Efficient synthesis of 5,6-dihydroxyindole dimers, key eumelanin building blocks, by a unified o-ethynylaniline-based strategy for the construction of 2-linked biindolyl scaffolds

Article abstract of DOI:10.1021/jo901259s

(Chemical Equation Presented) A unified convenient strategy for the synthesis of 5,6-dihydroxyindole-derived 2,7′-, 2,2′-, and 2,3′-biindolyls is reported, which is based on proper manipulation of key o-ethynylaniline precursors. By the same methodology 5

Full text of DOI:10.1021/jo901259s

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converted to tetramers.4 Hence, the availability of dimers
Efficient Synthesis of 5,6-Dihydroxyindole Dimers,
Key Eumelanin Building Blocks, by a Unified
o-Ethynylaniline-Based Strategy for the Construction
of 2-Linked Biindolyl Scaffolds
from 1 is of paramount importance to enquire into the broad
diversity of oligomeric architectures expected to concur with
eumelanin buildup.5 Additional motivations for pursuing
1-derived dimers as synthetic targets derived from recogni-
tion of eumelanin-like polymers as new prototypes of bioin-
spired functional materials.6-8 Moreover, 2,20-biindolyls are
of current interest as structural motifs for the preparation of
anion sensing architectures,9 and 1-based oligomers have
recently been shown to exhibit fluoride-sensing properties.10
Whereas numerous synthetic efforts have been directed
to 1,11,12 the current synthetic repertoire for the preparation
of related dimers is scanty, the only exception being the
synthesis of the 3,30-biindolyl.13 Considerable constraints to
the possible synthetic plans are posed by the highly oxidizable
o-dihydroxy functionality, which requires careful selection of
protecting groups, reagents, and reaction conditions. Accord-
ingly experimental control over oxidation pathways of 1 repre-
sented so far the only means of gaining access to small amounts
of dimers for structural investigations. While 2 can be practi-
cally obtained in sufficient amounts by oxidative coupling of 1,
the other dimers, especially 4, remain difficult to prepare and
are usually obtained in poor yields with significant impurities,
requiring cumbersome chromatographic purification steps.
Luigia Capelli, Paola Manini, Alessandro Pezzella,*
Alessandra Napolitano, and Marco d’Ischia
Department of Organic Chemistry and Biochemistry,
University of Naples Federico II, Complesso Universitario
Monte S. Angelo, via Cintia 4, I-80126 Naples, Italy
alessandro.pezzella@unina.it
Received June 12, 2009
A unified convenient strategy for the synthesis of 5,6-
dihydroxyindole-derived 2,70-, 2,20-, and 2,30-biindolyls is
reported, which is based on proper manipulation of key
o-ethynylaniline precursors. By the same methodology 5,6-
diacetoxy-7-iodoindole can also be obtained in good yield.
5,6-Dihydroxyindoles are naturally occurring, catechol-
containing heterocyclic compounds1 which provide the fun-
damental monomer precursors of eumelanins, the character-
istic black insoluble biopolymers found in human skin, hair,
and eyes.2 Chemical or enzymatic oxidation converts the
parent 5,6-dihydroxyindole (1) into black insoluble materials
virtually indistiguishable from natural pigments. This po-
lymerization reaction proceeds through oligomer intermedi-
ates that can be populated at the dimer level by up to four
main biindolyls, 2-5, sharing 2-linked indole units as a
common feature.1,3 This peculiar signature of the oxidation
behavior of 1 is lost in part when the dimers are oxidatively
(5) (a) Pezzella, A.; Panzella, L.; Crescenzi, O.; Napolitano, A.; Navaratman,
S.; Edge, R.; Land, E. J.; Barone, V.; d’Ischia, M. J. Am. Chem. Soc. 2006, 128,
15490–11221. (b) d’Ischia, M.; Crescenzi, O.; Pezzella, A.; Arzillo, M.; Panzella,
L.; Napolitano, A.; Barone, V. Photochem. Photobiol. 2008, 84, 600–607.
(6) d’Ischia, M.; Napolitano, A.; Pezzella, A.; Meredith, P.; Sarna, T.
Angew. Chem., Int. Ed. 2009, 48, 3914–3921.
(7) Meredith, P.; Sarna, T. Pigment Cell Res. 2006, 19, 572–594.
(8) Bothma, J. P.; de Boor, J.; Divakar, U.; Schwenu, P. E.; Meredith, P.
Adv. Mater. 2008, 20, 3539.
