Luminescent atropisomeric N,N-chelating ligands from copper-catalyzed one-pot C-N and C-C coupling reactions

Article abstract of DOI:10.1021/ol701485a

New atropisomeric N,N-chelating ligands with a 3,3′-bis[2-(2′- py)-indolyl] unit have been achieved via one-pot reactions that involve the formation of multiple C-N bonds between an indolyl and a brominated benzene and the indolyl 3,3′-C-C coupling. The n

Full text of DOI:10.1021/ol701485a

ORGANIC
LETTERS
2007
Vol. 9, No. 21
4087-4090
Luminescent Atropisomeric
N,N-Chelating Ligands from
Copper-Catalyzed One-Pot C
−N and
C−C Coupling Reactions
Theresa M. McCormick, Qinde Liu, and Suning Wang*
Department of Chemistry, Queen’s UniVersity, Kingston ON, K7L 3N6, Canada
wangs@chem.queensu.ca
Received June 21, 2007
ABSTRACT
New atropisomeric N,N-chelating ligands with a 3,3
of multiple C N bonds between an indolyl and a brominated benzene and the indolyl 3,3
intramolecular excimer emission (λmax 445 nm). Cu(I) ions bind to the new N,N-chelate ligands with a homochiral selectivity. The complex
[Cu(bpib)2][BF4] (bpib bis 3,3 -[N-phenyl-2-(2 -py)-indolyl] ) crystallizes as chiral crystals, thus allowing enantiomeric separation.
′
-bis[2-(2
′
-py)-indolyl] unit have been achieved via one-pot reactions that involve the formation
−
′-C−C coupling. The new ligands display distinct blue
)
)
{
′
′
}
Atropisomeric chelate ligands such as BINAP (2,2′-bis-
(diphenylphosphino)-1,1′-binaphthyl) are well-known for
their important roles in asymmetric catalysis involving
transition metals.1 The majority of previously known
atropisomeric ligands are based on 1,1′-binaphthyl with
phosphine binding sites.1 Atropisomeric ligands based on
3,3′-bi-indolyl are rare, but some examples with phosphine
donors have been reported.2 Compared to phosphine ligands,
pyridyl and polypyridyl ligands are in general harder donors,
are more stable toward oxidation, and can have rich
photophysical/photochemical properties when bound to metal
ions. Hence, atropisomeric chelate ligands based on pyridine
or polypyridine are attractive not only for their potential use
in certain asymmetric reactions but also for their applications
in chiral supramolecular assembly and chiral recognition.1,3
In spite of these, examples of atropisomeric ligands involving
pyridyls as donors are scarce, and only a few examples are
known in the literature.4 We report herein new atropisomeric
ligands that have a 3,3′-bis[2-(2′-py)indolyl] backbone with
multiple 2-pyridyl binding sites.
As shown in Figure 1, structurally the new atropisomeric
molecules, bpib, bbip, and btib (right column), can be
considered as the corresponding 3,3′-C-C coupled dimer
of pib, bib, and tib (left column), respectively. In fact, the
“dimer” ligands were isolated as a minor product from the
Ullmann condensation reaction of 2-(2′-pyridyl)indole with
bromobenzene, 1,4-bromobenzene, and 1,3,5-tribromo-
benzene, respectively, using CuSO4 as the catalyst and K2CO3
as the base, with the “monomer” pib, bib, and tib as the
(1) (a) Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser, M.
J.; Garner, J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384. (b)
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10.1021/ol701485a CCC: $37.00
© 2007 American Chemical Society
Published on Web 09/21/2007

and contribute to the low yield of the dimer. Indeed, insoluble
organic products were observed from the reaction mixtures
for bbip or btib synthesis. However, the insolubility has
prevented us from fully characterizing these high molecular
weight species.
