Transition-metal-catalyzed C-H bond functionalizations: Feasible access to a diversity-oriented β-carboline library

Article abstract of DOI:10.1002/chem.201304613

Diversification of the β-carboline skeleton has been demonstrated to assemble a β-carboline library starting from the tetrahydro-β- carboline framework. This strategy affords feasible access to heteroaryl-, aryl-, alkenyl-, or alkynyl-substituted β-carbolines at the C1, C3, or C8 position through three categorically different types of transition-metal- catalyzed C-C bond-forming reactions, in the presence of multiple potentially reactive positions. These site-selective functionalizations include; 1) the Cu-catalyzed C1/C3-selective decarboxylative C sp 3-C sp 2 and C sp 3-C _sp coupling of hexahydro-β-carboline-3-carboxylic acid with a C-H bond of a heteroarene or terminal alkyne; 2) the chelation-assisted Pd-catalyzed C1/C8-selective C-H arylation of hexahydro-β-carboline with aryl boron reagents; and 3) the chelation-assisted Pd-catalyzed C1/C3-selective oxidative C-H/C-H cross-coupling of β-carboline-N-oxide with arenes, heteroarenes, or alkenes. The saturated structural feature of the hexahydro-β-carboline framework can increase reactivity and control site selectivity. The robustness of these approaches has been demonstrated through the synthesis of hyrtioerectine analogues and perlolyrine. We believe that these strategies could provide inspiration for late-stage diversifications of bioactive core scaffolds.

Full text of DOI:10.1002/chem.201304613

DOI: 10.1002/chem.201304613
Full Paper
&
Synthetic Methods
Transition-Metal-Catalyzed CÀH Bond Functionalizations: Feasible
Access to a Diversity-Oriented b-Carboline Library
Ningjie Wu, Feijie Song, Lipeng Yan, Juan Li, and Jingsong You*[a]
Abstract: Diversification of the b-carboline skeleton has
been demonstrated to assemble a b-carboline library start-
ing from the tetrahydro-b-carboline framework. This strategy
affords feasible access to heteroaryl-, aryl-, alkenyl-, or alkyn-
yl-substituted b-carbolines at the C1, C3, or C8 position
through three categorically different types of transition-
metal-catalyzed CÀC bond-forming reactions, in the pres-
ence of multiple potentially reactive positions. These site-se-
lective functionalizations include; 1) the Cu-catalyzed C1/C3-
selective decarboxylative Csp3ÀCsp2 and Csp3ÀCsp coupling of
hexahydro-b-carboline-3-carboxylic acid with a CÀH bond of
a heteroarene or terminal alkyne; 2) the chelation-assisted
Pd-catalyzed C1/C8-selective CÀH arylation of hexahydro-b-
carboline with aryl boron reagents; and 3) the chelation-as-
sisted Pd-catalyzed C1/C3-selective oxidative CÀH/CÀH
cross-coupling of b-carboline-N-oxide with arenes, heteroar-
enes, or alkenes. The saturated structural feature of the hex-
ahydro-b-carboline framework can increase reactivity and
control site selectivity. The robustness of these approaches
has been demonstrated through the synthesis of hyrtioerec-
tine analogues and perlolyrine. We believe that these strat-
egies could provide inspiration for late-stage diversifications
of bioactive core scaffolds.
Introduction
ceuticals, and bioactive molecules. Some derivatives exhibit ef-
fects on the central nervous system (CNS), for example, dem-
onstrating an affinity for benzodiazepine receptors (BZRs), 5-
HT2A, and 5-HT2C receptors, and displaying antimicrobial, antivi-
ral, and antiparasitic activities, and antitumor properties (for
example, IkB kinase, PIM kinase, and cyclin-dependent kinase
(CDK) inhibition) (Scheme 1).[3,4] In the past decades, investiga-
tion of the structure–bioactivity relationships of functionalized
b-carboline derivatives has attracted intensive interest. A large
number of research reports have demonstrated that attach-
ment of the (hetero)aryl or alkenyl functional groups to the C1
and/or C3 site of the carboline scaffold is capable of increasing
In the field of modern drug discovery, rapidly accessing molec-
ular diversity, in compounds that are based on an identified
lead compound, can be challenging.[1] Transition-metal-cata-
lyzed cross-coupling reactions are some of the most reliable
methods for CÀC bond formations. Direct site-selective func-
tionalization of intrinsic functional groups in bioactive mole-
cules would be an ideal strategy to rapidly assemble a diversi-
ty-oriented library of drug candidates.[2] For these reactions to
occur, the compounds do not require preactivation, minimizing
the number of synthetic steps and avoiding the preparation of
organic halides and organometallic reagents. Nevertheless, the
application of this strategy may face three major challenges,
including; 1) site selectivity among multiple reactive positions;
2) divergent functionalizations at one site; and 3) nonproduc-
tive coordination of the heteroatom of heterocycles with metal
centers.
