Iron-catalyzed regioselective direct oxidative aryl-aryl cross-coupling

Article abstract of DOI:10.1021/jo202152b

Regioselective iron-catalyzed cross-dehydrogenative coupling (CDC) of two aromatic compounds using tert-BuOOH as oxidant under mild conditions has been reported. The direct oxidative coupling reaction is selective toward creation of a carbon-carbon bond at the position ortho to the functional groups of the substrates, completely preventing the homocoupled products. The C-C bond-forming reaction makes the method versatile, leading to functionalized 2,2′-disubstituted biaryls (Figure presented).

Full text of DOI:10.1021/jo202152b

Article
pubs.acs.org/joc
Iron-Catalyzed Regioselective Direct Oxidative Aryl−Aryl Cross-
Coupling
Malapaka Chandrasekharam,*,† Barreddi Chiranjeevi,† Kankatala S. V. Gupta,† and B. Sridhar‡
‡
†I&PC Division and Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Uppal Road, Tarnaka,
Hyderabad-500 607, India
S
* Supporting Information
ABSTRACT: Regioselective iron-catalyzed cross-dehydrogenative
coupling (CDC) of two aromatic compounds using tert-BuOOH as
oxidant under mild conditions has been reported. The direct
oxidative coupling reaction is selective toward creation of a carbon−
carbon bond at the position ortho to the functional groups of the
substrates, completely preventing the homocoupled products. The
C−C bond-forming reaction makes the method versatile, leading to
functionalized 2,2′ -disubstituted biaryls.
synthesis of tetrasubstituted 1,1′-binaphthyls has been reported
without preactivation of either of the coupling partners.8
Subsequently the reaction has been further explored using iron-
catalyzed cross-coupling as well.9
INTRODUCTION
■
Development of novel methods toward the formation of C−C
bonds is an important issue in the area of organic chemistry
research, and C−C bond-formation reactions leading to
dimerizations by self-coupling or cross-dehydrogenative cou-
plings have been thoroughly investigated. Several stoichio-
metric as well as catalytic versions of transition-metal-mediated
conversions are known to effect this fundamental reaction.
Among various types of C−C bond-formation reactions, aryl−
aryl bond formation is one of the most important tools in
organic synthesis owing to the occurrence of biaryl building
blocks in several biologically active molecules and functional
materials such as light-emitting diodes, electron transport
devices, liquid crystals, etc.1 Despite the availability of several
literature methods, selective cross-dehydrogenative coupling
(CDC) is still a challenge in organic chemistry for the
construction of a C−C bond without using prefunctionalized
substrates.2 Although transition-metal-catalyzed aryl−aryl cross-
coupling reactions have been known over the past few decades,
the mild and selective Suzuki coupling involving preactivation
of both coupling partners has almost completely replaced
classical methods of biaryl synthesis.3 Such a preactivation
needs inclusion of few more steps and hence serious efforts
have been made in the past decade, wherein one of two
coupling partners is preactivated while the second one is
subjected to direct coupling.4 In search of better alternatives,
increased attention is being further focused on direct arylation
processes that replace both of the preactivated substrates of the
cross-coupling partners with the simple arene itself.5 Although
several reports have been published on homocoupling of either
phenols/naphthols6 or aniline7 derivatives, to the best of our
knowledge generalized methods for the regioselective cross-
coupling of their unactivated analogues leading to functional-
ized biaryls under practical catalytic conditions are very rare. In
this regard, a copper-catalyzed selective cross-coupling of
various substituted 2-naphthols and 2-naphthylamines for the
In recent years iron, known to be a “cheap metal for noble
task”, has been extensively exploited in organic transformations
because of its inexpensive, nontoxic, and environmentally
benign characters.10,11 Sarhan and Bolm, in their excellent
recent article critically reviewed the use of iron(III) chloride in
oxidative C−C coupling of arenes and related unsaturated
compounds leading to highly selective dimerizations of phenol
derivatives, naphthols, and heterocyclic compounds.12 Although
the iron-catalyzed formation of C−C13and C−heteroatom
bonds14 has been developed recently, the direct formation of
C−C bonds without preactivation of the substrates especially
with control over chemo-, regio-, and stereoselectivity appears
to be a challenge.
In continuation of our program on various C−C and C−N
bond-forming reactions,15 we found that the regioselective
formation of biaryls by iron-catalyzed direct oxidative cross-
coupling is very interesting to explore, and in this article we
present a CDC reaction of various substituted N,N-dialkylani-
lines with 2-naphthol/1-naphthol under different catalytic and
solvent conditions.
RESULTS AND DISCUSSION
■
We discovered that stirring a toluene solution of equimolar
quantities of the N,N-dimethylaniline and 2-naphthol in
FeCl3·6H2O (20 mol %) and TBHP (2.0 equiv) for 4−5 h at
0 °C to room temperature under aerial conditions resulted in
the formation of cross-coupling product (Scheme 1). The
reaction proceeded with high regioselectivity under mild
conditions. Our Initial studies using variety of Lewis acid
Received: October 18, 2011
Published: November 9, 2011
© 2011 American Chemical Society
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benzoyl peroxide proved to be the second best in terms of yield
(Table 1, entry 19). Influence of solvents was also tested by
screening the reaction with several nonpolar (hydrocarbon)
and polar solvents (Table 1, entries 20−27), the latter
suppressed the yields drastically and led to the formation of
trace amounts of self-coupled products as well. Temperature
also played a crucial role in the formation of desired products.
When the reaction was performed at room temperature, few
unseparable complex mixtures of products were produced,
thereby diminishing the product yield. This problem was
circumvented by initially carrying out the reaction at 0 °C and
gradually allowing it to come to room temperature, thereby
reducing the formation of undesirable byproducts to a
considerable extent. In the course of the above reaction,
absence of either Fe(III) catalyst or TBHP rendered the
transformation unsuccessful, indicating that both catalyst and
oxidant were essential for the reaction to proceed. Loading 20%
of the catalyst proved to be optimal for the reaction and
brought about the best outcome.
