Regiospecifically Fluorinated Polycyclic Aromatic Hydrocarbons via Julia-Kocienski Olefination and Oxidative Photocyclization. Effect of Fluorine Atom Substitution on Molecular Shape

Article abstract of DOI:10.1021/acs.joc.5b02580

A modular synthesis of regiospecifically fluorinated polycyclic aromatic hydrocarbons (PAHs) is described. 1,2-Diarylfluoroalkenes, synthesized via Julia-Kocienski olefination (70-99% yields), were converted to isomeric 5- and 6-fluorobenzo[c]phenanthrene, 5-and 6-fluorochrysene, and 9- and 10-benzo[g]chrysene (66-83% yields) by oxidative photocyclization. Photocyclization to 6-fluorochrysene proceeded more slowly than conversion of 1-styrylnaphthalene to chrysene. Higher fluoroalkene dilution led to a more rapid cyclization. Therefore, photocyclizations were performed at higher dilutions. To evaluate the effect of fluorine atom on molecular shapes, X-ray data for 5- and 6-fluorobenzo[c]phenanthrene, 6-fluorochrysene, 9- and 10-fluorobenzo[g]chrysene, and unfluorinated chrysene as well as benzo[g]chrysene were obtained and compared. The fluorine atom caused a small deviation from planarity in the chrysene series and decreased nonplanarity in the benzo[c]phenanthrene derivatives, but its influence was most pronounced in the benzo[g]chrysene series. A remarkable flattening of the molecule was observed in 9-fluorobenzo[g]chrysene, where the short 2.055 ? interatomic distance between bay-region F-9 and H-8, downfield shift of H-8, and a 26.1 Hz coupling between F-9 and C-8 indicate a possible F-9···H-8 hydrogen bond. In addition, in 9-fluorobenzo[g]chrysene, the stacking distance is short at 3.365 ? and there is an additional interaction between the C-11-H and C-10a of a nearby molecule that is almost perpendicular.

Full text of DOI:10.1021/acs.joc.5b02580

Featured Article
pubs.acs.org/joc
Regiospecifically Fluorinated Polycyclic Aromatic Hydrocarbons via
Julia−Kocienski Olefination and Oxidative Photocyclization. Effect of
Fluorine Atom Substitution on Molecular Shape
†
†
†
,†,‡
§
§
Shaibal Banerjee, Saikat Sinha, Padmanava Pradhan, Alessio Caruso, Daniel Liebowitz,
∥
,§
Damon Parrish, Miriam Rossi,* and Barbara Zajc*
†
Department of Chemistry, The City College of New York, 160 Convent Avenue, New York, New York 10031, United States
The Ph.D. Program in Chemistry, The Graduate Center of The City University of New York, New York, New York 10016, United
‡
States
§
Department of Chemistry, Vassar College, Poughkeepsie, New York 12604, United States
∥
Naval Research Laboratory, Code 6030, 4555 Overlook Avenue, Washington, DC 20375, United States
*
S Supporting Information
ABSTRACT: A modular synthesis of regiospecifically fluorinated
polycyclic aromatic hydrocarbons (PAHs) is described. 1,2-Diaryl-
fluoroalkenes, synthesized via Julia−Kocienski olefination (70−99%
yields), were converted to isomeric 5- and 6-fluorobenzo[c]-
phenanthrene, 5-and 6-fluorochrysene, and 9- and 10-benzo[g]-
chrysene (66−83% yields) by oxidative photocyclization. Photo-
cyclization to 6-fluorochrysene proceeded more slowly than
conversion of 1-styrylnaphthalene to chrysene. Higher fluoroalkene
dilution led to a more rapid cyclization. Therefore, photocyclizations
were performed at higher dilutions. To evaluate the effect of fluorine
atom on molecular shapes, X-ray data for 5- and 6-fluorobenzo[c]-
phenanthrene, 6-fluorochrysene, 9- and 10-fluorobenzo[g]chrysene,
and unfluorinated chrysene as well as benzo[g]chrysene were obtained
and compared. The fluorine atom caused a small deviation from
planarity in the chrysene series and decreased nonplanarity in the benzo[c]phenanthrene derivatives, but its influence was most
pronounced in the benzo[g]chrysene series. A remarkable flattening of the molecule was observed in 9-fluorobenzo[g]chrysene,
where the short 2.055 Å interatomic distance between bay-region F-9 and H-8, downfield shift of H-8, and a 26.1 Hz coupling
between F-9 and C-8 indicate a possible F-9···H-8 hydrogen bond. In addition, in 9-fluorobenzo[g]chrysene, the stacking
distance is short at 3.365 Å and there is an additional interaction between the C-11−H and C-10a of a nearby molecule that is
almost perpendicular.
INTRODUCTION
nase−epoxide hydrolase pathway, where angular-ring diol
■
5
epoxides are formed. The electrophilic diol epoxides covalently
Fluoroaromatic compounds are of interest in diverse fields,
such as materials and supramolecular chemistry, environmental
analyses, and biological studies. As examples, applications of
fluoroaromatic compounds can be found in liquid crystalline
materials, organic light-emitting diodes, and organic field-effect
6
bind to DNA, ultimately resulting in adverse biological effects.
An alternate metabolic pathway involves formation of reactive7,
redox-active o-quinones that can lead to DNA damage.
Fluorine is a powerful modulator of biological activity, and
introduction of fluorine into a PAH is known to significantly
alter its biological activity. For example, 6-fluorobenzo[c]-
phenanthrene (6-F-BcPh) showed increased tumorigenicity as
1
,2
transistors. Recently, polymers containing fluorinated ar-
omatic building blocks have shown improved performance of
2
d
organic solar cells. Use of fluoroaromatics as internal
8
3
compared to benzo[c]phenanthrene (BcPh), whereas 6-
standards in GC−MS analyses has been reported. In the
arena of chemical carcinogenesis by polycyclic aromatic
hydrocarbons (PAHs),
been used in carcinogenicity studies.
fluorobenzo[a]pyrene (6-F-BaP) showed decreased tumor-
9
4
−10
igenicity as compared to benzo[a]pyrene (BaP). In the latter
fluorinated PAHs have frequently
8
−10
case, this is attributed to fluorine-atom-induced conformational
9b
change in the metabolite. Studies on the effect molecular
Polycyclic aromatic hydrocarbons (PAHs) are the products
of activities of modern society and are common contaminants
4
in the environment. PAHs that contain a bay or fjord region
Received: November 9, 2015
are known to undergo metabolic activation via a monoxyge-
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Figure 1. Retrosynthetic route to regiospecifically fluorinated PAHs via Julia olefination and oxidative photocyclization and structures of the targets
selected for this work.
1
6a
distortion of PAHs can have on metabolic activation and DNA
context of PAHs, synthesis of 4-aza-10-fluorophenanthrene,
16b
binding have been conducted using 1,4-difluorobenzo[c]-
9-fluorophenanthrene, 5- and 6-fluorochrysenes, and fluori-
16c
10
phenanthrene as a model compound. In order to better
understand the structure−activity relationships on a molec-
ular−genetic level, availability of sufficient quantities of
regiospecifically fluorinated PAHs is critical.
nated phenacenes
has been reported. Several fluorinated
PAHs (F-PAHs) were synthesized via indium(III)-catalyzed
cyclization of aryl- and cyclopentene-substituted 1,1-difluor-
1
7
oallenes followed by ring expansion and dehydrogenation.
16c,17
Our present goal was to explore a convenient, general route
to regiospecifically fluorinated PAHs, via the use of fluorinated
building blocks, for potential applications in diverse fields. To
date, various methods have been used for the introduction of
fluorine into polycyclic aromatic systems, such as diazotiza-
Whereas the latter two methods
are mechanistically
interesting, one potential limitation is a substrate-dependent
formation of isomeric monofluoro PAHs.
We describe herein a general route to a series of
regiospecifically fluorinated aryl hydrocarbons. To our knowl-
edge, the use of a fluoro Julia olefination to regiospecifically
place a fluorine atom followed by photocyclization has not been
studied to date.
1
1
12
tion−fluorination, direct electrophilic substitution, bro-
13
mine−fluorine exchange, and cyclizations of smaller fluori-
nated building blocks. Photocyclizations of stilbene-like
14
derivatives with appropriate fluorine atom-substituted and
10,15
RESULTS AND DISCUSSION
often commercially available aryl moieties are known,
and
■
recently, a photodehydrofluorination approach to polyfluori-
We have been involved with the use of the modified Julia−
15e
18
nated polycyclic aromatic hydrocarbons has been reported.
Kocienski olefination for novel approaches to variously
1
9,20
Although stilbene can be cyclized readily to phenanthrene, it
functionalized regiospecifically fluorinated olefins,
including
21
has been reported that α-fluorostilbene could not be cyclized to
1,2-diarylfluoroethenes. Since photodehydrocyclizations of a
15a
the fluoro analogue.
Introduction of an additional ring
variety of 1,2-diarylethenes to several classes of PAHs and
22
increases the feasibility of photocyclization, and β-fluoronaph-
thylstyrene has been converted to 6-fluorobenzo[c]-
helicenes have been well documented, we reasoned that
photocyclization of regiospecifically substituted 1,2-diarylfluor-
oethenes could offer a simple, modular approach to
regiospecifically fluorinated PAHs. Importantly, although 1,2-
diarylfluoroethenes are formed as E/Z mixtures in Julia−
Kocienski reactions, the alkene geometry is not critical to the
photocyclization, with alkene isomerization occurring under the
reaction conditions. Herein, we present a new approach to
regiospecifically fluorinated PAHs via a tandem fluoro Julia
1
1a
phenanthrene.
