Synthesis of biindolyls via palladium-catalyzed reactions

Article abstract of DOI:10.1021/jo801846b

(Chemical Equation Presented) An unprecedented synthesis of a range of high value homoand heterobiindolyls is presented. The one-pot Miyaura borylation and subsequent Suzuki-Miyaura coupling sequence allows for the construction of the highly sterically congested C-C bond between two bromoindoles in modest to good overall yields.

Full text of DOI:10.1021/jo801846b

Synthesis of Biindolyls via Palladium-Catalyzed
Reactions
Hung A. Duong, Sheena Chua, Paul B. Huleatt,* and
Christina L. L. Chai*
Institute of Chemical and Engineering Sciences, Agency for
Science, Technology and Research (A*STAR), 1 Pesek Rd,
Jurong Island, Singapore 627833
paul_brady_huleatt@ices.a-star.edu.sg;
christina_chai@ices.a-star.edu.sg
ReceiVed August 19, 2008
FIGURE 1. Indoles and ligands relevant to this study.
of eumelanin are 5,6-dihydroxyindole (DHI) and 5,6-dihydroxy-
indole-2-carboxylic acid (DHICA) (Figure 1), the precise
structure of the natural material has not been elucidated.
However, some insight has been gained from the study of a
series of DHI and DHICA biindolyls.5 Given the importance
of biindolyls, we sought to develop methodology for their
construction.
We envisioned that the Pd-catalyzed Suzuki-Miyaura cou-
pling could be a powerful method for the construction of
different C-C bonds between indole units.6 The requisite
boronic acid/ester coupling partner could be prepared in several
ways. Methods involving transmetalation between aryl magne-
sium or lithium intermediates and boron compounds were
avoided due to the extreme basic conditions that could lead to
unwanted side reactions.7 A recent advance in the preparation
of indolyl boronates is Ir-catalyzed C-H borylation.8,9 However,
this method is limited to C2 and C7 functionalization. An
alternative, mild method is via the Miyaura palladium catalyzed
An unprecedented synthesis of a range of high value homo-
and heterobiindolyls is presented. The one-pot Miyaura
borylation and subsequent Suzuki-Miyaura coupling se-
quence allows for the construction of the highly sterically
congested C-C bond between two bromoindoles in modest
to good overall yields.
Indoles are undoubtedly one of the most important structural
classes of compounds found in nature. The recurring prominence
in bioactive natural products as well as commercial drugs has
earned this structural motif a place as a “privileged structure”
in drug discovery.1 Indole oligomers such as biindolyls may
also serve as the backbone of chiral chelating diphosphine
ligands, which have played an important role in asymmetric
catalysis (i.e., BINAP),2 making use of their atropisomeric biaryl
scaffold.3 An interesting natural polymer that is derived from
indolic subunits is eumelanin. Eumelanin is a key brown/black
pigment, whose central role in man is believed to be photopro-
tection.4 While it is well-established that the monomeric units
(4) (a) Prota, G. Melanins and Melanogenesis; Academic: San Diego, CA,
1992. (b) Prota, G. Fortschr. Chem. Org. Naturst. 1995, 64, 93. (c) Prota, G.;
Thomson, R. H. EndeaVour 1976, 35, 32. (d) Kollias, N.; Sayre, R. M.; Zeise,
L.; Chedekel, M. R. Photochem. Photobiol. 1991, 9, 135. (e) Riley, P. A. Int.
J. Biochem. Cell Biol. 1997, 29, 1235. (f) Krol, E. S.; Liebler, D. C. Chem. Res.
Toxicol. 1998, 11, 1434.
(5) (a) d’Ischia, M.; Napolitano, A.; Tsiakas, K.; Prota, G. Tetrahedron 1990,
46, 5789. (b) Pezzella, A.; Panzella, L.; Natangelo, A.; Arzillo, M.; Napolitano,
A.; d’Ischia, M. J. Org. Chem. 2007, 72, 9225. (c) Pezzella, A.; Crescenzi, O.;
Natangelo, A.; Panzella, L.; Napolitano, A.; Navaratnam, S.; Edge, R.; Land,
E. J.; Barone, V.; d’Ischia, M. J. Org. Chem. 2007, 72, 1595. (d) d’Ischia, M.;
Crescenzi, O.; Pezzella, A.; Arzillo, M.; Panzella, L.; Napolitano, A.; Barone,
V. Photochem. Photobiol. 2008, 84, 600.
(6) (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 36,
3437. (b) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (c) Suzuki, A. In
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, Germany, 1998.