Scheme 1
catalysts for the coupling reaction of N,N-dimethyl p-toluidine
(DMT) and 2-naphthol in the presence of TBHP revealed that
copper, nickel, and other iron salts (Table 1, entries 2−8) were
ineffective in giving desired product, whereas Pd(OAc)2
afforded the product albeit in low yields (Table 1, entry 1).
The cross-coupling reaction with AlCl3 as catalyst also worked
and gave good yields of the product next to FeCl3 (Table 1,
entry 9). TBHP was identified as the best-suited oxidant, while
other oxidants turned out to be unreactive or failed to produce
the desired outcome (Table 1, entries 11−15), except for
K2S2O8, which produced moderate yields of the coupling
product (Table 1, entry 18). Oxidants such as H2O2 and DTBP
found to be unreactive even after prolonged reaction times
(Table 1, entries 16 and 17). The stoichiometric oxidant
Further, oxygen did not play any significant role in the
reaction course, as not much difference was observed in yields
when operated under the absence of oxygen. With these
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst (20 mol %)
oxidant (2 equiv)
solvent
time
24 h
yield (%)
c
1
Pd(OAc)2
TBHP
TBHP
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMSO
AcOH
<10
0
2
CuCl
30 min
30 min
30 min
90 min
5 h
3
CuBr
TBHP
0
4
Cul
TBHP
0
5
NiCl2
TBHP
traces
traces
traces
traces
60
6
Fe2(SO4)3·9H2O
NH4Fe(SO4)2·12H2O
NH4FeCl4·6H2O
AlCl3
TBHP
7
TBHP
5 h
8
TBHP
5 h
9
TBHP
5 h
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
TBHP
5 h
67
PhI(OAc)2
m-CPBA
O2
45 min
30 min
12 h
0
0
0
NBS
5 h
NR
NR
NR
NR
20
DDQ
24 h
H2O2 (30% aq)
DTBP
24 h
overnight
60 min
2 h
K2S2O8
(C6H5CO)2O
TBHP
40
60 min
30 min
2 h
0
TBHP
0
TBHP
CH2Cl2
THF
30
TBHP
2 h
29
TBHP
DME
2 h
22
TBHP
Et2O
2 h
46
TBHP
CH3CN
benzene
30 min
90 min
59
TBHP
60
a
All reactions were carried out with 0.4 mmol of 1a and 0.4 mmol of 2-naphthol. NR = no reaction. DTBP = di-tert-butyl peroxide, NBS = N-bromo
b
succinimide. DME = 1,2-dimethoxyethane, DDQ= 2,3-dichloro-5,6-dicyano-p-benzoquinone. TBHP used in all cases is 70% aq solution. Isolated
yields. Only 50% of the starting materials were consumed.
c
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a
Table 2. Substrate Scope
a
Substituted N-alkyl aniline (1 equiv), 2-naphthol (1 equiv), TBHP (2 equiv), and [Fe] (20 mol %); otherwise are mentioned. Reported yields are
based on N-alkyl aniline. NR = no reaction. (*) 12 h reaction.
optimal conditions in hand, reactions of various substituted
N,N-dialkylaniline derivatives with 2-naphthol were examined
for the generation of biaryls, and the results obtained are listed
in Table 2. Alkyl-substituted anilines 1a−6a afforded good
yields (Table 2, entries 1−6). Interestingly, in contrary to our
expectations, electron-donating alkoxy-substituted anilines
show a reduction in yield, which can be attributed to the
interference of oxygen that might have dampened their
reactivity (Table 2, entries 11, 19). 2-Substituted aniline 12a
failed to produce the biaryl product, indicating that the
presence of the ortho C−H is vital for the coupling reaction to
proceed. The steric factors also played a role in the reaction
course as 3,4-dimethylaniline derivative 3a participated in CDC
reaction at the less crowded 6-position (Table 2, entry-3), as
opposed to the 2-position, and 3,4,5-trimethoxyaniline 13a
derivative failed to react presumably due to steric hindrance.
Fluoro-, chloro-, bromo-, and iodo-substituted anilines were
tolerated in the reaction course (Table 2, entries 7−10),
thereby allowing room for further modifications at these
halogenated positions. The electron-withdrawing fluoro- and
bulky iodo-substituted aniline derivatives 7a and 10a delivered
lower yields of the coupling products 7b and 10b, respectively.
In the case of 4-cyano N,N-dimethylaniline 14a, drastically
reduced yield of the product (Table 2, entry 14) was observed,
while other electron-withdrawing moieties at the 4-position of
the N,N-dialkyl-substituted aniline such as p-nitro- and p-
trifluoromethyl N,N-dimethylanilines 15a and 16a completely
prevented the reaction from proceeding (Table 2, entries 15
and 16) due to decreased electron density of the phenyl ring. In
general it is noticed that electron-donating alkyl groups on the
aniline ring lower the Eox value and allow easy oxidation of the
substrate, giving higher yields compared to the substrates with
electron-withdrawing groups. 3-Substituted aniline derivatives
such as m-methoxy- and m-chloroanilines failed to produce the
cross-coupling product (not shown). The overall yields of the
reactions are in the range of 45−67%, and in most of the
reactions, the starting aniline is completely consumed and part
of the aniline is converted into unidentifiable complex mixture,
whereas the unreacted 2-naphthol is recovered in all the cases.
In order to gain insights into the effect of different N-
substitutions such as N-allyl and N-benzyl groups on the
reaction course, substrates 17a and 18a (Table 2, entries 17,
18) were also examined for the desired transformation under
similar conditions and produced 17b and 18b, respectively.
