Synthesis of sterically hindered 4,5-diarylphenanthrenes: Via acid-catalyzed bisannulation of benzenediacetaldehydes with alkynes

Article abstract of DOI:10.1039/c9sc00334g

The synthesis of sterically hindered phenanthrenes via acid-catalyzed bisannulation reaction is described. Treatment of 1,4-benzenediacetaldehyde with terminal aryl alkynes in the presence of B(C₆F₅)₃ provides 4,5-diarylphenanthrenes in good yields with excellent regioselectivity. The use of internal alkyne substrates enabled the synthesis of sterically hindered 3,4,5,6-tetrasubstituted phenanthrenes displaying augmented backbone helicity. Furthermore, 1,5-disubstituted, 1,8-disubstituted, 1,2,5,6-tetrasubstituted, and 1,2,7,8-tetrasubstituted phenanthrenes can be obtained through the reaction of alkynes with 1,3-benzenediacetaldehyde or 1,2-benzenediacetaldehyde disilyl acetal.

Full text of DOI:10.1039/c9sc00334g

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DOI: 10.1039/C9SC00334G
Journal Name
ARTICLE
Synthesis of Sterically Hindered 4,5-Diarylphenanthrenes via Acid-
catalyzed Bisannulation of Benzenediacetaldehydes with Alkynes
Received 00th January 20xx,
Accepted 00th January 20xx
a
ab
abc
Yuanming Li, Akiko Yagi and Kenichiro Itami*
DOI: 10.1039/x0xx00000x
The synthesis of sterically hindered phenanthrenes via acid-catalyzed bisannulation reaction is described. Treatment of
,4-benzenediacetaldehyde with terminal aryl alkynes in the presence of B(C provides 4,5-diarylphenanthrenes in
1
6 5 3
F )
www.rsc.org/
good yields with excellent regioselectivity. The use of internal alkyne substrates enabled the synthesis of sterically
hindered 3,4,5,6-tetrasubstituted phenanthrenes displaying augmented backbone helicity. Furthermore, 1,5-disubstituted,
1
,8-disubstituted, 1,2,5,6-tetrasubstituted, and 1,2,7,8-tetrasubstituted phenanthrenes can be obtained through the
reaction
of
alkynes
with
1,3-benzenediacetaldehyde
or
1,2-benzenediacetaldehyde
disilyl
acetal.
isomeric
1,3-benzenediacetaldehyde
and
1,2-
Introduction
benzenediacetaldehyde disilyl acetal with aryl alkynes gave
,5-disubstituted, 1,8-disubstituted, 1,2,5,6-tetrasubstituted
1
Angularly fused polycyclic aromatics (AF-PAHs; e.g.,
phenacenes and helicenes) are unique structural motifs that
are utilized in a wide array of materials ranging from organic
electronics1 to medicinal chemistry. Phenanthrene, the
simplest AF-PAH, is the distinct fundamental subunit of higher
AF-PAHs and the development of synthetic methods for the
preparation of functionalized phenanthrenes has received
extensive attention over the years (Figure 1a). The Mallory
cyclization of stilbene derivatives (i) and the annulation of
alkynylated biaryls (ii) are useful methods for the synthesis of
phenanthrene derivatives. Additionally, transition metal
catalyzed annulations of 2-substituted biphenyl with alkynes
have also been reported (iii). Other methods, such as ring-
and 1,2,7,8-tetrasubstituted phenanthrenes, respectively.
Inspired by the synthesis of naphthalene derivatives
1
2
through the annulation of phenylacetaldehydes with alkynes,
we envisioned that the acid-catalyzed reaction of 1,4-
2
1
3
benzenediacetaldehyde (1a) with phenylacetylene (2a) could
provide the intermediate naphthalene A (Figure 1c).