Key to this approach was a substrate-
dependent regioselective bromofluorination of β-fluoronaph-
thylstyrene, followed by elimination and photochemical closure.
On the other hand, synthesis of the isomeric 5-fluorobenzo-
11a
[c]phenanthrene required a completely different approach.
Transition-metal-catalyzed introduction of fluorine atom into
aromatics has been the focus of recent research, and in the
B
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Scheme 1. Synthesis of (Aryl)fluoromethyl BT Sulfones 2a−d
olefination and oxidative photocyclization. Figure 1 shows a
retrosynthetic approach to the modular synthesis of fluorinated
PAHs. Also shown in Figure 1 are structures of 5- and 6-
fluorobenzo[c]phenanthrene (5-F-BcPh and 6-F-BcPh), 5- and
obtained with increased substrate dilution, in a comparable
reaction time.
23
For comparison, the unfluorinated 1-styrylnaphthalene (E/Z
97:3) was subjected to photocyclization to form chrysene on a
1 g scale (4.38 mM concentration). Progress of the reaction,
6
-fluorochrysene (5-F-Ch and 6-F-Ch), and 9- and 10-
1
fluorobenzo[g]chrysene (9-F-BgCh and 10-F-BgCh), the
targets of our approach.
depicted in Figure 3, was monitored by H NMR by comparing
key resonances of the cis- and the trans-alkene to an aromatic
resonance of chrysene at 8.80 ppm (d, J = 8.3 Hz, 2H). Key
Previously, we have reported the high-yield synthesis of
regiospecifically fluorinated stilbene-like derivatives via the
2
4
resonances of the alkene were the vinylic H (C−H : 6.85
cis
21
ppm, d, J = 12.4 Hz, 1H; C−H : 7.17 ppm, d, J = 16.1 Hz,
Julia−Kocienski olefination. For this, fluorobenzyl heteroaryl
sulfones are required. We have previously developed a general
synthesis via heterogeneous metalation fluorination of hetero-
aryl benzyl sulfones and, more specifically, the 1,3-benzothiazol-
trans
24
1
7
1
H) and aromatic H (Ar−H of cis alkene: 8.09 ppm, br d, J =
.8 Hz, 1H; Ar−H of trans alkene: 8.24 ppm, d, J = 8.2 Hz,
H). In this case, conversion to chrysene was 97% complete
2
1
within 1 h.
2
-ylsulfonyl (BT-sulfonyl) derivatives. For the purpose of this
21
UV spectra of the alkene mixtures that were subjected to
study, fluoro(phenyl)methyl (2a), fluoro(1-naphthyl)methyl
2
0b
21
photocyclization (fluoroalkene E/Z 3:1 and 1-styrylnaphtha-
(
2
2b), and fluoro(2-naphthyl)methyl (2c) 1,3-benzothiazol-
-yl sulfones were synthesized (Scheme 1), as described.
Fluoro(phenanthren-9-yl)methyl 1,3-benzothiazol-2-yl sulfone
lene E/Z ≥ 97:3) were compared, each at 2.3 × 10−
5
M
concentration. The spectrum of the fluoroalkene mixture shows
a hypsochromic shift of both long- and short-wavelength
absorption maxima, as compared to the protio analogue. The
long-wavelength absorption of the E/Z fluoroalkenes shows
hypochromicity, whereas the short-wavelength absorption
shows hyperchromicity as compared to the protio olefins (see
the Supporting Information).
20b,21
(
2d) was prepared by analogous protocols.
Fluorination of
sulfones 1a−d using our heterogeneous conditions (LDA,
toluene, and addition of solid NFSI) afforded fluorinated
sulfone derivatives 2a−d in high 87−93% yields. The yields of
1
9
the critical fluorination step and F NMR data of fluoro
sulfones 2a−d are displayed in Scheme 1.
Photocyclization to 6-F-Ch in benzene, using a catalytic
amount of iodine in air, was also attempted on a 0.460 g scale
With sulfone reagents 2a−d, synthesis of regiospecifically
fluorinated vinyl compounds was performed via a modified Julia
olefination. Condensation of fluorinated BT-sulfones 2a−d
with appropriate aldehydes under basic conditions (LHMDS,
THF, 0 °C) afforded the E/Z monofluorodiarylethylenes
(
1.85 mM concentration). After 8 h, analysis of the reaction
19
mixture by F NMR showed resonance corresponding to 6-F-
Ch (29%) and E/Z fluoroalkene resonances (71%). Further
irradiation resulted in consumption of the fluoroalkene after 42
h, but only a trace of 6-F-Ch was isolated, and other
unidentified products were formed. Photocyclization to 6-F-
(Table 1), the key intermediates for the photocyclization.
Initially, photocyclization to 6-F-Ch (3) under Katz con-
2
3
ditions was performed on a 1 g scale (4.0 mM concentration)
25
Ch in acetone as solvent, under a nitrogen atmosphere, did
of the fluoroalkene (E/Z 74:26), and 6-F-Ch was isolated in
not proceed, and the starting material was recovered.
74% yield. However, the reaction was extremely slow, and it
In summary, these results indicated the following: (a) higher
fluoroalkene dilution gave a faster photocyclization, (b)
conditions involving catalytic iodine and air were not usable,
took 112 h to reach completion. Progress of the reaction was
monitored by 19F NMR and is depicted in Figure 2. Upon
conducting the photochemical ring closure at a higher dilution
23
(
c) use of Katz-modified photocyclization proceeded well,
(
1 mM) of the fluoroalkene, the reaction was complete within 8
and (d) photocyclization in acetone under nitrogen was
ineffective. On the basis of these results, photocyclizations
were performed in a Hanovia immersion-type photoreactor
using a 450 W Hg vapor lamp and a quartz filter. Reactions
were conducted in benzene as solvent, with a stoichiometric
amount of iodine as the oxidant and propylene oxide as the HI
sponge. Under these conditions, F-PAHs 4−8 were obtained in
66−83% yields. Table 1 shows the olefination partners,
h, and 6-F-Ch (3) was isolated in a comparable 72% yield.
Thus, it appears that the overall reaction time is dependent
upon substrate concentration, but a longer reaction time does
not have a detrimental effect on the yield. In this regard, Katz et
al. have shown that in reactions with stoichiometric iodine, a
higher substrate concentration led to lower conversion and
recovery of starting material, whereas excellent conversion was
C
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Table 1. Synthesis of Fluoroalkenes and the Regiospecifically
Fluorinated PAHs
Figure 2. Formation of 6-F-Ch (% conversion in green bars and the
1
9
E/Z fluoroalkene ratio in orange bars). Reaction was monitored by
F
NMR.
Figure 3. Formation of chrysene (% conversion in green bars and the
E/Z alkene ratio in orange bars).
The final fluorinated products 3−8 were crystallized for
analysis by X-ray crystallography. While this work was in
1
7
progress, independent syntheses and X-ray data for
compounds 3 and 4 were published. In the present work,
data analysis of compound 3 originates from the crystallo-
graphic information we obtained, whereas the analysis of data
for compound 4 comes from its published crystallographic
17
data.
In order to gain insight into the influence of the fluorine
atom on the shapes of these molecules, angles between the
rings of the PAHs were compared to the corresponding
unfluorinated PAH (Tables 2−4). Since the X-ray structures of
the unfluorinated chrysene (Ch) and benzo[g]chrysene (BgCh)
were unknown, we also obtained data on these two PAHs (both
are commercially available and can also be synthesized via the
Julia olefination−photocyclization approach presented here
using unfluorinated alkenes). Crystallographic structures
obtained in this work are shown in Figure 4, and details follow.
In the chrysene series (Table 2), Ch is completely planar (0°
angle between the four planes), and 6-F-Ch (3) shows a small
deviation from planarity, with angles between the planes in the
a
b
Yields are of isolated and purified products. E/Z olefin ratios in the
19
crude reaction mixtures were determined by F NMR prior to
isolation. Obtained at 282 MHz in CDCl with CFCl as an internal
reference. Obtained with resolution enhancement.
c
3
3
d
condensation yields, E/Z olefin ratios, and 19F NMR data of
intermediate fluoroalkenes, as well as the final photocyclization
1
9
products along with their yields. Notably, F NMR data of
PAHs 3−8 (Table 1) showed that the fluorine resonance
appears ca. 10 ppm more downfield when it resides in the
hydrocarbon bay region (entries 2 and 6), as opposed to when
it is not present in a bay region (compare data of PAHs 4 and 8
to those of 3, 5, 6, and 7).
17
range of 0.4−1.8°. Deviation from planarity for 5-F-Ch (4)
with a bay-region fluorine atom is larger, with angles between
the planes in the range of 1.0−5.9°. The overall distortion from
planarity (angle between planes A and D) is 1.8° for 6-F-Ch
(3), and 5.9° for 5-F-Ch (4).