(7) (a) Matteson, D. S. In The Chemistry of the Metal-Carbon Bond; Hartley,
F. R., Patai, S., Eds.; Wiley: New York, 1987; Vol. 4, p 307. (b) Vaultier, M.;
Carboni, B. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone,
F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, UK, 1995; Vol. 11, p 191. (c)
Miyaura, N.; Marouka, K. In Synthesis of Organometallic Compounds; Komiya,
S., Ed.; Wiley: New York, 1997; p 345.
(1) (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; Dipardo, R. M.; Freidinger,
R. M.; Whitter, W. L.; Lundell, G. F.; Verber, D. F.; Anderson, P. S.; Chang,
R. S. L.; Lotti, V. J.; Cerino, D. H.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.;
Springer, J. P.; Hirshfield, J. J. Med. Chem. 1988, 31, 2235. (b) Horton, D. A.;
Bourne, G. T.; Smythe, M. L. Chem. ReV 2003, 103, 893, and references cited
therein.
(2) Bringmann, G.; Mortimer, A. J. P.; Keller, P. A.; Gresser, M. J.; Garner,
J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384.
(3) (a) Berens, U.; Brown, J. M.; Long, J.; Selke, R. Tetrahedron: Asymmetry
1996, 7, 285. (b) Benincori, T.; Piccolo, O.; Rizzo, S.; Sannicolo, F. J. Org.
Chem. 2000, 65, 8340. (c) McCormick, T. M.; Liu, Q.; Wang, S. Org. Lett.
2007, 9, 4087.
(8) (a) Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew. Chem.,
Int. Ed. 2002, 41, 16. (b) Takagi, J.; Sato, K.; Hartwig, J. F.; Ishiyama, T.;
Miyaura, N. Tetrahedron Lett. 2002, 43, 5649.
(9) Paul, S.; Chotana, G. A.; Holmes, D.; Reichle, R. C.; Maleczka, R. E.;
Smith, M. R. J. Am. Chem. Soc. 2006, 128, 15552.
10.1021/jo801846b CCC: $40.75
Published on Web 10/22/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 9177–9180 9177

TABLE 1. Screening Conditions for Borylation of Indolesa
TABLE 2. Screening Conditions for Suzuki-Miyaura Coupling
To Prepare Biindolylsa
entry
bases
RB(pin) solvents conv (%)b 6 (%)b 7 (%)b
1
Et3N
Et3N
Et3N
Et3N
Et3N
HB(pin) toluene
HB(pin) toluene
HB(pin) toluene
HB(pin) toluene
HB(pin) dioxane
100
100
16
63
100
31
74
60
0
40
84
10
22
0
8
11
13
0
11
16
5
entry
L
bases
solvents
conv (%)b 8 (%)b,c
2c
3d
4e
5
1
2
3
4
5
6
7d
8
9
XPhos K3PO4 ·H2O dioxane/H2O (10:1)
100
100
100
64
100
94
100
100
100
67
61
67
35
trace
53
48
9
XPhos K3PO4
XPhos Cs2CO3
XPhos Et3N
dioxane/H2O (10:1)
dioxane/H2O (10:1)
dioxane/H2O (10:1)
dioxane
6
7
8
K3PO4 HB(pin) dioxane
K3PO4 B2(pin)2 dioxane
KOAc B2(pin)2 dioxane
XPhos K3PO4
29
9
SPhos K3PO4 ·H2O dioxane/H2O (10:1)
SPhos K3PO4 ·H2O dioxane/H2O (10:1)
XPhos K3PO4 ·H2O toluene/H2O (10:1)
XPhos K3PO4 ·H2O DMF/H2O (10:1)
0
a 1b (0.1 M), Pd2(dba)3 (1 mol %), XPhos (4 mol %), base (0.3 M),
RB(pin) (0.3 M), 110 °C, 14 h. b Determined by GC with naphthalene
as an internal standard. c SPhos was used instead of XPhos. d No ligand
was used. e Reaction was run at rt.