(9) (a) Chang, K.-J.; Chae, M. K.; Lee, C.; Lee, J.-Y.; Jeong, K.-S.
Tetrahedron Lett. 2006, 47, 6385–6388. (b) Lin, C.-I.; Selvi, S.; Fang,
J.-M.; Chou, P.-T.; Lai, C.-H.; Cheng, Y.-M. J. Org. Chem. 2007, 72,
3537–3542. (c) Chang, K.-J.; Moon, D.; Lah, M. S.; Jeong, K.-S. Angew.
Chem., Int. Ed. 2005, 44, 7926–7929.
(10) Panzella, L.; Pezzella, A.; Arzillo, M.; Manini, P.; Napolitano, A.;
d’Ischia, M. Tetrahedron 2009, 65, 2032–2036.
(11) Beer, R. J. S.; Clarke, K.; Khorana, H. G.; Robertson, A. Nature
1948, 161, 525.
(12) (a) d'Ischia, M.; Napolitano, A.; Pezzella, A. In Comprehensive Hetero-
cyclic Chemistry III; Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., Taylor,
R. J. K., Eds.; Elsevier Ltd.: Oxford, UK, 2008. (b) Bergman, J.; Janosik, T. In
Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden, C. A.,
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(c) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873–2920.
(13) Mee, S. P. H.; Lee, V.; Baldwin, J. E.; Cowley, A. Tetrahedron 2004,
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(1) d’Ischia, M.; Napolitano, A.; Pezzella, A.; Land, E. J.; Ramsden,
C. A.; Riley, P. A. Adv. Heterocycl. Chem. 2005, 89, 1–63.
(2) (a) Prota, G. Melanins and Melanogenesis; Academic Press: San Diego,
CA, 1992. (b) The Pigmentary System: Physiology and Pathophysiology;
Nordlund, J. J., Boissy, R. E., Hearing, V. J., King, R. A., Oetting, W. S., Ortonne,
J. P., Eds.; Blackwell Publishing: Malden, MA, 2006.
(3) (a) d’Ischia, M.; Napolitano, A.; Tsiakas, K.; Prota, G. Tetrahedron
1990, 46, 5789–5796. (b) Napolitano, A.; Corradini, M. G.; Prota, G.
Tetrahedron Lett. 1985, 26, 2805–2808. (c) Manini, P.; d’Ischia, M.; Milosa,
M.; Prota, G. J. Org. Chem. 1998, 63, 7002–7008.
(4) (a) Panzella, L.; Pezzella, A.; Napolitano, A.; d’Ischia, M. Org. Lett.
2007, 9, 1411–1414. (b) Pezzella, A.; Panzella, L.; Natangelo, A.; Arzillo, M.;
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DOI: 10.1021/jo901259s
r
Published on Web 08/11/2009
J. Org. Chem. 2009, 74, 7191–7194 7191
2009 American Chemical Society

Capelli et al.
JOCNote
SCHEME 1. Synthesis of 5,50,6,60-Tetrabenzyloxy-2,20-biindolyl
SCHEME 2. Synthesis of o-Ethynylaniline Building Blocks20
(4-Bn)15
Herein we report the first successful approach to the less
accessible dimers of 1, namely the 2,70-, 2,20-, and 2,30-
biindolyls 3-5, which relies on sequential coupling and
cyclization steps involving suitably protected o-ethynylani-
line intermediates.
SCHEME 3. Synthesis of 2,70-Biindolyl 3-Ac23
The possible strategy to the 2,20-biindolyl 4 was delineated
in recent papers9a,c,14 and was initially pursued by using 1,2-
dibenzyloxy-4-iodo-5-nitrobenzene (6) as the starting com-
pound (Scheme 1).
Compound 6 was readily obtained as described in the
previous synthesis of the 3,30-biindolyl.13 Easy removal of
benzyl groups by catalytic hydrogenation supported the
validity of the strategy for the purposes of this study.