However, an attempt to extend the scope of the reaction to
hetero aromatic compound, N,N-dimethylamino pyridine met
with a failure (not shown). N-Methyl aniline and aniline also
failed to give the cross-coupling product with 2-naphthol under
these reaction conditions presumably because of their higher
E
ox values of 1053 and 1135 mV, respectively,16 thus making it
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difficult for the substrate to generate easily the radical cation by
oxidation. The structures of all the new compounds were
confirmed by IR, 1H NMR, 13C NMR, and HRMS. The
regioselectivity of the coupling presumably arising from
hydrogen bonding between amino and hydroxyl groups was
unambiguously established from the single crystal X-ray studies
carried out on the cross-coupled product 1b.
Scheme 3. Proposed Reaction Pathway for the Oxidative
Coupling Reaction
To broaden the scope of the oxidative direct cross coupling
reaction, 1-naphthol was used in place of 2-naphthol, and it was
found that the desired product 20b was formed in good yield
(Scheme 2).
Scheme 2
FeCl3 is regenerated by the reaction of the reduced catalyst
with the oxidant TBHP. Finally we conclude that sufficiently
different oxidation potentials (difference 440 mV) of the two
coupling partners favors the cross-coupled product and that the
lower oxidation potential (Eox) of DMT (500 mV) compared to
that of 2-naphthol (940 mV) supports initial ready oxidation of
DMT to form the corresponding radical cation.20
In our hands simple phenols were found to be inert under
the reaction conditions. Oxidation at sp3 carbon on the
nitrogen of the substituted aniline was also envisioned;
however, no product resulting from such reaction was observed
in this case, proving this reaction to be chemoselective.17
To establish the mechanistic evidence for the FeCl3·6H2O-
catalyzed direct oxidative cross-coupling reaction, the ESR
spectrum of the reaction mixture was measured while the
reaction was under progress (Figure 1). Initially no radical was
CONCLUSION
■
In summary a promising protocol for a CDC coupling of N,N-
dimethylanilines with 2-naphthol/1- naphthol has been
established using an inexpensive catalyst oxidant Fe(III)/tert-
BuOOH system under mild conditions. The coupling reactions
are not sensitive to moisture or air and produced a variety of
dialkyl amino- and hydroxy-substituted biaryls. The reaction
was observed to be chemo- and regioselective, preventing the
formation of any of the homocoupled biaryls. This is a C−C
bond-forming reaction that is synthetically important for the
generation of functionalized biaryls, and further the aryl
substrates are not subjected to prefunctionalization and
defunctionalization or use of organometallic reagents. Interest-
ingly AlCl3 also promoted the cross-coupling reaction with
good catalytic activity, and detailed studies on the mechanism
and substrate scope of the AlCl3-catalyzed cross-coupling
reaction of aryl amines with naphthols need further
investigation.
EXPERIMENTAL SECTION
■
Figure 1. ESR spectrum of FeCl3·6H2O-catalyzed oxidative coupling
of N,N-dimethyl toluidine and 2-naphthol.
General Considerations. All commercially available chemicals
were used as received, and FeCl3·6H2O (Purity 97%) was purchased
from Sigma Aldrich. Thin-layer chromatography plates were visualized
by exposure to UV light/iodine and/or by immersion in an acidic
staining solution of phosphomolybdic acid followed by heating on a
detected when measured at room temperature, and hence the
reaction mixture was then cooled to −146 °C. The above figure
shows the sharp signal observed at g = 2.01595, which is
assigned to the radical species generated from 1a.18
We propose the following tentative radical mechanism for
the iron-catalyzed formation of cross-coupled products
(Scheme 3).19 Initial one electron transfer from N,N-dialkyl
aniline to FeCl3 gives rise to reduced form (Fe2+) and a radical
cationic species A. Subsequently the C−C bond is created by
electrophilic attack of 2-naphthol on the radical cationic species
at the ortho position. Finally dehydroaromatization of B takes
place by losing one electron to form the cross-coupled product.
1
hot plate. H and 13C NMR spectra were obtained on 300 and 500
MHz spectrometers with tetramethylsilane and chloroform-d1,
respectively, as the internal standard. Chemical shifts (δ) are reported
in ppm relative to the residual solvent signal (δ = 7.26 for H NMR
1
and δ = 77.0 for 13C NMR). Data for 1H NMR are reported as follows:
chemical shift (multiplicity, coupling constant, number of hydrogens).
Multiplicity is abbreviated as follows: s (singlet), d (doublet), dd
(double doublet), t (triplet), q (quartet), m (multiplet). IR samples
were analyzed as thin films on KBr plates. CAUTION: Mixing a metal
salt and peroxide can cause explosion.21 However in our experiments,
we did not encounter this problem.
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General Procedure for CDC Reaction of N,N-Dialkylaniline
Derivatives with 2-Naphthol. A 10-mL round bottomed flask was
charged with N,N-dialkylaniline (1.0 mmol), 2-naphthol (1.0 mmol),
and toluene (2 mL). The resulting mixture was kept at 0 °C, and
FeCl3·6H2O (20 mol %) and TBHP were added via syringe dropwise
under atmospheric air. Then the resulting solution was allowed to stir
at room temperature for 4−5 h. The reaction mixture obtained was
then Celite filtered and washed with ethyl acetate and water. The
combined organic layers were dried over Na2SO4, and solvent was
evaporated under reduced pressure. The crude product was purified by
column chromatography (100−200 mesh/60−120 mesh) using
hexane−ethyl acetate as eluent to give the product.
3H); 13C NMR (300 MHz, CDCl3, ppm): δ 153.8, 148.9, 137, 134.5,
130.1, 129.5, 128.5, 127.6, 126.7, 126.2, 123.2, 117.9, 116.1, 112, 109.4,
41.7, 20.1, 18.6; FTIR (cm−1): 2923, 2852, 1611, 1507, 1459, 1369,
1231, 815, 751, 408; MS (ESI) m/z: 292(M + H)+; HRMS (ESI)
calcd for C20H21NO (M + H)+: 292.1701; found: 292.1706.