The b-carboline derivatives, bearing a tricyclic pyrido[3,4-
b]indole core, are important indole alkaloids. These com-
pounds are widely distributed in natural products, pharma-
[a] N. Wu, Dr. F. Song, L. Yan, J. Li, Prof. Dr. J. You
Key Laboratory of Green Chemistry and Technology of Ministry of Educa-
tion, College of Chemistry, and State Key Laboratory of Biotherapy
West China Medical School
Sichuan University
29 Wangjiang Road, Chengdu 610064 (P. R. China)
Fax: (+86)28-85412203
E-mail: jsyou@scu.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304613.
Scheme 1. Natural products and pharmaceutical drugs containing a (hetero)-
aryl- or alkenyl-substituted b-carboline skeleton.
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the biological activity.[5] Thus, chemists have devoted
much effort towards developing new synthetic meth-
ods for the preparation of various functionalized b-
carboline derivatives. A multistep synthesis, including
either the Bischler–Napieralski cyclodehydration or
the Pictet–Spengler cyclization followed by sequen-
tial aromatization, has proven to be an efficient route
to 1-(hetero)aryl substituted b-carbolines.[6] However,
these methods have turned out to be less efficient
for introducing (hetero)aryl functional groups into
other positions of the tricyclic b-carboline skeleton.
The C1-, C3-, C4-, C5-, or C6-(hetero)aryl-substituted
b-carbolines can be obtained through traditional
transition-metal-catalyzed CÀX/CÀM cross-coupling
reactions, after the selective introduction of a halogen
atom into the corresponding site of the b-carboline
skeleton.[7] Nevertheless, these time-consuming and
tedious prefunctionalizations may limit the rapid as-
sessment of molecular diversity. In particular, 8-(het-
ero)aryl-substituted b-carbolines are surprisingly un-
derdeveloped, probably owing to the synthetic diffi-
Scheme 2. Design of a diversity-oriented b-carboline library from a tetrahydro-b-carbo-
line core.
culty in producing these compounds. Despite significant prog-
ress in synthetic methods, the development of a robust strat-
Pd-catalyzed C8-selective direct CÀH arylation of 9-substituted
hexahydro-b-carboline with aryl boron reagents; and 3) chela-
tion-assisted Pd-catalyzed C1-selective oxidative CÀH/CÀH
cross-coupling of b-carboline-N-oxide with arenes, heteroar-
enes, or alkenes. All substrates involved in the above-men-
tioned reactions are easily accessible from methyl tetrahydro-
b-carboline-3-carboxylate 1 (Scheme 2). The tetrahydro-b-car-
boline skeleton serves as a bridge to introduce various func-
tional groups (for example, heteroaryl, aryl, alkynyl, and alkenyl
groups) at the C1, C3, or C8 position through divergent func-
tionalizations, rapidly assembling a diversity-oriented b-carbo-
line library.
egy to assemble
a diversity-oriented b-carboline library
remains a challenge. Therefore, in line with our ongoing inter-
est in forging (hetero)aryl–(hetero)aryl, alkenyl–(hetero)aryl,
and alkynyl–(hetero)aryl structural units through direct CÀH
bond functionalization, we herein, highlight the viability of
these approaches in the diversity-oriented synthesis (DOS) of
(hetero)aryl, alkenyl, and alkynyl b-carbolines. Subsequently,
these strategies are successfully applied to the synthesis of hy-
rtioerectine analogues and perlolyrine.
