, J. Med. Chem.
1994, 37, 3503; c) P. M. Fresneda, P. Molina, S. Delgado,
Tetrahedron Lett. 1999, 40, 7275; d) P. M. Fresneda, P. Molina,
S. Delgado, Tetrahedron 2001, 57, 6197; e) T.-L. Ho, D.-G. Jou,
Helv. Chim. Acta 2002, 85, 3823; f) T. H. M. Jonckers, S.
van Miert, K. Cimanga, C. Bailly, P. Colson, M.-C. De Pauw-
Gillet, H. van den Heuvel, M. Claeys, F. Lemiꢁre, E. L. Esmans,
J. Rozenski, L. Quirijnen, L. Maes, R. Dommisse, G. L. F.
Lemiꢁre, A. Vlietinck, L. Pieters, J. Med. Chem. 2002, 45, 3497;
g) R. Engqvist, J. Bergman, Org. Prep. Proced. Int. 2004, 36, 386;
h) T. Dhanabal, R. Sangeetha, P. S. Mohan, Tetrahedron 2006,
62, 6258; i) P. T. Parvatkar, P. S. Parameswaran, S. G. Tilve,
Tetrahedron Lett. 2007, 48, 7870; j) S. Sharma, B. Kundu,
Tetrahedron Lett. 2008, 49, 7062; k) M. Miller, J. C. Vogel, W.
Tsang, A. Merrit, D. J. Procter, Org. Biomol. Chem. 2009, 7, 589;
l) P. T. Parvatkar, P. S. Parameswaran, S. G. Tilve, J. Org. Chem.
2009, 74, 8369; m) M. J. Haddadin, R. M. B. Zerdan, M. J. Kurth,
J. C. Fettinger, Org. Lett. 2010, 12, 5502; n) S. Hostyn, K. A.
Tehrani, F. Lemiꢁre, V. Smout, B. U. W. Maes, Tetrahedron 2011,
67, 655.
[20] a) W. Lawson, B. Witkop, J. Org. Chem. 1961, 26, 263; b) E. E.
Van Tamelen, J. P. Yardley, M. Miyano, W. B. Hinshaw, J. Am.
Chem. Soc. 1969, 91, 7333.
[21] This same oxidative rearrangement was recently reported: a) C.
Li, C. Chan, A. C. Heimann, S. J. Danishefsky, Angew. Chem.
2007, 119, 1470; Angew. Chem. Int. Ed. 2007, 46, 1448;
b) ref. [19j].
[22] In our initial Communication[11] the identity of the minor
product was assigned erroneously as the g-isomer. Re-examina-
tion of the reaction mixture revealed this minor product to be
decomposition of the starting pyridinium azide.
[25] a) K. Cimanga, T. De Bruyne, L. Pieters, J. Totte, L. Tona, K.
Kambu, B. D. Vanden, A. J. Vlietinck, Phytomedicine 1998, 5,
209; b) A. Jaromin, A. Kozubek, K. Suchoszek-Lukaniuk, M.
Malicka-Blaszkiewicz, W. Peczynska-Czoch, L. Kaczmarek,
Drug Delivery 2008, 15, 49; c) J. Lavrado, R. Moreira, A.
Paulo, Curr. Med. Chem. 2010, 17, 2348.
[23] a) M. H. M. Sharaf, P. L. Schiff, A. N. Tackie, C. H. Phoebe,
G. E. Martin, J. Heterocycl. Chem. 1996, 33, 239; b) K. Cimanga,
T. De Bruyne, L. Pieters, M. Claeys, A. Vlietinck, Tetrahedron
Lett. 1996, 37, 1703.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Synthetic Methods
Approaching all isomers: A range of a-, b-
and d-carbolinium ions are readily avail-
able from ortho-substituted aryl azides
using a rhodium(II) carboxylate catalyst
(see scheme). The carbolinium ions are
readily reduced to afford tryptolines or
A. L. Pumphrey, H. Dong,
T. G. Driver*
&&&& — &&&&
RhII -Catalyzed Synthesis of a-, b-, or d-
2
Carbolines from Aryl Azides
deprotonated to access pyridoindoles.
II
À
This Rh -catalyzed C H bond amination
was used in the synthesis of (Æ)-horsfi-
2
line and neocryptolepine.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!