Examples of one-pot or tandem reactions to form both
C-C and C-N in the product are known previously (with
Pd catalysts in most instances).6 However, simultaneous aryl
C-C coupling and the formation of multiple aryl C-N bonds
catalyzed by copper as shown in Scheme 1 are rare. Because
of the apparent monomer-dimer structural relationship
between pib and bpib, one possible explanation for the
formation of bpib is that pib is the precursor which undergoes
direct C-C coupling at the 3 position of indolyl to form the
dimer. To confirm this, direct coupling of pib to form bpib
was attempted using base and a copper catalyst at elevated
temperatures as in the original reaction, but no reaction was
observed. Li and co-workers have demonstrated copper-
catalyzed C-C coupling reactions at unfunctionalized sp2
carbon centers with the aid of an oxidant.7 Unfunctionalized
C-C bond formation for biaryl and bipyrroles has also been
reported using a hypervalent iodine radical source such as
phenyliodine bis(trifluoroactate) (PIFA).8 Our attempts to use
PIFA and other oxidants with or without copper using the
reaction conditions reported in the literature failed to convert
pib to bpib. However, if the reaction was carried out at high
temperature (210 °C) in the presence of PIFA (with or
without copper), some conversion of pib to bpib (∼15% by
NMR) along with a large amount of decomposition products
was observed. Our original one-pot reaction is therefore still
the simplest and the best way to produce bpib.
Figure 1. Structures of the monomers (left) and the atropisomeric
dimers (right).
intended targets. The isolated yields (not optimized) of the
monomer and the corresponding dimer from each reaction
are shown in Scheme 1. Copper-catalyzed Ullmann conden-
Direct C-C coupling of indole via either a potassium salt
or a lithium salt intermediate and the subsequent oxidation
by oxidants such as I2 was known to produce 3,3′-bi-indole
in low yield.9 In our reactions, brominated benzenes are likely
the source of radical oxidants generated under the high-
temperature reaction conditions. The 2-py group on the indole
ring likely functions as a directing group that binds to the
Cu ion initially, facilitating the activation of the C-H bond
and the subsequent 3,3′-C-C coupling. Similar ortho-assisted
1,1′-C-C coupling of naphthalene1a,5 and C-C coupling in
other molecules are well documented.10
Scheme 1
The new ligands listed in Figure 1 are fully characterized
by NMR, elemental analyses, or HRMS. The crystal struc-
tures of the dimer bpib and bbib have been determined by
X-ray diffraction analyses and are shown in Figure 2. Both
bpib and bbib have an approximate C2 symmetry. The
dihedral angle between the indolyl rings is 125.1° for bpib
sation reactions are commonly known for C-N bond
formation but not direct C-C bond coupling.5 The isolation
of the 3,3′-bi-indolyl products from these reactions is
therefore surprising. The isolated yield of the small dimer
bpib is modest. The isolated yields of the larger dimers bbip
and btib are low, which are caused mainly by their poor
solubility (slightly soluble in CH2Cl2) and the formation of
mono- and disubstituted (in the case of 1,3,5-tribromo-
benzene) C-N coupling side products. In addition, C-C
coupling involving the mono- and disubstituted monomers
can also occur. C-C homocoupling at the 3 position of the
terminal 2-(2′-py)indolyl in bpib and btib is also possible,
which can result in the formation of larger oligomeric species
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Nandakumar, M. V.; Verkade, J. G. Angew. Chem., Int. Ed. 2005, 44, 3115.
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Li, C. J. J. Am. Chem. Soc. 2005, 127, 3672. (c) Li, Z.; Li, C. J. Eur. J.
Org. Chem. 2005, 127, 3173. (d) Li, Z.; Bohle, D. S.; Li, C. J. PNAS 2006,
103, 8928.
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Org. Lett., Vol. 9, No. 21, 2007

Figure 3. Crystal structure of [Cu(bpib)2]+. The D2 symmetry
related four subunits are shown in different colors. The two 3,3′
C-C bonds are shown in gray.
