Regioselective hydrodebromination of polybrominated indoles

Article abstract of DOI:10.1002/ejoc.201400032

The mixture of sodium borohydride and N,N,N′,N′- tetramethylethylenediamine in combination with a palladium catalyst is a mild and efficient system for the regioselective hydrodebromination of polybrominated indoles with both N-donating and N-withdrawing substituents [N-methyl- and N-(methoxycarbonyl)indoles, respectively]. The mixture of NaBH ₄/N,N,N′,N′-tetramethylethylenediamine in combination with a palladium catalyst is a mild and efficient system for the regioselective hydrodebromination of polybrominated indoles with both N-donating and N-withdrawing substituents [N-methyl- and N-(methoxycarbonyl)indoles]. Copyright

Full text of DOI:10.1002/ejoc.201400032

Job/Unit: O40032
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Date: 29-04-14 18:32:30
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FULL PAPER
DOI: 10.1002/ejoc.201400032
Regioselective Hydrodebromination of Polybrominated Indoles
Giorgio Chelucci,*[a] Gérard A. Pinna,[b] and Giansalvo Pinna[b]
Keywords: Synthetic methods / Nitrogen heterocycles / Bromine / Reduction / Palladium
The mixture of sodium borohydride and N,N,NЈ,NЈ-tetra- hydrodebromination of polybrominated indoles with both N-
methylethylenediamine in combination with a palladium cat-
alyst is a mild and efficient system for the regioselective
donating and N-withdrawing substituents [N-methyl- and N-
(methoxycarbonyl)indoles, respectively].
strates occurred regioselectively to afford unsymmetrical
2,3-diarylindoles.[4d] Only one example that concerns the
competitive substitution between other differently substi-
tuted bromoindoles has been reported. On that occasion
Ohta and co-workers demonstrated that the first attack in
Suzuki–Miyaura reactions of N-tert-butyldimethylsilyl-pro-
tected 3,6-dibromoindole occurred at C-6 to give 6-aryl-3-
bromo-N-(tert-butyldimethylsilyl)indoles.[8]
From these results it appears that the regioselectivity de-
pends on both the nitrogen protective group and the type
of reaction. The key step in metal-catalyzed coupling reac-
tions is the oxidative addition of palladium, which usually
occurs first at the most electron-deficient carbon atom.[9] In
2,3-dibromo-N-methylindole the electron-donating charac-
ter of the N-methyl substituent increases the electronic den-
sity on C-3, thus favoring site-selective transformations at
C-2. However, the strong electron-withdrawing effect of the
sulfonyl group causes increased reactivity of both C-2 and
C-3 of the indole moiety, thus generating a less pronounced
difference between their electronic characters.
Introduction
Indoles bearing bromine substituents are valuable syn-
thetic intermediates, as well as important units in many bio-
logically active alkaloids and potential candidates for phar-
maceuticals.[1,2] Moreover, brominated indoles have been
isolated from a range of marine sources.[3] As a result, con-
siderable efforts have been devoted to the bromination of
indoles, which has resulted in a number of convenient ap-
proaches.[4]
Regioselectively substituted bromoindoles are generally
prepared by selective sequential bromination reactions.
However, this synthetic approach does not allow access to
all possible regioisomers. We considered that a possible
solution to this problem could be to reverse the process. In
other words, the heterocyclic ring could be polybrominated,
and then the bromine atoms could be progressively removed
by selective hydrodebromination. To achieve this goal a pro-
cess for the metal-catalyzed hydrodehalogenation of haloge-
nated heterocycles[5] is needed.