1-(2-(Dimethylamino)-5-ethylphenyl)naphthalen-2-ol (4b). Iso-
lated by column chromatography (ethyl acetate−hexane = 1:9, Rf =
1
0.6). The title compound was obtained as brownish solid. H NMR
(300 MHz, CDCl3, ppm): δ 7.78−7.72 (m, 3H), 7.33−7.28 (m, 2H),
7.23−7.18(m, 3H), 7.15−7.14(m, 1H), 2.69(s, 6H), 2.66−2.61 (m,
2H), 1.24−1.18 (m, 3H); 13C NMR (300 MHz, CDCl3, ppm): δ
152.2, 141.3, 137.8, 133.4, 132.3, 130.8, 129, 128.4, 127.8, 126.8, 122.9,
122.4, 119.3, 117.3, 41, 28.9, 14.2; FTIR (cm−1): 3435, 2959, 2926,
2855, 1737, 1625, 1503, 1459, 1346, 1272, 1120, 1082, 965, 893, 821,
750, 699, 551; MS (ESI) m/z: 292(M + H)+; HRMS (ESI) calcd for
C20H21NO (M + H)+: 292.1701; found: 292.1706.
General Procedure for the Formation of N,N-Dimethylani-
line Derivatives from Various Substituted Anilines. Forma-
tion of (4-Methoxy-phenyl)-dimethylamine (11a). To a purple
solution of 4-methoxyaniline (1.02 g, 8.28 mmol) in glacial acetic
acid (50 mL) under Ar(g) were added paraformaldehyde (2.44 g, 81.3
mmol) and sodium cyanoborohydride (2.46 g, 39.1 mmol). The
addition of sodium cyanoborohydride caused vigorous bubbling. After
stirring overnight, the reaction mixture was poured into a water−ice
mixture (∼100 mL) containing NaOH (40 g). The addition was
exothermic, and more ice was added to bring the total volume of the
quench mixture to ∼300 mL. This mixture (pH = 14) was extracted
with CH2Cl2 (350 mL). The combined organic layers were dried over
MgSO4(s), filtered, and concentrated under reduced pressure to
obtain a purple solid. Flash chromatographic purification of the crude
product provided a colorless solid (1.06 g, 7.01 mmol, 85%).
General Procedure for CDC Reaction of (4-Methoxy-
phenyl)-dimethylamine with 1-Naphthol. To an oven-dried 10-
mL two neck round bottomed flask equipped with a magnetic stir bar
were added 0.151 g (1.0 mmol, 1 equiv) of (4-methoxy-phenyl)-
dimethylamine and toluene (1.5 mL). The solution was kept in a dark
place, and 0.144 g (1.0 mmol, 1equiv) of 1-naphthol was added under
nitrogen atmosphere. The resulting solution was then kept at 0 °C,
and 0.030 g (20 mol %) of FeCl3·6H2O and 0.085 mL (2.0 mmol,
2equiv) of TBHP were added via syringe dropwise under nitrogen
atmosphere. The resulting solution was allowed to stir at 0 °C for 1 h.
The reaction mixture was then Celite filtered and washed with ethyl
acetate and water. The combined organic layers were dried over
Na2SO4, and solvent was evaporated under reduced pressure. The
crude product was purified by column chromatography (100−200
mesh/60−120 mesh) using hexane−ethyl acetate as eluent to give the
product 20b.
1-(2-(Dimethylamino)-5-isopropylphenyl)naphthalen-2-ol (5b).
Isolated by column chromatography (ethyl acetate−hexane = 1:9, Rf =
1
0.5). The title compound was obtained as reddish brown solid. H
NMR (500 MHz, CDCl3, ppm): δ 7.82−7.77 (m, 3H), 7.37−7.31 (m,
2H), 7.28−7.25 (m, 3H), 7.20−7.19 (m, 1H), 2.91−2.86(m, 1H), 2.67
(s, 6H), 1.24−1.22 (m, 6H); 13C NMR (300 MHz, CDCl3, ppm): δ
152.1, 147.7, 143.3, 133.5, 130.5, 129.9, 129.2, 128.1, 126.2, 125.9,
125.3, 122.9, 121.3, 120.7, 117.9, 43.6, 33.4, 23.9; FTIR (cm−1): 3418,
3051, 2959, 2925, 2870, 2797, 1666, 1613, 1588, 1496, 1461, 1390,
1361, 1332, 1302, 1268, 1228, 1182, 1137, 1093, 1042, 954, 926, 899,
819, 753, 683, 615, 570, 506, 474, 431; MS (ESI) m/z: 306(M + H)+;
HRMS (ESI) calcd for C21H23NO (M + H)+: 306.1857; found:
306.1850.
1-(5-tert-Butyl-2-(dimethylamino)phenyl)naphthalen-2-ol (6b).
Isolated by column chromatography (ethyl acetate−hexane = 1:9, Rf =
1
0.6). The title compound was obtained as pale yellowish solid. H
NMR (300 MHz, CDCl3, ppm): δ 7.84−7.77 (m, 3H), 7.44−7.25 (m,
5H), 7.21−7.18 (m, 1H), 2.67 (s, 6H), 1.29 (s, 9H); 13C NMR (300
MHz, CDCl3, ppm): δ 152.2, 147.4, 145.5, 133.5, 132.8, 130, 129.9,
129.2, 128.1, 125.9, 125.3, 125, 123, 121.4, 120.6, 117.6, 43.6, 34.3,
31.3; FTIR (cm−1): 3421, 3054, 2954, 2866, 1903, 1732, 1588, 1501,
1463, 1400, 1355, 1263, 1229, 1193, 1147, 1088, 1037, 925, 864, 819,
748, 680, 622, 566; MS (ESI) m/z: 320(M + H)+; HRMS (ESI) calcd
for C22H25NO (M + H)+: 320.2014; found: 320.2010.