a) Conventional synthesis of phenanthrenes
3
R
R'
R
4
(
i) h

, I2
(ii) Lewis acid
ref 4
R'
R
Ar
Ar'
ref 3
Ar
Ar'
Ar'
5
X
Ar
Ar'
X
(
iv) transition
6
7
R'
closing olefin metathesis, carbonyl-olefin metathesis,
Ar
Ar'
metal
(iii) R
Ar
8
9
McMurry cyclization, and carbene dimerization, have also
been used (iv). However, synthetic methods for the
construction of sterically hindered 4,5-disubstituted
phenanthrenes are particularly limited. For example, known
preparations of 4,5-diphenylphenanthrene require either a
four- or five-step synthesis and provide the product in low
X
X = CH2,6 O,7-8 N29
X = I,5a COOH,5b MgBr,5c Si5d
b) Conventional synthesis of 4,5-diphenyl phenanthrene
1
0
CHO
Cl
OH
Me
4 steps
ref 11a
5 steps
ref 11c
Ph
Ph Ph
1
1
overall yields (Figure 1b). Herein, we report the acid-
catalyzed bisannulation reaction of 1,4-
c) This work: Bisannulation of benzenediacetaldehydes with alkynes
benzenediacetaldehyde with aryl alkynes that can access
sterically hindered, twisted 4,5-disubstituted and 3,4,5,6-
tetrasubstituted phenanthrenes. Furthermore, reactions of
+
Ph
OHC
CHO
1a
2a
Lewis acid
less
hindered
Ph

Ph
Ph
a. Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University,
Chikusa, Nagoya 464-8602, Japan.
Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602,

CHO

-position
annulation

-position
annulation
b.
Ph Ph
3a
Ph
Ph
Japan.
more
nucleophilic
c.
4a
A
JST-ERATO, Itami Molecular Nanocarbon Project, Nagoya University, Chikusa,
Nagoya 464-8602, Japan.
Figure 1 Synthetic strategies leading to phenanthrenes.
Electronic Supplementary Information (ESI) available: Syntheses, NMR, UV-vis-
nearIR absorption, CV and crystallographic table. CCDC 1865671 (3c), 1865672
(3x), 1865673 (7a). See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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We initially anticipated that the second annulation with mechanism (Scheme 1, for details, see Supporting
View Article Online
DOI: 10.1039/C9SC00334G
6 5 3
another equivalent of alkyne could take place at the less Information). Initially, B(C F ) coordinates with the carbonyl
1
4
hindered -position of A to give 1,5-diphenylanthracene (4a). oxygen, which would trigger the nucleophilic attack of the
Surprisingly, however, we observed instead an unprecedented alkyne partner to give the vinyl carbocation A’. Subsequently,

-position
annulation
to
give
isomeric
4,5- intermediate A’ undergoes an intramolecular electrophilic
diphenylphenanthrene (3a), which is an even more interesting, aromatic substitution, followed by aromatization to provide
otherwise difficult-to-access AF-PAH.
the naphthalene A. A DFT calculation revealed that the
Mulliken atomic charge at -position is actually more negative
than -position in the naphthalene A (–0.275 compared to –
Results and discussion
0
.176, see Supporting Information for details). The electronic
bias of the C–C bond formation is overcoming the steric
parameters in the reaction of 1a and 1-ethyl-4-ethynylbenzene hindrance between the two phenyl rings in C, providing -
Thus, we investigated the effect of acids and other reaction
(
2b) as a model system (Table 1). Though the use of Brønsted position annulation product 3a exclusively.
1
2g
12c
12b
acid HNTf
2
,
2
Lewis acids CuCl /AgSbF
6
or TiCl
4
failed to
give more than trace amounts of target products (entries 1–3),
1
2d
12a
FeCl
3
and GaCl
3
were able to achieve the phenanthrene
transformation in 16% and 35% yield, respectively (entries 4
1
2f
and 5). A catalytic amount of BF
of 3b in 41% yield at 80 °C (entry 6). Subsequently, B(C
was found to give a higher yield (45%) under milder conditions
entry 7). The best result was achieved upon reacting 1a (1.0
equiv) with 2b (2.5 equiv) in the presence of 20 mol% B(C
and MS4Å in dichloromethane (DCM) at room temperature for
5 h, giving 3b in 65% isolated yield with excellent Scheme 1 A possible reaction mechanism.
3 2
·Et O
led to the formation
6 5 3
F )
(
6 5 3
F )
1
regioselectivity (entry 8). Notably, the anthracene product 4b
was not detected under any of the conditions tested. However,
the insoluble material formed during the reaction was isolated,
and we presume that the self-polymerization of 1a is the major
side reaction (see Supporting Information). The use of MS4Å
was necessary to suppress the hydration of the alkyne. A
solvent screening revealed that the initially tested DCM was
the optimal medium for this reaction (entries 9–12).
