Iron(III)-promoted oxidative coupling of naphthylamines: Synthetic and mechanistic investigations

Article abstract of DOI:10.1021/ol202058r

A facile route to the synthesis of 1,1′-binaphthyl-4,4′- diamines (naphthidines) and 1,1′-binaphthyl-2,2′-diamines (BINAMs) was developed by the oxidative homocoupling of 1- and 2-naphthylamines, respectively, using FeCl₃ as oxidant and K₂CO₃ as base in 1,2-dichloroethane under ambient conditions. A preliminary mechanistic investigation was performed by the ESR spectroscopy and intermediate-trapping technique.

Full text of DOI:10.1021/ol202058r

ORGANIC
LETTERS
2011
Vol. 13, No. 18
4950–4953
Iron(III)-Promoted Oxidative Coupling of
Naphthylamines: Synthetic and
Mechanistic Investigations
Xin-Le Li,†,‡ Jin-Hua Huang,†,‡ and Lian-Ming Yang*,†
Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of New
Materials, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China,
and Graduate School of Chinese Academy of Sciences, Beijing 100049, China
yanglm@iccas.ac.cn
Received July 29, 2011
ABSTRACT
A facile route to the synthesis of 1,10-binaphthyl-4,40-diamines (naphthidines) and 1,10-binaphthyl-2,20-diamines (BINAMs) was developed by the
oxidative homocoupling of 1- and 2-naphthylamines, respectively, using FeCl3 as oxidant and K2CO3 as base in 1,2-dichloroethane under ambient
conditions. A preliminary mechanistic investigation was performed by the ESR spectroscopy and intermediate-trapping technique.
1,10-Binaphthalene diamines represent a unique class
of building blocks in organic synthesis and chemical
materials.1ꢀ5 1,10-Binaphthyl-4,40-diamines (naphthidines)
are potentially attractive systems for the development
of efficient new hole-transport materials;1 1,10-bi-
naphthyl-2,20-diamines (abbreviated to BINAMs)
may constitute chelating or chiral (if enantiomeri-
cally resolved) ligands, which have found some syn-
thetic utilities in catalytic reactions2 and asymmetric
synthesis.3
However, systematic methods for the preparation of
naphthidines and BINAMs have been less studied. Only
recently has an efficient procedure for the synthesis
of naphthidines been found on the basis of the TiCl4-
mediated oxidative coupling of N,N-disubstituted
arylamines.1,5 In contrast, there has not yet been any
general method for the BINAM synthesis until now, and
only some sporadic cases appeared in the previous pub-
lications. For example, much earlier, Bridger et al.6
† Institute of Chemistry, Chinese Academy of Sciences.
‡ Graduate School of Chinese Academy of Sciences.
(1) Desmarets, C.; Champagne, B.; Walcarius, A.; Bellouard, C.;
Omar-Amrani, R.; Ahajji, A.; Fort, Y.; Schneider, R. J. Org. Chem.
2006, 71, 1351.
(2) For BINAM ligands used in catalytic cross-couplings, see: (a)
Prasad, D. J. C.; Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2009, 50,
1411. (b) Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2008, 49, 3147. (c)
Naidu, A. B.; Raghunath, O. R.; Prasad, D. J. C.; Sekar, G. Tetrahedron
Lett. 2008, 49, 1057. For BINAM-based catalysts used in olefin
polymerization, see: (d) Tonzetich, Z. J.; Schrock, R. R. Polyhedron
2006, 25, 469.
(3) For BINAM-based catalysts or reagents used in asymmetric
synthesis, see: (a) Zhou, X.-G.; Yu, X.-Q.; Huang, J.-S.; Li, S.-G.; Li,
ꢀ
ꢀ
ꢀ
L.-S.; Che, C.-M. Chem. Commun. 1999, 1789. (b) Vyskocil, S.; Jaracz,
ꢀ
S.; Smrcina, M.; Stı
ꢀ
ꢀ
ꢁꢀ
ꢁ
´
cha, M.; Hanus, V.; Polasek, M.; Kocovsky, P. J.
