Regioselective Synthesis of 4-Aryl-1,3-dihydroxy-2-naphthoates through 1,2-Aryl-Migrative Ring Rearrangement Reaction and their Photoluminescence Properties

Article abstract of DOI:10.1002/chem.202101459

4-Aryl-1,3-dihydroxy-2-naphthoates having the less accessible 1,2,3,4-tetrasubstituted naphthalene scaffold and that show photoluminescence emission from solid state as well as in solutions, were selectively synthesized from brominated lactol silyl ethers

Full text of DOI:10.1002/chem.202101459

Accepted Article
Accepted Article
Title: Regioselective Synthesis of 4-Aryl-1,3-dihydroxy-2-naphthoates
through 1,2-Aryl-migrative Ring Rearrangement Reaction and
Their Photoluminescence Properties
Authors: Hikaru Yanai, Teru Kawazoe, Nobuyuki Ishii, Bernhard
Witulski, and Takashi Matsumoto
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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To be cited as: Chem. Eur. J. 10.1002/chem.202101459
Link to VoR: https://doi.org/10.1002/chem.202101459
01/2020

10.1002/chem.202101459
Chemistry - A European Journal
FULL PAPER
Regioselective Synthesis of 4-Aryl-1,3-dihydroxy-2-naphthoates
through 1,2-Aryl-migrative Ring Rearrangement Reaction and
Their Photoluminescence Properties
Hikaru Yanai,*[a] Teru Kawazoe,[a] Nobuyuki Ishii,[a] Bernhard Witulski,*[b] and Takashi Matsumoto*[a]
[a]
Dr. Hikaru Yanai, Teru Kawazoe, Nobuyuki Ishii, Prof. Dr. Takashi Matsumoto
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
E-mail: yanai@toyaku.ac.jp (HY), tmatsumo@toyaku.ac.jp (TM). Twitter handle: @TUPLS_seizo
Prof. Dr. Bernhard Witulski
[b]
Laboratoire de Chimie Moléculaire et Thio-organique, CNRS UMR 6507
ENSICAEN & UNICaen, Normandie Univ.
6 Bvd Maréchal Juin, Caen, 14050, France.
E-mail: bernhard.witulski@ensicaen.fr
Supporting information for this article is given via a link at the end of the document.
Abstract: 4-Aryl-1,3-dihydroxy-2-naphthoates having the less
accessible 1,2,3,4-tetrasubstituted naphthalene scaffold and that
show photoluminescence emission from solid state as well as in
solutions, were selectively synthesized from brominated lactol silyl
ethers through the 1,2-aryl-migrative ring rearrangement reaction.
ether 1 with suitable fluoride sources (Eqn. 1).[7] This O C ring
rearrangement reaction proceeded via a desilylative ring-opening
that was followed by an intramolecular aldol reaction of the
thermodynamically favoured keto-enolate INT-3. Under similar
conditions, the C4-alkynyl substrate
3
selectively gave
naphthalene 4 bearing a different substituent pattern on the
consecutive 1–4 positions (Eqns. 1 vs 2).[8] In this case, the
intramolecular Michael reaction of allenyl ketone INT-4 was
Introduction
proposed being the ring-closing step (O C/C
rearrangement reaction).
C
ring
Structural diversity of polyketide natural products and their unique
biological activities have attracted much attention over the past
100 years.[1] For example, aromatic polyketides, which are
produced through biosynthetic pathways catalysed by type II
polyketide synthase (PKS) in bacteria,[2] are still regarded as
challenging targets for chemical synthesis because of difficulties
in the selective construction of highly-substituted polycyclic
aromatic scaffolds.[3] As shown in Figure 1, in the biosynthesis of
the antibiotic actinorhodin,[4] the acyclic intermediate INT-1 is
initially converted to the monocyclic intermediate INT-2, which
produces a series of secondary tricyclic metabolites including
actinorhodin.