The [Cu(bpib)2]+ cation has a crystallographically imposed
D2 symmetry, which is a consequence of chelation by two
identical enantiomers of bpib to the Cu(I) center. The crystal
structure shows that the preferential “picking” by the Cu(I)
ion for the same enantiomer is due to the favorable intra-
ligand interactions. Despite the formation of the large nine-
membered chelate ring, the fact that the bpib ligand can
replace PPh3 ligands on the Cu(I) center is an indication that
the bpib ligand can act as a very effective chelate. In solution,
1H NMR spectra showed that the phenyl groups in 1 display
hindered rotation around the phenyl-indolyl C-C bond due
to ortho-H interactions, similar to hindered rotations around
C-N bonds of aryl-benzimidazolyl ligands in Cu(I) com-
plexes.12 In addition, one of the ortho-H atoms on the phenyl
ring has an ∼3 ppm upfield shift due to its interaction with
the py “π-cloud”13 from the second bpib ligand.
Figure 2. Crystal structures of bpib (top) and bbib (bottom).
and 128.5° for bbib. There are significant π-π interactions
between the two central pyridyl rings with the atomic
separation distances being 3.57-4.00 Å for bpib and 3.50-
3.90 Å for bbib. Consistent with the π-π interactions
between the two py rings in solution is the distinct upfield
shift (∼0.4 ppm) by the C(6)-H proton of py in the 1H NMR
spectra, from monomer to dimer. DFT calculations performed
on bpib indicate that the rotation barrier around the 3,3′-
C-C bond is ∼92 kJ/mol, which, compared to the rotation
barriers reported for previously known axially chiral mol-
ecules,4,11 indicates that the enantiomers of bpib may be
resolvable at ambient temperature. However, despite numer-
ous attempts, our efforts to resolve the enantiomers of the
new ligands by repeated cocrystallization with optically pure
tartaric acid using procedures4 reported for 1,1′-bis(2-py-
naphthyl) resolution have not been successful, possibly due
to similar solubilities of the diastereomer salts.
The ability of the new 2-py functionalized 3,3′-bi-indolyls
to act as ligands for metal ions is demonstrated by the
formation and isolation of an orange Cu(I) complex
[CuI(bpib)2]BF4 (1), isolated initially from the reaction of
bpib with [CuI(PPh3)2(CH3CN)2]BF4 in a 1:1 ratio in good
yield (the 1:1 complex [CuI(bpib)(PPh3)2]BF4 was not
observed at all). Complex 1 was also obtained by the
stoichiometric reaction of pbib with [CuI(CH3CN)4]BF4. 1
is stable toward air in the solid state. It has a weak MLCT
absorption band at 380-450 nm in the UV-vis spectrum,
responsbile for its distinct orange color. The crystal structure
of 1 is shown in Figure 3.
Figure 4. Left: lattice packing diagram of 1 projected down the
c-axis. Cu, red; N, light blue; F, yellow; Cl, green; B, pink. Right:
space-filling diagram showing four stacked cations.
The crystals of 1 belong to the tetragonal chiral space
group I422. The Cu(I) center in 1 has a distorted tetrahedral
geometry with the N-Cu-N chelate bite angle being 137.1°.
Most interestingly, in the crystal lattice (Figure 4) 1 stacks
along the c-axis to form homochiral columns, and the
(11) (a) Spivey, A. C.; Maddaford, A.; Leese, D. P.; Redgrave, A. J. J.
Chem. Soc., Perkin Trans. 1 2001, 1785. (b) Spivey, A. C.; Charbonneau,
P.; Fekner, T.; Hochmuth, D. H.; Maddaford, A.; Malardier-Jugroot, C.;
Redgrave, A. J.; Whitehead, M. A. J. Org. Chem. 2001, 66, 7394.
(12) Jia, W. L.; McCormick, T. M.; Tao, Y.; Lu, J. P.; Wang, S. Inorg.
Chem. 2005, 44, 5706.
(13) Ting, Y.; Lai, Y.-H. J. Am. Chem. Soc. 2004, 126, 909.