Org. Chem. 1998, 63, 7727. (c) Yamamoto, Y.; Sakamoto, A.; Nishioka,
T.; Oda, J.; Fukazawa, Y. J. Org. Chem. 1991, 56, 1112.
(4) One inspiring example of preparing 7-membered N-heterocyclic
carbene ligand from 2,20-diaminobinaphthyl: Scarborough, C. C.; Popp,
B. V.; Guzei, I. A.; Stahl, S. S. J. Organomet. Chem. 2005, 690, 6143.
(5) Periasamy, M.; Jayakumar, K. N.; Bharathl, P. J. Org. Chem.
2000, 65, 3548.
(6) (a) Bridger, R. F.; Law, D. L.; Bowman, D. F.; Middleton, B. S.;
Ingold, K. U. J. Org. Chem. 1968, 33, 4329. (b) Bridger, R. F. J. Org.
Chem. 1970, 35, 1746.
r
10.1021/ol202058r
Published on Web 08/25/2011
2011 American Chemical Society

oxidative coupling of electron-rich (hetero)arenes and,
more importantly, cheap, nontoxic, commercially avail-
able, and environmentally benign. Herein we report our
findings concerning the FeCl3-mediated dimerization of 1-
and 2-naphthylamines.
Table 1. Screening of Reaction Conditions for Fe-Mediated
Oxidative Coupling of Naphthylaminesa
As a starting point, N-phenyl-1-naphthylamine (1a) was
chosen as a model substrate to screen suitable reaction
conditions (Table 1). Some initial experimentation demon-
strated that the homocoupling reaction was facilitated by
the use of additional bases which consume the Hþ ions
produced in the process, and K2CO3 (finely ground when
used) was the base of choice. The reaction was very
sensitive to the nature of solvents used (runs 1ꢀ8). Aro-
matic hydrocarbon (run 1) gave a mediocre yield of the
desired product 2a; polar solvents, such as acetonitrile (run 2),
methanol (run 3), and pyridine (run 4), seemed to be
poor; ethereal solvents (runs 5 and 6) performed relatively
well, and particularly THF (run 6) brought about a good
yield of 65%; and chlorinated alkanes (runs 7 and 8) were
found to be more suitable solvents for the coupling reac-
tion, among which 1,2-dichloroethane (run 8) was the best.
Apparently, the use of excess FeCl3 greatly accelerated the
reaction with a comparable high yield (run 9 vs run 8); in
contrast, decreasing the amounts of FeCl3 significantly
slowed the reaction and reduced the yield (runs 10 and 11).
In contrast, hydrated iron(III) chloride produced an ad-
verse effect on the reaction (run 12). For the other iron
sources used, Fe(acac)3 (run 13) and FeF3 (run 14), which
contain counteranions that are to dissociate from the
central iron ion, almost did not initiate the reaction;
Fe(NO3)3 9H2O (run 15) and Fe2(SO4)3 xH2O (run 16)
run
[Fe] (equiv)
FeCl3 (1.2)
solvent
time (h)
yieldb (%)
1
2
toluene
MeCN
MeOH
pyridine
THF
24
24
24
24
18
24
6
45
37
FeCl3 (1.2)
FeCl3 (1.2)
FeCl3 (1.2)
FeCl3 (1.2)
FeCl3 (1.2)
FeCl3 (1.2)
FeCl3 (1.2)
FeCl3 (4)
3
40
4
22
5
65
6
dioxane
CH2Cl2
DCEc
DCE
46
7
73
81
8
1
9
0.5
16
48
24
24
24
24
24
24
78
10
11
12
13
14
15
16
17
FeCl3 (0.5)
FeCl3 (0.1)
DCE
63
DCE
20
FeCl3 6H2O (1.2)
DCE
62
3
Fe(acac)3 (1.2)
FeF3 (1.2)
DCE
trace
trace
58
DCE
Fe(NO3)3 9H2O (1.2)
DCE
3
Fe2(SO4)3 xH2O (1.2)
DCE
21
3
FeSO4 7H2O (1.2)
DCE
0
3
a Conditions: 1a (1 mmol), K2CO3 (1 equiv), solvent (6 mL), room
temperature, in air; the proceeding of the reaction was monitored by
TLC. b Isolated yields. c 1,2-Dichloroethane.