There are only a few reports about regioselective metal-
catalyzed reactions concerning N-substituted polybromin-
ated indoles. All these reactions are cross-coupling reactions
that employ palladium complexes as catalysts and involve
regioselective discrimination between the 2- and 3-position
of the indole ring. Thus, Gribble and Liu reported that all
attempts to prepare monocoupling products or unsymmet-
rical 2,3-diarylindole derivatives, which contain two dif-
ferent aryl groups, by Suzuki–Miyaura reactions of N-phen-
ylsulfonyl-substituted 2,3-dibromoindole were unsuccess-
ful.[6] Recently, Langer described that the Heck reaction of
2,3-dibromo-N-methylindole proceeded without selectiv-
ity,[7] whereas the Suzuki–Miyaura reactions on these sub-
Based on this information we decided to examine the re-
gioselective hydrodebromination of polybrominated indoles
by a metal-catalyzed process. We recently demonstrated that
a
sodium borohydride/N,N,NЈ,NЈ-tetramethylethylenedi-
amine (NaBH4/TMEDA) mixture as the hydride source in
combination with a palladium catalyst is a mild and ef-
ficient system for the hydrodehalogenation of halogenated
heterocycles.[10] The good results obtained in that study
prompted us to assess this reducing system for the synthesis
of regioselectively substituted bromoindoles, which resulted
in the regioselective removal of bromine substituents from
polybrominated indoles with both N-donating and N-with-
drawing substituents, namely N-methyl- and N-(meth-
oxycarbonyl)indoles, respectively.
[a] Dipartimento di Agraria, Università di Sassari,
viale Italia 39, 07100 Sassari, Italy
E-mail: chelucci@uniss.it
http://agrariaweb.uniss.it/
Results and Discussion
[b] Dipartimento di Chimica e Farmacia, Università di Sassari,
Via F. Muroni 23/A, 07100 Sassari, Italy
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201400032.
To begin with we examined the reduction of polybromin-
ated N-(methoxycarbonyl)indoles, which were easily avail-
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FULL PAPER
Scheme 1. Method A: Heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol-%), PPh3 (20.0 mol-%), NaBH4 (3.4 equiv.), TMEDA (3.4 equiv.),
THF (13.2 mL) at room temp. Method B: Heterocycle (0.66 mmol), PdCl2(dppf) (5.0 mol-%), NaBH4 (3.4 equiv.), TMEDA (3.4 equiv.),
THF (13.2 mL) at room temp. DMF = dimethylformamide.
able in high yields from N-(methoxycarbonyl)indole (2)[11] tained from 2 (90%).[4e] With Method A the 2-bromine
(Scheme 1). The first reduction was of methyl 2,3-di- atom from indole 5 was selectively removed to give, after
bromoindole-1-carboxylate (3) that was prepared by bromin- 1.5 h, 3,6-dibromo analogue 6 in 81% yield (Scheme 1).
ation of indole 1 (95% yield).[4e] After careful examination Further reduction of 6 was problematic (Scheme 1). In fact,
of various reaction conditions, we concluded that the best when Method A was employed, the disappearance of start-
results for hydrodehalogenation were achieved by using ing material occurred after 6 h as determined by TLC, but
1
Pd(OAc)2 (5 mol-%) with PPh3 (20 mol-%) in combination led to a complex mixture of products. The H NMR spec-
with NaBH4 (3.4 equiv.) and TMEDA in tetrahydrofuran trum of this mixture showed signals corresponding to both
(THF) at room temperature (Method A). Under these reac- methyl 3-bromo- and 5-bromo-1H-indole-1-carboxylate
tion conditions selective removal of the 2-bromine atom and indolic products derived from N-carbodemethoxyl-
from 3 occurred within 1 h to afford methyl 3-bromo-1H- ation. When Pd(OAc)2/PPh3 was replaced by the more
indole-1-carboxylate (4) in 87% yield (Scheme 1). Next we active catalyst PdCl2[1,1Ј-bis(diphenylphosphanyl)ferro-
examined the hydrodebromination of methyl 2,3,6-tri- cene] (dppf; 5 mol-%) in combination with 3.4 equiv. of the
bromo-1H-indole-1-carboxylate (5) that was readily ob- reducing system (Method B), complete conversion occurred
Scheme 2. Method A: Heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol-%), PPh3 (20.0 mol-%), NaBH4 (3.4 equiv.), TMEDA (3.4 equiv.),
THF (13.2 mL) at room temp. Method B: Heterocycle (0.66 mmol), PdCl2(dppf) (5.0 mol-%), NaBH4 (3.4 equiv.), TMEDA (3.4 equiv.),
THF (13.2 mL) at room temp. Method C: Heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol-%), PPh3 (20.0 mol-%), NaBH4 (2.0 equiv.),
TMEDA (2.0 equiv.), THF (13.2 mL) at room temp. Method D: Heterocycle (0.66 mmol), PdCl2(dppf) (5.0 mol-%), NaBH4 (2.0 equiv.),
TMEDA (2.0 equiv.), THF (13.2 mL) at room temp.
