Photodecarboxylation of Substituted Naphthylmethyl Arylacetate Esters: Synthesis of Naphthylarylethanes

Article abstract of DOI:10.1021/acs.joc.9b01871

The synthesis of naphthylarylethanes via the photodecarboxylation of naphthylmethyl arylacetate esters is reported where the aryl group is able to stabilize a charge transfer reaction. The reaction proceeds via intramolecular charge transfer from the donor to acceptor, thereby enhancing a pathway to produce, within the solvent cage, the desired diarylethane products. These in-cage naphthylarylethanes are produced in good yields, in a single photochemical step, with the use of cyclohexane as a solvent providing optimal yields.

Full text of DOI:10.1021/acs.joc.9b01871

Article
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
pubs.acs.org/joc
Photodecarboxylation of Substituted Naphthylmethyl Arylacetate
Esters: Synthesis of Naphthylarylethanes
James W. Hilborn,* Reinaldo Moya-Barrios, and Alison Thompson*
Department of Chemistry, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia B3H 4R2, Canada
*
S Supporting Information
ABSTRACT: The synthesis of naphthylarylethanes via the photodecarboxylation of
naphthylmethyl arylacetate esters is reported where the aryl group is able to stabilize
a charge transfer reaction. The reaction proceeds via intramolecular charge transfer
from the donor to acceptor, thereby enhancing a pathway to produce, within the
solvent cage, the desired diarylethane products. These in-cage naphthylarylethanes
are produced in good yields, in a single photochemical step, with the use of cyclohexane as a solvent providing optimal yields.
INTRODUCTION
photodecarboxylation of naphthylmethyl acetate and benzylic
esters under mild conditions in dioxane or methanol at room
■
Diarylethanes are important for the preparation of pharma-
ceutically active species, such as the combretastatin analogues,
which exhibit antineoplastic properties,
16,17,19
temperature.
The viability of the mechanistic pathways
1
−4
involving naphthylmethyl ester substrates was elucidated in
as well as synthetic
methanol. Once excited, the ester (S ) undergoes homolytic
1
intermediates for the preparation of polycyclicaromatic hydro-
5
cleavage (denoted by the rate constant k ), whereupon two
R
carbons. Access to diarylethanes typically relies upon one of
6
7
processes then compete: path A, where the electron transfer
three strategies that involve either Wittig or Mizoroki-Heck
(
kET) provides cations and anions, which subsequently form
chemistry followed by reduction; carbon−hydrogen activation
8
ionic-derived products, and path B, where decarboxylation
of toluyl substrates; or the production and subsequent
R
2
•
(
kCO2 ) of the acyloxy radical (R -CH CO ) produces the
2 2
coupling of benzylic radicals produced from benzyl halides
and the use of chemical initiators.
9
−13
1
•
Although the latter route
benzylic-type radical that combines with R -CH to provide
2
is attractive, these radicals must successfully scavenge other
benzyl radicals to form the desired diarylethane. Reactions are
therefore fraught with challenges and result in low yields due
to the inevitability of other radical-derived reactions, undesired
scavenging, and the formation of unwanted by-products and
polymeric materials. These intermolecular reactions have thus
been limited to substrates that serve to provide, via geminate
radical pair combination reactions, diarylethane products
lacking substituents that would undesirably react with radicals.
Furthermore, the conditions typically used for these reactions
involve the use of toxic or expensive catalysts, as well as the use
of high temperature. For instance, recent examples utilize
nickel(II) chloride as the catalyst with samarium and a
tetrahydrofuran (THF)/hexamethylphosphoramide-mixed sol-
diarylethanes within the solvent cage. An alternative route,
path C, involves charge transfer (k ) from the initial excited
E
singlet state to produce an intramolecular exciplex, and
E
diarylethanes via kCO2 , i.e., decarboxylation from the intra-
molecular exciplex.
For this process to have synthetic utility in the preparation
of naphthylarylethanes, paths B (geminate combination only)
and C would need to become the dominant processes, thereby
reducing the potential for path A to be competitive. This could
potentially be achieved via the use of a nonpolar solvent, so as
to minimize path A, or by tuning the ester substrates to
stabilize intramolecular charge transfer (exciplex formation,
path C) and thereby support the formation of the desired
diarylethane product. For example, selecting naphthylmethyl
phenylacetate esters would present the acyloxy group of the
ester as a good donor that would stabilize a radical cation to
promote path C. Indeed, when a single methoxy group is
added to the phenylacyloxy group of the naphthylmethyl ester,
14
vent system at reflux temperature.
Preparation of diarylethanes could be envisioned within a
solvent cage by the extrusion of carbon dioxide (i.e.,
photodecarboxylation) of suitably substituted esters. In this
case, the respective moieties of the ester could be tuned so as
to produce species that combine, in-cage, to produce
diarylethanes. Thus, for this reaction to be without
complications, it would be advantageous for it to proceed
the charge transfer pathway (k ) leads to the production of
E
E
20
radical-derived products (kCO2 ). In methanol, this single
substituent preferentially directed the dominant mechanism to
proceed via the charge transfer (exciplex) to form the
diarylethane but was insufficient to effect the sole formation
of the exciplex. Given this, we suspect that the addition of a
through the singlet excited state (S ). Naphthylmethyl esters
1
1
5−18
are known
to exclusively cleave via the singlet excited
state, providing a unique platform for the proposed synthesis of
naphthylarylethanes as shown in Figure 1.
Reports show that unsymmetrical diarylethanes have been
produced, albeit within complex product mixtures, via the
Received: July 10, 2019
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Figure 1. Radical pathway to diarylethanes via decarboxylation of esters.
c
Table 1. Photolysis of Esters 1a−1i in Methanol
a
starting material
X
products
methylether
(3−6) (%)
total
(%)
ester 1 Np-position substitution
R2
out-of-cage naphthyl dimer (%) in-cage reaction product (2a−2i) (%)
a
b
c
d
e
f
g
h
i
1
1
2
2
1
2
1
1
1
H
H
H
H
H
H
4-Me
4-CN
4-CN
1-Np
2-Np
1-Np
2-Np
3,4,5-trimethoxy Ph
3,4,5-trimethoxy Ph
1-Np
NA
2
2
NA
3
ND
ND
ND
ND
51
46
45
62
30
31
22
33
19
10
15
2
81
79
69
95
86
64
b
b
b
b
86
96
47
54
23
62
56
26
1-Np
3,4,5-trimethoxy Ph
3
a
b
Yield determined by calibrated GC-FID. Yield determined by calibrated GC-mass spectrometry (MS) in an attempt to enable identification of
c
any other products of photolysis. ND, not detected; NA, not applicable; Np, naphthyl.
more effective electron donor on the acyloxy group of the
RESULTS AND DISCUSSION
■
ester, and an electron acceptor on the naphthalene (alkyl)
Herein we report our success promoting naphthylarylethane
formation by using either a naphthyl group or a 3,4,5-
trimethoxyphenyl group in the acyloxy moiety of the
E
group, would enhance the kCO2 pathway (path C and thus
E
kCO2 ≫ k ). Examples of intramolecular electron transfer
ER
2
(
exciplex formation) have been reported in corresponding
naphthylmethyl ester (R in Figure 1). The nature of the
2
1−24
1
systems.
For instance, in the 1-naphthylmethyl benzoate
naphthyl or substituted-naphthyl alkyl moiety of the ester (R
in Figure 1) tunes the electron-acceptor character of R CH
2
2
2
system, the electron transfer occurs between the naphthalene
ring and the benzene ring, paralleling the original naph-
thylmethyl phenylacetate work.