11
a 1b (0.1 M), 6 (0.1 M), Pd2(dba)3 (1 mol %), L (4 mol %), base (0.3
M). b Determined by 1H NMR with ferrocene as an internal standard.
c The mass balance could be accounted for by the formation of 7. d 2
mol % Pd(OAc)2 was used instead of Pd2(dba)3.
borylation of bromoindoles and this was considered appropriate
for application in the current study.10
TABLE 3. Suzuki-Miyaura Coupling of Boronate 6 with
Bromoindolesa
Buchwald and co-workers recently reported that the combina-
tion of their dialkylphosphinobiphenyl ligands (e.g., XPhos and
SPhos) (Figure 1) and a suitable Pd source efficiently catalyzed
the coupling of hindered arylboronic acids and aryl halides.11
The substrate scope was later extended to include heteroaryl
halides and heteroaryl boronic acids/esters.12 We have found
that highly congested biindolyls (homo- and heterodimers) can
also be conveniently prepared from bromoindoles via sequential
borylation and Suzuki-Miyaura cross-coupling.13,14 Herein, we
report the first directed synthesis of the positional isomers of
the homo- and heterodimers of DHI and DHICA derivatives
1-5 (Figure 1).15 Our study demonstrates the synthesis of
diverse, sterically hindered biindolyl systems and for the first
time, verifies the feasibility of constructing protected DHI and
DHICA oligomers via a transition metal mediated cross-coupling
protocol. Furthermore, this work showcases the application of
Pd-catalyzed reactions in forging the aryl-aryl σ-linkage of
highly substituted biaryl compounds (i.e., those containing four
(10) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60, 7508.
(b) Ishiyama, T.; Itoh, Y.; Kitano, T.; Miyaura, N. Tetrahedron Lett. 1997, 38,
3447. (c) Murata, M.; Watanabe, S.; Masuda, Y. J. Org. Chem. 1997, 62, 6458.
(d) Baudoin, O.; Guenard, D.; Gueritte, F. J. Org. Chem. 2000, 65, 9268. (e)
Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J. Org. Chem. 2000, 65,
164. (f) Murata, M.; Sambommatsu, T.; Watanabe, S.; Masuda, Y. Synlett 2006,
12, 1867.
(11) Barder, T. E.; Walker, S. D.; Joseph, R. M.; Buchwald, S. L. J. Am.
Chem. Soc. 2005, 127, 4685.
a 6 (0.1 M), Indolyl-Br (0.1 M), Pd2(dba)3 (1 mol %), XPhos (4 mol
%), K3PO4 ·H2O (0.3 M), dioxane/H2O (10:1), 100 °C.
(12) Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3358.
(13) For examples on the synthesis of biindolyls, see: (a) Zhang, S.; Zhang,
D.; Liebeskind, L. S. J. Org. Chem. 1997, 62, 2312. (b) Merlic, C. A.; McInnes,
D. M. Tetrahedron. Lett. 1997, 38, 7661. (c) Kuethe, J. T.; Wong, A.; Davies,
I. W. Org. Lett. 2003, 5, 3721. (d) Hee, S. P. H.; Lee, V.; Baldwin, J. E.; Cowley,
A. Tetrahedron 2004, 60, 3695. (e) Jones, A. W.; Wahyuningsih, T. D.; Pchalek,
K.; Kumar, N.; Black, D. S. Tetrahedron 2005, 61, 10490. (f) Rempel, S. P. N.;
Olsen, S.; Mahadevan, I. B.; Netchev, G.; Wilson, B. C.; Smith, S. C.; Dunlop,
H. R.; Meredith, P. Photochem. Photobiol. 2008, 84, 613.
(14) For examples on the preparation of symmetrical biaryls via one-pot
borylation and subsequent Suzuki-Miyaura reaction, see: (a) Baudoin, O.;
Cesario, M.; Guenard, D.; Gueritte, F. J. Org. Chem. 2002, 67, 1199. (b) Nising,
C. F.; Schmid, U. K.; Nieger, M.; Brase, S. J. Org. Chem. 2004, 69, 6830. (c)
Broutin, P. E.; Cerna, I.; Campaniello, I. M.; Leroux, F.; Colobert, F. Org. Lett.