The O C ring rearrangement
O
CO2Et
OH
TBSO
CO2Et
CO2Et
Ph
TBAF
THF
O
(1)
O
Ph
C4
Ph
Ph
Ph
Ph
INT-3
1
2 80%
The O C/C C ring rearrangement
CO2Et
TBSO
O
OH
CO2Et
H
CO2Et
O
TBAF
(2)
Ph
C4
n-Bu
n-Bu
THF
O
O
Ph
Ph
INT-4
n-Bu
O
O
Me
3
4
99%
OH
O
Me
1) 'min' PKS (actI)
2) KR (actIII)
12
O
O
O
This work: 1,2-aryl-migrative ring rearrangement
O
O
O
O
O
O
H
O
1
9
3) ARO (actVII)
O
CO2Et
ACT
ACT
O
TBSO
CO2Et
7
S
O
S
Et
INT-1
INT-2
Me
O
H
O
(3)
R
O
R
R
3
OH
O
Me
OH
O
O
- HX
Ar
O
4
C4
2
Ar
CO2H
OH
DMAC
Ar
X
X
O
CO2H
5
INT-5
6
OH
O
OH
Actinorhodin
Such a ‘ring rearrangement’ strategy using a lactol silyl ether
scaffold has the following remarkable features: (1) a synthetic
protocol for starting lactol derivatives with latent reactive
functionalities is highly reliable, (2) a variety of C4-substituents on
the isochromene backbone bring structural diversity of the
naphthalene substituents (Eqn. 1), (3) the cyclisation mode is also
switchable by changing the C4-substituents (Eqns. 1 vs 2), and
(4) the isolation of lactol silyl ethers allows detailed screening and
optimisation of the ring rearrangement conditions. Considering
Figure 1. Biosynthetic pathway of actinorhodin and related polyketides.
The conformationally restricted INT-2, that promotes follow-up
ring-closures, has prompted us to develop related sequential
reactions for poly-substituted aromatics.[5,6] In our early
achievement, naphthol 2 was synthesised by treating lactol silyl
1
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10.1002/chem.202101459
Chemistry - A European Journal
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the importance of natural product-like compounds having a
polycyclic aromatic scaffold in the fields of medicinal and material
chemistry,[9] challenging and less accessible 1,2,3,4-
tetrasubstituted naphthalenes are highly attractive targets.[10,11] In
this paper, we report that the C4-halogenated substrate 5
selectively gives the 4-aryl-1,3-dihydroxy-2-naphthoate 6 (Eqn. 3)
via the -haloketone intermediate INT-5. We also found that the
rigid molecular framework found in 6 with its two characteristic
intramolecular H-bonds became a potent molecular motif for
solution and solid-state fluorescent materials.
stable iodinated substrate 5a-I[7] was not fruitful at all (Table 1,
entry 6).
Table 1. Reactions of C4-halogenated lactol silyl ethers.
CO2Et
CO2Et
NaOAc
OH
OH
1
TBSO
CO2Et
Ph
CO2Et
OH
O
2
O
AcOH
70 °C
3
Ph
4
Ph
X
X
Ph
6a
X
5a-X
9a-X
10a-X
Entry
X
NaOAc
Time
Yield[a] (%)
Ratio[b]
(Equiv.)
(h)
9a
10a
6a
(9a:10a:6a)
Results and Discussion
1
2
3
4
5
6
Cl
Cl
Cl
Cl
Br
I
None
1
2.5
2.5
23
23
4
93
92
-
0
0
-
100 : 0 : 0
100 : 0 : 0
11 : 17 : 72
0 : 33 : 67
0 : 3 : 97
-
Development of a novel cascade reaction for 4-aryl-1,3-
dihydroxy-4-naphthoates
-
We started our investigation with the synthesis of the C4-
halogenated lactol silyl ethers 5a-X (X = Cl, Br, I). According to a
reported procedure,[12] 4-chloro- and 4-bromo-1H-isochromen-1-
ones 8a-Cl and 8a-Br were prepared from methyl o-iodobenzoate
over two steps (Scheme 1). By applying the zwitterion catalyst A
developed by us,[7,13] the addition reaction of a ketene silyl acetal
to the lactones gave 5a-X in excellent yields.
10
17
60
59
96
20
-
22
-
20
-
20
3
complex
[a] Isolated yield. [b] Determined by 1H NMR analysis of crude material.
Ph
CO2Me
CO2Me
I
(Ph3P)2PdCl2, CuI
Et3N, 55 °C
CuX2
The scope of this new ring rearrangement cascade that is
terminated by an 1,2-aryl migration was examined (Figure 2).
MeCN, reflux
Ph
7a
CO2Et
OH
1
O
TBSO
OTBS
CO2Et
O
O
NaOAc (20 equiv)
TBSO
OEt
OH
O
3
2
OEt
H
N
zwitterion A
O
AcOH, 70 °C
2.5-11 h
3
R
R
Ar
4
Br
4
Ar
Ph
CH2Cl2
0 °C, 1-2 h
Ph
Tf2C
4
4
X
5
6
X
zwitterion A
(R = n-C5H11
8a-Cl
5a-Cl
(X = Cl) 91%
8a-Br (X = Br) 90%
(X = Cl) 90%
5a-Br (X = Br) 89%
)
OH
OH
OH
CO2Et
OH
CO2Et
CO2Et
OH
Scheme 1. Preparation of 4-halogenated lactol silyl ethers.
OH
Me
X
6b (X = p-OMe) 92%
6c (X = o-OMe) 95%
6d (X = p-Me) 91%
With 5a-X in our hand, its reactivity was examined.