2
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Regioselective Hydrodebromination of Polybrominated Indoles
after 1 h, but the result was the same and indicated no selec- using NaBH4/TMEDA (2 equiv.) for 30 min. Thus, 3,5,6-
tivity in this reduction.
tribromo-1-methyl-1H-indole (13)[4e] was formed in 62%
Next, the reduction of polybrominated N-(methoxycarb- yield. Further reduction of 13 occurred with no selectivity.
onyl)indoles was investigated, which are easily available in A mixture of products that contained various brominated
high yields from N-(methoxycarbonyl)indoline (8) obtained N-(methoxycarbonyl)indoles and bromoindoles derived
in turn from indoline (7) (Scheme 2). The first one to be from the N-carbodemethoxylation reaction was obtained.
examined was methyl 2,3,5-tribromo-1H-indole-1-carboxyl-
The final reduction in this series was that of 3,5-di-
ate (9)[4e] (Scheme 2). Surprisingly, the reduction of this ind- bromo-1H-indole-1-carboxylate (10)[4e] that was performed
ole was less satisfactory than that of isomer 5 with the with PdCl2(dppf) (5 mol-%) in combination with 2.0 equiv.
bromine atom in 6-position of the benzene condensed ring. of the reducing system (Method D). Under these reaction
In fact, the removal of the 2-bromine atom was obtained conditions disappearance of the starting material occurred
after 1.25 h reaction time with Method A, but expected after 1.5 h as determined by TLC analysis, but the major
methyl 3,5-dibromo-1H-indole-1-carboxylate (10) was iso- isolated product was 3,5-dibromo-1H-indole (11;[4e] 56%
lated in lower yield (62%). After many reaction permuta- yield), derived from N-carbodemethoxylation of 10. By em-
tions (which included the amount of NaBH4/TMEDA and ploying Pd(OAc)2/PPh3 (Method C) a longer reaction time
the reaction temperature), no improvement in the yield and was required (18 h), but a similar final result was obtained
selectivity was found. Thus, the use of NaBH4/TMEDA with 11, which was isolated in 62% yield.
(1.2 equiv.) gave only partial conversion of the starting ma-
The next N-substituted indoles to be examined were po-
terial (about 50%) after 24 h both at room temperature and lybrominated N-methylindoles, prepared by selective brom-
50 °C. Moreover, by performing the reduction with NaBH4/ ination of N-methylindole (Scheme 3). The reduction of 2,3-
TMEDA (2 equiv.) for 2 h, dibromo compound 10 was iso- dibromo-1-methyl-1H-indole (16)[7] was successfully ac-
lated in about 50% yield.
complished with Method A, which afforded 3-bromo-1-
Next, we devoted our attention to more demanding methyl-1H-indole (17)[12] in 79% yield[10] (Scheme 3). The
tetrabromoindole 12[4e] that was obtained by bromination reduction of 16 was slowest (18 h) relative to methyl 2,3-
of tribromoindole 9 (Scheme 2). With this indole the best dibromoindole-1-carboxylate (3; 1 h), which confirms the
compromise between yield and selectivity was obtained by lower reactivity of C-2 with N-donating substituents on the
Scheme 3. Method A: Heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol-%), PPh3 (20.0 mol-%), NaBH4 (3.4 equiv.), TMEDA (3.4 equiv.),
THF (13.2 mL) at room temp. Method B: Heterocycle (0.66 mmol), PdCl2(dppf) (5.0 mol-%), NaBH4 (3.4 equiv.), TMEDA 3.4 equiv.),
THF (13.2 mL) at room temp. NBS = N-bromosuccinimide..