D
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Table 2. Angles between the Four Planes of Ch, 6-F-Ch, and
idealized hydrogen atom positions. That fluorine exhibits
positional disorder is well-established, and indeed, for 6-F-
a
26
5
-F-Ch
Ch (3) the fluorine atom occurs 78% of the time at the C-6
(
major occupancy position) and 22% of the time at the C-12
position. The remainder of the time, at these positions, fluorine
is replaced by a hydrogen atom. The C−F bond length of the
major occupancy fluorine is 1.343(3) Å, while the C−F bond
for the minor occupancy fluorine, as expected, is in between a
C−H and C−F bond length, 1.146(9) Å. From our
experimentally determined hydrogen atom positions, we can
see two dominant intermolecular interactions, a strong stacking
interaction and a C-8−H···F interaction (Figure 5). The
stacking interaction of 3.421(5) Å is between the planes of 6-F-
Ch (3) molecules. The second interaction is the hydrogen
bond between the major occupancy F (at C-6) and the H-8−C-
8
of a neighboring molecule at 2.516(9) Å that is perpetuated
throughout the crystal structure. This C−H···F distance is
shorter than the calculated distance of 2.619 Å from the
published crystal structure having calculated hydrogen atom
positions of C-6−F···H-8. We also see additional intermolecular
interactions between C−H and the ring carbon atoms of 2.844,
2.895, and 2.889 Å. These are approximately perpendicular
(Figure 5).
a
Angles between the planes of 5-F-Ch were calculated from the
17
published X-ray information.
Although our structure of 6-F-Ch (3) is the same as that
17
published by Fuchibe et al., our analysis of its crystal structure
differed in the treatment of the hydrogen atom fluorine atom
positions. All hydrogen atom positions were found and refined
In the BcPh series, the overall distortion from planarity in 5-
F-BcPh (5) and in 6-F-BcPh (6) is smaller than in the parent
17
from our X-ray data, whereas Fuchibe et al. calculated the
Figure 4. Crystal structures of PAHs and F-PAHs obtained in this work (C, gray; H, white; F, green).
E
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Table 4. Angles between the Five Planes of Unfluorinated
and Fluorinated BgCh
Figure 5. Intermolecular interactions in the X-ray crystal structure of
6
-F-Ch (3) (our data).
hydrocarbon (Table 3 and Figure 4). This is reflected in the
angle between rings A and D forming the fjord region and in
Table 3. Angles between the Four Planes of Unfluorinated
and Fluorinated BcPh
coupling constant. The downfield shift of the H-8 proton, its
coupling to F-9, and the large C-8−F coupling constant further
27,28
support possible hydrogen bonding between F-9 and H-8.
It is plausible, therefore, that the tendency toward F−H
bonding is responsible for the planarization in the B-, C-, E-ring
regions, decreasing the angles between these rings in 9-F-BgCh
(
8). The hydrogen atom positions in the 9-F-BgCh structure
were calculated. Additional strong intermolecular interactions
include the short stacking distance at 3.365 Å and two
additional short almost perpendicular interactions: one at 2.875
Å between the C-11−H and C-10a of a nearby molecule and
another at 2.872 between C-4−H and C-6 of a neighboring
molecule (Figure 6).
the angle between rings A and C. The angle between rings A
and D is 26.7° in BcPh and decreases to 24.3° and 23.6° in 6-F-
BcPh (6) and 5-F-BcPh (5), respectively. The angle between
rings A and C is 18.1° in BcPh, 16.2° in 6-F-BcPh (6), and
1
4.2° in 5-F-BcPh (5).
The most pronounced effect the fluorine atom has on the
molecular shape is in the benzo[g]chrysene series. Here again,
the overall distortion from planarity decreases upon fluorine
atom substitution (Table 4 and Figure 4). The angle between
rings A and D forming the fjord region is 36.0° in the parent
BgCh, and this decreases to 32.6° in 10-F-BgCh (7) and to
3
3.3° in 9-F-BgCh (8). However, the angles between rings B
Figure 6. Intermolecular interactions in the X-ray crystal structure of
and E, which form a bay region, show the most remarkable
difference. The angle between rings B and E is 20.1° in the
parent hydrocarbon, decreasing to 18.2° in 10-F-BgCh (7), and
this decreases dramatically to 9.2° in 9-F-BgCh (8). In 9-F-
BgCh (8), the fluorine atom resides in the bay region and the
interatomic distance between F-9 and the bay-region H-8 is
9
-F-BgCh (8).
In 5-F-Ch (4), which also has a fluorine atom residing in the
bay region, the interatomic distance between F-5 and the bay-
2
.055 Å, with a C−H···F angle of 128.73°, which suggests a
region H-4 is 2.069 Å, with a C−H···F angle of 126.80°, again
27,28
1
1
possible hydrogen bond.
In the H NMR spectrum of 9-F-
suggestive of intramolecular hydrogen bonding. The H and
1
3
BgCh (8), H-8 appears at 9.07 ppm and is shifted downfield as
compared to H-8 in unsubstituted BgCh, where it appears at
C NMR spectra of 5-F-Ch (4) show features similar to those
1
of 9-F-BgCh (8). In the H NMR spectrum of 5-F-Ch (4), the
bay-region H-4 appears at 9.25 ppm and is downfield shifted as
compared to H-4 in unsubstituted chrysene (Ch), which
2
9
8.63 ppm. The bay-region H-8 and F-9 resonances in
compound 8 show a small ∼2 Hz coupling (2.3 and 2.2 Hz,
respectively). In the C NMR spectrum of 9-F-BgCh (8), the
C-8 resonance appears at 128.0 ppm, as a doublet with a J =
1
3
30
appears at 8.79 ppm. The bay region H-4 and F-5 resonances
in compound 4 show a ∼3 Hz coupling (2.8 and 3.3 Hz,
26.1 Hz. This is a typical value for a scalar two-bond C−F
respectively). In the 13C NMR spectrum of 5-F-Ch (4), the
F
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
1
19
Figure 7. H− F HOESY spectra of 9-F-BgCh (8, left) and of 5-F-Ch (4, right).
bay-region C-4 appears at 128.0 ppm, as a doublet, with a large
the synthesis of fluoro PAHs and potentially to other fluoro
PAHs that contain additionally substituted aryl moieties.
It has recently been reported that introduction of a fluorine
2
6.6 Hz coupling constant with the fluorine atom.
Through-space spin−spin coupling has been a subject of
31
16c
research for several years now. In previous studies, other
investigators have reported comparable NMR spectral features
for PAHs containing a bay-region fluorine atom. Mallory et al.
suggested through-space H−F coupling interactions in 4-
fluorophenanthrene, where a 2.6 Hz H−F coupling was
observed between the bay-region fluorine atom and the bay-
atom into phenacenes does not change their shape.
However, in the present cases, we have observed that
fluorine-atom substitution does elicit influence on the shapes
of the molecules when compared to their unfluorinated
analogues. A small deviation from planarity was observed for
6
-F-Ch in comparison to chrysene, which is planar, and
3
2
deviation from planarity increased in 5-F-Ch containing a bay-
region fluorine atom. On the other hand, in comparison to
BcPh, both 5- and 6-F-BcPh are slightly less nonplanar. Also, as
reported by other investigators, we have observed positional
disorder in the fluorine atom positions. Additionally, the
molecular assemblies in the crystal structure are stabilized by
π−π stacking interactions as well as through the formation of
C−H···F intermolecular interactions. These features highlight
the important role that fluorine substitution plays in organic
region H-5. In the present case, resonances of bay-region H-8
and F-9 of compound 8 show a similar small ∼2 Hz coupling,
whereas resonances of bay-region H-4 and F-5 of compound 4
1
13
show a ∼3 Hz coupling. Sardella et al. studied H and
C
3
3
NMR spectra of PAHs containing a bay-region fluorine atom.
Similar to what we have observed for compounds 8 and 4, a C−
F coupling of 24.9 Hz across the bay region was reported, and
33
through-space C−F coupling interactions were suggested.
1
19
We also obtained H− F HOESY spectra of 9-F-BgCh (8,
left, Figure 7) and 5-F-Ch (4, right, Figure 7). The HOESY
spectrum of 9-F-BgCh (8) shows an intense interaction
between the fluorine atom and the H-8 resonance at 9.07
ppm, in support of C-8−H···F hydrogen bonding. The weaker
interaction is between the fluorine atom and the H-10
resonance at 7.67 ppm. The HOESY spectrum of 5-F-Ch (4)
shows an intense interaction between the fluorine atom and the
H-4 resonance at 9.25 ppm, in support of C-4−H···F hydrogen
bonding. The weaker interaction is between the fluorine atom
and the H-6 resonance at 7.68 ppm.
34
molecules. Previous studies by Thalladi et al. showed that, in
general, C−H···F hydrogen bonds were preferred to F···F
contacts. The marked difference in crystal packing behavior
between fluorine and the heavier halogens is confirmed with
our molecules. In more angularly fused BgCh series, a more
dramatic shape change occurred, with the most pronounced
effect in 9-F-BgCh. In this case, the fluorine atom resides in the
bay region and causes substantial planarization of B, C, and E
rings forming the bay region, possibly via intramolecular F···H
bonding.