described the KMnO4 oxidative dimerization of several
N-aryl-2-naphthylamines in low yields; 2,20-diamino-1,10-
binaphthyl was obtained via the thermal rearrangement of
2,20-hydrazonaphthalene7 or by the oxidative coupling of
2-aminonaphthalene using Cu,8a,b Fe,8c and m-CPBA,8d
respectively, as oxidants, and N,N0-diphenyl-2,20-diamino-
1,10-binaphthyl was provided in very low yield by an
electrochemical oxidation process.9 In view of the
foregoing, it remains desirable to explore new, general
methodology for the preparation of naphthidines and
BINAMs.
Our recent studies on nickel-catalyzed aromatic amina-
tions made N-substituted naphthylamines easily
accessible,10 allowing us to systematically investigate the
synthesis of naphthidines and BINAMs on the basis of
their oxidative coupling reactions. On the other hand,
iron(III) species were considered for utilization in this
study because they are the well-known promoters for the
3
3
gave the product in low yields; and no reaction occurred
when the iron(II) salt (FeSO4 7H2O) was used (run 17).
3
Finally, the optimized reaction conditions were set as run 8
in Table 1.
With the optimal reaction conditions in hand, an array
of 1- and 2-naphthylamine derivatives 1 was used as the
substrates in this reaction (Table 2). As can be seen in
Table 2, most of the N-monoaryl-substituted 1-naphthyl-
amines were excellent substrates, offering a clean conver-
sion of starting materials and high yields of the desired
naphthidines (2aꢀc and 2eꢀg). But in the cases of 2d, 2h,
and 2i, complete conversions could be achieved via a
prolonged reaction time, but some unindentified side
reactions occurred apparently, and thus the reduced yields
of the coupled products were afforded. In the above-
mentioned cases, the substituents on the N-aryl imposed
remarkable effects onthe reaction. Interestingly, the effects
depended largely on the site rather than the nature of
the substituents. The substituents at the para position of
N-aryl ring, whether electron-donating (2b and 2c vs 2a) or
electron-withdrawing (2f and 2g vs 2a), promoted the
reaction, but the ortho- or meta-substituents (2d, 2e, 2h,
and 2i vs 2a) would be unfavorable for the reaction.
Presumably, the reason might be related to the mechanism
of this reaction. 1-Naphthylamine with the free amino
group afforded a low yield of the dimer product
because the reaction was not only slow but also gave
large amounts of byproducts (2j). N-Monoalkyl (2kꢀm)
(7) (a) Miyano, S.; Nawa, M.; Mori, A.; Hashimoto, H. Bull. Chem.
Soc. Jpn. 1984, 57, 2171. (b) Shine, H. J.; Gruzecka, E.; Subotkowski,
W.; Brownawel, M.; San Filippo, J., Jr. J. Am. Chem. Soc. 1985, 107,
3219. (c) Brown, K. J.; Berry, M. S.; Murdoch, J. R. J. Org. Chem. 1985,
50, 4345.
ꢀ
ꢀ
ꢀ
ꢁ
(8) (a) Smrcina, M.; Lorene, M.; Hanus, V.; Kocovsky, P. Synlett
ꢀ
ꢀ
1991, 231. (b) Smrcina, M.; Lorene, M.; Hanus, V.; Sedmera, P.;
ꢀ
ꢁ
Kocovsky, P. J. Org. Chem. 1992, 57, 1917. (c) Stoddard, J. M.; Nguyen,
L.; Mata-Chavez, H.; Nguyen, K. Chem. Commun. 2007, 1240. (d)
Wang, K.; Hu, Y.; Wu, M.; Liu, Z.; Su, B.; Yu, A.; Liu, Y.; Wang, Q.