2
and thereby promotes path C, as well as enables investigation
of the tolerance of the methodology to these functional groups.
The desired esters (1a−1i) were synthesized through the
coupling of the respective alcohols and (activated) acids (see
GP1 and GP2 in the Experimental Section). This series was
selected so as to determine whether judicious use of
substituent effects within the acyloxy and alkyl groups of the
ester could serve to promote naphthylarylethane formation via
direct photolysis. Photolysis of methanolic solutions of esters
1a−1i was achieved using a 200 W Hanovia medium-pressure
Quartz Hg lamp in a Pyrex immersion well, as described in the
Experimental Section. Reactions were monitored using gas
chromatography (GC) and taken to completion for the
preparative scale runs. Analytical runs were monitored by
GC using previously isolated, purified, and characterized
Promoting paths B and C, and thereby a practical
preparation of diarylethanes from suitably substituted esters,
exploits the advantages of this synthetic strategy over reported
methods, i.e., room temperature, requires no catalyst, and the
reaction workup is straightforward. The photochemistry
promises to be relatively uncomplicated since it occurs
exclusively via the singlet excited state. The products are
rapidly formed and almost exclusively within the solvent
1
7,20
cage,
so that the substrate esters can include substituents
(
i.e., nitriles) that normally would react with radicals diffusing
through the solvent. For these ester substrates, this method-
ology eliminates the need for complex synthetic steps and
provides good yields of the desired naphthylarylethanes.
B
DOI: 10.1021/acs.joc.9b01871
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The Journal of Organic Chemistry
Article
Figure 2. Undesired methylether photoproducts.
a,b
Table 2. Photolysis of Esters 1a−1i in Cyclohexane
starting material
X
products
out-of-cage naphthyl dimer (%) in-cage reaction product (2a−2i) (%)
methylether
(3−6) (%)
ester 1 Np-position substitution
R
a
b
c
d
e
f
g
h
i
1
1
2
2
1
2
1
1
1
H
H
H
H
H
H
4-Me
4-CN
4-CN
1-Np
2-Np
1-Np
2-Np
3,4,5-trimethoxy Ph
3,4,5-trimethoxy Ph
1-Np
NA
ND
1
NA
6
72
55
60
74
81
65
79
71
50
1
ND
ND
ND
1-Np
3,4,5-trimethoxy Ph
a
b
Yield determined by calibrated GC-FID. ND, not detected; NA, not applicable; Np, naphthyl.
materials to enable quantitative analysis (see GP3, GP4, and
GP5 in the Experimental Section).
trimethoxy group, which provides supporting evidence that this
group is a better electron donor and therefore better stabilizes
the radical cation and perhaps directs more of the reaction to
proceed by path C.
For the naphthylmethyl esters (1a−1i) in methanol (Table
1
), the major product in each case was the desired diarylethane
(
2a−2i) formed by the in-cage reaction by the stabilization of
This same behavior is seen for the 2-substituted
naphthylmethyl esters (1c, 1d, and 1f), which also provide
increased yields of the naphthylarylethane products (2c, 2d,
and 2f), since the 3,4,5-trimethoxyphenylacetyloxy group is a
better electron donor than the naphthyl group and thereby
presumably stabilizes the radical cation enroute (via path C).
the charge transfer intermediate pathway (path C) and/or path
B. However, the methylethers (3−6, Figure 2) were also
obtained in significant amounts, courtesy of the respective
ionic-derived minor pathway being operative (path A, Figure
1
). For the mechanism given in Figure 1, the effects on the
product formation of inter- (k ) and intramolecular (k )
We can therefore propose that the acyloxy donor group of the
ET
E
2
charge/electron transfer, i.e., path A vs paths B and C,
ester (R CH in Figure 1) has a dominating influence in the
2
20
respectively, are understood. Nevertheless, overall conver-
sions were reasonably high (see Table 1), the exception being
ester 1i. It should be noted that, although considered, the
corresponding methylnaphthalene photoproducts were not
observed in these reactions, as consistent with previous studies
production of the naphthylarylethane coupling product (2a−
2i) than the position of the substituent on the naphthalene of
1
the alkyl acceptor (R CH ) group of the ester. This is
2
supported by the fact that photolysis of ester 1g, bearing an
electron-donating methyl group on the naphthalene ring,
results in a similar yield to those obtained for esters 1a and 1c.
For esters 1h and 1i, the incorporation of a nitrile group on the
naphthalene ring (alkyl group of the ester) with the same
donor group (acyloxy group of the ester) provides the most
extreme case for charge transfer (path C). However, the overall
yields for the naphthonitrile substrates (1h and 1i) are lower
for the photoreactions in methanol (Table 1) supporting the
15,17,20
involving 1-naphthylmethyl acetate esters.
For esters (1a−1h), the yields from the photolysis in
methanol (Table 1) ranged from 45−86% yield for the
naphthylarylethane products (2a−2h), while the methylether
(
3−6) was obtained in a 2−33% yield. These results
demonstrate that the undesired methylethers are produced in
significant amounts (via path A) even when the acyloxy group
2
2
of the ester (R CH in Figure 1, where R is a naphthyl or
notion that, although path C (k ) is dominant, another
2
E
3
,4,5-trimethoxyphenyl group) has been tuned to enhance the
pathway is also present. In a previous work, the photo-
chemistry of naphthonitrile in the presence of similar methoxy-
substituted phenylacetic acid derivatives provides a mixture of
electron-donor ability in an effort to form greater amounts of
the desired in-cage radical products. Evidently, since path A is
still operative, the substitution effects on the acyloxy donor of
the ester are insufficient to direct the reaction to the single
desired product. Evaluating the yields when using the same
naphthyl-substituted alkyl group (R CH in Figure 1) [1-
25
different products thereby supporting this conclusion.
From the results obtained in methanol (see Table 1), it is
clear that the substituent (electronic) effects were not sufficient
to influence the process to form only a single product
(diarylethane) and thereby direct the process exclusively
1
2
position on the naphthalene ring (1a, 1b, and 1e)] with a
different acyloxy donor (R CH ), the yield of the naphthylaryl-
2
through pathways B and C (k ). In an effort to promote
2
E
ethane increases going from the naphthalene ring to the 3,4,5-
radical production, the use of cyclohexane as a solvent was
C
DOI: 10.1021/acs.joc.9b01871
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The Journal of Organic Chemistry
Article
solvent signal at δ = 7.26 as an internal standard. 13C NMR spectra
were recorded using the proton-decoupled UDEFT pulse sequence,
and chemical shifts are reported in ppm referenced to the CDCl3
signal at δ = 77.2. Multiplicity is presented as follows: s = singlet, d =
doublet, dd = doublet of doublets, t = triplet, and m = multiplet.
Coupling constant(s), J, are reported in hertz (Hz), alongside
integration. HRMS data were obtained using a micrOTOF mass
spectrometer operating in a positive-ion APPI or ESI mode. Reaction
samples were analyzed using a GC-FID instrument equipped with a
DB-5 megabore column (30 m × 0.53 mm with a 1.5 μm film
thickness), an FID detector, and an AOC-20i autosampler: initial
temperature 140 °C for 4 min then a 25 °C/min ramp to 300 °C and
hold for 10 min; injector and detector temperatures set at 320 °C
with an injection volume of 3.0 μL. For the GC/MS analysis, a HP
investigated. The nonpolar and nonnucleophilic nature of
cyclohexane was expected to shut down the ionic-derived
photosolvolysis reaction (path A) and instead support the
formation of the radical-derived products. Cognizant that
success would result in a practical route to radical-derived
diarylethanes, solutions of esters 1a−1i in cyclohexane were
photolysed using the same conditions as used for reactions
involving methanol (Table 2). Gratifyingly, the desired
diarylethanes were essentially the only products observed.