Org. Lett., Vol. 9, No. 21, 2007
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resulting channels are occupied by the BF4 anions and
CH2Cl2 solvent molecules. The homochiral crystallization
of 1 from a racemic solution mixture is interesting due to
the relatively rare occurrence of such an event.14 More
important is that it allows us to separate the enantiomers by
the Pasteur method, namely, hand picking the crystals.
The CD spectra of two hand-picked crystals of 1 with
opposite chirality recorded in CH2Cl2 are shown in Figure
5. The spectra were monitored with time to determine the
Figure 6. Emission spectra of the ligands in CH2Cl2 (∼1 × 10-5
M). Inset: photograph of pib (right) and bpib (left) under UV light.
consistent with intramolecular excimer formation between
the two central py rings in the dimer, a phenomenon similar
to the recently reported intramolecular excimer emission
involving two carbazole rings15 or two pyrene rings in a
sterically constrained environment.16 The restricted rotation
around the 3,3′-C-C bond in the “dimer” molecules is
believed to facilitate the intramolecular py-py interaction
and the excimer formation.
Figure 5. CD spectra of two crystals of 1 with opposite chirality
recorded in CH2Cl2 at 298 K.
In summary, we have shown that new atropisomeric
ligands with py binding sites and a 3,3′-bi-indolyl backbone
along with the corresponding monomers can be obtained by
one-pot reactions catalyzed by copper ions. These reactions
involve the formation of multiple C-N and C-C bonds and
likely complex mechanisms that are not fully understood.
In addition, we have shown that the new “dimer” ligands
display intramolecular excimer emission and are capable of
forming chiral chelate metal complexes, which may find
applications in asymmetric catalysis and chiral sensing.
stability of 1 in solution at ambient temperature. We observed
that in the absence of air the CD spectrum does not change
for weeks, indicating that 1 retains its chiral structure in
solution. Our attempts to free the ligand from the copper
center by the addition of [N(C2H5)4]CN were unsuccessful.
Ligands bbib and btib contain more pyridyl binding sites
than bpib, thus more interesting and complex structures with
metal ions are anticipated, which are being investigated. The
results will be reported in due course.
The impact of the 3,3′-C-C coupling on the electronic
properties of the ligands was investigated by UV-vis and
fluorescent spectroscopic methods. Compared to the corre-
sponding monomer, the bi-indolyl molecules have a shoulder
peak at ∼350 nm in the UV-vis spectra, which most likely
originated from π-π interactions of the two central pyridyl
rings in the dimer, as revealed by the crystal structures of
bpib and bbib. The most significant difference between the
monomer and the dimer is observed in the fluorescent
spectra. As shown in Figure 6, all monomers emit in the
UV region with λmax ) 385-389 nm (Φ ) 0.45 for pib). In
Acknowledgment. We thank the Natural Sciences and
Engineering Research council of Canada for financial sup-
port.
Supporting Information Available: Synthetic proce-
dures, crystallographic tables, figures and cif files, NMR data,
molecular orbital details, UV-vis spectra, and low-temper-
ature emission spectra of pib and bpib. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL701485A
contrast, all dimers emit in the visible region with λmax
)
(15) Benten, H.; Ohkita, H.; Ito, S.; Yamamoto, M.; Sakumoto, N.; Hori,
K.; Tohda, Y.; Tani, K.; Nakamura, Y.; Nishimura, J. J. Phys. Chem. B
2005, 109, 19681.
(16) (a) Benniston, A. C.; Harriman, A.; Howell, S. L.; Sams, C. A.;
Zhi, Y. G. Chem.-Eur. J. 2007, 13, 4665. (b) Lodeiro, C.; Lima, J. C.;
Parola, A. J.; Seixas de Melo, J. S.; Capelo, J. L.; Covelo, B.; Tamayo, A.;
Pedra, B. Sens. Actuators, B 2006, 115, 276.
∼445 nm (Φ ) 0.22 for bpib). This dramatic spectral red
shift and the identical emission spectra by all dimers are
(14) Tamura, R.; Takahashi, H.; Fugimoto, D.; Ushio, T. Top. Curr.
Chem. 2007, 269, 53.
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