2004, 6, 4419. (d) Hashim, J.; Glasnov, T. N.; Kremsner, J. M.; Kappe, C. O.
J. Org. Chem. 2006, 71, 1707. (e) Billingsle, K. L.; Barder, T. E.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2007, 46, 5359. (f) Kikuchi, T.; Nobuta, Y.; Umeda,
J.; Yamamoto, Y.; Ishiyama, T.; Miyaura, N. Tetrahedron 2008, 22, 4967.
(15) Huleatt, P. B.; Choo, S. S.; Chua, S.; Chai, C. L. L. Tetrahedron Lett.
2008, 49, 5309.
ortho substituents), a construction that has been a persistent focus
of interest for synthetic chemists.2,16
At the outset, we explored the synthesis of the requisite
indolyl boronate coupling partners via a Miyaura borylation
reaction. With use of indole 1b as a representative precursor
for borylation, different reaction parameters, including Pd
sources, ligands, borylating reagents, bases, and solvents, were
screened (Table 1). Running the reaction in toluene in the
presence of triethylamine (3 equiv), pinacolborane (3 equiv),
and catalytic amounts of Pd2(dba)3 and XPhos resulted in a good
(16) Wallace, T. W. Org. Biomol. Chem. 2006, 4, 3197.
9178 J. Org. Chem. Vol. 73, No. 22, 2008

TABLE 4. Dimerization of Bromoindolesa
TABLE 5. Sequential One-Pot Two-Step Sequence Leading to
Homo- and Heterocoupled Biindolylsa
a Indolyl-Br (0.1 M), Pd2(dba)3 (1 mol %), XPhos (4 mol %),
K3PO4 ·H2O (0.3 M), B2(pin)2 (0.05 M), dioxane/H2O (10:1), 100 °C.
b 2 mol % Pd2(dba)3 and 8 mol % XPhos were employed.
yield of the desired borylated indole 6 with concomitant
formation of a small amount of the undesired product 7, resulting
from hydrodehalogenation of 1b (entry 1). Under this condition
(entry 1), bromoindole 1b was converted to 6 in 74% GC yield
and in 75% isolated yield. Reactions run in the presence of
SPhos as ligand (entry 2), without any ligand (entry 3), or at
room temperature (entry 4) all resulted in lower yields of 6. A
higher yield of 6 was obtained when dioxane was employed as
solvent instead of toluene (entry 5 vs entry 1). Conditions
reported by Buchwald et al.14e for borylation of aryl chlorides
only resulted in low yields of 6 (entries 7 and 8).
a (1) Indolyl1-Br (0.1 M), Pd)2(dba))3 (1 mol %), XPhos (4 mol %),
Et)3N (0.3M), HB(pin) (0.3 M), dioxane, 100 °C; (2) Pd2(dba)3 (1 mol
%), Indolyl2-Br (0.1 M), K3PO4 ·H2O (0.3 M), dioxane/H2O (10:1), 100
°C.
The pinacolboronates derived from other indoles, such as 2b
and 5, can also be synthesized with this method as confirmed
by ESI-LC/MS and 1H NMR spectroscopy. However, attempts
to isolate these boronates met with little success as they readily
decomposed during column chromatography on silica gel.
Conditions for the Suzuki-Miyaura coupling of 1b and 6
were then investigated (Table 2).11,12 The best yield of 8 was
obtained when the reaction was run in a mixture of dioxane/
H2O (10:1) in the presence of 1 mol % of Pd2(dba)3, 4 mol %
of XPhos, and 3 equiv of K3PO4 ·H2O (entry 1). The use of
anhydrous K3PO4 (entry 2) or Cs2CO3 (entry 3) instead of
K3PO4 ·H2O did not affect the reaction yields to any significant
extent. The use of triethylamine (entry 4) or strictly anhydrous
conditions (entry 5) resulted in the formation of 7 as the major
product and low yields of 8. The use of SPhos instead of XPhos
(entry 6) or Pd(OAc)2 instead of Pd2(dba)3 (entry 7) gave lower
yields of 8. Dioxane/water as solvent was superior to toluene/
water (entry 8) and DMF/water mixtures (entry 9). The latter
two solvent mixtures resulted in extensive formation of undes-
ired 7 at the expense of dimer 8.