EXPERIMENTAL SECTION
■
CONCLUSIONS
■
THF was distilled over LiAlH and then over sodium, toluene and
4
1
,2-Diarylfluoroethenes, which were synthesized via Julia−
benzene were distilled over sodium, and CH
Cl
2
2
was distilled over
CaCl . DMF was obtained from commercial sources and was used
Kocienski olefination, were subjected to oxidative photo-
cyclization to yield regiospecifically substituted monofluoro
PAHs. Photocyclizations of the 1,2-diarylfluoroethenes were
much slower as compared to those of their unfluorinated
analogues, and higher dilutions produced faster reactions. The
method is straightforward, highly modular, and applicable to
2
without further purification. For reactions performed in a nitrogen
atmosphere, glassware was dried with heat gun under vacuum. LDA
2.0 M solution in heptane/THF/EtPh) and LHMDS (1.0 M in THF)
were obtained from commercial sources. All other reagents were
obtained from commercial sources and were used as received. We have
previously reported syntheses of 2-[fluoro(phenyl)methylsulfonyl]-
(
G
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
2
1
benzo[d]thiazole (2a), 2-[fluoro(naphthalen-1-yl)methylsulfonyl]-
min and then warmed to rt, and stirring was continued for an
2
0b
benzo[d]thiazole (2b),
methylsulfonyl]benzo[d]thiazole (2c) and their precursor sulfones
a, 1b, and 1c. Photocyclizations of alkenes were performed in a
Hanovia immersion-type photoreactor using a 450 W Hg vapor lamp
and a quartz filter. Thin-layer chromatography was performed on glass-
backed silica gel plates (250 μm). Column chromatographic
and 2-[fluoro(naphthalen-2-yl)-
additional 50 min. Saturated aq NH Cl was added to the reaction
4
21
mixture, and the layers were separated. The aqueous layer was
21
20b
21
1
extracted with EtOAc (3×), and the combined organic layer was
washed with saturated aq NaHCO (30 mL) and brine (30 mL). The
3
organic layer was dried over anhydrous Na SO , and the solvent was
2
4
evaporated under reduced pressure. The crude product was purified by
1
purifications were performed on 200−300 mesh silica gel. H NMR
column chromatography (SiO , 20% EtOAc in hexanes) to yield pure
2
spectra were recorded at 500 MHz and were referenced to residual
2-{[fluoro(phenanthren-9-yl)methyl]sulfonyl}benzo[d]thiazole (2d)
protio solvent. 13C NMR spectra were recorded at 125 MHz and were
as a white solid (0.357 g, 70%). H NMR (500 MHz, CDCl ): δ
1
3
referenced to the carbon resonance of the deuterated solvent. 19
F
8.76−8.73 (m, 1H), 8.68 (d, J = 8.3 Hz, 1H), 8.34−8.32 (m, 2H), 8.21
NMR spectra were recorded at 282 MHz with CFCl as the internal
(s, 1H), 8.02 (d, J = 8.3 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.76−7.60
3
standard. Chemical shifts (δ) are reported in parts per million, and
coupling constants (J) are in hertz (Hz). On the basis of 2D NMR
data, some proton and carbon assignments were made for 5-
fluorochrysene (4), 10-fluorobenzo[g]chrysene (7), and 9-
fluorobenzo[g]chrysene (8). HRMS data were obtained using
FTICR−MS, and the ionization modes are specified under each
compound heading.
Synthesis of 2-{[Fluoro(phenanthren-9-yl)methyl]sulfonyl}-
benzo[d]thiazole 2d. 2-[(Phenanthren-9-ylmethyl)thio]benzo[d]-
thiazole. To a solution of the sodium salt of 1,3-benzo-2-thiazole
1.324 g, 7.00 mmol, 1.25 molar equiv) in DMF (20 mL) was added a
solution of 9-(bromomethyl)phenanthrene (1.518 g, 5.60 mmol) in
DMF (30 mL). The mixture was stirred at rt and monitored by TLC
SiO , 20% EtOAc in hexanes). After 6.0 h, complete consumption of
-(bromomethyl)phenanthrene was observed, and the reaction was
(m, 6H), 7.54 (d, J = 45.1 Hz, 1H). 13C NMR (125 MHz, CDCl ): δ
3
163.5, 153.1, 137.7, 131.8, three resonances at 131.0, 130.9, 130.8 (2C,
one s and one d), 130.4, 129.9, 129.1 (d, J = 6.5 Hz), 128.9, 128.6,
128.0, 127.6, 127.4 (2C), 125.9, 124.3, 123.5, 122.8, 122.5, 121.3 (d, J
= 17.3 Hz), 99.8 (d, J = 221.9 Hz). 19F NMR (282 MHz, CDCl ): δ −
3
+
171.5 (d, J = 42.7 Hz). HRMS (ESI) [M + Na] : calcd for
C H FNO S Na 430.0342, found 430.0339.
2
2
14
2 2
1
2a,16c,17,35
Synthesis of 6-Fluorochrysene (3).
Step 1. Con-
densation of 2a with 1-Naphthaldehyde. A solution of 1-
naphthaldehyde (0.491 g, 3.14 mmol) and sulfone 2a (1.161 g, 3.59
mmol, 1.14 molar equiv) in dry THF (60 mL) was cooled to 0 °C
under a nitrogen atmosphere. LHMDS (7.60 mL, 7.60 mmol, 2.42
molar equiv) was added dropwise at 0 °C. The mixture was stirred at 0
°C for 10 min, allowed to warm to rt, and stirred at rt. After 1 h, TLC
(10% EtOAc in hexanes) showed complete disappearance of the
(
(
2
9
quenched with aq NH Cl solution (30 mL). The mixture was
extracted with EtOAc (3×), and the combined organic layers were
washed aq NaHCO solution (30 mL) and brine (30 mL) and dried
aldehyde. Saturated aq NH Cl (30 mL) was added, and the mixture
4
4
was extracted with EtOAc (3×). The combined organic layer was
3
washed with NaHCO (30 mL) and brine (30 mL) and then dried
3
over anhydrous Na SO . The organic layer was concentrated under
over anhydrous Na SO . The solvent was evaporated under reduced
2
4
2
4
reduced pressure, and crude product was purified by column
chromatography (SiO , 10% EtOAc in hexanes) to yield pure 2-
(phenanthren-9-ylmethyl)thio]benzo[d]thiazole (1.821 g, 91%) as a
colorless solid. H NMR (500 MHz, CDCl ): δ 8.76 (br dd, J = 8.5,
pressure, and the crude product was purified by column chromatog-
2
raphy (SiO , eluted with hexanes, followed by 2% EtOAc in hexanes)
2
[
to yield pure (E/Z)-1-(2-fluoro-2-phenylvinyl)naphthalene (E/Z ratio
1
19
3
2.8:1) as a colorless liquid (0.773 g, 99%). F NMR (282 MHz,
1
1
7
1
.4 Hz, 1H), 8.67 (d, J = 8.3 Hz, 1H), 8.22 (br dd, J = 8.3, 1.9 Hz,
H), 7.98 (d, J = 8.3 Hz, 1H), 7.94 (s, 1H), 7.86 (d, J = 7.4 Hz, 1H),
.77 (d, J = 8.3 Hz, 1H), 7.72−7.64 (m, 3H), 7.59 (td, J = 7.4, 0.9 Hz,
H), 7.47 (td, J = 7.7, 1.2 Hz, 1H), 7.33 (td, J = 7.8, 0.9 Hz, 1H), 5.18
CDCl ): δ −100.0 (d, J = 21.4 Hz, 1F), −115.6 (d, J = 39.7 Hz, 1F).
3
+
HRMS (+APPI mode) [M] : calcd for C H F 248.0996, found
18
13
248.0997.
Step 2. Photocyclization of (E/Z)-1-(2-fluoro-2-phenylvinyl)-
(
s, 2H). 13C NMR (125 MHz, CDCl ): δ 166.7, 153.4, 135.6, 131.5,
naphthalene to 3.
12a,16c,17,35
(E/Z)-1-(2-Fluoro-2-phenylvinyl)-
3
1
1
31.1, 130.8, 130.5, 130.0, 129.4, 128.8, 127.3, 127.2, 127.1, 127.0,
naphthalene (E/Z ratio 2.8:1, 63.1 mg, 0.254 mmol) was dissolved
26.3, 124.63, 124.55, 123.6, 122.8, 121.8, 121.3, 36.4. HRMS (ESI)
in benzene (250 mL), I (71.1 mg, 0.280 mmol, 1.10 molar equiv) was
2
+
[
M + H] : calcd for C H NS 358.0719, found 358.0723.
added, and nitrogen was bubbled into the solution for 10 min.