The out-of-cage reaction products (naphthyl dimer) were
observed at trace levels. The reaction provides a single
synthetic step to the desired naphthylarylethanes (2a−2i, in-
cage products) from the corresponding esters. The use of
cyclohexane as a solvent renders path A unavailable, and
therefore photolysis presents only paths B and C and thus the
formation of only the in-cage product. In cyclohexane, no
appreciable differences were noticed in the individual product
6
890 GC with a HP 5973 mass selective detector was used equipped
with a HP-5 5% phenyl methyl siloxane column (30 m × 0.25 mm ×
.5 μm film thickness): initial temperature 140 °C for 4 min then a 25
C/min ramp to 300 °C and hold for 10 min; injector and detector
0
°
temperatures set at 230 °C with an injection volume of 1.0 μL.
Synthesis of Substituted 1- and 2-Naphthylmethyl Sub-
stituted Acetate Esters (1a−1i). General Procedure 1 (GP1) for
the Preparation of Esters (1a−1d, 1g). With the modification of a
yields by changing the substitution pattern of the donor
2
(
R CH ) at the 1- and 2-positions on the naphthalene ester
2
(
1a−1d), as seen in Table 2. Varying the substituents on the
15
reported procedure, pyridine (1 mL) was added to a well-stirred
solution of the naphthalenemethanol (20 mmol, 1 equiv; i.e., 3.16 g in
the case of 1-naphthalenemethanol to enable the preparation of 1a) in
toluene (50 mL). To this solution was slowly added a solution of the
required acid chloride (22 mmol, 1.1 equiv; i.e., 4.50 g in the case of
naphthalene ring on the acceptor (alkyl moiety of the ester),
while maintaining the 1-naphthalene group on the acyloxy
donor (1a, 1c, 1g, and 1h) provides the naphthylarylethane
(
in-cage) product (2a, 2c, 2g, and 2h) in similar yields, no
matter what the substitution pattern.
1-naphthylacetyl chloride to enable the preparation of 1a) in toluene
(
30 mL) over 30 min. Stirring was continued for an additional 16 h at
CONCLUSIONS
room temperature. The reaction was quenched by adding water and
the two layers were separated. The toluene layer was washed with
■
Naphthylmethyl esters (1a−1i) were photolyzed in methanol
and cyclohexane resulting in appropriately substituted
naphthylarylethanes (2a−2i) as the major product in each
case. In methanol, the ester photolysis does not produce the
diarylethanes exclusively as the charge transfer (exciplex)
pathway (via path C) does not dominate. The photolysis of
these same esters in cyclohexane renders the photosolvolysis
pathway (path A) unavailable and thereby provides a
synthetically useful method for the preparation of naphthylaryl-
ethanes in good yield. In short, solvent effects have a greater
impact on the product distribution than do changes to
substituent patterns around these substrates.
1
0% aq. HCl (2 × 50 mL), 5% aq. NaOH (50 mL), and water (50
mL). The organic layer was then dried (MgSO ), filtered, and the
4
solvent removed in vacuo to yield the crude ester. The crude material
was purified via column chromatography over silica gel using 3%
EtOAc/hexane as eluent. The resultant ester was crystallized from
hexane.
General Procedure 2 (GP2) for the Preparation of Esters (1e−1f,
1
h−1i). The acid (5.3 mmol, 1 equiv; i.e., 1.20 g in the case of 3,4,5-
trimethoxyphenylacetic acid to enable preparation of 1e) was
dissolved in dry THF (20 mL) and the solution cooled to 0 °C.
1
,1′-Carbonyldiimidazole (1.04 g, 6.4 mmol, 1.2 equiv) was then
added as a solid. The solution was allowed to warm to room
temperature and then stirred at this temperature for 1 h. To this
solution was added a solution of the alcohol (6.9 mmol, 1.3 equiv; i.e.,
EXPERIMENTAL SECTION
1
.01 g in the case of 1-naphthalenemethanol to enable the preparation
of 1e) dissolved in dry THF (10 mL), and stirring was continued for
2 h. The solvent was removed in vacuo and the residue dissolved in
EtOAc (50 mL). The solution was washed with aq. 5% HCl (20 mL),
aq. 2% NaHCO (20 mL), and water (20 mL). The organic layer was
■
All reactions were carried out under an inert atmosphere of nitrogen
or argon with magnetic stirring. Reagents and solvents were used as
received from commercial sources except as follows. 4-Methyl-1-
7
15
28
naphthalenemethanol, 1-naphthylacetyl chloride and 2-naphthy-
lacetyl chloride were prepared according to literature procedures. 4-
Cyano-1-naphthalenemethanol was prepared from the corresponding
3
28
then dried (MgSO ), filtered, and the solvent was removed in vacuo.
The residue was purified via column chromatography using 30%
EtOAc/hexane as eluent. The resultant ester was crystallized from
warm CH Cl /hexane.
4
26
27
benzyl bromide followed by hydrolysis using aq. CaCO and 1-
3
2
8
28
naphthylacetyl chloride and 2-naphthylacetyl chloride were
prepared according to literature procedures. Preparative reactions
were followed using TLC analysis involving precoated (silica gel 60
F254, 0.25 mm) plates with plastic backing and UV light as the
visualizing agent. Column chromatography was carried out using silica
gel (63−200 μm particle size, 70−230 mesh). Melting points were
measured using a Fisher−Johns Melting Point apparatus and are
uncorrected. IR spectra, provided in cm , were recorded using an
FTIR instrument after either preparing a KBr pellet or dissolving the
sample in CH Cl and allowing the solvent to evaporate to provide a
2 2
2
9
1-Naphthylmethyl 1-Naphthylacetate (1a). According to GP1,
the title compound was prepared from 1-naphthylacetyl chloride and
1-naphthalenemethanol; white solid; yield 73%; mp 103−104 °C;
3
4
4
UV: λmax 261 (ε 7.25 × 10 ), 271 (1.13 × 10 ), 281 (1.36 × 10 ), 292
3
−1
1
(9.65 × 10 ) nm; IR (KBr): 3038, 2959, 1728 cm . 500 MHz H
NMR δ: 7.95 (d, J = 8.1 Hz, 1H), 7.87−7.77 (m, 5H), 7.51−7.38 (m,
−
1
13
8H), 5.58 (s, 2H), 4.11 (s, 2H) ppm; 125 MHz C{1H} NMR δ:
171.5, 133.9, 133.7, 132.1, 131.6, 131.3, 130.5, 129.3, 128.7, 128.6,
128.1, 128.1, 127.5, 126.5, 126.3, 125.9, 125.8, 125.5, 125.2, 123.8,
123.6, 65.2, 39.3 ppm. [CAS 72977-58-3]. No literature data available.