Unfortunately, applying TBAF-induced conditions[7] to 5a-Cl led to
an intractable mixture of products. On the other hand, the E1
product 9a-Cl was obtained after heating at 70 °C in acetic acid
(Table 1, entry 1).[14] Interestingly, in the presence of NaOAc, 9a-
Cl, that now was in situ generated from 5a-Cl (reaction followed
by TLC), was converted to the unexpected product 6a. The latter
was, however, also accompanied by the expected product 10a-Cl
dependent on the amount of NaOAc used (Table 1, entries 2-4).
The reaction path to 6a can be best explained by a 1,2-aryl-
migration process. We noted that in a traditional synthesis of 1,3-
dihydroxy-2-naphthoates through the C-acylation of malonates
with acid chlorides followed by cyclisation in the presence of acid
promoters, which was reported by Meyer and Bloch in 1945,[15a]
the 4-substitued derivatives were not obtained effectively.[15b-d]
Consequently, our finding motivated to optimise this 1,2-aryl-
migrative rearrangement cascade. Eventually, we found that
replacing the chlorine atom by a bromine atom caused a
significant improvement of the yield of 6a: the reaction of 5a-Br in
an AcOH/NaOAc mixture gave 6a in 96% yield. Notably, now the
formation of 10a-Br was suppressed significantly (10a:6a = 3:97)
(Table 1, entry 5). However, the reaction with the thermally less
F
NMe2
6g
6i
93%
58%
6e (X = p-Cl)
84%
88%
6f
(X = p-F)
OH
OH
OH
CO2Et
OH
7
6
CO2Et
OH
CO2Et
R
OH
OMe
MeO
S
6k
6l
6m (R = 7-F)
91%
(3-thienyl) 93%
6j
95%
6n (R = 6-OMe) 81%
93%
(2-thienyl)
OH
OH
CO2Et
OH
CO2Et
OH
S
6o 81%
6p 90%
Figure 2. Ring rearrangement reaction of brominated lactol silyl ethers.
The p- and o-methoxyphenyl substrates 5b, 5c and the p-tolyl
substrate 5d gave the corresponding products 6b-d in excellent
2
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Me
yields. Likewise, the substrates 5e-5g bearing slightly electron-
deficient aryl groups were successfully converted to the desired
products 6e-6g. The p-dimethylamino derivative 6i was isolated
in 58% yield despite of the used acidic conditions. In addition, the
highly congested naphthoate 6j, was obtained in 95% yield. The
2- and 3-thienyl substrates 5k and 5l gave the corresponding
products 6k and 6l, respectively. Substitution of the isochromene
backbone did not affect the reaction outcome to give 6m and 6n
in good to excellent yields. In addition, a selective synthesis of the
anthracene 6o as well as the benzothiophene 6p was achieved.
The reaction with 5h bearing a strongly electron-withdrawing CF3
group deserves special notice: 4-bromonaphthalene 10h was
obtained as the major product (54% yield) together with 6h that
was obtained now in 20% yield only (Scheme 2).
CO2Et
AcO
O
AcO
CO2Et
TBSOH
TBSO
O
CO2Et
Ac2O
H+
O
O
O
E1
Ar
Ar
Br
Br
Ar
H
Br
INT-6
5
9
O
O
O
CO2Et
CO2Et
O
HBr
CO2Et
O
OH
Ar
semipinacol
rearr.
Ar
H
INT-5
Br
Ar
Br
INT-7
H
INT-8
tautomerism
H2O
OH
OH
CO2Et
Ar
CO2Et
OH
OH
CO2Et
OH
TBSO
CO2Et
OH
Br
10
Ar
6
CO2Et
NaOAc
O
AcOH
70 ºC
Scheme 4. Plausible reaction pathways.
Br
Br
CF3
CF3
5h
6h
10h
20%
54%
CF3
Considering the finding that NaOAc is essential for the molecular
transformation of 9, the acetate ion serves here as a nucleophile
to generate INT-6 – a vinylogue of acid anhydride. Sequential
intramolecular aldol reaction of -bromoketone INT-5 followed by
an acid-mediated semipinacol rearrangement are most likely
reaction steps.[16] 4-Bromonaphtalene 10 that is observed in some
cases, especially with 5h bearing a p-(trifluoromethyl)phenyl
group, is generated through the dehydration of INT-7. If the
substrate has less reactive electron deficient C3-aryl groups such
as 5h, the dehydration yielding 10 becomes a major path. On the
other hand, in most cases, the semipinacol process causes the
Scheme 2. Reaction of 5h bearing a strongly electron withdrawing CF3 group.
These results imply that the 1,2-aryl migration becomes more
favourable with increasing electron-donating character of the
migrating aryl group. Despite such a limitation, the present
reaction is still promising for the selective formation of a wide
range of 4-aryl-1,3-dihydroxy-2-naphthoates.