Propylene oxide (2.90 mL, 2.41 g, 41.4 mmol, 163 molar equiv) was
added, the solution was subjected to irradiation, and the reaction was
monitored by 19F NMR. After 8 h, F NMR showed consumption of
the (E/Z)-alkene. The solvent was evaporated, and the crude product
22
16
2
2
-[(Phenanthren-9-ylmethyl)sulfonyl]benzo[d]thiazole (1d). A
solution of 2-[(phenanthren-9-ylmethyl)thio]benzo[d]thiazole (0.943
g, 2.64 mmol) in CH Cl (40 mL) was added dropwise to a solution of
m-CPBA (1.365 g, 7.91 mmol, 3.00 molar equiv) in CH Cl (30 mL),
19
2
2
2
2
cooled to 0 °C. After complete addition, the mixture was stirred at rt
was purified by column chromatography (SiO , 2% EtOAc in hexanes)
to afford pure 6-fluorochrysene 3 (45.1 mg, 72%) as a white solid. For
2
overnight. The reaction was quenched with aq NaHCO (30 mL), and
3
the organic layer was separated and washed with aq NaHCO (30
X-ray analysis, this compound was crystallized from hexanes/2−3
3
1
mL), 5% aq NaOH (30 mL, twice), water, and then brine (30 mL
each), and dried over anhydrous Na SO . The solvent was removed
drops of CH Cl . H NMR (500 MHz, CDCl ): δ 8.79 (d, J = 8.3 Hz,
2
2
3
1H), 8.66 (d, J = 9.2 Hz, 1H), 8.63 (d, J = 8.3 Hz, 1H), 8.35 (d, J =
12.9 Hz, 1H), 8.29 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 8.3 Hz, 1H), 7.98
(d, J = 9.2 Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.72 (t, J = 7.6 Hz, 2H),
2
4
under reduced pressure, and crude product was purified by column
chromatography (SiO , 30% EtOAc in hexanes) to yield pure 2-
2
[
(phenanthren-9-ylmethyl)sulfonyl]benzo[d]thiazole (1d) as a color-
7.66 (t, J = 7.4 Hz, 1H). 13C NMR (125 MHz, CDCl ): δ 158.1 (d, J =
3
1
less solid (0.728 g, 71%). H NMR (500 MHz, CDCl ): δ 8.68 (d, J =
250.8 Hz), 132.6, 132.2 (d, J = 5.8 Hz), 130.4 (d, J = 4.4 Hz), 128.9
(one resonance of the doublet partially buried under a singlet), 128.8,
127.9, 127.0, 126.9, 126.7 (d, J = 2.2 Hz), 125.5, 123.9 (d, J = 17.8
3
8
(
7
(
.3 Hz, 1H), 8.64 (d, J = 8.3 Hz, 1H), 8.29 (d, J = 8.3 Hz, 1H), 8.11
d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.75 (s, 1H), 7.72 (d, J =
.8 Hz, 1H), 7.69−7.64 (m, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.57−7.51
m, 3H), 5.32 (s, 2H). 13C NMR (125 MHz, CDCl ): δ 165.6, 152.8,
Hz), 123.5 (d, J = 3.2 Hz), 123.4, 121.4 (d, J = 5.9 Hz), 121.1, 104.1
19
(d, J = 22.0 Hz). F NMR (282 MHz, CDCl ): δ −123.8 (d, J = 15.3
3
3
1
1
37.4, 133.0, 131.05, 130.98, 130.92, 130.5, 129.0, 128.2, 128.0, 127.8,
Hz).
1
6c,17
27.14, 127.12, 127.0, 125.6, 124.6, 123.3, 122.7, 122.4, 121.6, 58.7.
Synthesis of 5-Fluorochrysene (4).
Step 1. Condensation
+
HRMS (ESI) [M + H] : calcd for C H NO S 390.0617, found
of 2b with Benzaldehyde. A solution of benzaldehyde (38.8 mg,
0.366 mmol) and sulfone 2b (147 mg, 0.411 mmol, 1.12 molar equiv)
in dry THF (20 mL) was cooled to 0 °C under a nitrogen atmosphere.
LHMDS (0.980 mL, 0.980 mmol, 2.68 molar equiv) was added
dropwise at 0 °C. The mixture was stirred at 0 °C for 10 min, allowed
to warm to rt, and stirred at rt. After 1 h, TLC (5% EtOAc in hexanes)
22
16
2 2
3
90.0622.
-{[Fluoro(phenanthren-9-yl)methyl]sulfonyl}benzo[d]thiazole
2d). A stirring solution of sulfone 2d (0.488 g, 1.25 mmol) in dry
2
(
toluene (80 mL) was cooled under nitrogen gas to −78 °C (dry ice/
iPrOH). LDA (0.800 mL, 1.60 mmol, 1.28 molar equiv) was added,
and after 12 min, solid NFSI (0.488 g, 1.55 mmol, 1.24 molar equiv)
was added. The reaction mixture was allowed to stir at −78 °C for 50
showed complete disappearance of the aldehyde. Saturated aq NH Cl
4
(30 mL) was added, and the mixture was extracted with EtOAc (3×).
H
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
The combined organic layer was washed with NaHCO (30 mL) and
128.9, 128.4, 128.1 (d, J = 2.8 Hz), 127.7, 127.3, 126.7, 126.5 (d, J =
3.7 Hz), 126.4 (d, J = 1.4 Hz), 125.9, 124.9 (d, J = 17.4 Hz), 124.6 (d,
J = 2.3 Hz), 121.3 (d, J = 6.4 Hz), 108.9 (d, J = 20.1 Hz). F NMR
3
brine (30 mL) and then dried over anhydrous Na SO . The solvent
2
4
1
9
was evaporated under reduced pressure, and the crude product was
purified by column chromatography (SiO , eluted with 5% EtOAc in
(282 MHz, CDCl ): δ −125.4 (d, J = 9.2 Hz).
2
3
11a,15a,17
hexanes) to yield pure (E/Z)-1-(1-fluoro-2-phenylvinyl)naphthalene
Synthesis of 6-Fluorobenzo[c]phenanthrene 6.
Step
(
E/Z ratio 2.9:1, 73.5 mg, 81%). 19F NMR (282 MHz, CDCl ): δ
1. Condensation of 2c with Benzaldehyde. A solution of
benzaldehyde (228 mg, 2.15 mmol) and sulfone 2c (920 mg, 2.58
mmol, 1.20 molar equiv) in dry THF (28 mL) was cooled to 0 °C
under a nitrogen atmosphere. LHMDS (5.15 mL, 5.15 mmol, 2.40
molar equiv) was added dropwise at 0 °C, and the mixture was stirred
at 0 °C. After 2 h, TLC (10% EtOAc in hexanes) showed complete
3
−
84.4 (d, J = 18.3 Hz, 1F), −95.2 (d, J = 39.7 Hz, 1F). HRMS (+APPI
+
mode) [M] : calcd for C H F 248.0996, found 248.1000.
18
13
Step 2. Photocyclization of (E/Z)-1-(1-Fluoro-2-phenylvinyl)-
1
6c,17
naphthalene to 4.
(E/Z)-1-(1-Fluoro-2-phenylvinyl)-
naphthalene (E/Z ratio 2.9:1, 70.0 mg, 0.282 mmol) was dissolved
in benzene (250 mL), I (78.3 mg, 0.308 mmol, 1.10 molar equiv) was
disappearance of the aldehyde. Saturated aq NH Cl (30 mL) was
2
4
added, and nitrogen was bubbled into the solution for 10 min.
Propylene oxide (3.20 mL, 2.66 g, 45.8 mmol, 162 molar equiv) was
added, the solution was subjected to irradiation, and the reaction was
monitored by 19F NMR. After 16 h, F NMR showed consumption of
the alkene. The solvent was evaporated and the crude product was
purified by column chromatography (SiO , 2% CH Cl in hexanes) to
added and the mixture was extracted with EtOAc (3×). The combined
organic layer was washed with NaHCO (30 mL) and brine (30 mL)
3
and then dried over anhydrous Na SO . The solvent was evaporated
2
4
19
under reduced pressure, and the crude product was purified by column
chromatography (SiO , eluted with 5% EtOAc in hexanes) to yield
2
pure (E/Z)-2-(1-fluoro-2-phenylvinyl)naphthalene (E:Z ratio 2.75:1)
2
2
2
as an off-white solid (460 mg, 76%). 19F NMR (282 MHz, CDCl ): δ
yield pure 5-fluorochrysene 4 as a white solid (49.2 mg, 71%). For X-
ray analysis, this compound was crystallized from hexanes/2−3 drops
3
−96.6 (d, J = 21.4 Hz, 1F) and −114.9 (d, J = 39.7 Hz, 1F). HRMS
1
+
of CH Cl . H NMR (500 MHz, CDCl ): δ 9.25 (dd, J = 8.3, 2.8 Hz,
(+APPI mode) [M] : calcd for C H F 248.0996, found 248.0999.
2
2
3
18 13
1
H, H-4), 8.75 (dd, J = 7.8, 0.9 Hz, 1H, H-10), 8.73 (dd, J = 9.2, 2.3
Step 2. Photocyclization of (E/Z)-2-(1-Fluoro-2-phenylvinyl)-
1
1a,15a,17
Hz, 1H, H-11), 8.06 (d, J = 8.8 Hz, 1H, H-12), 8.02 (d, J = 7.8 Hz, 1H,
H-1), 7.93−7.91 (m, 1H, H-7), 7.73 (br t, J = 8.3 Hz, 1H, H-3), 7.68
naphthalene to 6.
(E/Z)-2-(1-Fluoro-2-phenylvinyl)-
naphthalene (E/Z ratio 2.75:1, 127 mg, 0.512 mmol) was dissolved
in benzene (250 mL), I (144 mg, 0.567 mmol, 1.11 molar equiv) was
13
(
d, J = 15.7 Hz, 1H, H-6), 7.69−7.64 (m, 3H, H-2, H-8, H-9).
C
2
NMR (125 MHz, CDCl ): δ 160.0 (d, J = 252.7 Hz, C-5), 132.9, 132.3
added, and nitrogen was bubbled into the solution for 10 min.
Propylene oxide (7.17 mL, 5.95 g, 102 mmol, 200 molar equiv) was
added, the solution was subjected to irradiation, and the reaction was
monitored by 19F NMR. After 26 h, F NMR showed consumption of
the alkene. The solvent was evaporated, and the crude product was
3
(
d, J = 11.4 Hz), 131.5 (d, J = 5.5 Hz), 129.2 (d, J = 1.4 Hz, C-12),
1
2
1
1
2
29.1 (d, J = 5.5 Hz), 128.7 (C-1), 128.04 (d, J = 1.1 Hz), 128.0 (d, J =
6.6 Hz, C-4), 127.7 (d, J = 5.0 Hz, C-7), 127.5 (d, J = 3.2 Hz), 127.4,
26.9 (d, J = 2.3 Hz), 126.0 (d, J = 2.3 Hz), 123.6 (d, J = 1.4 Hz, C-
0), 121.2 (d, J = 3.2 Hz, C-11), 120.1 (d, J = 11.9 Hz), 111.1 (d, J =
19
purified by column chromatography (SiO , 2.5% EtOAc in hexanes) to
2
4.7 Hz, C-6). 19F NMR (282 MHz, CDCl , resolution enhanced): δ
yield pure 6-fluorobenzo[c]phenanthrene 6 as a white solid (105 mg,
3
−
111.8 (br dt, J = 15.7, 3.3 Hz).