2
2
−
1
film on NaCl plates. Only the significant absorption bands (cm ) are
reported. UV spectra are provided in nanometer and were obtained in
acetonitrile using a UV−vis spectrophotometer, and the molar
3
0
1-Naphthylmethyl 2-Naphthylacetate (1b). According to GP1,
the title compound was prepared from 2-naphthylacetyl chloride and
1-naphthalenemethanol; white solid: yield 53%; mp 77−78 °C; UV:
−
1
−1
1
13
absorption coefficients (ε) are defined in L mol cm . H and
C
3
4
4
NMR spectra were obtained in deuterated chloroform (CDCl ) and
were recorded using a 500 MHz spectrometer. H chemical shifts are
reported in ppm relative to tetramethylsilane using the CDCl residual
λ
261 (ε 7.27 × 10 ), 271 (1.04 × 10 ), 280 (1.10 × 10 ), 289
max
3 1
3
1
−1
(7.99 × 10 ) nm; IR (KBr): 3044, 2962, 1727 cm . 500 MHz H
NMR δ: 7.91 (d, J = 8.4 Hz, 1H), 7.87−7.70 (m, 6H), 7.51−7.38 (m,
3
D
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H), 5.59 (s, 2H), 3.82 (s, 2H) ppm; 125 MHz 13C{1H} NMR δ:
71.4, 133.7, 133.5, 132.5, 131.6, 131.4, 131.3, 129.3, 128.7, 128.2,
28.0, 127.7, 127.6, 127.5, 127.4, 126.5, 126.1, 125.9, 125.8, 125.2,
10 ), 300 (1.10 × 10 ) nm; IR (film): 3061, 2227, 1744 cm . 500
4
4
−1
7
1
1
1
1
MHz H NMR δ: 8.24 (d, J = 8.3 Hz, 1H), 7.91−7.74 (m, 5H), 7.67
(t, J = 7.3 Hz, 1H), 7.53−7.35 (m, 6H), 5.58 (s, 2H), 4.14 (s, 2H)
30
13
23.6, 65.1, 41.6 ppm. [CAS 86328-64-5]. Only mass spectral
ppm; 125 MHz C{1H} NMR δ: 171.1, 137.2, 133.8, 132.4, 132.0,
literature data available.
-Naphthylmethyl 1-Naphthylacetate (1c). According to GP1,
the title compound was prepared from 1-naphthylacetyl chloride and
-naphthalenemethanol; white solid: yield 83%; mp 75−76 °C
132.0, 130.8, 130.1, 128.8, 128.4, 128.3, 128.2, 128.0, 126.4, 125.9,
125.9, 125.5, 125.3, 124.0, 123.6, 117.6, 111.0, 64.0, 39.3 ppm;
3
1
2
+
HRMS (ESI/TOF) m/z: [M + Na] calculated for C H NO Na
2
4
17
2
2
374.1152; found 374.1161.
3
1
3
although literature 57−59 °C; UV: λ 261 (ε 7.25 × 10 ), 272
4-Cyano-1-naphthylmethyl 3,4,5-Trimethoxyphenylacetate (1i).
According to GP2, the title compound was prepared from 3,4,5-
trimethoxyphenylacetic acid and 4-cyano-1-naphthalenemethanol;
max
4
4
3
(
1.02 × 10 ), 280 (1.05 × 10 ), 292 (6.11 × 10 ) nm; IR (KBr):
−
1 1
3
7
1
045, 2958, 1725 cm . 500 MHz H NMR δ: 8.00−7.99 (m, 1H),
.87−7.85 (m, 1H), 7.81−7.75 (m, 3H), 7.72−7.68 (m, 1H), 7.63 (s,
pale yellow solid: yield 63%; mp 120−121 °C; UV: λ
287 (ε
max
3
3
3
H), 7.48−7.45 (m, 4H), 7.43−7.41 (m, 2H), 7.32 (dd, J = 8.4 Hz,
7.60 × 10 ), 289 (9.21 × 10 ), 308 (7.51 × 10 ) nm; IR (film): 3088,
1 1
1
−
J = 1.5 Hz, 1H), 5.28 (s, 2H), 4.14 (s, 2H) ppm in accord with
3071, 3007, 2970, 2946, 2838, 2230, 1740 cm . 500 MHz H NMR
δ: 8.29 (d, J = 8.3 Hz, 1H), 7.98 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 7.3
Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.63 (t, J = 7.7 Hz, 1H), 7.56 (d, J =
7.4 Hz, 1H), 6.45 (s, 2H), 5.62 (s, 2H), 3.83 (s, 3H), 3.75 (s, 6H),
2
31
13
literature; 125 MHz C{1H} NMR δ: 171.4, 133.9, 133.2, 133.1,
1
1
1
33.0, 132.1, 130.5, 128.7, 128.2, 128.1, 128.1, 127.9, 127.6, 127.0,
26.4, 126.2, 126.2, 125.8, 125.6, 125.5, 123.8, 66.7, 39.2 ppm [CAS
29633-45-0].
1
3
3.62 (s, 2H) ppm; 125 MHz C{1H} NMR δ: 171.1, 153.3, 137.4,
137.3, 132.5, 132.1, 131.0, 129.0, 128.6, 128.2, 126.1, 125.7, 124.2,
117.5, 111.2, 106.4, 64.2, 60.9, 56.1, 41.6 ppm; HRMS (ESI/TOF)
1
7
2
-Naphthylmethyl 2-Naphthylacetate (1d). According to GP1,
the title compound was prepared from 2-naphthylacetyl chloride and
-naphthalenemethanol; white solid: yield 87%; mp 138−140 °C;
+
2
m/z: [M + Na] calculated for C H NO Na 414.1312; found
2
3
21
5
3
3
3
UV: λ 257 (ε 6.82 × 10 ), 268 (9.18 × 10 ), 275 (9.66 × 10 ), 286
414.1326.
max
3
−1
1
(
6.43 × 10 ) nm; IR (KBr): 3051, 2950, 1732 cm . 500 MHz H
Irradiations. Analytical Photolysis. Irradiations for analytical
work were carried out using a medium-pressure Hanovia 200 W
Quartz Hg lamp in a Pyrex 400 mL water-jacketed immersion well.
The ester, 1a−1i (∼300 mg) was dissolved in the solvent (methanol
or cyclohexane) and irradiated at room temperature. The progress of
the reaction was monitored via the GC-FID analysis.
NMR δ: 7.82−7.70 (m, 8H), 7.48−7.38 (m, 6H), 5.30 (s, 2H), 3.85
17
13
(s, 2H) ppm in accord with the literature; 125 MHz C{1H} NMR
δ: 171.4, 133.5, 133.3, 133.2, 133.1, 132.5, 131.4, 128.3, 128.3, 128.0,
1
1
28.0, 127.7, 127.7, 127.6, 127.4, 127.2, 126.3, 126.2, 126.2, 125.8,
25.7, 66.8, 41.6 ppm [CAS 53342-33-9].
1
-Naphthylmethyl 3,4,5-Trimethoxyphenylacetate (1e). Accord-
Analytical Standards. Preparative Photolysis. General Proce-
dure 3 (GP3) for the Isolation of the Major Photoproduct (2a−2i).