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G. Chelucci, G. A. Pinna, G. Pinna
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Scheme 4. Method A: Heterocycle (0.66 mmol), Pd(OAc)2 (5.0 mol-%), PPh3 (20.0 mol-%), NaBH4 (3.4 equiv.), TMEDA (3.4 equiv.),
THF (13.2 mL) at room temp.
indole ring. Unexpectedly, the reduction of 2,3,6-tribromo-
Finally, we examined the selective hydrodebromination
1-methylindole (18)[13] was faster than 16, and under of 2,3,5-tribromo-1-methylindole (24), which was conve-
Method A the removal of the 2-bromine atom occurred se- niently prepared in two steps from parent tribromoindole 9
lectively within 3 h to give 3,6-dibromo-1-methylindole (19) according to a well-described procedure (Scheme 4).[4e] For
in 76% yield.
this reduction the use of Method A was effective, and di-
For the hydrodebromination of 3,6-dibromoindole 19 the bromoindole 22 was obtained in 79% yield after 1 h.
use of Pd(OAc)2/PPh3 as catalyst was unsatisfactory; thus,
the more active catalyst PdCl2(dppf) was employed
(Method B). Under these reaction conditions the disappear-
ance of the starting material was observed within 6 h, which
gave a complex mixture of products from which 3-bromo-
1-methylindole (17) was isolated in 45% yield.
Conclusions
The use of sodium NaBH4/TMEDA in combination with
a palladium catalyst is a mild and efficient system for the
regioselective hydrodebromination of polybrominated ind-
oles with both N-donating and N-withdrawing substituents
[N-methyl and N-(methoxycarbonyl)indoles, respectively].
The results obtained in this study show that the polybrom-
ination followed by selective hydrodebromination is a valu-
able procedure, which should be taken into account for the
selective synthesis of complex bromoindole-containing mo-
lecules.
We then turned our efforts to 2,3,5,6-tetrabromo-1-
methyl-1H-indole (20);[14] the reduction was most challeng-
ing and required a number of experiments. With Method A,
complete conversion of 20 was achieved within 1 h, but the
selectivity was very low. The reaction product was a mixture
of products that contained 3,5,6-tribromo-1-methyl-1H-
indole (21;[4b] 66%), 3,5-dibromo-1-methyl-1H-indole (22;
31%) and 5,6-dibromo-1-methyl-1H-indole (3%)[15] in a
molar ratio of about 22:10:1. When the amount of NaBH4/
TMEDA was reduced, the ratio 21/22 increased signifi-
cantly from 2.2:1 to 4.6:1 (by using 1.2 equiv.), but the con-
version was incomplete. Also, the use of the catalytic system
formed by Pd2(dba)3/XantPhos (2.5 and 5 mol-%, respec-
tively) with NaBH4/TMEDA (3.4 equiv.) was unsatisfactory
Experimental Section
General Information: All reactions were carried out under argon in
and gave 21 and 22 in a 1.4:1 ratio. Surprisingly, when oven-dried glassware with magnetic stirring. Unless otherwise
noted, all materials were obtained from commercial suppliers and
were used without further purification. All solvents were reagent
grade. THF was distilled from sodium benzophenone ketyl and de-
gassed thoroughly with dry argon directly before use. Unless other-
wise noted, organic extracts were dried with anhydrous Na2SO4,
filtered through a fritted glass funnel, and concentrated with a ro-
tary evaporator (20–30 Torr). Flash chromatography was per-
formed with silica gel (200–300 mesh) by using the mobile phase
indicated. The NMR spectra were measured with a 400 MHz
Bruker Avance spectrometer at 400.1 and 100.6 MHz, for 1H for
PdCl2(dppf) was used as catalyst (Method B), complete
conversion was observed after 1 h, and the 21/22 ratio in-
creased dramatically to 13:1 and afforded 21 in 55% iso-
lated yield. On this basis, tribromoindole 21 was reduced
under Method B and led to dibromoindole 22 in 68% yield
after 1 h.