The one-pot conversion of the bromolactones
8 was
alternatively possible (Scheme 3). As a result, the desired
naphthalenes 6a and 6e were obtained in high yields from 8a-Br
and 8e, respectively. Note that 6a was obtained without
considerable changes of the yield in a gram-scale reaction using
8a-Br. This one-pot protocol enables to avoid the isolation of
unstable lactol silyl ethers. Although lactol silyl ether 5q derived
from 8q was not isolable, biphenyl 6q was obtained in 53% yield
from 8q by applying the one-pot protocol.
1,2-aryl-migration to give the 1,3-dihydronaphthoates
6
selectively. In other words, the 6/10 selectivity reflects the relative
rate difference between the 1,2-aryl migration and the
dehydration step.
Solid State and Solution Phase Structures
The molecular structure of 6a was undoubtedly proven by
single-crystal X-ray diffraction study.[17] As shown in Figure 3A,
the structure of 6a and its molecular geometry suggested twofold
intramolecular H-bonds (O1‒H•••O3 and O2‒H•••O4). Such
characteristic bonding was successfully visualized by Bader’s
Quantum Theory of Atoms in Molecules (QTAIM) analysis[18]
using the DFT-optimized geometry and wave function (Figure 2B).
The corresponding bond paths and bond critical points (BCPs)
OTBS
O
OH
1)
OEt
zwitterion , 0 °C
CO2Et
OH
O
A
Ar
2) evaporation
Br
3) NaOAc-AcOH, 70 °C
Ar
8a-Br
6a
6e
(Ar = Ph)
95% (91%)
79%
8e
(Ar = p-ClC6H4)
within a reasonable range of QTAIM parameters, including the
2
electron density ( BCP) and the Laplacian (
BCP), as the O‒
O
OH
O
CO2Et
Ph
TBSO
H•••O interaction were computed.[19] The delocalization index (DI)
of the O‒H•••O interactions,[20] which may be regarded as a
covalent bond order, are 0.101 (for BCP 1) and 0.073 (for BCP 2),
respectively.
same as above
Ph
O
OEt
OH
O
Br
Ph
Br
5q
8q
6q
unstable
53%
Scheme 3. One-pot synthesis of poly-substituted naphthalene and biphenyl.
The yield of the gram-scale synthesis of 6a is shown in parentheses.
A plausible mechanism for the present cascade reaction is
shown in Scheme 4.
3
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Photophysical properties
Although the photophysics of 1- and 3-monohydroxy-2-
naphthoates found so far little interest in the literature,[21] we
recognized that the 1,3-dihydroxy-2-naphthoate products showed
bright PLE from the solid state as well as in solutions.
Photophysical data of selected compounds (4-phenyl compounds
6a-f, 6i, 6m and thienyl analogue 6k) that all show a bright PLE
from the solid state and in solution are listed in Table 2, and
representative UV-Vis absorption and PLE solution spectra are
compiled in Figure 5 (see, Supporting Information for the
complete data and spectra sets).
The solution UV-Vis absorption spectra of 6 are characterised by
a broad low-energy charge-transfer band in the 325-450 nm
region. In a series of 4-phenyl-1,3-dihydroxy-2-naphthoates 6a,
6b, 6d-f bearing p-substituents on the phenyl group, the band
maxima are slightly red-shifted with increasing donor strength
induced by the substituent. Bathochromic shifts, though more
pronounced, were also found in the PLE spectra of this series
where the emission bands cover the 420-650 nm region. The
corresponding Stokes shifts have values of 4200-4700 cm–1. In
addition, the Stokes shifts correlated very well with the Hammett–
Taft substituent parameter
of the substituents (H, p-OMe, p-
R
Me, p-Cl, p-F) on the 4-phenyl group.[22] This strongly implies the
underlying intramolecular charge transfer (ICT) character
associated with the longest wavelength absorption and emission
bands (Insert of Figure 5). That is, the 4-phenyl-1,3-dihydroxy-2-
naphthoates 6a, 6b, 6d-f resemble a considerable ‘push-pull’
system capable for ICT in the excited state. Here, the p-
substituted phenyl group acts as an electron donor and the
naphthoate moiety serves as an electron acceptor. Notably, the
o-methoxyphenyl derivative 6c showed similar PLE, but the 2,6-
dimethoxyphenyl derivative 6j was not so. Such results suggest
that electronic communication in ground and Franck–Condon
excited states seems still to be effective despite the partially
twisted nature around the C–C bond axis between the
naphthalene backbone and the phenyl substituent. An exception
is the fully twisted and ‘locked’ case of 6j, where its average twist
angle is increased (ideally 90°) in comparison to 6c that is more
conformationally flexible around the biaryl bond axis.[23]
Figure 3. (A) ORTEP drawing of 6a. Twisting angle around C4-C5 biaryl bond
axis was 81.8°. H-atoms attached by calculation in the refinement process. (B)
2
QTAIM view of 6a. BCP1, 0.333 e Å‒3
,
BCP2, 0.260 e Å‒3
;
BCP1, +3.784 e Å‒5
,
2
BCP2, +3.680 e Å‒5 (BCPs are shown by green sphere).