Results and Discussion
C3-selective Csp3-decarboxylative coupling of hexahydro-b-
carboline-3-carboxylic acid for the preparation of hyrtioerec-
tine analogues
Molecular design
The b-carboline core possesses seven different reactive CÀH
bonds, possibly leading to low reactivity or lack of selectivity
for CÀH bond functionalizations. Thus, it is a substantial chal-
lenge to establish a diversity-oriented library of (hetero)aryl, al-
kenyl, and alkynyl b-carbolines through site-selective CÀH
bond cleavage of the carboline scaffold. On the other hand,
the saturated analogue of b-carboline, the tetrahydro-b-carbo-
line (THBC) core, is frequently found in many naturally occur-
ring and synthetic indole alkaloids, exhibiting various impor-
tant biological activities.[8] Herein, we disclose that this saturat-
ed structural feature can unlock reactivity and control site se-
lectivity. Thereby, divergent functionalizations could become
a feasible and concise route to the diversity-oriented synthesis
of substituted b-carbolines. Our blueprint for the synthesis of
a variety of b-carbolines is illustrated in Scheme 2. The current
methodology involves three categorically different types of
site-selective functionalizations, in the presence of multiple re-
active positions; 1) Cu-catalyzed C3-selective Csp3-decarboxyla-
tive coupling of hexahydro-b-carboline-3-carboxylic acid with
a CÀH bond of a heteroarene or alkyne; 2) chelation-assisted
Usually, the synthesis of 3-(hetero)aryl-substituted b-carbolines
relies on sequential aromatization of tetrahydro-b-carboline-3-
carboxylic acid, Curtius rearrangement, diazotization, bromina-
tion, and transition-metal-catalyzed CÀX/CÀM cross-coupling
reactions.[7a] Therefore, it is highly desirable to develop step-
economical routes towards 3-substituted b-carbolines. In
recent years, decarboxylative coupling reactions have emerged
as an important synthetic tool for CÀC bond formations be-
cause a large number of carboxylic acid substrates are readily
available.[9] Li and co-workers have developed intermolecular
decarboxylative Csp3ÀCsp3, Csp3ÀCsp2 and Csp3ÀCsp cross-coupling
reactions of a-amino acids with various nucleophiles by using
copper or iron catalysts.[9d–f] However, to date the decarboxyla-
tive coupling reactions have scarcely been applied to the syn-
thesis of complex bioactive molecules. Tetrahydro-b-carboline-
3-carboxylic acids contain a six-membered cyclic a-amino acid
unit and, thus, may perform selective functionalizations at the
C3 position by decarboxylative coupling reactions with nucleo-
philes. With this in mind, we started our investigation by treat-
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ment of tetrahydro-b-carboline-3-carboxyl acid 2 with the NH-
free indole 5a, in a copper-catalyzed system. Disappointedly,
only a trace amount of desired coupled product 3 was ob-
served [Eq. (1)] (Bn=benzyl; TMEDA=N,N,N’,N’-tetramethyle-
thylenediamine; DTBP=di-tert-butyl peroxide).
indole ring, such as methoxyl, bromo, and chloro groups, that
could then be subjected to further transformations. In addi-
tion, phenyl acetylene provided the C3-alkynyl b-carboline
(Scheme 3, 6 f).[11]
Hyrtioerectine analogues, isolated from the marine sponge
Hyrtios reticulatus, contain a 3-heteroaryl b-carboline skeleton,
which exhibits potent cytotoxic activities against human tumor
cells.[3f] The synthesis of the hyrtioerectine analogue 9a was
achieved by using coupled product 6a as the starting material
(Scheme 4). Initially, compound 6a was transformed into 7a by
Subsequently, we were pleased to discover that hexahydro-
b-carboline-3-carboxylic acid 4, which was synthesized by
means reduction of the indole double bond of 2,[10] could
smoothly undergo the Csp3ÀCsp2 decarboxylative coupling with
5a to afford coupled product 6a with complete C3 selectivity.
Although it is possible that the reaction might proceed via an
imine-type intermediate,[9d] none of the C1-coupled product
was observed, probably because of the steric hindrance
caused by the benzyl groups at the N2 and N9 positions. After
screening several parameters (for example copper source,
ligand, oxidant, and solvent) the highest yield obtained was
56% (Table S1, see the Supporting Information). The optimized
catalytic system was composed of CuBr (15 mol%), TMEDA
(30 mol%), and DTBP (1.5 equivalents) in toluene, at 1108C for
10 h.