Reduction of 6 to the iodoaniline 7 was successfully achieved
with sodium dithionite in 1:1 acetone-0.1 M phosphate
buffer (pH 7.4). Sonogashira coupling16 with trimethylsily-
lacetylene followed by deprotection with potassium fluoride
led to the o-ethynylaniline 9-Bn. Oxidative dimerization with
ring iodination. Moreover, the acetyl groups can be con-
veniently removed in situ by a very mild hydrolytic step just
prior to oxidative polymerization experiments.4 Central to
this strategy was reduction of the nitro group prior to
iodination, which was envisioned to lead to a diacetoxyani-
line more amenable to iodination. In line with this expecta-
tion, 4-nitrocatechol (11), was acetylated and then subjected
to catalytic hydrogenation to give the corresponding diace-
17
Cu(OAc)2 followed by intramolecular cyclization with
CuI18 gave 5,50,6,60-tetrabenzyloxy-2,20-biindolyl (4-Bn) in
satisfactory overall yield. Notably, direct cyclization of 9-Bn
yielded 1-Bn in good yield. This procedure is probably one of
the best so far developed for the preparation of 1-Bn.19
Efforts to extend the above chemistry to the preparation of
dimer 3, featuring the challenging 2,70-biindolyl skeleton,
were unsuccessful, due to difficulties with the preparation of
a crucial intermediate, 3,4-dibenzyloxy-6-ethynyl-2-iodoani-
line, by iodination of 9-Bn. These difficulties were attributed
to the electron-donating benzyloxy groups increasing the
reactivity of the aromatic ring and preventing control over
iodination. In seeking an alternative strategy for protection
of the catechol function, we opted for acetyl groups, since
these latter were expected to blunt the electron-donating
effect of the hydroxyl groups thus allowing for controlled
toxyaniline 12 (Scheme 2).
Iodination of 12 with NaI/NaClO2
21a
gave an o,o-diio-
doaniline (13), which eventually led to the desired 3,4-
diacetoxy-6-ethynyl-2-iodoaniline (15) in good overall yield
following a regioselective Sonogashira coupling. An efficient
deiodination step then afforded the key intermediate 4,5-
diacetoxy-2-ethynylaniline (9-Ac). This latter compound
could not be obtained via controlled iodination of 12, since
attempts to insert only one iodo substituent failed under a
variety of conditions.
With the same synthetic approach it was possible to obtain
5,50,6,60-tetraacetoxy-2,70-biindolyl (3-Ac) in satisfactory
yields via cyclization of 15 to give a 7-iodoindole derivative
(16), followed by coupling with 9-Ac and final cyclization to
give the 2-substituted indole moiety (Scheme 3). In this
sequence, the yield of the CuI-promoted intramolecular
cyclization of 15 could not be increased above 50% due to
(14) Koradin, C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P.
Tetrahedron 2003, 59, 1571–1587.
(15) Reagents and conditions: (a) Na2S2O4, acetone/0.1 M phosphate buffer
(pH 7.4), 60 °C, 2h ; (b) PPh3, CuI, (PPh3)2PdCl2, trimethylsilylacetylene, TEA/
toluene, Ar atm, 60 °C, 30 min ; (c) KF, DMF, 2 h ; (d) Cu(OAc)2, dry pyr, Ar atm,
16 h ; (e) CuI, dry DMF, Ar atm, 110 °C, 3 h. Yields refer to the isolated compound.
(16) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
16, 4467–4470.
(20) Reagents and conditions: (a) Ac2O, pyr, 320 W, 6 min ; (b) 10% Pd/C,
20 atm H2, CHCl3, 6 h ; (c) NaClO2, NaI, HCl, H2O/methanol, 1 h ; (d) PPh3, CuI,
(PPh3)2PdCl2, trimethylsilylacetylene, TEA/toluene, Ar atm, 60 °C, 30 min ;
(e) Zn, AcOH, 30 min ; (f) KF H2O/DMF, 30 min. Yields refer to the isolated
compounds.
(21) (a) Lista, L.; Pezzella, A.; Napolitano, A; d’Ischia, M. Tetrahedron
2008, 64, 234–239. (b) Pezzella, A.; Crescenzi, O.; Natangelo, A.; Panzella,
L.; Napolitano, A.; Navaratman, S.; Edge, R.; Land, E. J.; Barone, V.;
d’Ischia, M. J. Org. Chem. 2007, 72, 1595–1603.
(17) Cresp, T. M.; Ojima, J.; Sondheimer, F. J. Org. Chem. 1977, 42,
2130–2138.
ꢀ
(18) Ezquerra, J.; Pedregal, C.; Lamas, C.; Barluenga, J.; Perez, M.;
Garcia-Martin, M. A.; Gonzaalez, J. M. J. Org. Chem. 1996, 61, 5804–5812.
(19) (a) Benigni, J. D.; Minnis, R.L. J. Heterocycl. Chem. 1965, 2, 387–
392. (b) Murphy, B. P.; Banks, H. D. Synth. Commun. 1985, 15, 321–329.