1-(2-(Dimethylamino)-5-fluorophenyl)naphthalen-2-ol (7b). Iso-
lated by column chromatography (ethyl acetate−hexane = 1:9, Rf =
1
0.3). The title compound was obtained as brownish viscous liquid. H
1-(2-(Dimethylamino)-5-methylphenyl)naphthalen-2-ol (1b).
Isolated by column chromatography (ethyl acetate−hexane = 1:9, Rf
NMR (300 MHz, CDCl3, ppm): δ 7.84−7.77 (m, 3H), 7.43−7.28 (m,
3H), 7.23−7.07 (m, 3H), 2.67 (s, 6H); 13C NMR (300 MHz, CDCl3,
ppm): δ 152.3, 146.3, 146.24, 146.20, 133.2, 130, 128.4, 126.6, 124.9,
123.5, 121.9, 120.9, 119.7, 119.4, 115.2, 114.8, 44; FTIR (cm−1): 3431,
3060, 2923, 2851, 2796, 1735, 1616, 1595, 1493, 1461, 1410, 1360,
1337, 1273, 1231, 1171, 1148, 1089, 1042, 1009, 959, 929, 889, 817,
751, 676, 637, 601, 568, 541, 478, 432; MS (ESI) m/z: 282(M + H)+ ;
HRMS (ESI) calcd for C18H16NOF (M + H)+: 282.1294; found:
282.1284.
1-(5-Chloro-2-(dimethylamino)phenyl)naphthalen-2-ol (8b).
Isolated by column chromatography (ethyl acetate−hexane = 1:9, Rf
= 0.4). The title compound was obtained as brownish yellow solid. 1H
NMR (300 MHz, CDCl3, ppm): δ 7.78−7.69 (m, 3H), 7.40−7.28 (m,
4H), 7.21−7.13 (dd, J = 16.1 Hz, 2H), 2.68 (s, 6H); 13C NMR (300
MHz, CDCl3, ppm): δ 152, 148.6, 134.6, 132.9, 132.3, 129.8, 128.2,
128, 126.5, 124.8, 123.3, 120.5, 119.7, 119.4, 43.5; FTIR (cm−1): 3048,
2925, 2740, 1730, 1663, 1622, 1591, 1482, 1400, 1339, 1270, 1234,
1149, 1114, 1038, 991, 952, 924, 888, 853, 817, 746, 718, 633, 586,
540, 513; MS (ESI) m/z: 298(M + H)+; HRMS (ESI) calcd for
C18H16NOCl (M + H)+: 298.0998; found: 298.0994.
1
= 0.7). The title compound was obtained as colorless solid. H NMR
(300 MHz, CDCl3, ppm): δ 7.83−7.75 (m, 3H), 7.39−7.14 (m, 6H),
2.65 (s, 6H), 2.31 (s, 3H); 13C NMR (300 MHz, CDCl3, ppm): δ
152.1, 147.5, 135.7, 133.3, 132.4, 130.4, 129.9, 129.2, 128.9, 128.1,
125.9, 125.3, 123, 121.1, 120.7, 117.9, 43.7, 20.6; FTIR (cm−1): 3034,
2922, 2743, 1727, 1658, 1620, 1587, 1501, 1460, 1430, 1403, 1341,
1273, 1233, 1179, 1151, 1113, 1036, 986, 956, 925, 892, 819, 747, 633,
585, 544, 472; MS (ESI) m/z: 278(M + H)+; HRMS (ESI) calcd for
C19H19NO (M + H)+: 278.1544; found: 278.1548.
1-(2-(Dimethylamino)phenyl)naphthalen-2-ol (2b). Isolated by
column chromatography (ethyl acetate−hexane = 1:9, Rf = 0.6). The
1
title compound was obtained as yellow solid. H NMR (300 MHz,
CDCl3, ppm): δ 7.77−7.71 (m, 3H), 7.39−7.26 (m, 4H), 7.22−7.19
(m, 2H), 7.14−7.09 (m, 1H), 2.69 (s, 6H); 13C NMR (300 MHz,
CDCl3, ppm): δ 152, 149.9, 135.3, 133.3, 130.6, 129.9, 129.3, 128.4,
128.1, 126, 125.3, 123, 122.9, 120.9, 120.6, 118, 43.5; FTIR (cm‑1):
3418, 3016, 2920, 2865, 2792, 1927, 1736, 1589, 1459, 1401, 1365,
1330, 1298, 1234, 1202, 1149, 1117, 1091, 1038, 981, 922, 819, 752,
669, 621, 554; MS (ESI) m/z: 264(M + H)+; HRMS (ESI) calcd for
C18H17NO (M + H)+: 264.1388; found: 264.1376.
1-(5-Bromo-2-(dimethylamino)phenyl)naphthalen-2-ol (9b).
Isolated by column chromatography (ethyl acetate−hexane = 1:9, Rf
1
= 0.5). The title compound was obtained as reddish sticky solid. H
1-(2-(Dimethylamino)-4,5-dimethylphenyl)naphthalen-2-ol
(3b). Isolated by column chromatography (ethyl acetate−hexane =
1:9, Rf = 0.6). The title compound was obtained as brownish viscous
NMR (300 MHz, CDCl3, ppm): δ 7.77−7.69 (m, 4H), 7.42−7.18 (m,
4H), 7.08−7.06 (m, 1H), 2.65 (s, 6H); 13C NMR (300 MHz, CDCl3,
ppm): δ 152.1, 149.2, 137.6, 133, 132.7, 131.2, 129.97, 129.93, 129.3,
128.3, 126.7, 124.7, 123.4, 120.5, 119.7, 96.2, 43.5; FTIR (cm−1):
1
liquid. H NMR (300 MHz, CDCl3, ppm): δ 7.76−7.68 (m, 3H),
7.33−7.13 (m, 4H), 6.97 (s, 1H), 2.66 (s, 6H), 2.34 (s, 3H), 2.22 (s,
10233
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Article
3422, 3062, 2924, 2853, 1663, 1620, 1594, 1506, 1463, 1399, 1343,
1310, 1271, 1215, 1167, 1030, 949, 815, 751, 515; MS (ESI) m/z:
342(M + H)+, 344(M + 2 + H)+; HRMS (ESI) calcd for C18H16NOBr
(M + H)+: 342.0493; found: 342.0501.