Scheme 4. Synthesis of hyrtioerectine analogue 9a.
debenzylation with Pd/C under a hydrogen atmosphere. Sub-
sequently, aromatization with Pd/C in xylene[12a] gave 8a, fol-
lowed by deprotection, to afford desired product 9a, by using
KOtBu in DMSO in the presence of O2.[12b] The current strategy
not only streamlined the traditional synthetic routes, based on
CÀX/CÀM coupling, but also tolerated various functional
groups.[7a,b]
With the optimized conditions in hand, we explored the
scope of indoles. As shown in Scheme 3, a variety of indoles
could be used in this coupling reaction to afford the corre-
sponding products in acceptable yields (Scheme 3, 6a–e). This
process was amenable to various functional groups on the
Selective direct C8 arylation of 9-substituted hexahydro-b-
carboline
The synthesis of 8-aryl b-carbolines has, thus far, been underre-
presented. As mentioned above, the introduction of a (hetero)-
aryl substituent on the benzene ring of b-carbolines usually re-
quires time-consuming and tedious prefunctionalization.[7d–g]
Recently, great progress has been made in Pd-catalyzed direct
CÀH bond arylation, directed by functional groups, such as
pyridine, amide, carboxylic acid, imine, and oxime groups.[13]
Thus, we initially focused on the C8-selective arylation of b-car-
boline 10a–d and tetrahydro-b-carboline 10e–h with diarylio-
donium salts, aryl halides, or borates by the introduction of
various directing groups (DGs), for example, acetyl (COMe),
N,N-dimethylcarbamoyl (CONMe2), 2-pyridylmethyl (CH2(2-Py)),
and 2-pyrimidyl (2-Pym), at the N9 position, [Eq. (2)] and
[Eq. (3)]. Despite several attempts, the above reactions did not
exhibit promising results. We presumed that the rigidity of
skeleton might not facilitate the formation of the six-mem-
bered cyclopalladated intermediate.
Scheme 3. Reactions were carried out by using 4 (0.25 mmol), 5 (1.5 equiv),
CuBr (15 mol%), TMEDA (30 mol%), DTBP (1.5 equiv), and toluene (1 mL) at
1
110 8C for 10 h, under N2. Yields based on 4. The NOESY and H NMR analysis
indicated that coupled products 6a–e contained two diastereoisomers with
cis/trans ratios in the range of 1: 0.62–0.95. The alkynylation afforded the
trans-diastereospecific C3-alkynyl b-carboline.
On the basis of these observations, we envisioned that more
flexible 9-substituted hexahydro-b-carbolines 10i–j could be
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b-carboline was performed. Firstly, 12a was subjected to de-
benzylation, to form 13a, with Pd/C and ammonium formate.
Next, aromatization with Pd/C in xylene gave 14a. The hydrol-
ysis of 14a with LiOH in MeOH and H2O, and the subsequent
decarboxylation, produced 15a in moderate yield.[15] Finally,
the pyrimidyl group was removed by using NaOEt in DMSO at
1208C, affording desired product 16a (Scheme 6). We antici-
pate that this efficient approach to 8-aryl b-carbolines could
provide a starting point for the investigation of the biological
activity of these compounds.
coupled with various arylating reagents by tethering a suitable
and readily removable directing group at the N9 position
[Eq. (4)] (Table S2, see the Supporting Information). The cou-
pling reaction between 9-(pyrimidin-2-yl) hexahydro-b-carbo-
line, 10j, and potassium phenyltrifluoroborate, 11 a, gave the
desired C8-aryl product, 12a, in 28% yield by using Pd(OAc)2
(10 mol%), Ag2CO3 (2.0 equivalents), BQ (1.0 equivalent; BQ=
1,4-benzoquinone), and tBuOH as a solvent. After screening
several parameters (ligand, oxidant, solvent, and temperature),
the best result provided a 62% yield (Table S2, see the Sup-
porting Information). Under the optimized reaction conditions,
we screened the scope of potassium aryltrifluoroborate cou-
pling partners (Scheme 5). We were pleased to find that a varie-
ty of potassium aryltrifluoroborates afforded the corresponding
products, 12b–f, in satisfactory yields.[14]
Scheme 6. Synthesis of 8-aryl b-carboline 16a.
C1-selective oxidative CÀH/CÀH cross-coupling of b-carbo-
line-N-oxide
To further highlight the usefulness of our strategy, the syn-
thesis of 8-aryl b-carboline from 8-aryl-substituted hexahydro-
After completing the C3- and C8-selective functionalizations,
we turned our attention to the C1-selective functionalization
of b-carboline. Recently, transition-metal-catalyzed oxidative
CÀH/CÀH cross-coupling between a heteroarene and an olefin,
a simple arene, or a heteroarene has proven to be one of the
most promising routes towards the synthesis of heteroaryl–al-
kenyl, heteroaryl–aryl and heteroaryl–heteroaryl structural
units, effectively avoiding time-consuming prefunctionalization
of both coupling partners.[16] Given that the C1ÀH bond is lo-
cated ortho to the nitrogen atom of the pyridine ring,[17] the
catalytic oxidative CÀH/CÀH cross-coupling of b-carboline-N-
oxides with various (hetero)arenes or alkenes could be an ideal
strategy to form C1-(hetero)aryl and C1-alkenyl b-carbolines.