7192 J. Org. Chem. Vol. 74, No. 18, 2009

Capelli et al.
JOCNote
SCHEME 4. Synthesis of 2,30-Biindolyl 5-Ac24
SCHEME 5. Summarizing Scheme of the Unified Strategy to
3-Ac-5-Ac
15, which, in turn, can be obtained from a common pre-
cursor, 14.
partial decomposition of the unstable iodoindole product. In
the same scheme, change to aluminum chloride as the
catalyst for cyclization of 17 was prompted by the low
efficiency of CuI due probably to unfavorable steric interac-
tions of this bulky cation with the hindered substrate. To the
best of our knowledge, this is the first total synthesis of a 2,70-
biindolyl system that does not rely on heavily substituted
preformed indole precursors.23
Attempts at synthesizing dimer 2-Ac by a proper variant of
the unified strategy were thwarted by difficulties encoun-
tered with the preparation of 4,5-diacetoxy-2-ethynyl-3-io-
doaniline as the necessary intermediate. Since this dimer is
easily available by oxidation of 1, the search for alternate
approaches was postponed to studies currently under devel-
opment.
The successful strategy to 3-Ac was next applied to the
synthesis of the 2,30-biindolyl as the acetyl derivative (5-Ac)
(Scheme 4).
Experimental Section
Synthesis of 4,5-Dibenzyloxy-2-(trimethylsilylethynyl)aniline
(8-Bn). Asolutionof7(500 mg, 1.2 mmol) in triethylamine (9.5 mL)
and toluene (9.5 mL) was treated with PPh3 (30 mg, 0.12 mmol), CuI
(22 mg, 0.12 mmol), (PPh3)2PdCl2 (40 mg, 0.06 mmol), and
trimethylsilylacetylene (900 μL, 6.3 mmol) under an argon atmo-
sphere at 60 °C. After 30 min the reaction mixture was extracted with
a 10% water solution of NH4Cl and toluene. The organic layers
were dried over anhydrous sodium sulfate and evaporated under
reduced pressure to afford pure 8-Bn (456 mg, 98%, Rf 0.53, eluant:
petroleum ether/EtOAc 8:2 (v/v)).
Thus, 9-Ac was converted to 5,6-diacetoxyindole (1-Ac)
via CuI-promoted intramolecular cyclization, and then re-
gioselectively iodinated at the 3-position by a recently devel-
oped preocedure21b to give 5,6-diacetoxy-3-iodoindole (18).
Reaction of 18 with 9-Ac under Sonogashira conditions was
unsuccessful. However, the problem was circumvented by
N-acetylating the indole substrate just prior to the Sonoga-
shira coupling. The N-acetylation of 18 with acetic anhydride
and dimethylaminopyridine makes the iodoindole derivative
more prone to the coupling with 9-Ac, giving the 3-alkynyl-
substituted 5,6-diacetoxy-1-acetylindole 19 in good yields;
this latter was subjected to the final cyclization step to afford
5-Ac.
A straightforward extension of this chemistry to the 2,20-
biindolyl system eventually led to the acetyl derivative 4-Ac
via oxidative dimerization of 9-Ac to 10-Ac (86%) followed
by double concerted intramolecular cyclization (70%), using
the same reaction conditions detailed in Scheme 1 for 4-Bn
synthesis.
In a final set of experiments a representative dimer, 3-Ac,
was efficiently deacetylated by treatment with t-BuO- in
MeOH under an Ar atmosphere, and pure 3 was completely
characterized for the first time by NMR (see the SI).
In conclusion, we have reported the first total synthesis of
2,20-, 2,30-, and 2,70-biindolyls based on the unified strategy
summarized in Scheme 5. This allows access to diverse
biindolyl scaffolds and monomer derivatives by manipula-
tion of only two key o-ethynylaniline derivatives, 9-Ac and
8-Bn: 1H NMR (300 MHz, CDCl3) δ (ppm) 0.27 (9H, s,
Si(CH3)3), 3.80 (2H, br s, NH2), 5.02 (2H, s, OCH2Ph), 5.08 (2H,
s, OCH2Ph), 6.31 (1H, s, H-6), 6.96 (1H, s, H-3), 7.0-7.2 (10H,
m, H-2, H-3, H-4, H-5, H-6/OBn); 13C NMR (50 MHz, CDCl3)
δ (ppm) 0.47 (Si(CH3)3), 71.1 (OCH2Ph), 73.1 (OCH2Ph), 98.8
(;CtC;Si), 100.1 (;CtC;Si), 101.8 (C-6), 102.2 (C-2),
120.2 (C-3), 127-129 (10 ꢀ CH, C-2, C-3, C-4, C-5, C-6/OBn),
137.1 (C-1/OBn), 137.8 (C-1/OBn), 141.2 (C-1), 144.9 (C-4),
151.9 (C-5); HRMS (ESI) m/z C25H28NO2Si [M þ H]þ calcd
402.1889, found 402.1893.