With the optimized conditions in hand, we investigated the
substrate scope with respect to the alkyne coupling partner
(Scheme 2). Installing electron-donating groups on the para-
position of the phenylacetylene aromatic ring did not
significantly alter the reaction outcome (3a-d). Interestingly,
the reaction of p-ethynyltolane (containing both terminal and
disubstituted alkyne moieties) with 1a selectively gave 3e in
56% yield. With the dimethylamino substituent, the desired
product 3f was not formed. This may be due to the formation
Table 1. The Reaction Optimization.a
1
5
of N/B frustrated Lewis pairs.
However, acetamide
Et
Et
substituent was tolerated and target product 3g was obtained
in 27% yield. Under the optimized reaction conditions, the
reaction of 1a with alkyne bearing electron-withdrawing
groups at the para-position gave the target products 3h-j in
low yield. Further optimization revealed that the yields of 3h-j
increased to 44%, 37%, and 34%, respectively, in the presence
of 0.25 mL hexafluoroisopropanol (HFIP). This is likely because
of the effect of HFIP on the stabilization of vinyl cations (see
+
Et
1
a
+
Et
Et
2
b
3b
4b
3bd
(%)
4bd
(%)
Additive
equiv)
Temp
(°C)
Time
(h)
Entry
Solvent
(
1
2
3
4
5
6
7
HNTf
CuCl /AgSbF
2
(0.15)
rt
55
rt
80
40
80
rt
rt
rt
rt
rt
15
22
3
15
6
15
15
15
15
15
15
15
DCE
DCM
DCM
DCE
DCM
DCE
DCM
DCM
DCE
n.d.
n.d.
n.d.
n.d.
trace n.d.
b
2
6
1
6
the proposed mechanism). An aryl alkyne bearing a strong
electron-withdrawing trifluoromethyl group in the para-
position did not afford the desired product 3k. The para-
boronic acid pinacol (Bpin) ester-substituted aryl alkyne
provided the product 3l in 21% yield. The meta-substituents of
the aryl acetylene moiety were also tolerated to give the
corresponding products 3m-p. To our delight, the ortho-
methyl-substituted aryl alkyne afforded the product 3q in good
TiCl
4
(2.0)
FeCl
GaCl
BF
B(C
B(C
B(C
B(C
B(C
B(C
3
(0.10)
(0.20)
16
35
41
45
67
59
48
7
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
3
3
2
·Et O (0.05)
6
F
6
F
6
F
6
F
6
F
6
F
5
)
5
)
5
)
5
)
5
)
5
)
3
3
3
3
3
3
(0.20)
(0.20)
(0.20)
(0.20)
(0.20)
(0.20)
c
8
9
1
1
1
c
0c
1
2
toluene
c
CHCl
THF
3
c
rt
trace n.d.
17
yield as well. Due to the higher rotational barrier, product 3q
a
b
Reaction conditions: 1a (0.10 mmol) and 2b (0.25 mmol) in solvent (2.5 mL). exists in solution as a mixture of multiple rotamers as
CuCl (0.08)/AgSbF
(0.16). c100 mg MS4Å (1/16) were added. dYield was
NMR spectroscopy. n.d. not detected. rt room
2
6
1
confirmed by variable temperature H NMR and 1D NOE
1
determined by
temperature.
H
=
=
1
8
experiments. Even the more hindered substrate (2,4,6-
trimethylphenyl)acetylene underwent bisannulation to give
the target product 3r in 7% yield. Moreover, the reactions of
1a with heteroaromatic alkynes such as 2-ethynylthiophene
Based on the reported reaction mechanism of
1
2
phenylacetaldehydes with alkynes, we suggest the following
2
| J. Name., 2012, 00, 1-3
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Scheme 2 The reaction of 1a with Alkynes. Reaction conditions: 1a (0.10 mmol),
and 3-ethynylthiophene gave the products 3s and 3t in 47%
and 61%, respectively. Unfortunately, aliphatic alkynes (1-
View Article Online
2
1
(0.25 mmol). Conditions A: 20 mol% B(C
6
F
5
)
3
/MS4Å, DCM, rt, 15 h. Conditions B:
DOI: 10.1039/C9SC00334G
50 mol% TfOH, CF Ph/HFIP = 10:1, 30 °C, 15 h. Yields given correspond to
3
a
octyne) and methyl acetylenecarboxylate were not tolerated isolated yields. Note: Solvent: DCM/HFIP = 10:1.