The key challenge in achieving C1 functionalization is control
of the regioselectivity between the C1 and C3 positions. By
using three equivalents of Ag2CO3 as an oxidant and one equi-
valent of pyridine as an additive, in the presence of Pd(OAc)2
(10 mol%), in 1,4-dioxane at 1258C, for 24 h, the oxidative CÀ
H/CÀH cross-coupling of N9-methyl-b-carboline-N-oxide, 17b,
with N-methylindole, 18a, provided the C1-heteroarylated
product in 40% yield. However, the homocoupled product of
18a was also produced. Subsequently, we found that the che-
lation-assisted strategy could not only enhance the C1 reactivi-
ty of b-carboline-N-oxide, but could also prevent homocou-
pling. After screening different directing groups, it was found
that the N,N-dimethylcarbamoyl group gave the highest yield
Scheme 5. Reactions were carried out by using 10j (0.15 mmol), 11
(3.0 equiv), Pd(OAc)2 (10 mol%), BQ (1.0 equiv), AgOAc (2.0 equiv), DMSO
(4.0 equiv), and tBuOH (1.2 mL) at 1308C for 24 h, under N2. Yields of isolated
product are based on 10j. The NOESY analysis showed that the relative con-
figuration of 10j remained intact for products 12a–f.
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ties.[3d] In 2011, Detert and co-workers developed a synthetic
route towards perlolyrine, starting from commercially available
2-iodoaniline, in an overall yield of 15–20% in 11 steps.[18]
Herein, we demonstrate a new pathway for the synthesis of
perlolyrine, involving a Pd-catalyzed oxidative CÀH/CÀH cross-
coupling reaction (Scheme 9). Firstly, b-carboline was installed
Scheme 7. Screening of the directing groups. Reactions were carried out by
using N-substituted b-carboline-N-oxide 17 (0.25 mmol), N-methylindole 18a
(3.0 equiv), Pd(OAc)2 (10 mol%), Ag2CO3 (3.0 equiv), pyridine (1.0 equiv), and
1,4-dioxane (1 mL) at 1258C for 24 h, under N2. Yields of isolated product are
based on 17.
(Scheme 7). The cross-coupling of b-carboline-N-oxide 17e
with 18a afforded 1-substituted b-carboline-N-oxide 19a in
68% (Table S3, see the Supporting Information).
We next examined the scope of the reaction with respect to
the heteroarene coupling partners. It was gratifying to find
that this catalyst system could accelerate the C1ÀH bond func-
tionalization of N,N-dimethylcarbamoyl-b-carboline-N-oxide
17e with various electron-rich heteroarenes (for example, in-
doles, furans, and thiophenes; Scheme 8, 19a–f). In addition,
simple arenes and alkenes could also couple with 17e to
afford the C1-aryl- and C1-alkenyl-substituted b-carboline-N-
oxides, respectively (Scheme 8, 19g and 19h). It is noteworthy
that 3-substituted and 1,3-disubstituted b-carboline-N-oxides
were not detected in these cross-coupling reactions.
Scheme 9. Synthesis of perlolyrine.
with the N,N-dimethylcarbamoyl group, followed by oxidation
to afford corresponding N-oxide 17e in 63% yield over two
steps. Subsequently, the C1-selective oxidative CÀH/CÀH cross-
coupling reaction was used as the key step to furnish the
furan moiety. The sequential reductions, by PCl3 and NaBH4,
and the deprotection of N,N-dimethylcarbamoyl by using KOH
afforded the target molecule in 23.4% overall yield in six steps.
Perlolyrine is a b-carboline alkaloid that displays strong
yellow fluorescence as well as remarkable biological activi-
Conclusion
In summary, we have demonstrated the diversification of the
b-carboline core and the assembly of a b-carboline library.