958, 870, 817, 752, 611; MS (ESI) m/z: 320(M + H)+; HRMS (ESI)
calcd for C21H21NO2 (M + H)+: 320.1650; found: 320.1645.
2-(2-(Dimethylamino)-5-methoxyphenyl)naphthalen-1-ol
(20b). Isolated by column chromatography (ethyl acetate−hexane =
1:9, Rf = 0.8). The title compound was obtained as red suspension. 1H
NMR (300 MHz, CDCl3, ppm): δ 8.40−8.38 (m, 1H), 7.73−7.72 (m,
1H), 7.45−7.37 (m, 4H), 7.13−7.11 (m, 1H), 6.98−6.97 (m, 1H),
6.86−6.84 (m, 1H), 3.76 (s, 3H), 2.62 (s, 6H); 13C NMR (300 MHz,
CDCl3, ppm): δ 156.4, 151.7, 141.6, 136.5, 134.3, 128.5, 127, 126.9,
126.4, 125, 123.7, 120.4, 119.6, 119.2, 118.7, 113.2, 55.6, 43.9; FTIR
(cm−1): 3449, 3054, 2924, 2853, 1736, 1660, 1603, 1576, 1509, 1460,
1378, 1333, 1289, 1247, 1177, 1091, 1040, 935, 870, 810, 755, 720,
676, 581, 533, 477, 430; MS (ESI) m/z: 294(M + H)+.
1-(2-(Dimethylamino)-5-iodophenyl)naphthalen-2-ol (10b). Iso-
lated by column chromatography (ethyl acetate−hexane = 1:9, Rf =
1
0.6). The title compound was obtained as brownish solid. H NMR
(300 MHz, CDCl3, ppm): δ 7.77−7.65 (m, 4H), 7.41−7.17 (m, 4H),
6.97−6.93 (m, 1H), 2.66 (s, 6H); 13C NMR (300 MHz, CDCl3, ppm):
δ 152.1, 150, 143.5, 137.2, 133.1, 132.9, 129.9, 128.3, 126.7, 124.8,
123.4, 120.5, 120, 119.5, 96.3, 86.4, 43.4; FTIR (cm−1): 3422, 2924,
2853, 1741, 1593, 1461, 1356, 1230, 1156, 1099, 930, 816, 750, 557;
MS (ESI) m/z: 390(M + H)+; HRMS (ESI) calcd for C18H16NOI (M
+ H)+: 390.0354; found: 390.0339.
ASSOCIATED CONTENT
1-(2-(Dimethylamino)-5-methoxyphenyl)naphthalen-2-ol
■
(11b). Isolated by column chromatography (ethyl acetate−hexane =
S
* Supporting Information
1
1:9, Rf = 0.4). The title compound was obtained as brownish solid. H
1
IR, H and 13CNMR, HRMS data for all new compounds and
NMR (500 MHz, CDCl3, ppm): δ 7.79−7.71 (m, 3H), 7.33−7.24 (m,
2H), 7.21−7.19 (d, J = 8.76 Hz, 1H), 7.14−7.13 (d, J = 8.76 Hz, 1H),
6.92−6.89 (m, 2H), 3.73 (s, 3H), 2.65 (s, 6H); 13C NMR (300 MHz,
CDCl3, ppm): δ 155, 152.2, 143.4, 133.3, 132.1, 129.8, 129.4, 128.1,
126, 125.2, 123, 120.8, 120.7, 119.9, 119, 114, 55.6, 43.9; FTIR
(cm−1): 3418, 2924, 2855, 1744, 1596, 1500, 1459, 1335, 1237, 1164,
1035, 920, 869, 815, 748, 606, 541; MS (ESI) m/z: 294(M + H)+;
HRMS (ESI) calcd for C19H19NO2(M + H)+: 294.1494; found:
294.1504.
CIF file of 1b. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: chandra@iict.res.in.
■
ACKNOWLEDGMENTS
4-(Dimethylamino)-3-(2-hydroxynaphthalen-1-yl)benzonitrile
■
(14b). Isolated by column chromatography (ethyl acetate−hexane =
B.C. and K.S.V.G. thank CSIR and UGC New Delhi,
respectively, for Junior Research Fellowships. The authors
thank CIL, HCU for providing ESR measurements. This article
is dedicated to Professor H. Junjuppa on the eve of his 75th
birthday.
1
3:7, Rf = 0.4). The title compound was obtained as brownish solid. H
NMR (300 MHz, CDCl3, ppm): δ 8.11−8.08 (m, 1H), 7.79−7.76 (m,
2H), 7.56−7.53 (m, 1H), 7.45−7.31 (m, 3H), 7.21 (s, 1H), 7.18 (s,
1H), 2.71 (s, 6H); 13C NMR (300 MHz, CDCl3, ppm): δ 153.8, 151.5,
138.9, 133.7, 132.4, 130.4, 130.1, 129.8, 129.4, 128.4, 127, 124.4, 123.7,
119.8, 118.5, 43; FTIR (cm−1): 3418, 3062, 2924, 2855, 2219, 1696,
1597, 1507, 1457, 1344, 1275, 1224, 1135, 953, 817, 749, 715, 606,
606, 548; MS (ESI) m/z: 289(M + H)+; HRMS (ESI) calcd for
C19H16N2O (M + H)+: 289.1340; found: 289.1353.
REFERENCES
■
(1) (a) Hassan, J.; Sevignon, M.; Gojji, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 1359. (b) Alberico, D.; Scott, M. E.; Lautens, M.