Synthesis of 5-Fluorobenzo[c]phenanthrene 5.
83%). For X-ray analysis, this compound was crystallized from
1
1a,15a
1
Step 1.
hexanes/2−3 drops of CH
2
Cl
2
. Mp: 72−73 °C. H NMR (500 MHz,
Condensation of 2a with 2-Naphthaldehyde. A solution of 2-
naphthaldehyde (393 mg, 2.51 mmol) and sulfone 2a (880 mg, 2.86
mmol, 1.10 molar equiv) in dry THF (25.0 mL) was cooled to 0 °C
under a nitrogen atmosphere. LHMDS (6.50 mL, 6.50 mmol, 2.40
molar equiv) was added dropwise at 0 °C. The mixture was stirred at 0
CDCl ): δ 9.12 (d, J = 8.3 Hz, 1H), 9.10 (d, J = 9.2 Hz, 1H), 8.17 (d, J
3
= 8.8 Hz, 1H), 8.06 (d, J = 7.8 Hz, 1H), 7.99−7.95 (m, 2H), 7.73−
1
3
7.66 (m, 3H), 7.63 (t, J = 3.5 Hz, 1H), 7.56 (d, J = 10.6 Hz, 1H).
C
NMR (125 MHz, CDCl ): δ 157.2 (d, J = 251.3 Hz), 133.9, 133.3 (d, J
3
= 10.6 Hz), 130.1 (d, J = 2.8 Hz), 129.5 (d, J = 4.8 Hz), 129.0, 128.3
(one resonance of the doublet partially buried under a singlet), 128.24,
128.22, 128.19, 128.0, 126.78, 126.77, 126.73, 125.5 (d, J = 1.9 Hz),
123.0 (d, J = 18.2 Hz), 118.7 (d, J = 8.6 Hz), 109.1 (d, J = 20.1 Hz).
°
C for 10 min, allowed to warm to rt, and stirred at rt. After 2 h, TLC
(10% EtOAc in hexanes) showed complete disappearance of the
aldehyde. Saturated aq NH Cl (30 mL) was added and the mixture
was extracted with EtOAc (3×). The combined organic layer was
washed with NaHCO (30 mL) and brine (30 mL) and then dried
over anhydrous Na SO . The solvent was evaporated under reduced
pressure, and the crude product was purified by column chromatog-
raphy (SiO , eluted with hexanes, followed by 2% EtOAc in hexanes)
4
19
F NMR (282 MHz, CDCl ): δ −125.8 (d, J = 12.2 Hz).
3
3
Synthesis of 10-Fluorobenzo[g]chrysene 7. Step 1. Con-
2
4
densation of 2a with Phenanthrene-9-carboxaldehyde. A solution
of phenanthrene-9-carboxaldehyde (79.7 mg, 0.386 mmol) and sulfone
2a (149 mg, 0.459 mmol, 1.19 molar equiv) in dry THF (10 mL) was
cooled to 0 °C under a nitrogen atmosphere. LHMDS (0.90 mL, 0.90
mmol, 2.33 molar equiv) was added dropwise at 0 °C. The mixture
was stirred at 0 °C for 10 min, allowed to warm to rt, and stirred at rt.
After 1 h, TLC (5% EtOAc in hexanes) showed complete
2
2
1
to yield pure (E/Z)-2-(2-fluoro-2-phenylvinyl)naphthalene (E:Z
ratio 2.9:1) as a yellowish solid (581 mg, 99%). 19F NMR (282
MHz, CDCl ): δ −96.2 (d, J = 18.3 Hz, 1F), −114.4 (d, J = 39.7 Hz,
3
+
1F). HRMS (+APPI mode) [M] : calcd for C H F 248.0996, found
18
13
2
48.0995.
disappearance of the aldehyde. Saturated aq NH Cl (30 mL) was
4
Step 2. Photocyclization of (E/Z)-2-(2-Fluoro-2-phenylvinyl)-
added, and the mixture was extracted with EtOAc (3×). The
1
1a,15a
naphthalene to 5.
naphthalene (E/Z ratio 2.9:1, 60.0 mg, 0.241 mmol) was dissolved
in benzene (250 mL), I (64.4 mg, 0.253 mmol, 1.05 molar equiv) was
(E/Z)-2-(2-Fluoro-2-phenylvinyl)-
combined organic layer was washed with NaHCO (30 mL) and
3
brine (30 mL) and then dried over anhydrous Na SO . The solvent
2
4
2
was evaporated under reduced pressure, and the crude product was
added, and nitrogen was bubbled into the solution for 10 min.
Propylene oxide (2.80 mL, 2.32 g, 40.0 mmol, 166 molar equiv) was
added, the solution was subjected to irradiation, and the reaction was
monitored by 19F NMR. After 12 h, F NMR showed consumption of
purified by column chromatography (SiO , eluted with 5% EtOAc in
2
hexanes) to yield pure (E/Z)-9-(2-fluoro-2-phenylvinyl)phenanthrene
1
9
(
E/Z ratio 3.1:1) as a colorless liquid (80.7 mg, 70%). F NMR (282
19
MHz, CDCl ): δ −100.3 (d, J = 21.4 Hz, 1F), −115.2 (d, J = 36.6 Hz,
3
+
(
E/Z)-2-(2-fluoro-2-phenylvinyl)naphthalene. The solvent was evapo-
rated, and the crude product was purified by column chromatography
SiO , 2% CH Cl in hexanes) to yield pure 5-fluorobenzo[c]-
1
F). HRMS (+APPI mode) [M] : calcd for C H F 298.1152, found
22 15
2
98.1159.
(
2
2
2
Step 2. Photocyclization of (E/Z)-9-(2-Fluoro-2-phenylvinyl)-
phenanthrene to 7. (E/Z)-9-(2-Fluoro-2-phenylvinyl)phenanthrene
(E/Z ratio 3.1:1, 80.7 mg, 0.270 mmol) was dissolved in benzene (250
phenanthrene 5 as a white solid (39.1 mg, 66%). For X-ray analysis,
this compound was crystallized from hexanes/2−3 drops of CH Cl .
2
2
1
H NMR (500 MHz, CDCl ): δ 9.16 (d, J = 8.3 Hz, 1H), 9.07 (d, J =
mL), I (84.1 mg, 0.331 mmol, 1.23 molar equiv) was added, and
3
2
8
.3 Hz, 1H), 8.33 (d, J = 7.8 Hz, 1H), 8.03 (d, J = 7.8 Hz, 1H), 7.91
nitrogen was bubbled into the solution for 10 min. Propylene oxide
(3.12 mL, 2.59 g, 44.6 mmol, 165 molar equiv) was added, the
solution was subjected to irradiation, and the reaction was monitored
(
(
d, J = 8.3 Hz, 1H), 7.77−7.68 (m, 4H), 7.63 (t, J = 7.8 Hz, 1H), 7.49
d, J = 10.6 Hz, 1H). 13C NMR (125 MHz, CDCl ): δ 157.4 (d, J =
3
19
19
252.7 Hz), 133.2, 132.0 (d, J = 5.0 Hz), 131.2 (d, J = 9.2 Hz), 130.4,
by F NMR. After 8.5 h, F NMR showed consumption of (E/Z)-9-
I
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
(
2-fluoro-2-phenylvinyl)phenanthrene. The solvent was evaporated,
and the crude product was purified by column chromatography (SiO2,
% EtOAc in hexanes) to yield pure 10-fluorobenzo[g]chrysene 7 as a
X-ray data for compound 3 (CIF)
X-ray data for compound 5 (CIF)
X-ray data for compound 6 (CIF)
X-ray data for compound 7 (CIF)
X-ray data for compound 8 (CIF)
X-ray data for compound chrysene (CIF)
X-ray data for compound benzo[g]chrysene (CIF)
4
white solid (61.3 mg, 77%). For X-ray analysis, this compound was
1
crystallized from hexanes/2−3 drops of CH Cl . Mp: 141 °C. H
NMR (500 MHz, CDCl ): δ 8.95 (d, J = 7.4 Hz, 1H), 8.81 (d, J = 7.8
2
2
3
Hz, 1H), 8.72 (d, J = 8.3 Hz, 1H), 8.71−8.68 (m, 1H), 8.50−8.48 (m,
1
(
H), 8.31−8.29 (m, 1H), 8.24 (d, J = 12.4 Hz, 1H, H-9), 7.72−7.62
m, 6H). 13C NMR (125 MHz, CDCl ): δ 158.3 (d, J = 251.7 Hz, C-
3
1
1
1
0), 131.9 (d, J = 5.0 Hz), 130.7, 130.4, 129.5 (d, J = 3.5 Hz), 129.4,
29.2, 128.7 (d, J = 2.7 Hz), 127.8, 127.6, 127.2, 126.7, 126.5, 126.4,
24.6 (d, J = 17.4 Hz), 124.3 (d, J = 2.6 Hz), 124.0, 123.7, 123.4, 121.0
AUTHOR INFORMATION
Corresponding Authors
*Contact for X-ray-related data. Tel: (845) 437-5746. E-mail:
rossi@vassar.edu.