under the reaction conditions and the corresponding products
3
u and 3v were not detected, which emphasized the effect of
The structures of 3c and 3x were unambiguously
the aromatic moiety of the phenylacetylenes on the determined by X-ray crystallographic analysis (Figure 2). The
stabilization of vinyl cations (see the proposed mechanism). torsion angle of the phenanthrene moiety of 3c was 27.5(2)°
However, the reaction of 1a with ethoxyacetylene provided a (measured through the C4-C4a-C4b-C5 torsion). The two para-
trace amount of 4,5-diethoxyphenanthrene (3w), and the tert-butyl substituted phenyl rings (ring D and E) are oriented
mono-annulation
product
2-(8-ethoxynaphthalen-2- roughly parallel to each other (see Figure 2a, side view, within
yl)acetaldehyde was obtained in 8% yield. To show practicality, 13.2°). On the other hand, the increased steric demands
we ran a 2.0 mmol large-scale experiment with 2b to give 3b in caused by the 3,4,5,6-tetraphenyl substitution in 3x led to
5
5% isolated yield (425 mg prepared). To our delight, the 2.0 greater twisting of the phenanthrene backbone with a C4-C4a-
mmol large-scale reaction of 2l with 1a gave the target product C4b-C5 torsion angle of 35.21(16)°. In addition, the two phenyl
l at comparable yield (25%) using 2.0 equivalent BF ·Et
rings (ring D and E) are oriented roughly parallel to each other
3
3
2
O
instead of 20 mol% B(C
Information).
F )
6 5 3
(for details, see Supporting as well (see Figure 2b, side view, within 11.1°). These
nonplanar features of overcrowded phenanthrenes should be
The scope of the bisannulation reaction with internal beneficial in some of device-oriented applications, such as
alkyne substrates such as diphenylacetylene is also shown in organic light emitting diodes, where the strong π-π
Scheme 2. Further optimization revealed that this intermolecular interactions cause detrimental effects.
transformation is better conducted in the presence of 150
mol% triflic acid (TfOH) using CF
for 15 h. Sterically
tetraphenylphenanthrene (3x) was thus readily synthesized in
1% yield. This protocol could be extended to the use of
bromide-substituted phenylacetylene to give 1.1:1.0
3
Ph and HFIP as solvent at 30
(a) 3c
A
D
°
C
hindered 3,4,5,6-
A
D
C4
C4a
B
27.5(2)o
BC4b
C C5
4
E
C
E
a
regioisomeric mixture of 3y and 3y’ (for details, see Supporting
top view
side view
Information).
(b) 3x
R2
R1
R1
R2
CHO
R2
Conditions A: B(C F )
Conditions B: TfOH
6
5
3
A
C4
A
D
+
C4a
D
o
B
B
35.21(16)
R1
C4b
E
CHO
C
C5
E
C
1a
2a-y
3a-y
R3
R1
R2
R1
top view
side view
2
R
R
2
R
R1
Figure 2 X-ray structure of (a) 3c and (b) 3x at 50% thermal probability.
R
R1
R2
R3
Conditions A
Conditions A
Conditions A
2
Furthermore, the chiral resolution of 3b, 3n, and 3x were
achieved by HPLC at 25 °C. The racemization of 3b and 3x was
observed at elevated temperature (see Supporting
Information). The configurational stability of 4,5-
diarylphenanthrene with ortho- or meta-substituents in the
aryl moiety (such as 3m-r) are comparatively higher than 3a
1
2
3q, R = R = H, R3 = Me, 58%
1
3
3
3
3
3
3
3
3
3
3
3
3
a, R = H, 48%
b, R = Et, 65%
c, R = t-Bu, 56%
d, R = OMe, 67%
3m, R = H, R = Me, 58%
1
2
a
3r, R = R = R = Me, 7%a
1
2
3
3n, R = R = t-Bu, 35%
3o, R1 = R2 = Ph, 25%a
p, R = R = OMe, 27%
1
2
a
3
e, R =
Ph, 56%
f, R = NMe2, n.d.