Synthesis of 4,5-Dibenzyloxy-2-ethynylaniline (9-Bn). A solu-
tion of 8-Bn (320 mg, 0.8 mmol) in DMF (7.2 mL) was treated
with KF (70 mg, 1.2 mmol) at room temperature. After 2 h the
reaction mixture was extracted with chloroform and a 10%
water solution of NH4Cl, and the organic layers were dried over
anhydrous sodium sulfate and evaporated under reduced pres-
sure to afford pure 9-Bn (257 mg, 98%, Rf 0.35, eluant: petro-
leum ether/EtOAc 7:3 (v/v)).
9-Bn: FT-IR (CHCl3) ν 2096 (;CtC;), 3400-3500 (NH2)
1
cm-1; H NMR (300 MHz, (CD3)2CO) δ (ppm) 3.84 (1H, s,
;CtCH), 4.81 (2H, br s, NH2), 5.02 (2H, s, OCH2Ph), 5.08
(2H, s, OCH2Ph), 6.60 (1H, s, H-6), 6.97 (1H, s, H-3), 7.3-
7.5 (10H, m, H-2, H-3, H-4, H-5, H-6/OBn); 13C NMR (50
MHz, (CD3)2CO) δ (ppm) 70.8 (OCH2Ph), 73.1 (OCH2Ph), 81.7
(;CtCH), 82.7 (;CtCH), 98.0 (C-2), 101.5 (C-6), 120.9
(C-3), 128-129 (10 ꢀ CH, C-2, C-3, C-4, C-5, C-6/OBn), 137.9
(C-1/OBn), 138.7 (C-1/OBn), 140.6 (C-1), 147.1 (C-4), 152.6 (C-
5); HRMS (ESI) m/z C22H20NO2 [M þ H]þ calcd 330.1494,
found 330.1489.
(22) (a) Black, D. St. C.; Ivory, A. J.; Kumar, N. Tetrahedron 1996, 52,
7003–7012. (b) Black, D. St. C.; Ivory, A. J.; Kumar, N. Tetrahedron 1996,
52, 4697–708.
(23) Reagents and conditions: (a) CuI, TEA/toluene, Ar atm, 130 °C, 1.5 h ;
(b) PPh3, CuI, (PPh3)2PdCl2, 9-Ac, TEA/toluene, Ar atm, 60 °C, 1 h ; (c) AlCl3,
toluene, Ar atm, 110 °C, 3.5 h. Yields refer to the isolated compound.
(24) Reagents and conditions: (a) CuI, TEA/toluene, Ar atm, 130 °C, 1.5 h ;
(b) oxone, NH4I, I2, acetonitrile, 2 h ; (c) DMAP, Ac2O, toluene, 30 min ; (d) PPh3,
CuI, (PPh3)2PdCl2, 9-Ac, TEA/toluene, Ar atm, 60 °C, 1 h ; (e) CuI, dry DMF, Ar
atm, 110 °C, 1.5 h. Yields refer to the isolated compound.
Synthesis of 2-[40-(200-Amino-400,500-dibenzyloxyphenyl)-10,30-
butadiinyl]-4,5-dibenzyloxyaniline (10-Bn). A solution of 9-Bn
J. Org. Chem. Vol. 74, No. 18, 2009 7193

Capelli et al.
JOCNote
(682 mg, 2.1 mmol) in dry pyridine (7 mL) was treated with
Cu(OAc)2 (455 mg, 2.3 mmol) at room temperature under an
argon atmosphere. After 16 h the reaction mixture was filtered
on Celite, evaporated under reduced pressure, and extracted
with chloroform and a saturated solution of NaHCO3. The
organic layers were washed with brine, dried over anhydrous
sodium sulfate, and evaporated under reduced pressure and the
residue was fractionated on silica gel (cyclohexane/EtOAc,
gradient from 7:3 to 6:4) to afford pure 10-Bn (272 mg, 40%,
Rf 0.44, eluant: cyclohexane/EtOAc 6:4 (v/v)).