To obtain the major photoproduct products (in-cage coupling) for
full characterization and use as standards for the subsequent
photolysis-based analytical work, these compounds were prepared
from preparatory photolysis of each of the corresponding esters. Thus,
a solution of the ester (∼300 mg) in cyclohexane was placed in a
Pyrex 400 mL water-jacketed immersion well. In some cases, the
solvent was warmed to dissolve the ester. The solution was bubbled
with argon before and during the irradiation. The temperature for the
irradiations was maintained at room temperature. The light source
was a 200 W medium-pressure Hanovia Quartz Hg lamp. The
irradiations were continued for 48 h. After this period of time, the
photolysis solutions were filtered through a filter paper to remove any
insoluble products (dimeric/polymeric material) and the solvent was
evaporated to dryness. The above procedure was performed twice to
obtain sufficient material to be used as a standard. The resultant oil
was purified via column chromatography using 2% EtOAc/hexane as
the eluent. The first eluting fractions were always the in-cage reaction
ing to GP2, the title compound was prepared from 3,4,5-
trimethoxyphenylacetic acid and 1-naphthalenemethanol; white
3
solid: yield 50%; mp 73−74 °C; UV: λ 262 (ε 4.75 × 10 ), 270
max
3
3
3
(
6.96 × 10 ), 279 (7.82 × 10 ), 290 (5.07 × 10 ) nm; IR (film):
−1 1
2
997, 2960, 2939, 2837, 1735 cm . 500 MHz H NMR δ: 7.93−7.91
(
m, 1H), 7.87−7.84 (m, 2H), 7.52−7.50 (m, 3H), 7.46 (t, J = 7.7 Hz,
1
2
1
1
H), 6.44 (s, 2H), 5.59 (s, 2H), 3.82 (s, 3H), 3.71 (s, 6H), 3.59 (s,
1
3
H) ppm; 125 MHz C{1H} NMR δ: 171.5, 153.3, 137.2, 133.8,
31.7, 133.3, 129.5, 129.4, 128.7, 127.7, 126.6, 126.0, 125.3, 123.6,
06.3, 65.2, 60.8, 56.0, 41.8 ppm; HRMS (ESI/TOF) m/z: [M +
Na] calculated for C H O Na 389.1359; found 389.1358 [CAS
+
2
2
22
5
1
003966-04-8].
2
-Naphthylmethyl 3,4,5-Trimethoxyphenylacetate (1f). Accord-
ing to GP2, the title compound was prepared from 3,4,5-
trimethoxyphenylacetic acid and 2-naphthalenemethanol; white
3
solid: yield 70%; mp 75−76 °C; UV: λ 266 (ε 5.16 × 10 ), 274
max
3
3
(
5.49 × 10 ), 286 (3.32 × 10 ) nm; IR (film): 2962, 2943, 2831, 1732
−
1 1
cm . 500 MHz H NMR δ: 7.83−7.77 (m, 4H), 7.50−7.47 (m, 2H),
7
3
.41 (dd, J = 8.4 Hz, J = 1.5 Hz, 1H), 6.50 (s, 2H), 5.31 (s, 2H),
products.
1
2
1
3
11,32
.83 (s, 3H), 3.78 (s, 6H), 3.62 (s, 2H) ppm; 125 MHz C{1H}
1-(1-Naphthyl)-2-(1-naphthyl)ethane (2a).
Prepared accord-
NMR δ: 171.3, 153.2, 137.2, 133.2, 133.1, 133.1, 129.4, 128.3, 127.9,
27.7, 127.3, 126.3, 126.3, 125.7, 106.3, 66.7, 60.8, 56.0, 41.6 ppm;
ing to GP3 using ester 1a; light beige solid; mp 164−165 °C,
33
1
1
literature 162−163 °C; 500 MHz H NMR δ: 8.13 (d, J = 8.3 Hz,
2H), 7.89−7.87 (m, 2H), 7.75 (d, J = 8.2 Hz, 2H), 7.55−7.48 (m,
4H), 7.40 (t, J = 7.6 Hz, 2H), 7.35 (d, J = 6.3 Hz, 2H), 3.52 (s, 4H)
+
HRMS (ESI/TOF) m/z: [M + Na] calculated for C H O Na
2
2
22
5
3
89.1359; found 389.1367.
1
3
4
-Methyl-1-naphthylmethyl 1-Naphthylacetate (1g). According
ppm; 125 MHz C{1H} NMR δ: 138.1, 134.0, 131.9, 128.9, 126.8,
125.9, 125.9, 125.6, 125.5, 123.7, 34.1 ppm [CAS 15374-45-5]. Only
melting point data available in the literature.
to GP1, the title compound was prepared from 1-naphthylacetyl
chloride and 4-methyl-1-naphthalenemethanol; white solid: yield
4
4
3
2
5
1
4%; mp 73−74 °C; UV: λ 276 (ε 1.30 × 10 ), 281 (1.42 × 10 ),
1-(1-Naphthyl)-2-(2-naphthyl)ethane (2b/c). Prepared according
to GP3 using either ester 1b or 1c; light beige solid; mp = 84−85 °C;
max
4
−1
85 (1.39 × 10 ) nm; IR (film): 3069, 3045, 2964, 2947, 1733 cm .
00 MHz H NMR δ: 8.02 (d, J = 8.3 Hz, 1H), 7.95 (d, J = 8.6 Hz,
H), 7.85 (d, J = 8.3 Hz, 2H), 7.77 (t, J = 4.6 Hz, 1H), 7.53 (t, J = 8.0
1
1
500 MHz H NMR δ: 8.15 (d, J = 8.6 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.83−7.77 (m, 3H), 7.71 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H),
Hz, 1H), 7.47−7.38 (m, 5H), 7.35 (d, J = 7.1 Hz, 1H), 7.24 (s, 1H),
7.56−7.36 (m, 6H), 7.31 (d, J = 6.8 Hz, 1H), 3.47 (t, J = 8.3 Hz, 2H),
1
3
13
5
.54 (s, 2H), 4.08 (s, 2H), 2.68 (s, 3H) ppm; 125 MHz C{1H}
3.22 (t, J = 8.2 Hz, 2H) ppm; 125 MHz C{1H} NMR δ: 139.6,
NMR δ: 171.5, 135.8, 133.9, 132.9, 132.1, 131.7, 130.5, 129.5, 128.7,
137.8, 134.0, 133.8, 132.2, 131.9, 128.9, 128.0, 127.7, 127.5, 127.4,
126.9, 126.5, 126.1, 126.0, 125.6, 125.6, 125.5, 125.4, 123.7, 37.3, 35.1
1
1
28.1, 128.1, 127.5, 126.4, 126.2, 126.0, 125.8, 125.8, 125.5, 124.8,
+
24.2, 123.9, 65.4, 39.3, 19.6 ppm; HRMS (ESI/TOF) m/z: [M +
ppm; HRMS (APPI) m/z: [M] calculated for C H 282.1408;
2
2
18
+
Na] calculated for C H O Na 363.1356; found 363.1362.
found 282.1413 [CAS 83313-24-0]. No literature data available.
2
4
20
2
34
4
-Cyano-1-naphthylmethyl 1-Naphthylacetate (1h). According
1-(2-Naphthyl)-2-(2-naphthyl)ethane (2d). Prepared according
35
to GP2, the title compound was prepared from 1-naphthaleneacetic
to GP3 using ester 1d; white solid; mp = 185−186 °C, literature
1
acid and 4-cyano-1-naphthalenemethanol; pale yellow solid: yield
182−184 °C; 500 MHz H NMR δ: 7.81−7.75 (m, 6H), 7.65 (s,
2H), 7.46−7.40 (m, 4H), 7.36 (dd, J = 8.4 Hz, J = 1.6 Hz, 2H), 3.18
4
5
8%; mp 127−128 °C; UV: λmax 282 (ε 1.13 × 10 ), 292 (1.21 ×
1
2
E
DOI: 10.1021/acs.joc.9b01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(
s, 4H) ppm in accord with the literature; 125 MHz 13C{1H} NMR
δ: 139.3, 133.7, 132.1, 127.9, 127.6, 127.5, 127.4, 126.5, 125.9, 125.2,
8.0 ppm [CAS 21969-45-9].
-(1-Naphthyl)-2-(3,4,5-trimethoxyphenyl)ethane (2e). Prepared
34
room temperature and then the methanol was removed in vacuo. The
residue was dissolved in CH Cl (50 mL) and washed with 1% aq.