g, R = NHCOCH3, 27%
h, R = F, 44%
R
a
a
S
S
R
a
S
i, R = Br, 37%
a
S
17
j, R = I, 34%
(Scheme 3). A kinetic study of the thermal racemization of 3n
a
k, R = CF3, n.d.
l, R = Bpin, 21%
Conditions A
a
u, R = n-hexyl, n.d.a
was performed, corresponding to a racemization barrier of 126
3
a
−1
Conditions A
Conditions A
3v, R = COOMe, n.d.
kJ mol at 100 °C. Using the solution of highly enantioenriched
3
w, R = OEt, 2%a
3
s, 47%
3t, 61%
3
n in 1,2-dichloroethane, only a small drop in e.r. was
observed after heating at 85 °C for 3 h (from 96.8:3.2 to
4.0:6.0). These results (for details, see Supporting
Br
Br
Br
9
Et
Et
Et
Br
Information) demonstrate that the configurational stability of
these helically chiral compounds can in fact be tuned by
judicious substituent choice – an important advantage with
respect towards their potential use as chiral materials. The
preliminary investigation of the direct asymmetric
bisannulation of 1,4-benzenediacetaldehyde with alkynes were
3y
3y'
Et
Conditions B: 3x, 41%
Conditions B: 3y:3y' = 20%:19%
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Journal Name
conducted as well. However, the use of BINOL-phosphoric acid
and DL-10-Camphorsulfonic acid failed to give the target
products (for details, see Supporting Information).
View Article Online
1
R
Conditions A: B(C6F5)3
DOI: 10.1039/C9SC00334G
R2 Conditions B: TfOH
2
R
+
CHO
R1
OHC
R1
R2
1b
2
5a-d
R1 R2
R1
R1
7 ()
R2
R2
5a, R1 = 4-EtC6H4, R2 = H , Conditions A: 42%
Heat
1
b, R = 4-MeOC6H4, R2 = H , Conditions A: 23%
1
5
2
6
R2
5c, R = Ph, R2 = Ph , Conditions B: 23%
1
CHO
5
()
R2
5d, R1 4-EtC6H4, R2 = Br , Conditions B: 46%
=
R1
3
4
R1
Intermediate B
(P)
(M)
3
3
a, R1 = R2 = H, rapid racemization at room temperature
n, R = R = t-Bu, slow racemization at 85 ºC
R1
R1
1
2
R2
Conditions A: B(C6F5)3
Conditions B: TfOH
Et3SiO
Et3SiO
OSiEt3
OSiEt3
R1
R2
R2
+
Scheme 3 The racemization of 4,5-diarylphenanthrenes.
1c'
2
6a-d
Interestingly, we observed a different outcome when using
other benzenediacetaldehyde positional isomers (e.g., 1,3-
benzenediacetaldehyde (1b)) as substrates in the
bisannulation reaction (Scheme 4). Under the optimized
reaction conditions, the reaction of 1b with terminal alkynes
provided unsymmetrical 1,5-disubstituted phenanthrenes 5a
7
5
R1
1
6a, R1 = Ph, R2 = H , Conditions A: n.d.
6 ()
OSiEt3
2
6b, R = 4-MeOC6H4, R2 = H , Conditions A: 12%
1
R2
c, R1 = Ph, R2 = Ph , Conditions B: 10%
6d, R
6
3
4
1
=
4-EtC6H4, R2 = Br , Conditions B: 22%
OSiEt3
Intermediate C
Scheme 4 The reaction of 1b and 1c’ with Alkynes. Reaction conditions: 1b or 1c’
0.10 mmol), 2 (0.25 mmol). Conditions A: 20 mol% B(C /MS4Å, DCM/HFIP =
0:1, rt, 15 h. Conditions B: 150 mol% TfOH, CF Ph/HFIP = 10:1, 30 °C, 15 h.