dimers 8, 9, and 10 in 60%, 85%, and 73% yield, respectively
(Table 3). The pentacyclic adduct 10 resulted from an in situ
intramolecular lactamization event postformation of the hetero-
coupled dimer.17
Gratifyingly, the homocoupled products could be prepared
via a one-pot, tandem borylation/Suzuki-Miyaura coupling
reaction in dioxane/H2O (10:1) (Table 4).14e Modest to good
overall yields of homodimers were obtained. Dimerization of
the 5,6-dimethoxyindole carboxylates 1b and 2b gave rise to
dimers 8 (49%) and 11 (71%) (entries 1 and 2), respectively.
The one-pot procedure could be applied to the direct synthesis
of dimers 12 and 13, starting from the respective 5,6-
dimethoxyindoles 4 and 5 (entries 3 and 4). A higher catalyst
loading (2 mol %) was required for >90% conversion of indole
4 to the desired dimer. In contrast, 1a, 2a, and 3 almost
exclusively gave rise to hydrodehalogenated products as ob-
served by GC-MS analysis of the reaction mixtures. It is possible
that the presence of the electron-withdrawing ester functional
Under our optimized Suzuki-Miyaura coupling conditions,
boronate 6 was coupled with bromides 1b, 2b, and 5 to afford
(17) Mentzel, U. V.; Tanner, D.; Tonder, J. E. J. Org. Chem. 2006, 71, 5807.
J. Org. Chem. Vol. 73, No. 22, 2008 9179

TABLE 6. Synthesis of DHI-Dimers via Saponificationa and
Decarboxylationb Sequence
to be readily prepared from bromoindoles. Significantly, highly
sterically hindered biindolyls could be obtained conveniently
in modest to good yields with or without N-protecting groups.
Applications of this methodology in the preparation of biologi-
cally interesting compounds as well as unique biindolyl ligands
for catalysis are ongoing in our laboratories and the results will
be reported in due course.
Experimental Section
General Procedure for the Dimerization of Bromoindoles.
An oven-dried 10-mL Schlenk flask was charged with bromoindole,
bis(pinacolato)diboron (0.05 equiv), K3PO4 · H2O (3 equiv),
Pd2(dba)3 (1 mol %), and XPhos (4 mol %). The flask was
evacuated and refilled with argon three times. Dioxane and degassed
water were added and the flask was equipped with a reflux
condenser. The reaction mixture was heated at reflux overnight.
Purification on silica gel column chromatography afforded the
desired coupling product.
Methyl 3-(2-(Methoxycarbonyl)-1-benzyl-5,6-dimethoxy-1H-in-
dol-3-yl)-1-benzyl-5,6-dimethoxy-1H-indole-2-carboxylate, 8. 1H
NMR (400 MHz, acetone-d6, ppm) δ 7.32-7.28 (m, 4H), 7.23-7.21
(m, 2H), 7.16-7.13 (m, 6H), 6.73 (s, 2H), 6.07 (d, 2H, 16 Hz),
5.85 (d, 2H, 16 Hz), 3.85 (s, 6H), 3.64 (s, 6H), 3.42 (s, 6H); 13C
{1H} NMR (100 MHz, acetone-d6, ppm) δ 163.4, 151.5, 147.5,
140.1, 134.8, 129.3, 127.8, 127.2, 124.6, 120.7, 118.3, 103.3, 94.4,
56.3, 56.2, 51.3, 48.6; IR (cm-1, CH2Cl2 film) 2988, 2949, 1697;
LC-HRMS calcd for C38H36N2O8 ([M + Na]+) 671.23639, obsd
671.23496; mp 205.8-206.2 °C. Anal. Calcd for C38H36N2O8: C,
70.36; H, 5.59; N, 4.32. Found: C, 70.41; H, 5.67; N, 4.25.