This twofold H-bonding should be considered of being not only
present in the solid state but also in the solution phase. For
example, in the 1H NMR analysis of 6a in CDCl3, the singlets for
the hydrogen atoms of the C1- and C3-phenolic OH groups are
found at 11.61 and 9.28 ppm respectively; and the chemical shifts
were not changed significantly by changing the concentration of
6a. Such a twofold intramolecular H-bonding situation was also
found in the X-ray structures of 6d, 6f, 6i, 6j, 6k, 6m, and 6p
obtained from single crystal structure analysis (Figure 4 and
Supporting Information).
8
6a (-H)
R
6b (p-OMe)
-NMe2
-OMe
-F
-0.56
-0.43
-0.33
-0.16
-0.13
0.00
40000
30000
20000
10000
0
7
6
5
4
6d (p-Me)
6e (p-Cl)
6f (p-F)
-NMe
2
-Cl
-CH3
-H
6i (p-NMe2)
-OMe
-CH
3
-H
-F
-Cl
-0.6
-0.4
-0.2
0.0
R
300
400
500
600
700
Wavelength (nm)
Figure 5. Overlay of UV-Vis absorption spectra (solid lines) and PLE spectra
(dashed lines) of the p-substituted phenyl naphthoates 6a, 6b, 6d-f, and 6i in
CH2Cl2 (10-5 M). Insert: Correlation of Stokes shift versus Hammett-Taft
substituent parameter
.
R
Figure 4. ORTEP drawings of 6d, 6f, 6i, and 6j.
4
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Table 2. Photophysical data of selected compounds 6
H
H
H
O
O
O
O
O
O
O
O
O
R
H
O
6a (X = H)
O
O
Et
Et
F
Et
O
H
O
H
O
H
6b (X = OMe)
R
O
H
O
6d
(X = Me)
O
6e (X = Cl)
6f (X = F)
Ar
Ph
1-hydroxy-2-naphthoate
3-hydroxy-2-naphthoate
6c (Ar = o-MeOC6H4)
6k (Ar = 3-thienyl)
6m
6i
(X = NMe2)
X
Comp.
Solution[a]
Solution[a]
(M-1 cm-1)
3840
Solution[a]
Solid
max
Solution[a]
Stokes shift
(cm-1)
Solution[b]
Solid[c]
abs
em
em
max
max
F
F
(nm)
(nm)
468
482
466
474
466
467
555
480
474
(nm)
477
475
471
482
476
478
501
479
496
6a
6b
6c
6d
6e
6f
391
393
390
392
390
390
398
393
398
4210
4700
4180
4410
4180
4230
7110
6412
4130
0.39
0.39
0.39
0.38
0.36
0.36
0.19
0.36
0.42
0.33
0.07
0.28
0.18
0.52
0.39
0.18
0.22
0.27
4320
3980
3590
4450
4110
6i
4400
6k
6m
4100
4560
[a] 10-5 M solution in CH2Cl2. [b] Absolute quantum yield measured with an integration sphere, solutions of 6 in PhCl (10–5 M) were purged with Ar for 20 min prior
to measurement. [c] Absolute quantum yields measured with integration sphere.
As shown in Figure 6, the time-dependent DFT simulation under
PCM(CH2Cl2)-TD-B3LYP/6-311+G(d,p) level of theory well
represents the ‘push-pull’ character of 6a. In the HOMO, the 4-
phenyl group and the 3-hydroxy group communicate with the
naphthalene backbone orbital (Figure 6A). On the other hand, the
LUMO is mainly localized on the 1-hydroxy-2-naphthoate
structure (Figure 6B).
its electronic distribution in 6i are likewise responsible for a
significant PLE efficiency decrease in solutions.
Solvatochromism studies with 6a (H), 6b (p-OMe), 6e (p-Cl),
and 6i (p-NMe2) show significant bathochromic shifts of the PLE
bands with Reichardt’s normalized solvent polarity parameter EN
T
(Figure 7 and Supporting Information).[24] Such a positive
solvatochromism is indicative for an ICT originated from
molecules having a donor-acceptor dyad. Notably, in these novel
‘push-pull’ structures, the acceptor ability is enhanced through a
twofold intramolecular hydrogen bonding of the hydroxyl groups
on the C1 and C3 atoms towards
protic solvents
aprotic solvents
22
20
18
Figure 6. HOMO (A) and LUMO (B) of 6a under PCM(CH2Cl2)-TD-B3LYP/6-
311+G(d,p) level of theory with PCM (CH2Cl2).