The hydrodebromination in this series was completed
through the examination of 3,5-dibromo-1-methyl-1H-ind-
ole (22). By carrying out the reduction by using
PdCl2(dppf) (Method B) until disappearance of the starting 13C, respectively, in CDCl3 solution with tetramethylsilane as in-
ternal standard. Chemical shifts are given in ppm (δ) and are refer-
enced to the residual proton resonances of the solvents. Indoline
(7), indole (14) and 1-methyl-1H-indole (15) were commercial com-
pounds. Methyl-1H-indole-1-carboxylate (2),[11] 2,3-dibromoind-
ole-1-carboxylate (3),[4e] methyl 2,3,6-tribromo-1H-indole-1-carb-
oxylate (5),[4c] N-(methoxycarbonyl)indoline (8),[17] methyl 2,3,5-
tribromo-1H-indole-1-carboxylate (9),[4e] methyl 2,3,5,6-tetra-
bromo-1H-indole-1-carboxylate (12),[4e] 2,3-dibromo-1-methyl-1H-
indole (16),[7] 2,3,6-tribromo-1-methyl-1H-indole (18)[13] and
2,3,5,6-tetrabromo-1-methyl-1H-indole (20)[14] were prepared ac-
cording to reported procedures. Analytical and spectral data of
material (18 h) as determined by TLC, the major observed
product was 1-methyl-1H-indole (15). However, by stop-
ping the reaction after 6 h, a mixture which consisted of
starting indole 22, and products 15, 3-bromo-1-methyl-1H-
indole (17) and 5-bromo-1-methyl-1H-indole (23),[6] in a
4:5:1:3 ratio was obtained. Although some selectivity in
favor of bromoindole 23 (23/17 = 3:1) has been achieved in
this reaction, further fast reduction of the initially formed
monobromoindoles to fully debrominated indole 15 makes
this hydrodebromination impractical.
4
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Regioselective Hydrodebromination of Polybrominated Indoles
products methyl 3,5-dibromo-1H-indole-1-carboxylate (12),[4e] 3,5-
dibromo-1H-indole (11),[4e] 3-bromo-1-methyl-1H-indole (17),[12]
(dd, J = 8.8, 2.0 Hz, 1 H), 7.13 (d, J = 8.8 Hz, 1 H), 7.00 (s, 1 H),
3.72 (s, 3 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 134.9,
3,5,6-tribromo-1-methyl-1H-indole (21),[4b] 5-bromo-1-methyl-1H- 128.9, 128.8, 125.5, 121.8, 113.5, 111.0, 88.5, 33.2 ppm. C9H7Br2N
indole (23)[16] and 5,6-dibromo-1-methyl-1H-indole[15] were iden-
tical to those reported in the literature.
(288.97): calcd. C 37.41, H 2.44, N 4.85; found C 37.22, H 2.48, N
4.89.
General Procedures for the Hydrodebromination of Polybrominated
Indoles
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for all new compounds.
Method A: Anhydrous THF (13.2 mL) was degassed by bubbling
argon for a few minutes, then Pd(OAc)2 (7.2 mg, 0.033 mmol,
5 mol-%) and PPh3 (17.7 mg, 1.132 mmol, 20 mol-%) were added,
and the resulting mixture was stirred at room temperature for
30 min. The halogenated heterocycle (0.66 mmol), TMEDA
(0.260 g, 2.24 mmol, 3.4 equiv.) and finally NaBH4 (85.0 mg,
2.24 mmol, 3.4 equiv.) were introduced in sequence. The mixture
was stirred at room temperature under argon for the proper time.
The residue was taken up in brine and extracted with ethyl acetate.
The organic phase was separated, dried, the solvent was evapo-
rated, and the residue was purified by flash chromatography (mix-
tures of petroleum ether/ethyl acetate) to give pure bromoindoles.
Acknowledgments
We are grateful to Regione Autonoma della Sardegna (RAS) for
financial support (project CRP-26417).
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Method B: A mixture of the halogenated heterocycle (0.66 mmol)
in anhydrous THF (13.2 mL) was degassed by bubbling argon for
a few minutes. Then, PdCl2(dppf)·CH2Cl2 (27.0 mg, 0.033 mmol,
5.0 mol-%), TMEDA (0.260 g, 2.24 mmol, 3.4 equiv.) and finally
NaBH4 (85.0 mg, 2.24 mmol, 3.4 equiv.) were introduced in se-
quence. The mixture was stirred at room temperature under argon
for the specific time and then worked up as described above.
Method C: The procedure of Method A was applied except that
TMEDA (0.133 g, 1.32 mmol, 2.0 equiv.) and NaBH4 (50.0 mg,
1.32 mmol, 2.0 equiv.) were used.
Method D: The procedure of Method B was applied except that
TMEDA (0.133 g, 1.32 mmol, 2.0 equiv.) and NaBH4 (50.0 mg,
1.32 mmol, 2.0 equiv.) were used.