Chem. Rev. 2007, 107, 174.
1-(2-(Benzyl(methyl)amino)phenyl)naphthalen-2-ol (17b). Iso-
lated by column chromatography (ethyl acetate−hexane =1:9, Rf =
(2) (a) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009, 38,
2447. (b) Li, C.-J. Acc. Chem. Res. 2009, 42, 335. (c) Li, Z.; Bohle, D.
S.; Li, C.-J. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 8928. (d) Li, Z.; Li,
C.-J. J. Am. Chem. Soc. 2005, 127, 3672. (e) Li, Z.; Li, C.-J. J. Am.
Chem. Soc. 2005, 127, 6968. (f) Li, B.-J.; Tian, S.-L.; Fang, Z.; Shi, Z.-J.
Angew. Chem., Int. Ed. 2008, 47, 1115. (g) Li, Y.-Z.; Li, B.-J.; Lu, X.-Y.;
Lin, S.; Shi, Z.-J. Angew. Chem., Int. Ed. 2009, 48, 3817. (h) Wei, Y.; Su,
W. J. Am. Chem. Soc. 2010, 132, 16377. (i) Li, H.; Liu, J.; Sun, C.-L.;
Li, B.-J.; Shi, Z.-J. Org. Lett. 2011, 13, 276.
(3) Suzuki couplings: (a) Nguyen, H. N.; Huang, X.; Buchwald, S. L.
J. Am. Chem. Soc. 2003, 125, 11818. (b) Bermejo, A.; Ros, R.;
Fernandez, R.; Lassaletta, J. M. J. Am. Chem. Soc. 2008, 130, 15798.
(c) Lipshutz, B. H.; Petersen, T. B.; Abela, A. R. J. Am. Chem. Soc.
2008, 10, 1333.
(4) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am.
Chem. Soc. 2003, 125, 1698. (b) Chen, X.; oodhue, C. E.; Yu, J. Q. J.
Am. Chem. Soc. 2006, 128, 12634. (c) Giri, R.; Maugel, N.; Li, J. J.;
Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am. Chem.
Soc. 2007, 129, 3510. (d) Shi, Z.; Li, B.; Wan, X.; Cheng, J.; Fang, Z.;
Cao, B.; Qin, C.; Wang, Y. Angew. Chem., Int. Ed. 2007, 46, 5554.
(e) Sun, C.-L.; Liu, N.; Li, B.-J.; Yu, D.-G.; Wang, Y.; Shi, Z.-J. Org.
Lett. 2010, 12, 184. (f) Chu, J.-H.; Chen, C.-C.; Wu, M. J.
Organometallics 2008, 27, 5173. (g) Sun, C.-L.; Li, B.-J.; Shi, Z.-J.
Chem. Commun. 2010, 46, 677.
1
0.7). The title compound was obtained as brownish solid. H NMR
(300 MHz, CDCl3, ppm): δ 7.78−7.74 (m, 3H), 7.43−7.33 (m, 4H),
7.28−7.27 (m, 1H), 7.19−7.18 (m, 5H), 6.94−6.93 (m, 2H), 3.92−
3.85 (m, 2H), 2.64 (s, 3H); 13C NMR (300 MHz, CDCl3, ppm): δ
153.3, 134.5, 130.9, 129.7, 129.2, 129, 128.8, 128.7, 128.6, 127.7, 127.2,
126.7, 126.4, 126.2, 123.5, 123.1, 123, 119.6, 117.9, 117.7, 112.9, 109.4,
59.5, 39.9; FTIR (cm−1): 3420, 3059, 2923, 2853, 1735, 1595, 1494,
1455, 1366, 1223, 1166, 1079, 816, 752, 698, 555, 469; MS (ESI) m/z:
340(M + H)+; HRMS (ESI) calcd for C24H21NO (M + H)+:
340.1701; found: 340.1699.
1-(2-(Allyl(methyl)amino)-5-methoxyphenyl)naphthalen-2-ol
(18b). Isolated by column chromatography (ethyl acetate−hexane =
1:9, Rf = 0.3). The title compound was obtained as red viscous liquid.
1H NMR (300 MHz, CDCl3, ppm): δ 7.84−7.78 (m, 3H), 7.40−7.30
(m, 3H), 7.23−7.20 (m, 1H), 6.99−6.94 (m, 2H), 5.63−5.52 (m, 1H),
5.08−4.98 (m, 2H), 3.76 (s, 3H), 3.42−3.32 (m, 2H), 2.76 (s, 3H);
13C NMR (300 MHz, CDCl3, ppm): δ 158.4, 151.8, 140.2, 133.7,
132.8, 129.6, 128.2, 126.1, 125, 123, 120.7, 120.2, 119.8, 119.5, 119.9,
115.3, 114, 60.4, 55.6, 39.5, 29.7; FTIR (cm−1): 3377, 2924, 2854,
1726, 1619, 1509, 1461, 1246, 1031, 821, 749; MS (ESI) m/z: 320(M
+ H)+; HRMS (ESI) calcd for C21H21NO2 (M + H)+: 320.1650;
found: 320.1665.
1-(5-Methoxy-2-(pyrrolidin-1-yl)phenyl)naphthalen-2-ol (19b).
Isolated by column chromatography (ethyl acetate−hexane = 1:9, Rf
= 0.3). The title compound was obtained as colorless crystalline solid.
1H NMR (300 MHz, CDCl3, ppm): δ 7.83−7.77 (m, 3H), 7.40−7.28
(m, 3H), 7.22−7.19 (m, 1H), 6.95−6.92 (m, 2H), 3.749 (s, 3H),
3.12−2.89 (m, 4H), 1.80 (s, 4H); 13C NMR (300 MHz, CDCl3, ppm):
δ 153.5, 134.6, 129.7, 128.1, 127.7, 126.4, 126.3, 125.2, 123.4, 123.2,
119.9, 119.5, 118.4, 117.8, 114.4, 109.4, 55.7, 52.3, 24.2; FTIR (cm−1):
3428, 2927, 2853, 1617, 1502, 1463, 1341, 1278, 1233, 1170, 1039,
(5) David, R. Stuart.; Keith, Fagnou. Science 2007, 316, 1172.