NH4Cl. The organic layers were dried over anhydrous sodium
sulfate and evaporated under reduced pressure and the residue
was fractionated on preparative TLC (eluant: benzene/acetone
9:1 (v/v) plus 1% acetic acid) to afford pure 4-Bn (102 mg, 60%,
Rf 0. 62, eluant: benzene/acetone 9:1 (v/v) plus 1% acetic acid).
4-Bn: UV-vis (DMSO) λ 357, 376 nm; 1H NMR (400 MHz,
(CD3)2CO) δ (ppm) 5.15 (2H ꢀ 2, s, OCH2Ph), 5.17 (2H ꢀ 2, s,
OCH2Ph), 6.71 (1Hꢀ2, s, H-3, H-30), 7.06 (1Hꢀ2, s, H-7, H-70),
7.20 (1Hꢀ2, s, H-4, H-40), 7.3-7.6 (10Hꢀ2, m, H-2, H-3, H-4,
H-5, H-6/OBn), 10.40 (1H ꢀ 2, br s, NH); 13C NMR (50 MHz,
(CD3)2CO) δ (ppm) 71.8 (2ꢀOCH2Ph), 72.2 (2ꢀOCH2Ph), 98.0
(C-3, C-30), 98.5 (C-7, C-70), 106.8 (C-4, C-40), 123.3 (C-4a,
C-4a0), 127-129 (10 CH ꢀ 2, C-2, C-3, C-4, C-5, C-6/OBn),
131.3 (C-2, C-20), 132.6 (C-7a, C-7a0), 138.3 (4ꢀC-1/OBn)þ, 145.4
(C-5, C-50), 147.3 (C-6, C-60); MS (ESIþ) m/z 657 ([MþH] ), 679
([M þ Na]þ); HRMS (ESI) m/z C44H37N2O4 [M þ H]þ calcd
657.2753, found 657.2762.
10-Bn: FT-IR (CHCl3) ν 2200 (;CtC;), 3400-3500
1
(NH2) cm-1; H NMR (400 MHz, (CD3)2CO) δ (ppm) 4.95
(2Hꢀ2, br s, NH2), 5.03 (2Hꢀ2, s, OCH2Ph), 5.12 (2Hꢀ2, s,
OCH2Ph), 6.57 (1H ꢀ 2, s, H-6, H-300), 6.93 (1H ꢀ 2, s, H-3,
H-600), 7.2-7.6 (10Hꢀ2, m, H-2, H-3, H-4, H-5, H-6/OBn); 13C
NMR (50 MHz, (CD3)2CO) δ (ppm) 71.0 (2 ꢀ OCH2Ph), 73.1
(2 ꢀ OCH2Ph), 78.9 (;CtC;CtC;), 80.9 (;CtC;
CtC;), 97.4 (C-2, C-100), 101.5 (C-6, C-300), 120.8 (C-3,
C-600), 128-129 (10 CH ꢀ 2, C-2, C-3, C-4, C-5, C-6/OBn),
138.1 (2 ꢀ C-1/OBn), 138.9 (2 ꢀ C-1/OBn), 141.0 (C-5, C-400),
148.7 (C-1, C-200), 153.5 (C-4, C-500); MS (MALDI) m/z 657
([M þ H]þ); HRMS (ESI) m/z C44H37N2O4 [M þ H]þ calcd
657.2753, found 657.2758.
Synthesis of 5,50,6,60-Tetrabenzyloxy-2,20-biindolyl (4-Bn). A
solution of 10-Bn (170 mg, 0.25 mmol) in dry DMF (2.6 mL) was
treated with CuI (99 mg, 0.50 mmol) at 110 °C under an argon
atmosphere. After 3 h the reaction mixture was filtered on Celite
and extracted with chloroform and a 10% solution water of
Acknowledgment. This study was supported in part by
grants from the Italian MIUR (PRIN 2006 project).
Supporting Information Available: Material and methods
and experimental procedures, and NMR spectra for compounds
1-Ac, 1-Bn, 3, 3-Ac, 4-Ac, 4-Bn, 5-Ac, 7, 8-Ac, 8-Bn, 9-Ac, 9-Bn,
10-Ac, 10-Bn, 11-Ac, 12, 13, 14, 15, 16, 17, 18-Ac, 19. This
material is available free of charge via the Internet at http://
pubs.acs.org.
7194 J. Org. Chem. Vol. 74, No. 18, 2009