(
1
6 5 3
F )
1
9
and 5b with excellent regioselectivity. The reaction with
3
diphenylacetylene still occurred with excellent regioselectivity Yields given correspond to isolated yields. n.d. = not detected.
to give 1,2,5,6-tetraphenylphenanthrene (5c) in 23% yield. The
The multisubstituted phenanthrenes derived from
2,6-dibromo-1,5-bis(4- bisannulation reactions can serve as useful building blocks for
corresponding
ethylphenyl)phenanthrene (5d) was obtained in 46% yield with the synthesis of organic materials and ligands. To demonstrate
excellent regioselectivity. Noteworthy, 5d could serve as a the utility of this method, the new helical, chiral diphosphine
2
0
valuable building block in cross-coupling reactions to prepare ligand 3z was prepared via the coupling reaction of 3j with
multisubstituted phenanthrenes. The observed outcome is HPPh (Scheme 5). When treating 3z with [PdCl (CH CN) ],
2
2
3
2
consistent with the reaction going through an intermediate interesting binuclear palladium complex 7a was generated in
2
1
1
,2,6-trisubstituted naphthalene (Scheme 4, Intermediate B), 90% yield. The X-ray structural analysis showed that 7a
where the -position (5 position) again presents a more consists of two molecules of 3z with same chiral sense. There
favorable pathway for the second annulation than the - is no bonding between two Pd atoms and the complex
position (7 position).
features a trans-spanned chelating coordination with slightly
We further continued our studies by investigating the distorted Cl-Pd-Cl angles (171.38(4)° and 170.76(4)°). The P1-
scope with 1,2-benzenediacetaldehyde (1c). However, 1c is P2 distance (6.9277(12) Å) is much larger than the P1-P4
unstable and cannot be isolated. The disilyl acetal 1c’, which is distance (4.6528(12) Å). Such a large P-P distance and the
the precursor of 1c, was used as its synthetic equivalent helical structure of 3z might provide the opportunity to
2
2
(
Scheme 4). The reactions of 1c’ with 2a did not provide 1,8- interact with metal ions in unique coordination patterns to
2
3
diphenylphenanthrene (6a). With more reactive alkyne (4- give a good catalytic activity.
ethynylanisole), the target product 6b was isolated in 12%
yield. Diphenylacetylene was also prone to react to give the
HPPh2
target product 1,2,7,8-tetraphenylphenanthrene (6c) in 10%
yield. The reaction with bromide-substituted phenylacetylene
gave 6d in 22% yield with excellent regioselectivity. The
second annulation of the intermediate 1,2,5-trisubstituted
naphthalene (Scheme 4, Intermediate C) with alkynes only
Pd(OAc)2
PPh2
3j
PPh2
z, 44%
3
PdCl2(CH3CN)2
DCM, rt
7a, 90%a
1
2d
underwent through the -position (6 position). Some -aryl-
substituted diacetaldehyde and diketones were also tested, Scheme 5 The synthesis of a unique chiral diphosphine ligand 3z and binuclear
a
Pd complex 7a. Note: X-ray structure of binuclear Pd complex 7a at 50% thermal
but no corresponding products were formed under the current
conditions (see Supporting Information).
probability. Hydrogen atoms, phenyl groups, and solvent molecules are omitted
for clarity.
Conclusions
In summary, we have developed a concise acid-catalyzed
cascade annulation to prepare sterically hindered 4,5-
disubstituted phenanthrenes with high regioselectivity from
readily available 1,4-benzenediacetaldehyde and terminal aryl
alkynes. However, the terminal aryl alkynes with strong
4
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electron-withdrawing substituents are not reactive. With
internal aryl alkynes, 3,4,5,6-tetrasubstituted phenanthrenes
are provided in moderate yield. Furthermore, this method
could be extended to reactions of alkynes with isomeric 1,3-
benzenediacetaldehyde and 1,2-benzenediacetaldehyde disilyl
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6
7
8
9
3
acetal
to
provide
regioselective
multisubstituted
2
phenanthrenes. In addition, a new helical chiral diphosphine
ligand was prepared. The reaction presented here is not only
interesting in terms of the regioselective annulation, but it is
also valuable for the preparation of twisted phenanthrenes
and multisubstituted phenanthrenes.
3
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Conflicts of interest
There are no conflicts to declare.
1
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Acknowledgements
This work was supported by the ERATO program from JST
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Chaolumen for constructive criticism of the manuscript, Dr.
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postdoctoral fellowship to Y. L.. ITbM is supported by the
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DOI: 10.1039/C9SC00334G
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