Methyl 3-Bromo-1H-indole-1-carboxylate (4): Oil. 1H NMR
(400.1 MHz, CDCl3): δ = 8.14 (d, J = 0.8 Hz, 1 H), 7.63 (s, 1 H),
7.51 (d, J = 7.6 Hz, 1 H), 7.37 (dt, J = 7.6, 1.2 Hz, 1 H), 7.31 (dt,
J = 7.6, 1.2 Hz, 1 H), 4.01 (s, 3 H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 150.6, 134.5, 129.3, 125.6, 124.3, 123.5, 119.5, 115.0,
98.8, 54.0 ppm. C10H8BrNO2 (254.08): calcd. C 47.27, H 3.17, N
5.51; found C 47.65, H 3.13, N 5.56.
Methyl 3,6-Dibromo-1H-indole-1-carboxylate (6): White solid. M.p.
106–107 °C. 1H NMR (400.1 MHz, CDCl3): δ = 8.33 (s, 1 H), 7.60
(s, 1 H), 7.43 (dd, J = 8.4, 1.6 Hz, 1 H), 7.36 (d, J = 8.4 Hz, 1 H),
4.05 (s, 3 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 150.3,
135.0, 128.3, 126.9, 124.8, 120.8, 119.6, 118.2, 98.6, 54.3 ppm.
C10H7Br2NO2 (332.98): calcd. C 36.07, H 2.12, N 4.21; found C
36.35, H 2.15, N 4.18.
Methyl 3,5,6-Tribromo-1H-indole-1-carboxylate (13): White solid.
M.p. 134–136 °C. 1H NMR (400.1 MHz, CDCl3): δ = 8.42 (s, 1 H),
7.72 (s, 1 H), 7.60 (s, 1 H), 4.06 (s, 3 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 150.0, 133.7, 129.9, 125.8, 123.9, 121.6,
119.9, 119.5, 97.3, 54.5 ppm. C10H6Br3NO2 (411.87): calcd. C
29.16, H 1.47, N 3.40; found C 29.44, H 1.43, N 3.45.
3,6-Dibromo-1-methyl-1H-indole (19): Oil. 1H NMR (400.1 MHz,
CDCl3): δ = 7.43 (d, J = 1.6 Hz, 1 H), 7.31 (d, J = 8.4 Hz, 1 H),
7.26 (d, J = 8.4 Hz, 1 H, 0.8 Hz), 6.99 (s, 1 H), 3.68 (s, 3 H) ppm.
13C NMR (100.6 MHz, CDCl3): δ = 136.9, 128.3, 126.2, 123.4,
120.6, 116.4, 112.5, 89.6, 33.1 ppm. C9H7Br2N (288.97): calcd. C
37.41, H 2.44, N 4.85; found C 37.88, H 2.41, N 4.81.
[6] Y. Liu, G. W. Gribble, Tetrahedron Lett. 2000, 41, 8717–8721.
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[8] I. Kawasaki, M. Yamashita, S. Ohta, Chem. Pharm. Bull. 1996,
44, 1831–1839.
3,5-Dibromo-1-methyl-1H-indole (22): White solid. M.p. 59–60 °C.
1H NMR (400.1 MHz, CDCl3): δ = 7.67 (d, J = 2.0 Hz, 1 H), 7.31
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O40032
/KAP1
Date: 29-04-14 18:32:30
Pages: 7
G. Chelucci, G. A. Pinna, G. Pinna
FULL PAPER
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Received: January 8, 2014
Published Online: ᭿
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O40032
/KAP1
Date: 29-04-14 18:32:30
Pages: 7
Regioselective Hydrodebromination of Polybrominated Indoles
Indole Derivatives
The mixture of NaBH4/N,N,NЈ,NЈ-tetra-
methylethylenediamine in combination
with a palladium catalyst is a mild and ef-
ficient system for the regioselective hydro-
debromination of polybrominated indoles
with both N-donating and N-withdrawing
substituents [N-methyl- and N-(methoxy-
carbonyl)indoles].
G. Chelucci,* G. A. Pinna,
G. Pinna ............................................ 1–7
Regioselective Hydrodebromination of
Polybrominated Indoles
Keywords: Synthetic methods / Nitrogen
heterocycles / Bromine / Reduction / Pal-
ladium
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