(6) (a) Whiting, D. A. In Comprehensive Organic Synthesis, ed. Trost,
B.;Fleming, I.; Pattenden, G. Pergamon, Oxford, 1991, 3, pp 659−703.
(b) Stanforth, S. P. Tetrahedron 1998, 54, 263.
(7) (a) Kirchgessner, M.; Sreenath, K.; Gopidas, K. R. J. Org. Chem.
2006, 71, 9849. (b) Vyskoci
I.; Brooks, R. D.; Kulagowski, J. J.; Langer, V.; Farrugia, L. J.;
Kocovsky, P J. Org. Chem. 2001, 66, 1359.
̌ ̌ ̌ ́
l, S.; Smrcina, M .; Lorenc, M.; Tislerova,
̌
́
10234
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Article
(8) (a) Smrci
P. J. Org. Chem. 1992, 57, 1917. (b) Vyskocil, S.; Smrci
M.; Hanus, V.; Polasek, M.; Kocovsky, P. Chem. Commun. 1998, 5,
585.
̌
na, M.; Lorenc, M.; Hanus, V.; Sedmera, P.; Koco
̌
vsky,
̌
na, M.; Lorenc,
̌
(9) Ding, K.; Xu, Q.; Wang, Y.; Liu, J.; Yu, Z.; Du, B.; Wu, Y.;
Koshima, H.; Matsuura, T. Chem. Commun. 1997, 7, 693.
(10) Furstner, A.; Majima, K.; Martin, R.; Krause, H.; Kattnig, E.;
Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc. 2008, 130, 1992.
(11) Iron-catalyzed C−H bond activation: (a) Ilies, L.; Asako, S.;
Nakamura, E. J. Am. Chem. Soc. 2011, 133, 7672. (b) Matsumoto, A.;
Ilies, L.; Asako, S.; Nakamura, E. J. Am. Chem. Soc. 2011, 133, 6551.
(c) Nakamura, E.; Yoshikai, N. J. Org. Chem. 2010, 75, 6061. (d) Qian,
B.; Xie, P.; Xie, Y.; Huang, H. Org. Lett. 2011, 13, 2580.
(12) (a) Sarhan, A. A. O.; Bolm, C. Chem. Soc. Rev. 2009, 38, 2730.
(b) Bolm, C.; Legros, J.; Paih, J. L.; Zani, L. Chem. Rev. 2004, 104,
6217.
(13) F Cat. C−C bond-forming reaction: (a) Hatakeyama, T.;
Hashimoto, S.; Ishizuka, K.; Nakamura, M. J. Am. Chem. Soc. 2009,
131, 11949. (b) Czaplik, W. M.; Mayer, M.; Wangelin, A. J. Angew.
Chem., Int. Ed. 2009, 48, 607. (c) Hatakeyama, T.; Nakamura, M. J.
Am. Chem. Soc. 2007, 129, 9844. (d) Nagano, T.; Hayashi, T. Org. Lett.
2005, 7, 491.
(14) (a) Fe Cat. C−N bond-forming reaction: Pan, S.; Liu, J.; Li,
H.; Wang, Z.; Guo, X.; Li, Z. Org. Lett. 2010, 12, 1932. (b) Correa, A.;
Bolm, C. Angew. Chem., Int. Ed. 2007, 46, 8862. (c) Guo, D.; Huang,
H.; Xu, J.; Jiang, H.; Liu, H. Org. Lett. 2008, 10, 4513.
(15) (a) Basu, D.; Chandrasekharam, M.; Mainkar, P. S.;
Chandrasekhar, S. ARKIVOC 2011, 355. (b) Singh, S. P.; Vijaya
Kumar, T.; Chandrasekharam, M.; Giribabu, L.; Reddy, P. Y. Synth.
Commun. 2009, 39, 3982. (c) Liang, K.-W.; Chandrasekharam, M.;
Liu, R.-S. J. Org. Chem. 1998, 63, 7289. (d) Chandrasekharam, M.; Liu,
R.-S. J. Org. Chem. 1998, 63, 9122. (e) Liang, K.-W.;
Chandrasekharam, M.; Li, C.-L.; Liu, R.-S. Organometallics 1998, 17,
2683. (f) Shieh, S.-J.; Fan, J.-S.; Chandrasekharam, M.; Liao, F.-L.;
Wang, S.-L.; Liu, R.-S. Organometallics 1997, 16, 3987.
(g) Chandrasekharam, M.; Bhat, L.; Ila, H.; Junjuppa, H.
Tetrahedron Lett. 1993, 34, 6439.
(16) Fieser, L. F. J. Am. Chem. Soc. 1930, 52, 5204.
(17) Kumaraswamy, G.; Narayanamurthy, A.; Pitchaiah, A. J. Org.
Chem. 2010, 75, 3916.
(18) Griffin, B. W. Arch. Biochem. Biophys. 1978, 190, 850.
(19) Wang, K.; Lu, M.; Yu, A.; Zhu, X.; Wang, Q. J. Org. Chem. 2009,
74, 935.
(20) (a) Ashenhurst, J. A. Chem. Soc. Rev. 2010, 39, 540. (b) Ito, Y.
Tetrahedron 2007, 63, 3108. (c) Sioda, R. E.; Barbara Frankowska, B.
Tetrahedron Lett. 2005, 46, 2747.
(21) Jones, A. K.; Wilson, T. E.; Nikam, S. S. In Encyclopedia of
Reagents for Organic Synthesis; Paquette, L. A., Ed.; John Wiley & Sons,
Inc.: New York, 1995; Vol. 2, p 880.
10235
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