6e (p-Cl)
6a (-H)
6b (p-OMe)
6i (p-NMe2)
Among the series of 4-phenyl naphthalenes, the p-
(dimethylamino)phenyl derivative 6i is a noteworthy exception: It
shows a remarkable large Stokes shift of 7110 cm–1 in CH2Cl2
(Table 2). In this case, 6i after excitation most likely undergoes a
TICT (twisted intramolecular charge-transfer) state that
necessarily involves major changes in the molecular geometry of
the vibrationally relaxed excited state. The TICT mechanism and
0.0
0.2
0.4
ETN
0.6
0.8
5
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Figure 7. PLE band maxima as a function of Reichardt’s solvent polarity
parameter ENT of compounds 6a, 6b, 6e and 6i.
C4-phenyl group and the naphthoate acceptor strengthened by
the twofold intramolecular H-bonding.
HOMO/LUMO energy levels of 6a and 6k were investigated
by a combination of cyclic voltammetry and the onset values of
the low energy absorption bands (for details, see Supporting
Information). Within the solvent/electrolyte window (0.1 M
Bu4NPF6 in CH2Cl2), the parent compound 6a and its 3-thienyl
analogue 6k show non-reversible oxidation half-waves with a first
oxidation potential E1/2 of 1.34 V and 1.22 V, respectively (Figure
9). From the onset of the first oxidation half-wave oxEonset (1.19 V
for 6a and 1.13 V for 6k) and the optical band gap optEgap (2.84 eV
for 6a and 2.09 eV for 6k), that was taken from the onset of the
UV-vis absorption spectra, the HOMO/LUMO energies were
estimated to be –5.83/–2.99 eV (6a) and –5.77/–3.68 eV (6k).[26]
the ester function on the C2 atom. This characteristic H-bonding
also rigidifies the molecular structure being a reason for the
observed high PLE quantum efficiencies (Table 2). Noteworthy to
mention, these twofold H-bonds remain intact even in protic
solvents like alcohols as being expressed by the fitting correlation
of the band maxima
of UV-Vis absorption and PLE spectra
max
with the solvent polarity parameter EN (Figure 7). Solution and
T
solid state PLE spectra of 6 are quite similar with respect to their
emission maxima and band shape with the notable exception of
6i (see, Supporting Information for overlay of solution and solid
state PLE spectra): Compared to the other examples in this series,
the PLE band maxima of 6i in chlorobenzene (em max = 555 nm)
is significantly red-shifted to that of the solid state (em
= 501
max
nm). This again points to a favourable emission of 6i through the
TICT state in solutions.
0.0002
6a
6k
Further insight into molecular structure and electronic
properties of the excited state were gained from the Lippert-
Mataga plots of 6a, 6b, 6d, 6e-f, and 6i (Figure 8).
0.0001
0.0000
6i (p-NMe2)
OH
O
OH
O
7
OEt
OEt
OH
6b (p-OMe)
OH
6d (p-Me)
6a (H)
6e (p-Cl)
S
6k
6a
-0.0001
6
0.0
0.5
1.0
1.5
2.0
6f (p-F)
Vf (V)
5
Figure 9. Cyclic voltammetry plot of 6a and 6k (10–3 M in CH2Cl2 / 0.1 M n-
Bu4PF6) at room temperature with internal Fc+/Fc (E1/2 = 0.46 V vs SCE) for
calibration purpose. Scan rate 100 mV/s, working electrode Pt, auxiliary
electrode Pt wire, and the reference electrode SCE.
4
3
Conclusion
0.0
0.1
0.2
0.3
f
In conclusion, we successfully developed an effective route to
less accessible 4-aryl-1,3-dihydroxy-2-naphthoates through a
cascade reaction of brominated lactol silyl ethers including a
sequential ring-opening/ring-closing process. The work illustrates
that the bioinspired strategy is promising not only for natural
product synthesis but also for discovering ‘unnatural’
polyaromatics with potent fluorescent properties characterised by
‘push-pull’ systems with ICT and TICT behaviour.
Figure 8. Lippert-Mataga plots of 6a, 6b, 6d, 6e, 6f and 6i as correlation of
Stokes shift versus orientation polarizability f. Protic solvents were not
considered.
Stokes shifts show a good correlation with Lippert’s orientation
polarizability f that quantifies the difference in polarization
between the first excited and the ground states of a chromophore.