HCl (25 mL) and water (25 mL). The organic layer was dried
2
2
3
1
(MgSO ), filtered, and the solvent was removed in vacuo. The crude
4
according to GP3 using ester 1e; off-white solid; mp = 98−99 °C; 500
material was purified via column chromatography using 5% EtOAc/
hexane as eluent. The resulting oil was further purified by a bulb-to-
bulb distillation to obtain a colorless oil.
1
MHz H NMR δ: 8.05 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H),
7
7
3
.72 (d, J = 8.3 Hz, 1H), 7.51−7.47 (m, 2H), 7.38 (t, J = 7.6 Hz, 1H),
.28 (d, J = 6.8. Hz, 1H), 6.37 (s, 2H), 3.83 (s, 3H), 3.79 (s, 6H),
.37 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H) ppm; 125 MHz
C{1H} NMR δ: 153.2, 137.7, 136.5, 134.0, 131.9, 128.9, 126.8,
1
5
1-Naphthylmethyl Methylether (3). Prepared according to GP4
using 1-methylnaphthalene; yield 0.65 g (27%); liquid, bp 105−108
1
3
15
1
°C (5 Torr), literature 108−110 °C (5 Torr); 500 MHz H NMR
δ: 8.11 (d, J = 7.9 Hz, 1H), 7.86−7.78 (m, 2H), 7.55−7.39 (m, 4H),
1
(
26.2, 125.9, 125.6, 125.5, 123.7, 105.6, 60.9, 56.2, 37.5, 35.0 ppm
15
one 13C signal missing); HRMS (ESI/TOF) m/z: [M + H]
+
4.89 (s, 2H), 3.44 (s, 3H) ppm in accord with literature; 125 MHz
C{1H} NMR δ: 133.9, 133.7, 131.8, 128.7, 128.6, 126.5, 126.3,
1
3
calculated for C H O 323.1642; found 323.1643.
21
23
3
1
-(2-Naphthyl)-2-(3,4,5-trimethoxyphenyl)ethane (2f). According
125.8, 125.2, 124.0, 73.3, 58.3 ppm [CAS 5903-23-1].
1
to GP3 using ester 1f; white solid; mp = 86−87 °C; 500 MHz H
2-Naphthylmethyl Methylether (4). Prepared according to GP4
using 2-methylnaphthalene; yield 1.0 g (41%); liquid; bp 133−136 °C
NMR δ: 7.81−7.75 (m, 3H), 7.60 (s, 1H), 7.46−7.40 (m, 2H), 7.33
1
(
=
d, J = 8.3 Hz, 1H), 6.38 (s, 2H), 3.83 (s, 3H), 3.78 (s, 6H), 3.08 (t, J
(5 Torr); 500 MHz H NMR δ: 7.84−7.78 (m, 4H), 7.47−7.44 (m,
1
3
36
7.5 Hz, 2H), 2.95 (t, J = 7.9 Hz, 2H) ppm; 125 MHz C{1H}
3H), 4.62 (s, 2H), 3.42 (s, 3H) ppm in accord with the literature
NMR δ: 153.1, 139.2, 137.5, 136.4, 133.7, 132.1, 127.9, 127.6, 127.5,
27.4, 126.6, 126.0, 125.3, 105.6, 60.9, 56.1, 38.3, 38.2 ppm; HRMS
[CAS 42101-92-8].
1
General Procedure 5 (GP5) for the Preparation of Ethers for the
+
Synthesis of Substituted Naphthylmethyl Methylethers (5−6). The
(ESI/TOF) m/z: [M + H] calculated for C H O 323.1642; found
21 23 3
4-methyl- and 4-cyano-1-naphthylmethyl methylethers (5 and 6) were
3
23.1655 [CAS 162408-75-5].
-(4-Methyl-1-naphthyl)-2-(1-naphthyl)ethane (2g). Prepared
according to GP3 using ester 1g; white solid; mp = 114−115 °C;
prepared by dissolving the corresponding alcohols (3.1 mmol; i.e.,
.53 g in the case of 4-methyl-1-naphthalenemethanol to enable the
1
0
1
preparation of 5) in dry THF (10 mL). To the solution was added
sodium hydride (80 mg, 3.3 mmol) as a solid, previously washed with
pentane and dried. Effervescence was observed immediately. After
stirring for 5 min, methyl iodide (200 μL, 3.2 mmol) was added. The
reaction mixture was stirred at room temperature for 48 h. The
solvent was removed in vacuo and the residue was then dissolved in
EtOAc (50 mL). The solution was washed with 3% aq. HCl (25 mL),
5
3
7
3
1
1
00 MHz H NMR δ: 8.15−8.10 (m, 2H), 8.04 (dd, J = 6.4 Hz, J =
1
2
.2 Hz, 1H), 7.87 (d, J = 7.1 Hz, 1H), 7.73 (d, J = 7.7 Hz, 1H), 7.54−
.45 (m, 4H), 7.41−7.33 (m, 2H), 7.23 (s, 2H), 3.48 (s, 4H), 2.67 (s,
1
3
H) ppm; 125 MHz C{1H} NMR δ: 138.3, 136.3, 134.0, 133.1,
32.8, 132.0, 131.9, 128.9, 126.8, 126.4, 126.0, 126.0, 125.7, 125.7,
25.6, 125.6, 125.4, 125.0, 124.3, 123.8, 34.3, 34.1, 19.5 ppm; HRMS
ESI/TOF) m/z: [M + H] calculated for C H 297.1638; found
+
(
2
3
21
5
% aq. NaHCO (25 mL), and water (25 mL). The organic layer was
2
3
then dried (MgSO ), filtered, and the solvent was removed in vacuo
4
to provide the crude oil.
according to GP3 using ester 1h; white solid; mp = 146−147 °C;
1
5
1
4-Methyl-1-methoxymethylnaphthalene (5). Prepared accord-
ing to GP5 using 4-methyl-1-naphthalenemethanol. The crude oil was
purified via column chromatography over silica using 10% EtOAc/
hexane as the eluent. The residual oil was further purified via bulb-to-
bulb distillation to obtain a colorless oil. Yield 0.28 g (48%); liquid,
5
1
7
00 MHz H NMR δ: 8.30 (d, J = 8.0 Hz, 1H), 8.16 (d, J = 8.3 Hz,
H), 8.04 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 7.0 Hz, 1H), 7.80 (d, J =
.1 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.70 (t, J = 7.4 Hz, 1H), 7.64
(
t, J = 7.7 Hz, 1H), 7.55−7.47 (m, 2H), 7.36 (t, J = 7.7 Hz, 1H), 7.31
(
d, J = 7.3 Hz, 1H), 7.23 (t, J = 7.1 Hz, 1H), 3.60−3.56 (m, 2H),
15
1
3
bp 147−150 °C (5 Torr), in accord with the literature, 89−93 °C
3
1
1
.51−3.48 (m, 2H) ppm; 125 MHz C{1H} NMR δ: 144.5, 137.0,
1
(
1
0.2 Torr); 500 MHz H NMR δ: 8.16−8.09 (m, 1H), 8.04−7.98 (m,
H), 7.56−7.49 (m, 2H), 7.37 (d, J = 7.0 Hz, 1H), 7.26 (d, J = 7.2
Hz, 1H), 4.87 (s, 2H), 3.42 (s, 3H), 2.68 (s, 3H) ppm in accord with
34.0, 132.8, 132.4, 131.7, 131.6, 129.0, 128.2, 127.6, 127.2, 126.2,
26.1, 126.1, 125.7, 125.6, 125.3, 124.4, 123.3, 118.2, 108.8, 34.3, 33.7
+
ppm; HRMS (ESI/TOF) m/z: [M + H] calculated for C H N
2
3
18
15
1
3
the literature; 125 MHz C{1H} NMR δ: 134.9, 133.1, 131.9,
31.9, 126.5, 125.9, 125.9, 125.7, 124.7, 124.6, 73.4, 58.0, 19.7 ppm.