Tetrahedron 2010, 66, 9135.
(9) Hornback, J. M.; Gssage, H. E. J. Org. Chem. 1985, 50, 541.
(10) (a) Gao, C.-Y.; Yang, L.-M. J. Org. Chem. 2008, 73, 1624. (b)
Huang, J.-H.; Yang, L.-M. Org. Lett. 2011, 13, 3750.
Org. Lett., Vol. 13, No. 18, 2011
4951

homocoupled with a complete conversion rate and an
acceptable yield of 46% (3e).
Table 2. FeCl3-Mediated Oxidative Couplings of 1- and
2-Naphthylaminesa
Our studies next identify the mechanistic pathway of the
reaction. According to previous studies on the metal-
mediated oxidative homocouplings of aromatic amines,1,5,11
the present transformation might be rationalized by the two
possible pathways outlined in Scheme 1: one involving
radical cation intermediate III (route A) and the other
naphthyl iron intermediate V (route B).
Scheme 1. Proposed Possible Pathways for the FeCl3-Mediated
Homocoupling of Naphthylamines
a Conditions: 1- or 2-naphthylamine 1 (1 mmol), FeCl3 (1.2 mmol),
K2CO3 (1 mmol), 1,2-dichloroethane (6 mL), room temperature, 1 h;
isolated yields. b 6 h. c 60 °C, 5 h. d 2 mmol of FeCl3, 5 h. e 2 mmol of
FeCl3, 60 °C, 20 h.
and N,N-dialkyl (2nꢀq) 1-naphthylamines underwent the
reaction smoothly with the completely comsumed starting
materials, providing the corresponding naphthidines in
good or appreciable yields. N,N-Diphenyl-1-naphthyla-
mine (2r) was inert in the reaction, and only the starting
material was recovered. The performance of 2-naphthyla-
mine derivatives in this transformation was generally not
as successful as the 1-position counterparts, often with
slow reaction rate and significant quantities of byproducts
(3a, 3b, and 3dꢀh). N-Monoaryl-2-naphthylamines could
provide the coupled dimers in mediocre to good yields
(3aꢀc). In the case of N-p-anisyl-2-naphthylamine (3d), it
was found that the starting material was rapidly consumed
to furnish a high conversion rate of the unidentified
byproduct. N,N-Diaryl- or N-monoalkyl-2-naphthyl-
amines (3f and 3h) did not undergo the reaction with
almost quantitative recovery of the starting materials.
Under more forced conditions, the reaction of aliphatic
secondary cyclic amino 2-naphthalene could go to
completion with a mediocre yield (3g). In addition,
2-naphthylamine with the free amino group could be
Figure 1. ESR spectra during the FeCl3-mediated oxidative
homocoupling of N-phenyl-1-naphthylamine. Key: (a) ESR
spectrum for a system consisting of FeCl3 (1 mmol) and
K2CO3 (1 mmol) in 1,2-dichloroethane (6 mL). (bꢀd) Time-
dependent ESR spectra for the system of FeCl3 (1 mmol) and
K2CO3 (1 mmol) in 1,2-dichloroethane (6 mL) being treated
with N-phenyl-1-naphthylamine (1 mmol): (b) 5 min later; (c)
15 min later; and (d) 60 min later.
We first monitored the ESR spectra in the course of
the oxidative coupling of N-phenyl-1-naphthylamine 1a
(Figure 1). The Fe3þ species in a 1,2-dichloroethane shows
a sharp, strong signal around 3480 G (Figure 1a; relative
(11) Kirchgessner, M.; Sreenath, K.; Gopidas, K. R. J. Org. Chem.
2006, 71, 9849. (b) Sreenath, K.; Suneesh, C. V.; Kumar, V. K. R.;
Gopidas, K. R. J. Org. Chem. 2008, 73, 3245.