It allows the estimation of the change of dipole moment for the
transition from ground to the exited state (Supporting Experimental Section
Information).[25] Plotting Stokes’s shifts vs f = ( -1)/(2 +1)-(n2-
1)/(2n2+1), where is the permittivity and n is the refractive index
of the solvent, yield dipole moment changes between the ground
General procedure for zwitterion-induced addition reaction: To a
solution of halolactone 8 (0.5-3.0 mmol) and zwitterion A (1 mol%) in
CH2Cl2, a solution of tert-butyl((1-ethoxyvinyl)oxy)dimethylsilane (KSA,
1.2-1.6 equiv) in CH2Cl2 (0.3 mL) was slowly added over 30-50 min by
using a syringe pump at 0 °C. After being stirred additionally at the same
temperature, the reaction mixture was quenched with a saturated NaHCO3
aqueous solution (30 mL) and extracted with EtOAc (30 mL x 3). The
combined organic layer was washed with brine (30 mL) and evaporated.
Chromatographic purification of thus obtained residue was effective to
isolate the desired lactol silyl ether 5.
(
g) and the exited ( e) states of 15.5, 15.9, 16.5, 17.6, 19.4, and
30.7 D for respectively 6a (H), 6f (p-F), 6e (p-Cl), 6d (p-Me), 6b
(p-OMe), and 6i (p-NMe2). For all investigated compounds 6 a
solvent cavity (Onsager) radius of ca. 4.6 Å was estimated. This
increase of
–
e
in the set of 6a, 6f, 6e, 6d, 6b, and 6i again
g
emphasizes on the ICT and ‘push-pull’ character originated by the
interplay of donor strength variations by the substituents on the
6
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Ethyl
2-(4-bromo-1-((tert-butyldimethylsilyl)oxy)-3-phenyl-1H-
Keywords: Synthetic methods • Domino reactions •
Rearrangement • Polycycles • Fluorescence
isochromen-1-yl)acetate (5a-Br): According to the general procedure,
this compound was obtained in 89% yield (1.35 g, 2.68 mmol) by the
reaction of bromolactone 8a-Br (904 mg, 3.00 mmol) with KSA (968 mg,
4.78 mmol) in the presence of zwitterion catalyst A (15.9 mg, 30.3 mol)
in CH2Cl2 (15 mL). The KSA was added over 30 min at 0 °C, then the
mixture was additionally stirred for 30 min at the same temperature.
Isolation of the product was achieved by column chromatography on silica
gel (hexane/EtOAc = 20 : 1). Colourless crystals (from hexane); IR (ATR)
2954, 2926, 2856, 1731, 1600, 1334, 1226, 1193, 1150, 1013, 836, 781,
753, 694 cm–1; 1H NMR (400 MHz, CDCl3) –0.15 (3H, s), –0.09 (3H, s),
0.89 (9H, s), 1.15 (3H, t, J = 7.2 Hz), 3.02 (1H, d, J = 13.6 Hz), 3.17 (1H,
d, J = 13.6 Hz), 4.00-4.14 (2H, m), 7.33 (1H, td, J = 7.6, 1.2 Hz), 7.38-7.46
(5H, m), 7.60 (1H, dd, J = 7.6, 1.2 Hz), 7.85-7.90 (2H, m); 13C NMR (100
MHz, CDCl3) –3.7, –3.3, 14.0, 18.0, 25.7, 46.9, 60.6, 98.3, 100.9, 124.2,
124.9, 127.7, 127.8, 129.1, 129.3, 129.9, 130.0, 132.5, 134.4, 148.5,
168.4; HRMS (ESI-TOF) calcd for C25H31BrNaO4Si [M+Na]+, 525.1073;
found, 525.1071. Anal. Calcd for C25H31BrO4Si: C, 59.64; H, 6.21. Found:
C, 59.64; H, 6.20.
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General procedure for the ring-rearrangement reaction: To a solution
of lactol silyl ether 5 (0.2-0.5 mmol) in AcOH (0.1 mol L–1), NaOAc (20
equiv) was added. After being stirred for 2.5-11 h at 70 °C, the reaction
mixture was directly concentrated under reduced pressure. The resulting
residue was dissolved in water (50 mL) and extracted with EtOAc (30 mL
x 3). The combined organic layer was washed with brine (30 mL) and
evaporated. The resulting residue was purified by column chromatography
on neutral silica gel eluting with hexane/EtOAc mixtures to give the desired
4-aryl-1,3-dihydroxy-2-naphthoate 6.
[6]
[7]
a) Review, see: K. Krohn, Eur. J. Org. Chem., 2002, 1351; b) G.
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Ethyl 1,3-dihydroxy-4-phenyl-2-naphthoate (6a): According to the
general procedure, this compound[15b] was obtained in 93% yield (71.2 mg,
0.231 mmol) by the reaction of lactol silyl ether 5a-Br (125 mg, 0.248
mmol) in AcOH (2.5 mL) containing NaOAc (412 mg, 5.02 mmol) for 4 h at
70 °C and the following column chromatography on silica gel
(hexane/EtOAc = 20 : 1). The molecular structure was also confirmed by
single crystal X-ray structural analysis. Yellow crystals (from Et2O); Mp.