CAS 71235-76-2]
4-Methoxymethyl-1-naphthonitrile (6). Prepared according to
3
1
[
Prepared according to GP3 using ester 1i; white solid; mp = 120−
3
7
1
1
7
=
21 °C; 500 MHz H NMR δ: 8.29 (d, J = 7.7 Hz, 1H), 8.13 (d, J =
.7 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H), 7.73−7.62 (m, 2H), 7.32 (d, J
GP5 using 4-cyano-1-naphthalenemethanol. The crude oil was
purified via column chromatography over silica using 1% MeOH/
CH Cl as the eluent. The residual oil was further purified via
7.3 Hz, 1H), 6.34 (s, 2H), 3.83 (s, 3H), 3.80 (s, 6H), 3.43 (t, J = 7.9
Hz, 2H), 3.00 (t, J = 7.9 Hz, 2H) ppm; 125 MHz C{1H} NMR δ:
1
3
2
2
crystallization from CH Cl /hexane to provide a white solid. Yield 0.2
1
1
(
53.2, 144.2, 136.6, 132.7, 132.3, 132.3, 131.6, 128.2, 127.5, 126.1,
25.4, 124.4, 118.1, 108.8, 105.5, 60.9, 56.1, 37.1, 35.2 ppm; HRMS
2
2
37
1
g (35%); mp = 70−71 °C, literature 70.5−71.0 °C; 500 MHz H
NMR δ: 8.28 (d, J = 7.5 Hz, 1H), 8.10 (d, J = 7.7 Hz, 1H), 7.89 (d, J
ESI/TOF) m/z: [M + H]+ calculated for C H NO 348.1594;
2
2
22
3
=
7.3 Hz, 1H), 7.73−7.65 (m, 2H), 7.59 (d, J = 7.4 Hz, 1H), 4.94 (s,
37
found 348.1609.
2H), 3.51 (s, 3H) ppm in accord with the literature; 125 MHz
General Procedure 4 (GP4) for the Synthesis of Naphthylmethyl
Methylethers (3−4). The 1- and 2-naphthylmethyl methylethers were
prepared by the benzylic bromination of the corresponding
methylnaphthalenes. Thus, a solution of the appropriate methylnaph-
thalene (14 mmol; i.e., 2.00 g in the case of 1-methylnaphthalene to
enable preparation of 3), NBS (3.1 g, 17 mmol), and a catalytic
amount of benzoyl peroxide were added to carbon tetrachloride (35
mL). The solution was heated to the reflux temperature and stirring
continued at this temperature for 4 h. The reaction mixture was then
cooled to room temperature and filtered. The filtrate was diluted with
CHCl (50 mL) and washed with 5% aq. NaHCO (25 mL) and
1
3
C{1H} NMR δ: 140.0, 132.5, 132.2, 130.9, 128.3, 127.8, 125.9,
124.5, 124.3, 117.9, 110.3, 72.3, 58.7 ppm [CAS 112929-94-9].
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.9b01871.
■
*
S
NMR spectra of the products (PDF)
3
3
water (25 mL). The organic layer was dried (MgSO ), filtered, and
the solvent removed in vacuo. The resultant oil was dissolved in
methanol (50 mL). To the solution was added sodium methoxide
4
AUTHOR INFORMATION
Corresponding Authors
*E-mail: jimwhilborn@gmail.com (J.W.H.).
*E-mail: alison.thompson@dal.ca (A.T.).
■
(
0.65 g, 12 mmol) as a solid and the mixture was then warmed until
the solution was homogeneous. The solution was stirred for 20 h at
F
DOI: 10.1021/acs.joc.9b01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
ORCID
(15) DeCosta, D. P.; Pincock, J. A. Photochemistry of Substituted 1-
Naphthylmethyl Esters of Phenylacetic and 3-Phenylpropanoic Acid:
Radical Pairs, Ion Pairs, and Marcus Electron Transfer. J. Am. Chem.
Soc. 1993, 115, 2180.
(16) Givens, R. S.; Matuszewski, B.; Levi, N.; Leung, D.
Photodecarboxylation. A Labeling Study. Mechanistic Studies in
Photochemistry. J. Am. Chem. Soc. 1977, 99, 1896.
Alison Thompson: 0000-0003-4231-3446
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(17) Givens, R. S.; Matuszewski, B.; Neywick, C. V. Mechanistic and
JWH would like to thank J., M. & J., Dr. James Pincock, Teng
Fei Qin, Pankaj Subedi, Dr. Scott Banfield, Scott MacLellan,
Kelly Swyers, and Margo Frost. The authors also thank Mr.
Xiao Feng (mass spectrometry) and Dr. Mike Lumsden
Synthetic Studies in Organic Photochemistry. XII. Photodecarbox-
ylation of Esters. Photolysis of Alpha- and Beta-naphthalenemethyl
Derivatives. J. Am. Chem. Soc. 1974, 96, 5547.
(18) Pincock, J. A. Photochemistry of Arylmethyl Esters in
Nucleophilic Solvents: Radical Pair and Ion Pair Intermediates. Acc.
Chem. Res. 1997, 30, 43.
(
NMR) for assistance acquiring data at Dalhousie University.
Dr. Norman Schepp is thanked for access to laboratory
infrastructure. This work was supported by the Natural
Sciences and Engineering Research Council of Canada
(
19) Pincock, J. A.; Wedge, P. J. The Photochemistry of
Conformationally Rigid Benzylic Esters: 2,2-Dimethyl-1-indanyl
Acetates and Pivalates. J. Org. Chem. 1995, 60, 4067.
(
NSERC).
(
20) Hilborn, J. W.; Pincock, J. A. Photolysis of the 1-
Naphthylmethyl Ester of Substituted Phenylacetic Acids: Intra-
molecular Charge Transfer and Rates of Decarboxylation of
Arylacyloxy Radicals. Can. J. Chem. 1992, 70, 992.
(21) Coyle, J. D.; Kingston, D. H. Electron Transfer in the
Photochemistry of Substituted Benzoate and Naphthoate Esters. J.
Chem. Soc. Perkin Trans. 2 1976, 1475.
REFERENCES
■
(
1) Medarde, M.; Ramos, A.; Caballero, E.; Clairac, R. P.-L. d.;
Lopez, J. L.; Gravalos, D. G.; Feliciano, A. S. Synthesis and
́
́
Antineoplastic Activity of Combretastatin Analogues: Heterocom-
bretastatins. Eur. J. Med. Chem. 1998, 33, 71.
(
2) Maya, A. B. S.; del Rey, B.; Pelaez Lamamie de Clairac, R.;
(22) DeCosta, D. P.; Pincock, J. A. Intramolecular Electron Transfer
in the Photochemistry of Substituted 1-Naphthylmethyl Esters of
Benzoic Acids. Can. J. Chem. 1992, 70, 1879.
(23) Slocum, G. H.; Schuster, G. B. Photochemistry of
Naphthylmethyl Halides. Direct and Sensitized Paths to Homolytic
and Heterolytic Carbon-halogen Bond Cleavage. J. Org. Chem. 1984,
49, 2177.