*Tel: (212) 650-8926. Fax: (212) 650-6107. E-mail: bzajc@
ccny.cuny.edu.
Notes
■
d, J = 5.5 Hz), 104.1 (d, J = 21.5 Hz, C-9). 1 F NMR (282 MHz,
9
(
+
CDCl ): δ −124.3 (d, J = 12.2 Hz). HRMS (+APPI mode) [M] :
calcd for C H F 296.0996, found 296.0998.
3
22
13
Synthesis of 9-Fluorobenzo[g]chrysene 8. Step 1. Condensa-
tion of 2d with Benzaldehyde. A solution of benzaldehyde (59.7 mg,
0
.563 mmol) and sulfone 2d (270 mg, 0.664 mmol, 1.18 molar equiv)
The authors declare no competing financial interest.
in dry THF (10 mL) was cooled to 0 °C under a nitrogen atmosphere.
LHMDS (1.40 mL, 1.40 mmol, 2.49 molar equiv) was added dropwise
at 0 °C. The mixture was stirred at 0 °C for 10 min, allowed to warm
to rt, and stirred at rt. After 1 h, TLC (10% EtOAc in hexanes) showed
ACKNOWLEDGMENTS
This work was supported by the National Science Foundation
(Grant No. CHE-1058618) and partially by the NIH (NIGMS)
■
complete disappearance of the aldehyde. Saturated aq NH Cl (30 mL)
was added, and the mixture was extracted with EtOAc (3×). The
combined organic layer was washed with NaHCO (30 mL) and brine
4
(
Grant No. S06 GM008168) and by PSC CUNY awards.
3
Infrastructural support was provided by the National Institutes
of Health (Grant No. 8G12MD007603) from the National
Institute on Minority Health and Health Disparities. We thank
Dr. Andrew Poss (Honeywell) for a sample of NFSI and Dr.
Sakilam Satishkumar for his assistance with obtaining some
(
30 mL) and then dried over anhydrous Na SO . The solvent was
2 4
evaporated under reduced pressure, and the crude product was
purified by column chromatography (SiO , eluted with 5% EtOAc in
2
hexanes) to yield pure (E/Z)-9-(1-fluoro-2-phenylvinyl)phenanthrene
(
E/Z ratio 2.88:1) as a colorless liquid (149 mg, 89%). 19F NMR (282
MHz, CDCl ): δ −85.0 (d, J = 21.4 Hz, 1F), −95.3 (d, J = 36.6 Hz,
1
̌
NMR spectra. We thank Ms. Wei Wei, Ms. Marikone Gasi, and
3
+
F). HRMS (+APPI mode) [M] : calcd for C H F 298.1152, found
Mr. Michael Benavidez for resynthesis of 1-styrylnaphthalene
and (E/Z)-1-(2-fluoro-2-phenylvinyl)naphthalene for the UV
measurements and Ms. Karen Lo for obtaining the UV spectra
of these alkenes. We thank Mr. Satish Lakshman (Pixiedust) for
the final design of the cover art and Professor Mahesh
Lakshman (CCNY) for his help and advice with the musical
aspects represented in the cover art.
22
15
2
98.1151.
Step 2. Photocyclization of (E/Z)-9-(1-Fluoro-2-phenylvinyl)-
phenanthrene to 8. (E/Z)-9-(1-Fluoro-2-phenylvinyl)phenanthrene
(
E/Z ratio 2.88:1, 76.1 mg, 0.255 mmol) was dissolved in benzene
(
250 mL), I (71.3 mg, 0.281 mmol, 1.10 molar equiv) was was added,
2
and nitrogen was bubbled into the solution for 10 min. Propylene
oxide (2.80 mL, 2.32 g, 40.0 mmol, 157 molar equiv) was added, the
solution was subjected to irradiation, and the reaction was monitored
by F NMR. After 8 h, F NMR showed consumption of the alkene.
The solvent was evaporated, and the crude product was purified by
19
19
REFERENCES
■
(
1) (a) Kirsch, P. Modern Fluoroorganic Chemistry. Synthesis,
column chromatography (SiO , 2% EtOAc in hexanes) to yield pure 9-
2
Reactivity, Applications; Wiley−VCH, 2004. (b) Okazaki, T.; Laali, K.
K. Fluorinated Polycyclic Aromatic Hydrocarbons (PAHs) and
Heterocyclic Aromatic Hydrocarbons (Hetero-PAHs): Synthesis and
Utility. In Modern Organofluorine ChemistrySynthetic Aspects; Laali,
K. K., Ed.; Bentham Science Publishers, 2006; Vol. 2, pp 353−380.
fluorobenzo[g]chrysene 8 as a white solid (55.1 mg, 73%). For X-ray
analysis, this compound was crystallized from EtOH/2−3 drops of
benzene/1 drop of CH Cl . H NMR (500 MHz, CDCl ): δ 9.07 (dt,
1
2
2
3
J = 8.1, 2.2 Hz, 1H, H-8), 8.82 (d, J = 8.3 Hz, 1H), 8.79 (d, J = 8.3 Hz,
1
H), 8.71 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 7.4 Hz, 1H, H-11), 7.75−
(
4
2) (a) Kirsch, P.; Bremer, M. Angew. Chem., Int. Ed. 2000, 39, 4216−
235. (b) Babudri, F.; Farinola, G. M.; Naso, F.; Ragni, R. Chem.
7.70 (m, 3H), 7.67 (d, J = 15.2 Hz, 1H, H-10), 7.65−7.55 (m, 3H).
1
3
C NMR (125 MHz, CDCl ): δ 159.3 (d, J = 251.7 Hz, C-9), 133.2
3
Commun. 2007, 1003−1022. (c) Berger, R.; Resnati, G.; Metrangolo,
(
d, J = 11.0 Hz), 131.5, 131.3 (d, J = 4.1 Hz), 130.4, 130.1, 129.2 (d, J
P.; Weber, E.; Hulliger, J. Chem. Soc. Rev. 2011, 40, 3496−3508.
=
2.4 Hz), 129.0, 128.0 (d, J = 26.1 Hz, C-8), 127.8, 127.7, 127.6,
(
(
1
d) Xu, T.; Yu, L. Mater. Today 2014, 17, 11−15.
1
27.4, 127.2 (d, J = 5.0 Hz, C-11), 126.9, 126.4, 125.2, 123.8, 123.1,
3) (a) Andersson, J. T.; Weis, U. J. Chromatogr. A 1994, 659, 151−
61. (b) Luthe, G.; Ramos, L.; Dalluge, J.; Brinkman, U. A. Th.
Chromatographia 2003, 57, 379−383.
1
19.9 (d, J = 11.5 Hz, C-10a), 111.3 (d, J = 24.7 Hz, C-10). 19F NMR
̈
(
2
282 MHz, CDCl , resolution enhanced): δ −114.6 ppm (dd, J = 15.1;
+
3
.3 Hz). HRMS (+APPI mode) [M] : calcd for C H F 296.0996,
22 13
(4) Harvey, R. G. Polycyclic Aromatic Hydrocarbons: Chemistry and
Carcinogenicity; Cambridge University Press: Cambridge, 1991.
found 296.1002.
(
5) Jerina, D. M.; Sayer, J. M.; Agarwal, S. K.; Yagi, H.; Levin, W.;
ASSOCIATED CONTENT
Wood, A. W.; Conney, A. H.; Pruess-Schwartz, D.; Baird, W. M.;
Pigott, M. A.; Dipple, A. Reactivity and Tumorigenicity of Bay-Region
Diol Epoxides Derived from Polycyclic Aromatic Hydrocarbons. In
Biological Reactive Intermediates III; Kocsis, J. J., Jollow, D. J., Witmer,
C. M., Nelson, J. O., Snyder, R., Eds.; Plenum Press: New York, 1986;
pp 11−30.
■
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02580.
S
1H and 13C NMR spectra, 2D NMR spectra for
compounds 4, 7, and 8, and UV spectra of 1-
styrylnaphthalene and (E/Z)-1-(2-fluoro-2-phenylvinyl)-
naphthalene (PDF)
Details of the X-ray crystallographic analysis and ORTEP
figures (PDF)
(6) (a) Jerina, D. M.; Chadha, A.; Cheh, A. M.; Schurdak, M. E.;
Wood, A. W.; Sayer, J. M.: Covalent Bonding of Bay-Region Diol
Epoxides to Nucleic Acids. In Biological Reactive Intermediates IV;
Witmer, C. M., Snyder, R., Jollow, D. J., Kalf, G. F., Kocsis, J. J., Sipes,
I. G., Eds.; Plenum Press: New York, 1991; pp 533−553. (b) Dipple,
A. Reactions of Polycyclic Aromatic Hydrocarbons with DNA. In DNA
J
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Adducts: Identification and Biological Significance; Hemminki, K.,
(d) Chowdhury, M.; Mandal, S. K.; Banerjee, S.; Zajc, B. Molecules
2014, 19, 4418−4432. (e) Kumar, R.; Singh, G.; Todaro, L. J.; Yang,
L.; Zajc, B. Org. Biomol. Chem. 2015, 13, 1536−1549.
̈
Dipple, A., Shuker, D. E. G., Kadlubar, F. F., Sagerback, D., Bartsch,
H., Eds.; Scientific Publication No. 125, International Agency for
Research on Cancer: Lyon, 1994; pp 107−129. (c) Szeliga, J.; Dipple,
A. Chem. Res. Toxicol. 1998, 11, 1−11.
(21) Ghosh, A. K.; Zajc, B. Org. Lett. 2006, 8, 1553−1556.