123-124 °C; IR (ATR) 3407, 2923, 2853, 1656, 1635, 1400, 1297, 1232,
[10] Selected examples for synthesis of 1,2,3,4-tetrasubstitued naphthalenes,
see: a) J.-Y. Wang, P. Zhou, G. Li, W.-J. Hao, S.-J. Tu, B. Jiang, Org.
Lett., 2017, 19, 6682; b) G. Naresh, R. Kant, T. Narender, Org. Lett.,
2015, 17, 3446; c) B. S. Kale, R.-S. Liu, Org. Lett., 2019, 21, 8434; d) T.
Hamura, M. Miyamoto, T. Matsumoto, K. Suzuki, Org. Lett., 2002, 4, 229.
[11] Recent synthesis of 1,2,3,4-tetrasubstitued carbazoles, see: a) S. Singh,
R. Samineni, S. Pabbaraja, G. Mehta, Org. Lett., 2019, 21, 3372; b) T. N.
Poudel, Y. R. Lee, Chem. Sci., 2015, 6, 7028.
806, 771, 758, 697, 572 cm–1 1H NMR (400 MHz, CDCl3) 1.51 (3H, t, J
;
= 7.2 Hz), 4.63 (2H, q, J = 7.2 Hz), 7.32 (1H, ddd, J = 8.4, 6.4, 1.2 Hz),
7.34-7.39 (3H, m), 7.40-7.47 (2H, m), 7.49-7.55 (2H, m), 8.35 (1H, d, J =
8.4 Hz), 9.28 (1H, brs, OH), 11.61 (1H, brs, OH); 13C NMR (100 MHz,
CDCl3) 14.2, 63.2, 97.0, 114.8, 119.5, 123.0, 124.1, 124.5, 127.2, 128.4,
130.4, 131.2, 136.0, 137.1, 150.1, 161.3, 170.3; HRMS (ESI-TOF) calcd
for C19H17O4 [M+H]+, 309.1127; found, 309.1118. Anal. Calcd for
C19H16O4: C, 74.01; H, 5.23. Found: C, 73.75; H, 5.23.
[12] a) L.-Y. Chin, C.-Y. Lee, Y.-H. Lo, M.-J. Wu, J. Chin. Chem. Soc., 2008,
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One-pot synthesis of 6a: To a solution of 4-bromo-3-phenyl-1H-
isochromen-1-one 8a-Br (151 mg, 0.501 mmol) and zwitterion A (2.7 mg,
5.1 mol) in CH2Cl2 (2.2 mL), a solution of KSA (162 mg, 0.801 mmol) in
CH2Cl2 (0.3 mL) was slowly added. After being stirred for 0.5 h at 0 °C, the
reaction mixture was evaporated. Thus obtained residue was dissolved in
AcOH (5.0 mL) and treated with NaOAc (820 mg, 10.0 mmol) for 4 h at
70 °C. After extractive workup and evaporation, the crude material was
purified by column chromatography on silica gel (hexane/EtOAc = 15 : 1)
to give the desired naphthalene 6a in 95% yield (146 mg, 0.474 mmol)
over two steps.
[15] a) K. Meyer, H. S. Bloch, Org. Synth. 1945, 25, 73; b) J. Nieuwenhuis, J.
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[17] Deposition Numbers 2011888 (6a), 2011882 (6d), 2011887 (6f),
2011881 (6i), 2011885 (6j), 2011883 (6k), 2011886 (6m), and 2011884
(6p) contain the supplementary crystallographic data for this paper.
These data are provided free of charge by the joint Cambridge
Crystallographic Data Centre and Fachinformationszentrum Karlsruhe
Access Structures service www.ccdc.cam.ac.uk/structures.
Acknowledgements
Financial supports by KAKENHI (20K06947), Japan, and the
research cluster Labex EMC3 (energy materials and clean
combustion center) and Région Normandie, France, are gratefully
acknowledged.
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7
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FULL PAPER
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8
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Under gentle heating conditions in NaOAc/AcOH, brominated lactol silyl ethers were selectively converted to 4-aryl-1,3-dihydroxy-2-
naphthoates – a naphthalene scaffold with a fully substituted benzene unit. The present reaction including a 1,2-aryl migration process
was successfully applied to construct a wide range of polycyclic systems including biphenyl, anthracene, and benzothiophene structures.
In addition, the 4-aryl-1,3-dihydroxy-2-naphthoate products showed bright photoluminescence emmission from solid-state as well as in
several organic solvents.
9
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