4952
Org. Lett., Vol. 13, No. 18, 2011

intensity: 100). Followed by the addition of 1a, the
signal decayed rapidly with time up to almost complete
disappearance (Figure 1bꢀd; relative intensity: 13.2, 8.5
and 1.2, respectively, from Figure 1b to c and d), during
which time no new signal corresponding to organic radical
cations was observed. The ESR spectral facts provided
initial evidence against route A in Scheme 1 as the possible
mechanism of the present oxidative coupling.
Table 3. FeCl3-Catalyzed Oxidative Coupling of 1- and
2-Naphthylamine Derivativesa
Scheme 2
a Conditions: 1- or 2-naphthylamine (1 mmol), FeCl3 (5 mol %),
m-CPBA (1 equiv), DCE (6 mL), room temperature, 1.5 h, in air.
Then, a control experiment for the oxidative coupling of
1a was carried out under the standard conditions as
described above except with the use of additional radical-
trapping agents (Scheme 2). It was found that the addition
of a radical inhibitor, 2,2,6,6-tetramethylpiperidinyl-N-
oxyl (TEMPO), only slowed down the oxidative coupling
(roughly and qualitatively evaluated by TLC) but did not
lead to an obvious decrease in yields. The results also
should rule out the reasonability of the mechanistic path-
way (route A) involving radical cation intermediates.
use of metal-based oxidants would be developed into a
catalytic process. A preliminary attempt was made to use
catalytic amounts of iron(III) chloride associated with other
terminal oxidants to achieve efficient oxidative dimerization
of naphthylamines. After surveying various terminal oxi-
dants including molecular oxygen, BPO (benzoyl peroxide),
DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone), DTBP
(di-tert-butyl peroxide), and m-CPBA (3-chloroperbenzoic
acid), we found that 5 mol % of FeCl3 in conjunction with
1 equiv of m-CPBA in 1,2-dichloroethane at room tempera-
ture served as optimal conditions for the catalytic transfor-
mation (see Tables S1, Supporting Information). Table 3
demonstrates that several naphthylamine substrates can
undergo FeCl3-catalyzed oxidative homocouplings, provid-
ing the desired products in good yields. Work is underway to
apply the catalytic coupling reaction in a wider range of
naphthylamine substrates.
Scheme 3
In conclusion, we have developed a simple, benign, and
efficient protocol for the preparation of naphthidines and
BINAMs by the iron(III)-promoted oxidative coupling of
naphtylamine derivatives, and further, a catalytic version
of the transformation has been explored. The method is
expected to have broad applications in synthetic studies
and material synthesis. Additionally, a possible mecha-
nism for this reaction was clarified preliminarily, from
which some interesting newsubjects of researcheswould be
derived.
Further, we probed for the possible intermediacy of
naphthyl iron by studying a reaction of aldehydes with
N-phenyl-1-naphthylamine 1a in THF at room temperature
in the presence of FeCl3 (Scheme 3). In the designed reaction,
reactant 1a was consumed, the homocoupled product 2a
was obtained in considerable yields, and larger quantities of
other unidentified byproducts were produced. Nevertheless,
we indeed separated a class of products, resulting from the
reaction between aldehydes and organometallic specie, with
appreciable amounts, showing the possibility that organoir-
on species like the intermediate V in Scheme 1 occurred in
the reaction. The results implied that the FeCl3-promoted
oxidative coupling proceeded more likely via a pathway
involving the naphthyl iron intermediate (route B) rather
than the free-radical species (route A).
Acknowledgment. We thank National Natural Science
Foundation of China (Project No. 20872142) for financial
support of this work.
Supporting Information Available. Experimental pro-
cedures and characterization data for the compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
From the standpoint of synthetic studies, it is a necessary
task that such a transformation involving the stoichiometric
Org. Lett., Vol. 13, No. 18, 2011
4953