(22) (a) Laarhoven, W. H. Recl. Trav. Chim. Pays-Bas 1983, 102,
185−204. (b) Mallory, F. B.; Mallory, C. W. Org. Reactions 1984, 30,
1−456. (c) Jørgensen, K. B. Molecules 2010, 15, 4334−4358.
(23) Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem.
1991, 56, 3769−3775.
(
7) (a) Penning, T. M.; Burczynski, M. E.; Hung, C.-F.; McCoull, K.
D.; Palackal, N. T.; Tsuruda, L. S. Chem. Res. Toxicol. 1999, 12, 1−18.
b) Bolton, J. L.; Trush, M. A.; Penning, T. M.; Dryhurst, G.; Monks,
T. J. Chem. Res. Toxicol. 2000, 13, 135−160.
8) (a) Jerina, D. M.; Sayer, J. M.; Yagi, H.; Croisy-Delcey, M.; Ittah,
(
(
́
(24) Alacid, E.; Najera, C. Adv. Synth. Catal. 2006, 348, 2085−2091.
Y.; Thakker, D. R.; Wood, A. W; Chang, R. L.; Levin, W.; Conney, A.
H. Highly Tumorigenic Bay-Region Diol Epoxides from the Weak
Carcinogen Benzo[c]phenanthrene. In Biological Reactive Intermediates
II Part A; Snyder, R., Parke, D. V., Kocsis, J. J., Jollow, D. J., Gibson, C.
G., Witmer, C. M., Eds.; Plenum Press: New York, 1982; pp 501−523.
(25) Lackner, B.; Bretterbauer, K.; Schwarzinger, C.; Falk, H.
Monatsh. Chem. 2005, 136, 2067−2082.
(26) Nayak, S. K.; Reddy, M. K.; Chopra, D.; Row, T. N. G.
CrystEngComm 2012, 14, 200−210.
(27) Champagne, P. A.; Desroches, J.; Paquin, J.-F. Synthesis 2015,
47, 306−322.
(
b) Prasad, G. K. B.; Mirsadeghi, S.; Boehlert, C.; Byrd, R. A.; Thakker,
D. R. J. Biol. Chem. 1988, 263, 3676−3683.
9) (a) Buhler, D. R.; Unlu, F.; Thakker, D. R.; Slaga, T. J.; Conney,
A. H.; Wood, A. W.; Chang, R. L.; Levin, W.; Jerina, D. M. Cancer Res.
983, 43, 1541−1549. (b) Chang, R. L.; Wood, A. W.; Conney, A. H.;
(28) Arunan, E.; Desiraju, G. R.; Klein, R. A.; Sadlej, J.; Scheiner, S.;
Alkorta, I.; Clary, D. C.; Crabtree, R. H.; Dannenberg, J. J.; Hobza, P.;
Kjaergaard, H. G.; Legon, A. C.; Mennucci, B.; Nesbitt, D. J. Pure Appl.
Chem. 2011, 83, 1619−1636.
(
1
(29) Laali, K. K.; Okazaki, T. J. Org. Chem. 2001, 66, 780−788.
(30) Lutnaes, B. F.; Luthe, G.; Brinkman, U. A. Th.; Johansen, J. E.;
Yagi, H.; Sayer, J. M.; Thakker, D. R.; Jerina, D. M.; Levin, W. Proc.
Natl. Acad. Sci. U. S. A. 1987, 84, 8633−8636. (c) Cavalieri, E.; Rogan,
E.; Cremonesi, P.; Higginbotham, S.; Salmasi, S. J. Cancer Res. Clin.
Oncol. 1988, 114, 10−15. (d) Cavalieri, E.; Rogan, E.; Higginbotham,
S.; Cremonesi, P.; Salmasi, S. J. Cancer Res. Clin. Oncol. 1988, 114, 16−
Krane, J. Magn. Reson. Chem. 2005, 43, 588−594 and references cited
therein.
(31) See, for example: (a) Mallory, F. B.; Mallory, C. W. Coupling
through Space in Organic Chemistry. In Encyclopedia of Nuclear
Magnetic Resonance; Grant, D. M., Harris, R. K., Eds.; J. Wiley & Sons:
Chichester, 1996; Vol. 3, pp 1491−1501 (online 2007). (b) Hierso, J.-
C. Chem. Rev. 2014, 114, 4838−4867.
22.
(
10) Bae, S.; Mah, H.; Chaturvedi, S.; Jeknic, T. M.; Baird, W. M.;
Katz, A. K.; Carrell, H. L.; Glusker, J. P.; Okazaki, T.; Laali, K. K.; Zajc,
B.; Lakshman, M. K. J. Org. Chem. 2007, 72, 7625−7633.
(
32) Mallory, F. B.; Mallory, C. W.; Ricker, W. M. J. Am. Chem. Soc.
975, 97, 4770−4771.
33) Sardella, D. J.; Boger, E. Magn. Reson. Chem. 1989, 27, 13−20.
34) Thalladi, V. R.; Weiss, H.-C.; Blaser, D.; Boese, R.; Nangia, A.;
Desiraju, G. R. J. Am. Chem. Soc. 1998, 120, 8702−8710.
35) Laali, K. K.; Hollenstein, S.; Harvey, R. G.; Hansen, P. E. J. Org.
Chem. 1997, 62, 4023−4028.
(
11) (a) Mirsadeghi, S.; Prasad, G. K. B.; Whittaker, N.; Thakker, D.
1
(
R. J. Org. Chem. 1989, 54, 3091−3096. (b) Laali, K. K.; Hansen, P. E. J.
Org. Chem. 1993, 58, 4096−4104. (c) Fukuhara, T.; Sekiguchi, M.;
Yoneda, N. Chem. Lett. 1994, 1011−1012. (d) Yang, T.; Huang, Y.;
Cho, B. P. Chem. Res. Toxicol. 2006, 19, 242−254.
(
̈
(
(
12) (a) Laali, K. K.; Tanaka, M.; Forohar, F.; Cheng, M.; Fetzer, J.
C. J. Fluorine Chem. 1998, 91, 185−190. (b) Zajc, B.: Application of
Xenon Difluoride in Synthesis. In Modern Organofluorine Chemistry−
Synthetic Aspects; Laali, K. K., Ed.; Bentham Science Publishers, 2006;
Vol. 2, pp 61−157.
(
(
13) Zajc, B. J. Org. Chem. 1999, 64, 1902−1907.
14) (a) Girke, W.; Bergmann, E. D. Chem. Ber. 1976, 109, 1038−
1
045. (b) Harvey, R. G.; Cortez, C. Tetrahedron 1997, 53, 7101−7118.
(
15) (a) Marx, G. S.; Bergmann, E. D. J. Org. Chem. 1972, 37, 1807−
810. (b) Ittah, Y.; Jerina, D. M. J. Fluorine Chem. 1980, 16, 137−144.
c) Weis, U.; Andersson, J. T. Polycyclic Aromat. Compd. 2002, 22, 71−
5. (d) Li, H.; He, K.-H.; Liu, J.; Wang, B.-Q.; Zhao, K.-Q.; Hu, P.;
1
(
8
Shi, Z.-J. Chem. Commun. 2012, 48, 7028−7030. (e) Li, Z.; Twieg, R. J.
Chem. - Eur. J. 2015, 21, 15534−15539.
(
16) (a) Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2008, 130, 10060−
10061. (b) Lee, H. G.; Milner, P. J.; Buchwald, S. L. J. Am. Chem. Soc.
2
014, 136, 3792−3795. (c) Fuchibe, K.; Morikawa, T.; Shigeno, K.;
Fujita, T.; Ichikawa, J. Org. Lett. 2015, 17, 1126−1129.
(
17) Syntheses of several F-PAHs, including 9-fluorophenanthrene,
5
- and 6-fluorochrysene, 6-fluorobenzo[c]phenanthrene, and 5-
fluorobenzo[k]chrysene: Fuchibe, K.; Mayumi, Y.; Zhao, N.;
Watanabe, S.; Yokota, M.; Ichikawa, J. Angew. Chem., Int. Ed. 2013,
5
(
2, 7825−7828.
18) (a) Blakemore, P. R. J. Chem. Soc., Perkin Trans. I 2002, 2563−
585. (b) Plesniak, K.; Zarecki, A.; Wicha, J. Top. Curr. Chem. 2007,
2
2
1
75, 163−250. (c) Aïssa, C. Eur. J. Org. Chem. 2009, 2009, 1831−
844.
(
19) For reviews on fluoroolefination using the Julia-Kocienski
approach, see: (a) Zajc, B.; Kumar, R. Synthesis 2010, 2010, 1822−
1
1
(
836. (b) Pfund, E.; Lequeux, T.; Gueyrard, D. Synthesis 2015, 47,
534−1546.
20) For our recent efforts in this area, see: (a) Kumar, R.; Pradhan,
P.; Zajc, B. Chem. Commun. 2011, 47, 3891−3893. (b) Mandal, S. K.;
Ghosh, A. K.; Kumar, R.; Zajc, B. Org. Biomol. Chem. 2012, 10, 3164−
3167. (c) Kumar, R.; Zajc, B. J. Org. Chem. 2012, 77, 8417−8427.
K
DOI: 10.1021/acs.joc.5b02580
J. Org. Chem. XXXX, XXX, XXX−XXX