Caballero, E.; Barasoain, I.; Andreu, J. M.; Medarde, M. Design,
Synthesis and Cytotoxic Activities of Naphthyl Analogues of
Combretastatin A-4. Bioorg. Med. Chem. Lett. 2000, 10, 2549.
(
3) Maya, A. B. S.; Per
́
ez-Melero, C.; Mateo, C.; Alonso, D.;
z, R.; Caballero, E.;
Fernandez, J. L.; Gajate, C.; Mollinedo, F.; Pelae
Medarde, M. Further Naphthylcombretastatins. An Investigation on
the Role of the Naphthalene Moiety. J. Med. Chem. 2005, 48, 556.
(
G.; Medarde, M.; Rojas de Arlas, A.; San Felicianoa, A.
Leishmanicidal Activity of Combretastatin Analogues and Hetero-
analogues. Bioorg. Med. Chem. Lett. 1999, 9, 2711.
́
́
(24) Michiko, I.; Kazuko, T.; Noboru, K.; Hiizu, I. Photoreactivity of
4) del Rey, B.; Ramos, A. C.; Caballero, E.; Inchaustti, A.; Yaluff,
1
-Pyrenylmethyl Esters. Dependence on the Structure of the
Carboxylic Acid Moieties and the Nature of the Excited States.
Chem. Lett. 1987, 16, 1729.
(
25) Libman, J. Light Induced Charge Transfer Processes.
(
5) Okamoto, H.; Yamaji, M.; Gohda, S.; Kubozono, Y.; Komura,
N.; Sato, K.; Sugino, H.; Satake, K. Facile Synthesis of Picene from
,2-Di(1-naphthyl)ethane by 9-Fluorenone-sensitized Photolysis. Org.
Lett. 2011, 13, 2758.
6) Mamidyala, S. K.; Ramu, S.; Huang, J. X.; Robertson, A. A. B.;
Photochemical Behavior of 1-Cyanonaphthalene in the Presence of
Phenylacetic Acid Derivatives. J. Am. Chem. Soc. 1975, 97, 4139.
1
(26) Dewar, M. J. S.; Grisdale, P. J. Substituent Effects. II.1a The
Preparation of a Series of Substituted 1-Naphthoic Acids. J. Am.
Chem. Soc. 1962, 84, 3541.
(
Cooper, M. A. Efficient Synthesis of Anacardic Acid Analogues and
their Antibacterial Activities. Bioorg. Med. Chem. Lett. 2013, 23, 1667.
(
Phosphine-free Palladium Catalyzed Mizoroki−Heck Reaction using
Hydrazone as a Ligand. J. Org. Chem. 2006, 71, 6834.
(
Coupling Reaction Between Two sp3C-sp3C Centers Under Metal-
free Condition. Tetrahedron Lett. 2016, 57, 3476.
(
of Phenanthroindolizidine Alkaloids via Asymmetric Deprotonation of
N-Boc-pyrrolidine. RSC Adv. 2014, 4, 14979.
(27) Smith, J. G.; Dibble, P. W.; Sandborn, R. E. The Preparation
and Reactions of Naphtho[1,2-c]furan and Naphtho[2,3-c]furan. J.
Org. Chem. 1986, 51, 3762.
7) Mino, T.; Shirae, Y.; Sasai, Y.; Sakamoto, M.; Fujita, T.
(
28) Das, G.; Bharadwaj, P. K.; Basu Roy, M.; Ghosh, S.
Photophysical Studies of Cryptand Based Fluorophore Systems in
Different Environments. Chem. Phys. 2002, 277, 145.
8) Sahoo, S. K. An Unprecedented Oxidative Intermolecular Homo
(29) Beecroft, R. A.; Davidson, R. S.; Goodwin, D.; Pratt, J. E.
Quenching of singlet and triplet excited aromatic hydrocarbons by
sulphides:- the amine and sulphide enhanced photo-induced
degradation of chloro- and cyanoaromatic hydrocarbons. Tetrahedron
9) Deng, M.; Su, B.; Zhang, H.; Liu, Y.; Wang, Q. Total Synthesis
1
(
984, 40, 4487.
(
10) Gozhina, O. V.; Thomassen, I. K.; Lejon, T. Ultrasound-
promoted Dimerization of Benzylic Halides. Synth. Commun. 2013,
3, 1867.
11) Iyoda, M.; Sakaitan, M.; Otsuka, H.; Oda, M. Reductive
30) Corina, D. L.; Isaac, K. Gas Chromatographic and Mass
Spectrometric Properties of Naphthalenemethyl Esters and Cyclo-
hexanemethyl Esters of Organic Acids. J. Chromatogr. A 1983, 260,
4
(
5
(
1.
Coupling of Benzyl Halides using Nickel(0)-complex Generated in
situ in the Presence of Tetraethylammonium Iodide, a Simple and
Convenient Synthesis of Bibenzyls. Chem. Lett. 1985, 14, 127.
31) Holdcroft, S.; Yuen, K. H.; Guillet, J. E. Studies of the
Photolysis of Aromatic Esters in Solution and in Polymer Films. J.
Polym. Sci., Part A: Polym. Chem. 1990, 28, 1495.
(12) Kumar, P.; Guntreddi, T.; Singh, R.; Singh, K. N. A Practical
(32) Carpino, L. A. Synthesis and Alkaline Degradation of the
Protocol for the Synthesis of Bibenzyls via C(sp3)−H Activation of
Methyl Arenes under Metal-free Conditions. Org. Chem. Front. 2017,
Arenesulfonyl Derivatives of α-Menaphthyl- and 1,1-Di-α-menaph-
thylhydrazine. J. Org. Chem. 1965, 30, 321.
4
(
, 147.
13) Liu, J.; Li, B. Facile Synthesis of Bibenzyl by Reductive
Homocoupling of Benzyl Halides in Aqueous Media. Synth. Commun.
007, 37, 3273.
14) Liu, Y.; Xiao, S.; Qi, Y.; Du, F. Reductive Homocoupling of
(33) Schorigin, P. Weitere Versuche uber die Umsetzungen von
̈
̈
Athern mit metallischem Natrium. Ber. Dtsch. Chem. Ges. A/B 1926,
59, 2510.
2
(
(34) Inaba, S.; Matsumoto, H.; Rieke, R. D. Highly Reactive Metallic
Nickel: Reductive Homocoupling Reagent for Benzylic Mono- and
Polyhalides. J. Org. Chem. 1984, 49, 2093.
Organohalides using Nickel(II) Chloride and Samarium Metal. Chem.
Asian J. 2017, 12, 673.
G
DOI: 10.1021/acs.joc.9b01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(35) Friedmann, W. Einwirkung von Schwefel auf β-Methyl-
naphthalin unter Druck. Ber. Dtsch. Chem. Ges. 1916, 49, 1352.
́
36) Alvarez-Bercedo, P.; Martin, R. Ni-Catalyzed Reduction of
(
Inert C−O Bonds: A New Strategy for Using Aryl Ethers as Easily
Removable Directing Groups. J. Am. Chem. Soc. 2010, 132, 17352.
(37) Foster, B.; Gaillard, B.; Mathur, N.; Pincock, A. L.; Pincock, J.
A.; Sehmbey, C. Substituent Effects on Homolytic versus Heterolytic
Photocleavage of (1-Naphthylmethyl)trimethylammonium Chlorides.
Can. J. Chem. 1987, 65, 1599.
H
DOI: 10.1021/acs.joc.9b01871
J. Org. Chem. XXXX, XXX, XXX−XXX