General Procedure for Sequential One-Pot Two-Step Coupling
Leading to Homo- and Heterocoupled Biindolyls. An oven- dried
10-mL Schlenk flask was charged with the first bromoindole,
Pd2(dba)3 (1 mol %), and XPhos (4 mol %). The flask was
evacuated and refilled with argon three times. Dioxane, triethy-
lamine (3 equiv), and pinacolborane (3 equiv) were added and the
flask was equipped with a reflux condenser. The reaction mixture
was heated at reflux for 2 h. After the reaction mixture was cooled
to rt, degassed water (10% v/v) was added. A solution of the second
bromoindole (1 equiv) in dioxane was added followed by Pd2(dba)3
(1 mol %) and K3PO4 ·H2O (3 equiv). The reaction mixture was
heated at reflux overnight. Purification on silica gel column
chromatography afforded the desired coupling product.
a LiOH (15 equiv), THF/H2O/MeOH (3:1:1). b Microwave, 250 °C.
group in these nonprotected indoles facilitates the competing
hydrodehalogenation reaction.18
To avoid the need to isolate indolyl boronates, a one-pot
sequential coupling procedure was developed for the construc-
tion of homo- and heterodimers (Table 5). For example, at the
completion of the borylation reaction of bromoindole 3 in
dioxane (entry 1), water (10% v/v) was added followed by
bromoindole 3 (1 equiv), K3PO4 ·H2O (3 equiv), and Pd2(dba)3
(1 mol %). After the reaction, purification by chromatography
afforded the homodimer 14 in 75% yield over two steps (entry
1). It should be noted that decomposition of Pd(0) as black
precipitate was observed during the first step (borylation). Thus,
a new batch of Pd(0) was needed in the Suzuki coupling step.
In a similar manner, mixed dimers 15 and 16 were obtained in
37% and 55% yield (entries 2 and 3). The sequential addition
of 5 and 4 led to the dimethoxyindole dimer 17 in 75% yield
overtwosteps(entry4).Amixeddimethoxyindole-dimethoxyindole
carboxylate dimer 18 was also prepared in 72% yield over 2
steps (entry 5). These examples demonstrate that N-protecting
groups can be avoided under these coupling conditions.
An alternative method to prepare dimethoxyindole ho-
modimers would be via saponification followed by decarboxy-
lation of dimethoxyindole carboxylate homodimers or mixed
dimethoxyindole-dimethoxyindole carboxylate dimers. To dem-
onstrate this, compounds 19, 20, 21, and 22 were prepared in
modest yields from dimers 8, 9, 11, and 18, respectively (Table
6).
Dimethyl 5,5′,6,6′-Tetramethoxy-1H,1′H-7,7′-biindole-2,2′-di-
1
carboxylate, 14. H NMR (400 MHz, CD2Cl2, ppm) δ 9.37 (s,
2H), 7.21 (s, 2H), 7.01 (d, 2H, 2.0 Hz), 3.97 (s, 6H), 3.64 (s, 6H),
3.55 (s, 6H); 13C {1H} NMR (100 MHz, CD2Cl2, ppm) δ 162.5,
149.7, 147.7, 131.7, 127.5, 123.3, 111.8, 109.2, 103.8, 61.4, 56.2,
52.0; IR (cm-1, CH2Cl2 film) 3260, 2925, 1685; LC-HRMS calcd
for C24H24N2O8 ([M + Na]+) 491.14249, obsd 491.14124; mp
222.2-223.0 °C. Anal. Calcd for C24H24N2O8: C, 61.53; H, 5.16;
N, 5.98. Found: C, 61.48; H, 5.28; N, 5.94.
Acknowledgement. This work was supported by the Science
and Engineering Research Council of A*STAR (Agency for
Science, Technology and Research), Singapore, and by Johnson
& Johnson Asia Pacific. Helpful comments and suggestions from
the anonymous reviewers are gratefully acknowledged.
In conclusion, the methodology reported herein has allowed,
for the first time, homo- and heterobiindolyls (i.e., positional
permutations of dimers of DHI and DHICA derivatives 1-5)
Supporting Information Available: Experimental proce-
1
dures and H, 13C NMR, and IR data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(18) Handy, S. T.; Bregman, H.; Lewis, J.; Zhang, X.; Zhang, Y. Tetrahedron
Lett. 2003, 44, 427.
JO801846B
9180 J. Org. Chem. Vol. 73, No. 22, 2008