These strategies involve three categorically different types of
transition metal-catalyzed CÀC bond-forming reactions, in the
presence of multiple reactive positions, affording an efficient
route towards heteroaryl-, aryl-, alkenyl-, and alkynyl-substitut-
ed b-carbolines at the C1, C3, or C8 position. The saturated
structural feature of the hexahydro-b-carboline framework can
unlock reactivity and control site selectivity. The feasibility of
this method has been demonstrated by the total synthesis of
perlolyrine and the rapid preparation of hyrtioerectine ana-
logues. We believe that our strategy could become a promising
method for the late-stage diversifications of drug molecules.
Experimental Section
General procedure for the Csp3-decarboxylative coupling of
hexahydro-b-carboline-3-carboxylic acid with heteroarenes
and alkynes
Scheme 8. Reactions were carried out by using 17e (0.25 mmol), 18
(3.0 equiv), Pd(OAc)2 (10 mol%), Ag2CO3 (3.0 equiv), pyridine (1.0 equiv), and
1,4-dioxane (1 mL) at 1258C for 24 h, under N2. Yields of isolated product are
based on 17e. [a] Benzene (1 mL) was used instead of 1,4-dioxane.
[b] PivOH (3.0 equiv) was added instead of pyridine.
A flame-dried Schlenk tube with a magnetic stirrer bar was
charged with 4 (59.8 mg, 0.15 mmol), heteroarene or alkyne 5
(0.23 mmol, 1.5 equivalents), CuBr (3.3 mg, 22.5 mmol, 15 mol%),
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General procedure for the direct arylation of 9-(pyrimidin-2-
yl) hexahydro-b-carboline with potassium aryltrifluorobo-
rates
A pressure tube with a magnetic stirrer bar was charged with 10j
(60.1 mg, 0.15 mmol), potassium aryltrifluoroborate 11 (0.45 mmol,
3.0 equivalents), Pd(OAc)2 (3.4 mg, 15 mmol, 10 mol%), 1,4-benzo-
quinone (16.2 mg, 0.15 mmol, 1.0 equivalent), AgOAc (50.1 mg,
0.30 mmol, 2.0 equivalents), DMSO (42.6 mL, 0.60 mmol, 4.0 equiva-
lents), and tBuOH (1.2 mL). The reaction mixture was successively
stirred at room temperature for 10 min and at 1308C for 24 h,
under a N2 atmosphere. After being cooled to ambient tempera-
ture, the reaction was diluted with CH2Cl2 (20 mL), filtered through
a Celite pad, and washed with CH2Cl2 (10 mL). The filtrate was
washed with an aqueous solution of Na2CO3 (1m, 5 mL) and the re-
sulting aqueous phase was extracted with CH2Cl2 (3ꢁ5 mL). The
combined organic phases were washed with water (5 mL), dried
over anhydrous Na2SO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel
to provide the desired product.
General procedure for the oxidative CÀH/CÀH cross-cou-
pling of b-carboline-N-oxide with heteroarenes, arenes, and
alkenes
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A flame-dried pressure tube with a magnetic stirrer bar was
charged with 17e (63.8 mg, 0.25 mmol), heteroarene, arene, or
alkene 18 (0.75 mmol, 3.0 equivalents), Pd(OAc)2 (5.6 mg,
25.0 mmol, 10 mol%), pyridine (20.1 mL, 0.25 mmol, 1.0 equivalent),
Ag2CO3 (206.8 mg, 0.75 mmol, 3.0 equivalents), and 1,4-dioxane
(1.0 mL) under a N2 atmosphere. The reaction mixture was stirred
at room temperature for 10 min, and then warmed to and stirred
at 1258C for 24 h. After being cooled to ambient temperature, the
reaction mixture was diluted with CH2Cl2 (20 mL), filtered through
a Celite pad, and washed with CH2Cl2 (10–20 mL). The combined
organic phases were concentrated and the residue was purified by
column chromatography on silica gel to provide the desired prod-
uct.
Acknowledgements
This work was supported by grants from the National Basic Re-
search Program of China (973 Program, 2011CB808601), and
the National NSF of China (21272160, 21025205, 21321061 and
J1103315/J0104).
Keywords: arylation
decarboxylative coupling
carboline
·
CÀH bond functionalization
·
·
oxidative cross-coupling
·
b-
Chem. Eur. J. 2014, 20, 3408 – 3414
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Full Paper
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Received: November 25, 2013
Published online on February 12, 2014
Chem. Eur. J. 2014, 20, 3408 – 3414
www.chemeurj.org
3414
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim