Switchable Synthesis of Arylalkynes and Phthalides via Controllable Palladium-Catalyzed Alkynylation and Alkynylation-Annulation of Benzoic Acids with Bromoalkynes

Article abstract of DOI:10.1021/acs.joc.9b01102

A ligand-promoted palladium(II)-catalyzed synthesis of arylalkynes and phthalides from benzoic acids and bromoalkynes via carboxylate-assisted ortho-C-H activation is reported. A series of phthalides with various functional groups are prepared via ortho-a

Full text of DOI:10.1021/acs.joc.9b01102

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Article
Switchable Synthesis of Arylalkynes and Phthalides
via Controllable Palladium-Catalyzed Alkynylation and
Alkynylation-Annulation of Benzoic Acids with Bromoalkynes
Shuai Shi, Cui-Hong Chen, Yun Chai, Li-Ting Zhang, Jia-Wei Li, Bin Liu, Yue-Jin Liu, and Ming-Hua Zeng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01102 • Publication Date (Web): 02 Jul 2019
Downloaded from http://pubs.acs.org on July 2, 2019
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Switchable Synthesis of Arylalkynes and Phthalides via Controllable Palladium-
Catalyzed Alkynylation and Alkynylation-Annulation of Benzoic Acids with
Bromoalkynes
Shuai Shi,a Cui-Hong Chen,a Yun Chai,a Li-Ting Zhang,a Jia-Wei Li,a Bin Liu,a Yue-Jin Liu,*, a and Ming-Hua
Zeng* a,b
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a
Department of Hubei Collaborative Innovation Center for Advanced Chemical Materials, Ministry of Education Key
Laboratory for the Synthesis and Application of Organic Functional Molecules, and College of Chemistry and Chemical
Engineering, Hubei University, Wuhan, 430062, China.
b Department of Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry
and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, China.
푆
○
Supporting Information
O
COOH
+
Pd(OAc)2
N-Ac-Phe-OH
Pd(OAc)2
N-Ac-Val-OH
COOH
O
Si
H
Ag2O
Na3PO4
AgOAc
Si
Si
Br
ABSTRACT: A ligand-promoted palladium(II)-catalyzed synthesis of arylalkynes and phthalides from benzoic acids and bromoalkynes via
carboxylate-assisted ortho-C−H activation is reported. A series of phthalides with various functional groups are prepared via ortho-
alkynylation and alkynylation-annulation. Moreover, the key ortho-alkynylated products are also obtained by controlling the reaction
conditions. In addition, heteroaryl acids could react smoothly to form the corresponding alkynylation and cyclization products.
INTRODUCTION
group reported the construction of phthalides via rhodium-
catalyzed oxidative coupling of benz-
Over the past decade, manifold complex molecules have
been successfully constructed based upon the strategy of
transition metal-catalyzed C−H activation1. In this regard, the
carboxylic acid group has two main merits, which could
function as an effective intrinsic directing group and
subsequently could be easily converted into diverse
functional groups or undergo decarboxylation,2-3 which
would be beneficial since this motif is widely found in natural
products, biologically active molecules and functional
materials.4 Although selective functionalization of benzoic
acids through transition-metal catalyzed C−H activation has
received considerable attention,5 direct ortho-C−H
alkynylation of benzoic acid is less investigated, presumably
caused by the weak coordination of carboxylate group and
instability of the ortho-alkynylated products.6 In this area,
Scheme 1 Transition-Metal Catalyzed Cross-coupling Reactions
of Benzoic Acid with Bromoalkynes.
previous work:
–
direct C H alkynylation of benzoic acid derivatives with bromoalkynes
a)
Zeng and Echavarren groups
COOH
COOH
Si
Ir or Ru catalyst
+
Br
H
Si
b)
c)
Ackermann group
O
COOH
COOH
+
Si
+
O
[RuCl2(p-cymene)]2
H
Br
Si
Si
2 examples
this work:
contorllable C–H alkynylation and cyclization of benzoic acid with bromoalkynes
O
COOH
+
Pd(OAc)2
N-Ac-Phe-OH
Pd(OAc)2
N-Ac-Val-OH
COOH
Zeng group developed
a
carboxylate-directed C−H
O
Si
H
Ag2O
Na3PO4
AgOAc
alkynylation of benzoic acids under iridium or ruthenium
catalysis (Scheme 1a).6a-6b Meanwhile, Echavarren6c group
reported a ruthenium catalyzed C−H alkynylation of benzoic
acids with bromoalkyne (Scheme 1a), in which phthalides, an
important family of naturally occurring five-membered
lactones which exhibit a broad range of important
bioactivities, such as antibacterial, anti-HIV and
immunosuppressive activities7 were generated along with
aryl alkynes. The C−H activation strategy has emerged as a
promising tool for the preparation of phthalides in virtue of
the advantages including step- and atom-economy over
conventional methods.8 Although several advancements
have been made on construction of phthalide motif, most of
these methods are using alkene as coupling reagent.9 You
Si
Si
Br
16 examples
oic acids with terminal alkynes.10 However, synthesis of
phthalides and arylalkynes from benzoic acids via regulation
of reaction conditions are underdeveloped. Ackerman group
has successfully synthesized phthalides and arylalkynes from
benzoic acid with bromoalkyne via Ru(II)-catalyzed C−H
activation (Scheme 1b).11 Unfortunately, only 2 examples of
phthalides were achieved. To broaden the scope of substrate
and improve the efficiency of reaction, we herein report a
switchable synthesis of phthalides and arylalkynes from
benzoic acids and 1-alkynyl bromides via mono-protected
amino acid-promoted Pd(II)-catalyzed ortho-C−H activation
(Scheme 1c), which as our continuous endeavor on C−H
functionalizations.12
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RESULTS AND DISCUSSION
t-AmylOH (1 mL), at 80 °C for 24 h under air. Isolated yields. bDCE
(1 ml) at 60 °C for 24h under air. 12 h, Na3PO4 (0.1 mmol),
Na2HPO4 (0.05 mmol). eTriisopropylacetylene instead of 2.
c
d
In consideration of the similarity between phenyl acetic
acid and benzoic acid, we used our previous C−H alkynylation
conditions as the initial reaction conditions (Table 1):13
Pd(OAc)2 (10 mol %), N-Boc-Phe-OH (30 mol %), AgOAc (2
equiv), NaOAc (2 equiv) in DCE (1 ml) under air at 60 °C for 12
h. To our delight, the annulated product 4-ylidenephthalide
(3a) was obtained with the yields of 22%, but ortho-
alkynylated product (4a) was hardly examined (entry 1).
When the Na2HPO4 replaced NaOAc in t-AmylOH at 80 °C, a
higher yield of 3a (58%) was obtained and the ortho-
alkynylated product (4a) was obtained in 12% yield (entry 2).
Then, a series of acid ligands were examined, and the result
showed that most of the acids could promote the
reaction (entries 3-7). The mono-protected amino acid N-Ac-
Val-OH gave the best result for synthesis of phthalide (3a) in
75% yield (entry 6). We further study the effect of silver salts
on the reaction such as Ag2CO3 and Ag2O (entries 8-9).
Although silver oxide and silver carbonate can also promote
the reaction, silver acetate works best. Gratifyingly, when
reaction time was reduced to 12 h, the selectivity of phthalide
(3a) and ortho-alkynylated product (4a) was further
improved (up to 10:1) (entry 10). After we obtained the
annulation product phthalide (3a) in high selectivity, we tried
to control the synthesis of ortho-alkynylated product.
Although the yield of the ortho-alkynylated benzoic acid (4a)
was low, this result showed the potential of the oxidant and
ligand to promote C−H alkynylation (entry 5), which
prompted us to further investigate suitable conditions for
achieving an improved yield. Optimization studies were
started by surveying a series of potential oxidant, including
Ag2O, BQ and Ag2CO3 (entries 11-13). It is notable that the
alkynylated product (4a) was detected when Ag2O and
Ag2CO3 were employed (entries 11, 13). However, the organic
oxidant (BQ) had no effe-
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Table 1 Optimization of the Reaction Conditions.a
O
Pd(OAc)2
liagnd
MeO
COOH
TIPS
MeO
MeO
COOH
O
+
+
oxidant
base
Br
2
TIPS
TIPS
4a
1a
3a
t-AmylOH, 80
℃, 24
h
entry
oxidan
AgOA
ligand
base
3a/4a
t
(%)
e
1b
2
N-
Boc-Phe-
OH
NaOAc
22/trac
c
AgOA
N-
Boc-Phe-
OH
Na2HPO4
58/12
c
Scheme 2 Scope of Phthalides.a
O
Pd(OAc)2 10 mol %
N-Ac-Val-OH 30 mol %
3
AgOA
AgOA
AgOA
AgOA
AgOA
Ag2O
Ag2CO
AgOA
Ag2O
BQ
1-
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na3PO4
51/trac
51/trac
67/22
75/13
62/20
70/13
50/12
75/8
COOH
TIPS
c
c
c
c
c
AdCOOH
e
e
O
R
R
+
AgOAc 2 equiv
Br
Na2HPO4 1.5 equiv
4
PivO
H
TIPS
O
℃
t -AmylOH, 80 , 12 h
2
1
3
MeO
5
N-Ac-
O
O
O
O
MeO
MeO
Me
Phe-OH
O
O
O
6
N-Ac-
MeO
Val-OH
TIPS
TIPS
TIPS
TIPS
MeO
3a,
3e,
3b,
3c,
3d,
75%
O
63%
58%
O
66%
O
7
N-Ac-
O
Ala-OH
Me
O
O
O
O
8
N-Ac-
Me
Val-OH
TIPS
TIPS
TIPS
TIPS
55%
3f,
3j,
70%
3g,
Ph
3h,
9
N-Ac-
71%
O
67%
O
Cl
Val-OH
O
O
3
F
Ph
10
11
12
13
14
15
16
17
N-Ac-
O
O
O
O
c
c
Val-OH
TIPS
TIPS
b
TIPS
70%
TIPS
b
N-Ac-
11/43
0
3i
, 30%
3k,
3o,
3l,
40%
75%
O
Phe-OH
Br
O
O
O
S
N-Ac-
O
O
O
O
Cl
Phe-OH
N
Me
TIPS
TIPS
TIPS
TIPS
Ag2CO
Ag2O
Ag2O
Ag2O
AgOA
N-Ac-
22/41
0/48
3p,
65%
60%
Phe-OH
3m, 72%
3n, 66%
OH
3
OH
N-Ac-
COOH
COOH
COOH
COOH
Phe-OH
COOH
, 0%
HOOC
OH
, 0%
N-Ac-
Na3PO4+Na2HP
Na3PO4+Na2HP
Na2HPO4
0/62
3q
, 0%
3r
3s
3t
, 0%
d
d
e
Phe-OH
O4
aReaction conditions A: 1 (0.1 mmol), 2 (0.15 mmol), Pd(OAc)2 (10
mol %), N-Ac-Val-OH (30 mol %), AgOAc (0.2 mmol), Na2HPO4
(0.15 mmol), t-AmylOH (1 mL), at 80 °C for 12 h under air.
Isolated yields are presented. bConducted at 120 °C.
N-Ac-
33/42
0
Val-OH
O4
N-Ac-
c
Val-OH
aReaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), Pd(OAc)2 (10
mol %), ligand (30 mol %), oxidant (0.15 mmol), base (0.15 mmol),
ct on the reaction (entry 12). Inorganic bases could greatly
affect the selectivity of the products of the reaction and
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sodium phosphate gave the alkynylation products (4a) in
of heterocycles (Scheme 3, 4j). Unfortunately, other
substrates such as thiophenecarboxylic acid, benzaldehyde,
salicylic acid, phthalic acid, terephthalic acid, 2,6-
dihydroxybenzoic acid and phenyl acetic acid had no
reactivity (Scheme 3, 4l-4r).
single and medium yields (entry 14). Mixed bases of Na3PO4
and Na2HPO4 could further improve the yield (62%) of
alkynylation products (4a) (entry 15). Unfortunately, when
the N-Ac-Val-OH replaced N-Ac-Phe-OH as ligands, the
selectivity of the reaction is reduced (entry 16). No ortho-
Scheme 3. Scope of Ortho-Alkynylation Reaction.a
alkynylation
product
was
detected
when
Pd(OAc)2 10 mol %
triisopropylacetylene was used as coupling reagent instead of
2 (entry 17).
N-Ac-Phe-OH 30 mol %
9
TIPS
COOH
COOH
Ag2O 1.5 equiv
Na3PO4 1.0 equiv
Na2HPO4 0.5 equiv
R
R
+
10
11
12
13
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53
54
55
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57
58
59
60
Br
1
2
4
TIPS
With the optimized conditions in hand, we probed the
scope of the cyclization reaction by examining various
benzoic acids (Scheme 2). The benzoic acids with methoxy
and methy-substituents at ortho-, meta- and para-positions
could give the annulation product in moderate to good yields
(Scheme 2, 3a-3c, 3e-3g). Notably, the disubstituted
methoxybenzoic acid 1d furnished desired product 3d in a
comparably high isolated yield (Scheme 2, 3d). To our delight,
benzoic acid with halogen groups, such as chloro- and fluoro-
successfully generated the desired annulation products at a
higher temperature (Scheme 2, 3i-3j). For the substrates with
phenyl-substituted at the ortho or meta position, high yields
of 70% and 75% (Scheme 2, 3k-3l) were obtained,
respectively. Moreover, α- or β-Naphthoic acid also reacted
with 2, giving the desired products in good yield (Scheme 2,
3m-3n). Encouragingly, heteroaromatic substrates, such as
thiophene-2-carboxylic acid and indole-3-carboxylic acid
generated the desired product in moderate yields (Scheme 2,
3o-3p). Other benzoic acid substrates such as salicylic acid,
phthalic acid, terephthalic acid, and 2,6-dihydroxybenzoic
acid did not work under reaction conditions as there strong
coordination to palladium catalyst (Scheme 2, 3q-3t).
℃
t -AmylOH, 80 , 24 h
COOH
MeO
COOH
Me
COOH
Me
TIPS
TIPS
TIPS
4a,
4d,
62%
COOH
4b,
%
63
4c,
52%
COOH
COOH
tBu
F
TIPS
TIPS
TIPS
4fb,
4e,
58%
46%
trace
Me
COOH
COOH
Ph
COOH
TIPS
TIPS
TIPS
4h,
43%
4g,
trace
4i,
56%
COOH
COOH
COOH
N
S
N
H
Me
TIPS
TIPS
TIPS
4kc,
4jc,
50%
53%
4l,
trace
OH
OH
CHO
COOH
OH
COOH
4m
4n
, 0%
, 0%
4o
, 0%
The substrate scope for the palladium-catalyzed C−H
alkynylation of benzoic acids is depicted in Scheme 3. A series
of ortho-alkynylated benzoic acids were isolated in moderate
yields because further annulation reaction of most products
will proceed during the separation process. Benzoic acids
with electron-donating substituents on the benzene ring,
such as methoxy and methyl, provided the corresponding ortho-
alkynylated products in medium yields (Scheme 3, 4a-4c).
However, the substrate with electron-withdrawing group
such as fluoro- gave very trace amounts of product under this
reaction condition (Scheme 3, 4d). To our delight, the
reaction of p-tert-butylbenzoic acid proceeded smoothly
under our conditions (Scheme 3, 4f). In addition, when ortho-
substituted benzoic acid was subjected to the reaction
condition, trace of product was obtained due to the steric
effect (Scheme 3, 4g). Treatment of meta-phenylbenzoic acid
and 2-naphthalenecarboxylic acid under the standard
conditions gave the corresponding products in 43% and 56%
yield, respectively (Scheme 3, 4h-4i). Notably, N-methyl
indole-3-carboxylic acid could also give the alkynylated
product (Scheme 3, 4k), which is an important synthetic
intermediate. Importantly, indole-3-carboxylic acid without
protecting group could directly react under reaction
conditions, which has more step economy for the synthesis
COOH
COOH
MeO
COOH
HOOC
COOH
, 0%
4r
, trace
4p
4q
, 0%
aReaction conditions B: 1a (0.1 mmol), 2 (0.2 mmol), Pd(OAc)2 (10
mol %), N-Ac-Phe-OH ( 30 mol %), Ag2O (0.15 mmol), Na3PO4 (0.1
mmol), Na2HPO4 (0.05 mmol), t-AmylOH (1 mL), at 80 °C for 24 h
under air. Isolated yields. K2CO3. CF3COOAg and N-Ac-Ala-OH
were used.
b
c
To prove the practicality of our protocol, the reaction of 3-
methoxybenzoic acid (1a) with 1-alkynyl bromides 2 on a 4
mmol scale was conducted and gave the product 3a in 78%
yield with gram-scale (Scheme 4a). And the silyl protecting
group could be removed under mild reaction conditions,
giving the product 3a’ in moderate isolated yield (Scheme 4b,
for more details, see the Supporting Information).
Scheme 4. Gram-Scale Reaction and Removal of Silyl Protecting
group.
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O
Me
Me
Me
O
TIPS
Br
Pd(OAc)2 10 mol %
N-Ac-Val-OH 30 mol %
MeO
COOH
Me
H
TIPS
MeO
COOH
reaction condition A/B
O
O
(a)
(b)
+
(a)
AgOAc 2 equiv
Na2HPO4 1.5 equiv
Me
H
Br
TIPS
5
6
, 0%
℃
t-AmylOH, 80
12 h.
,
1a
3a
0.93g, 78%
2
Me
ONa
4 mmol
Pd(OAc)2
O
O
CO2Na
O
MeO
MeO
Pd
AcO
1,4-dioxane, 100 ºC
TBAF
O
O
(b)
THF, 25 ºC
2
9
3a'
, 60%
TIPS
7
int-A
O
3a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Me
Me
ONa
O
In order to understand the formation process of the
annulation product, several controlled experiments were
conducted to gain some insights into the possible reaction
mechanism as shown in Table 2 (for more details, see the
Supporting Information). To explore the feasibility of the
intramolecular esterification of the resulted alkynylated
benzoic acids, the arylalkynes (4a) was added in the standard
reaction conditions A. As expected, the desired annulation
product 3a was obtained in 87% yield (Table 2, entry 1). To
further investigate the annulation process, a series of control
experiments were performed. Up to 85% yield of 3a was
obtained when only AgOAc was added (Table 2, entry 2).
However, no annulation product 4a was detected in the
presence of Pd(OAc)2, Na2HPO4, or N-Ac-Val-OH, which
indicated AgOAc could promote the cyclization reaction
(Table 2, entries 3-5).
reaction condition A
O
(c)
Pd
AcO
TIPS
2
3e
, 36%
int-A
int-A
10 mol %
Me
O
Me
AgOAc 2 equiv
N-Ac-Val-OH 30 mol %
Na2HPO4 1.5 equiv
t-AmylOH, 80 ºC, 12 h
COOH
O
(d)
(e)
TIPS
, 23%
3e
1e
O
COOH
reaction condition A
O
H4/D4
H /D
5
5
2 h
TIPS
kH/kD = 1.4
1h/
1h
[D]-
3h
3h
/[D]-
While the mechanism is still under examination, a tentative
process is proposed on the basis of the above results and
previous reports (Scheme 6). The possible mechanism is
depicted in the chelation of Pd(II) to sodium benzoate
followed by the subsequent C−H activation to produce
intermediate A. Then oxidative addition of bromoalkyne 2 to
the Pd(II) center of intermediate A to provide intermediate B,
which gives the desired product 4 via reductive elimination
and regenerated Pd(II) species to enter the next catalytic
cycle. The alkynylation product 4 undergoes further
annulation reaction promoted by silver salt, giving the
Table 2. Control Experiments.
O
Pd(OAc)2 10 mol %
N-Ac-Val-OH 30 mol %
AgOAc 2 equiv
Na2HPO4 1.5 equiv
t-AmylOH, 80 ºC, 12 h
MeO
COOH
MeO
O
TIPS
TIPS
3a
4a
entry
reaction condition
3a (%)
1
2
3
4
5
standard reaction
with AgOAc
87
85
0
phthalide product 3
.
with Pd(OAc)2
with Na2HPO4
with N-Ac-Val-OH
Scheme 6. Proposed Catalytic Cycle.
0
0
3
product
COOH
Pd(OAc)2
AgOAc
To further insight into this ortho-alkynylatio and annulation
process, a series of mechanistic experiments were carried out
(Scheme 5). When 2,6-dimethylbenzoic acid reacted with 2
under standard reaction conditions, the possible
intermediate 6 was not detected, which ruled out the
mechanism of previous report (Scheme 5a)2f. The C-H
activation intermediate int-A of 1e was prepared according
to the previous method (Scheme 5b)14. Catalytic and
stoichiometric reactions showed that the int-A may be a key
intermediate in this catalytic process (Scheme 5c-5d).
Intermolecular kinetic study indicated that C-H activation
step maybe involved in the rate-determining process
(Scheme 5e, for more details, see the Supporting
Information).
4
product
1
C–H
activation
reductive
elimination
O
O
O
O
Pd
PdL2
L
Br
Si
B
L
A
oxidative
addition
Si
Br
Scheme 5 Mechanistic experiments
2
CONCLUSION
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In summary, we have developed a ligand-promoted palladium-
at room temperature. Water was removed in a rotary evaporator,
the white solid was washed with CH2Cl2 (2 mL × 3) to remove
excess of ortho-toluic acid and dried under vacuum at 100 °C to
get sodium ortho-toluate 7 (124.4 mg, 79% yield). Palladium
acetate (112.0 mg, 0.5 mmol) was added to a suspension of
sodium ortho-toluate 7 (79.0 mg, 0.5 mmol) in CH2Cl2 (5 mL) or
1,4-dioxane (5 mL) and heated to 100 °C for 2 h. The reaction
mixture was filtered, the dark residue was washed with CH2Cl2 (3
× 5 mL) and dried under vacuum to get the int-A (132 mg, 69%
yield). 1H NMR (501 MHz, DMSO) δ 7.60 (s, 1H), 6.91 (t, J = 7.5 Hz,
2H), 6.83 (d, J = 7.0 Hz, 1H), 2.47 (s, 3H), 1.79 (s, 3H).
catalyzed synthesis of arylalkynes and phthalides from benzoic
acids and bromoalkynes via carboxylate-directed ortho-C−H
activation. The reaction demonstrates broad substrate scope and
a range of phthalides are synthesized via ortho-alkynylation and
alkynylation-annulation. By tuning the reaction conditions, a
series of ortho-alkynylation products of benzoic acids are also
prepared in this protocol. The synthetic application of this
protocol has been proved by gram-scale reaction.
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EXPERIMENTAL SECTION
Analytical Characterization Data of Products.
General information All reactions were carried out in a flame-
dried, sealed Schlenk reaction tube under an atmosphere of air.
Analytical thin-layer chromatography was performed on glass
plates coated with 0.25 mm 230-400 mesh silica gel containing a
fluorescent indicator (Merck). Flash silica gel column
chromatography was performed on silica gel 60N (spherical and
neutral, 140-325 mesh) as described by Still. NMR spectra were
measured on a Varian INOVA600 spectrometer .1H NMR spectra
were recorded at 500 MHz in CDCl3 were referenced internally to
tetramethylsilane as a standard, and 13C NMR spectra were
recorded at 125 MHz and referenced to the solvent resonance.
High resolution mass spectra (HRMS) were recorded on the
Thermo Scientific Exactive Plus equipped with ESI ionization
source.
Preparation of starting materials. Unless otherwise noted,
materials were purchased from Tokyo Chemical Industry Co.,
Aldrich Inc., Alfa Aesar, Adamas, and other commercial suppliers
and used as received. Pd(OAc)2 was purchased from Alfa Aesar and
used as received.
General procedure for the synthesis of phthalides. In a tube
were placed a mixture of 1a (0.1 mmol), Pd(OAc)2 (10 mol %), 2
(0.2 mmol), N-Ac-Val-OH (30 mol %), AgOAc (0.2 mmol) and
Na2HPO4 (0.15 mmol), tertiary-amyl alcohol (1 mL) in a 35 mL
sealed tube was heated in oil bath (80 °C) for 12 h under air
atmosphere. The reaction mixture was cooled to room
temperature and concentrated under a reduced pressure. The
crude residue was purified through a silica gel column using
petroleum ether and ethyl acetate (PE/EA = 25/1, v/v) as eluent to
give the desired product.
General procedure for the synthesis of alkynylation
benzoic. A mixture of 1a (0.1 mmol), Pd(OAc)2 (10 mol %), 2 (0.2
mmol), N-Ac-Phe-OH (30 mol %), Ag2O (0.15 mmol) , Na3PO4
(0.1mmol) and Na2HPO4 (0.05 mmol), tertiary-amyl alcohol (1 mL)
in a 35 mL sealed tube was heated in oil bath (80 °C) for 12 h under
air atmosphere. The reaction mixture was cooled to room
temperature. After reaction completed, 1 ml of HCl (3 mol/L) was
added to the reaction and stirred for 30 minutes at room
temperature. The mixture was extracted for 2-3 times with EA,
and then concentrated under a reduced pressure. The crude
residue was purified through a silica gel column using petroleum
ether, ethyl acetate and acetic acid (PE/EA/HOAc = 5/1/0.05,
v/v/v) as eluent to give the desired product.
(Z)-6-methoxy-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3a): Yellow oil, 25 mg (75% yield), Purified by column
chromatography (petroleum ether/ethyl acetate = 25/1, Rf = 0.6).
1H NMR (501 MHz, CDCl3) δ 7.63 (d, J = 8.5 Hz, 1H), 7.29 (d, J = 1.5
Hz, 1H), 7.24 (d, J = 2.0 Hz, 1H), 5.41 (s, 1H), 3.88 (s, 3H), 1.34 (m,
3H), 1.10 (d, J = 7.5 Hz, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ
167.7, 156.9, 141.0, 137.2, 135.6, 125.3, 125.0, 120.8, 99.8, 21.6,
18.9, 11.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H29O3Si
333.1886; Found 333.1877.
(Z)-7-methoxy-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3b)10: White solid, 21 mg (63% yield), M.p. = 109-111
°C. Purified by column chromatography (petroleum ether/ethyl
acetate = 25/1, Rf = 0.6). 1H NMR (501 MHz, CDCl3) δ 7.63 (t, J = 8.0
Hz, 1H), 7.30 (d, J = 7.5 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 5.55 (s, 1H),
4.01 (s, 3H), 1.36 (m, 3H), 1.10 (d, J = 7.0 Hz, 18H); HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C19H29O3Si 333.1886; Found 333.1877.
(Z)-5-methoxy-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3c): Yellow oil, 19 mg (58% yield), Purified by column
chromatography (petroleum ether/ethyl acetate = 25/1, Rf = 0.6).
1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 1H), 7.13 (s, J = 2.0
Hz, 1H), 7.07 (dd, J = 8.8, 2.0 Hz, 1H), 5.52 (s, 1H), 3.95 (s, 3H), 1.36
(m, 3H), 1.12 (d, J = 7.6 Hz, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ
167.3, 165.2, 156.7, 142.03, 126.7, 118.7, 117.7, 104.0, 100.6,
56.1, 18.9, 11.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H29O3Si
333.1886; Found 333.1878.
(Z)-4,6-dimethoxy-3((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3d): Yellow solid, 24 mg (66% yield), M.p. = 105-107 °C.
Purified by column chromatography (petroleum ether/ethyl
acetate = 25/1, Rf = 0.6). 1H NMR (501 MHz, CDCl3) δ 6.91 (s, 1H),
6.70 (s, 1H), 5.77 (s, 1H), 3.96 (s, 3H), 3.87 (s, 3H), 1.33 (m, 3H),
1.10 (d, J = 7.5 Hz, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ 168.0,
163.0, 156.6, 154.5, 128.2, 121.0, 105.3, 104.0, 98.3, 56.1, 56.04,
19.0, 11.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H31O4Si
363.1991; Found 363.1984.
(Z)-7-methyl-3-((triisopropylsilyl)methylene)isobenzofuran
1(3H)-one (3e)10: White solid, 17 mg (55% yield), M.p. = 109-111
°C. Purified by column chromatography (petroleum ether/ethyl
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acetate = 25/1, Rf = 0.6). H NMR (400 MHz, CDCl3) δ 7.58 – 7.52
(m, 2H), 7.32 – 7.27 (m, 1H), 5.53 (s, 1H), 2.69 (s, 3H), 1.35 (m, 3H),
1.11 (d, J = 7.5 Hz, 18H); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C19H29O2Si 317.1937; Found 317.1928.
(Z)-6-methyl-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3f): White solid, 22 mg (70% yield), M.p. = 106-109 °C.
Purified by column chromatography (petroleum ether/ethyl
The synthesis of int A. Ortho-toluic acid 3e (136.0 mg, 1.0
mmol) was treated with NaOH (32.0 mg, 0.8 mmol) in water (1 mL)
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acetate = 25/1, Rf = 0.6). 1H NMR (400 MHz, CDCl3) δ 7.68 (s, 1H),
7.94 (dd, J = 8.4, 1.6 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.64 – 7.61
(m, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.44 – 7.40 (m, 1H), 5.62 (s, 1H),
1.37 (m, 3H), 1.13 (d, J = 7.6 Hz, 18H); 13C{1H} NMR (101 MHz,
CDCl3) δ 167.6, 156.7, 143.9, 139.5, 138.2, 133.5, 129.3, 128.5,
127.4, 125.9, 123.4, 121.4, 101.2, 19.0, 11.9; HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C24H31O2Si 379.2093; Found 379.2085.
7.64 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 5.50 (s, 1H), 2.49 (s,
3H), 1.35 (m, 3H), 1.11 (d, J = 7.2 Hz, 18H); 13C{1H} NMR (101 MHz,
CDCl3) δ 167.7, 156.9, 141.0, 137.2, 135.6, 125.3, 125.04, 120.8,
99.8, 21.6, 18.9, 11.8. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C19H29O2Si 317.1937; Found 317.1926.
(Z)-5-methyl-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3g): White solid, 22 mg (71% yield), M.p. = 85-87 °C.
Purified by column chromatography (petroleum ether/ethyl
(Z)-3-((triisopropylsilyl)methylene)naphtho[1,2-c]furan-1(3H)-
one (3m)10: Yellow solid, 25 mg (72% yield), M.p. = 127-130 °C.
Purified by column chromatography (petroleum ether/ethyl
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acetate = 25/1, Rf = 0.6). H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
acetate = 25/1, Rf = 0.6). H NMR (501 MHz, CDCl3) δ 8.92 (d, J =
8.0 Hz, 1H), 7.55 (s, 1H), 7.36 (d, J = 8.0 Hz, 1H), 5.55 (s, 1H), 2.52
(s, 3H), 1.35 (m, 3H), 1.11 (d, J = 7.2 Hz, 18H); HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C19H29O2Si 317.1937; Found 317.1928.
8.0 Hz, 1H), 8.13 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.74
(dd, J = 16.0 Hz, 2H), 7.63 (t, J = 8.0 Hz, 1H), 5.73 (s, 1H), 1.41 (m,
3H), 1.15 (d, J = 7.5 Hz, 18H); HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C22H29O2Si 353.1937; Found 353.1927.
(Z)-3-((triisopropylsilyl)methylene)isobenzofuran-1(3H)-one
(3h)10: Yellow oil, 20 mg (67% yield), Purified by column
chromatography (petroleum ether/ethyl acetate = 25/1, Rf = 0.6).
1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 8.0
Hz, 1H), 7.74 – 7.69 (t, J = 7.2 Hz, 1H), 7.60 – 7.53 (t, J= 7.6 Hz, 1H),
5.59 (s, 1H), 1.36 (m, 3H), 1.12 (d, J = 7.2 Hz, 18H); HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C18H27O2Si 303.1780; Found: 303.1761.
(Z)-4-fluoro-3-((triisopropylsilyl)methylene)isobenzofuran-1(3H)-
one (3i): Yellow solid, 9 mg (30% yield), M.p. = 75-77 °C. Purified
by column chromatography (petroleum ether/ethyl acetate =
25/1, Rf = 0.6). 1H NMR (501 MHz, CDCl3) δ 7.74 (dd, J = 8.5, 4.0 Hz,
1H), 7.53 (dd, J = 7.0, 2.0 Hz, 1H), 7.42 (dt, J = 8.5, 2.0 Hz, 1H), 5.54
(s, 1H), 1.35 (m, 3H), 1.11 (d, J = 7.5 Hz, 18H); 13C{1H} NMR (101
MHz, CDCl3) δ 166.4 (d, J = 3.9 Hz), 164.0 (d, J = 250.7 Hz), 155.9,
135.5 (d, J = 2.3 Hz), 127.0 (d, J = 9.2 Hz), 123.0 (d, J = 8.8 Hz), 122.7
(d, J = 24.4 Hz), 111.4 (d, J = 23.9 Hz), 101.3 (d, J = 1.8 Hz), 18.9,
11.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H26FO2Si
321.1686; Found 321.1679.
(Z)-7-chloro-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3j): White solid, 13 mg (40% yield), M.p. = 107-109 °C.
Purified by column chromatography (petroleum ether/ethyl
acetate = 25/1, Rf = 0.6). 1H NMR (501 MHz, CDCl3) δ 8.26 (s, 1H),
7.65 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 6.65 (s, 1H), 1.39
(m, 3H), 1.15 (d, J = 7.5 Hz, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ
163.5, 162.5, 135.0, 134.5, 134.3, 128.9, 127.0, 123.1, 116.2, 18.6,
10.7; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H26Cl35O2Si
337.1391; Found 337.1372. [M + H]+ Calcd for C18H26Cl37O2Si
339.1311; Found 339.1344.
(Z)-3-((triisopropylsilyl)methylene)naphtho[2,3-c]furan-1(3H)-
one (3n): Yellow solid, 23 mg (66% yield), M.p. = 125-127 °C.
Purified by column chromatography (petroleum ether/ethyl
acetate = 25/1, Rf = 0.6). 1H NMR (501 MHz, CDCl3) δ 8.46 (s, 1H),
8.21 (s, 1H), 8.02 (dd, J = 20.5, 8.5 Hz, 2H), 7.67 (t, J = 7.5 Hz, 1H),
7.61 (t, J = 7.5 Hz, 1H), 5.69 (s, 1H), 1.39 (m, 3H), 1.15 (d, J = 7.5
Hz, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ 167.7, 156.9, 136.6,
134.1, 133.9, 130.2, 129.3, 129.0, 127.7, 126.7, 122.8, 120.4, 99.0,
19.0, 11.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H29O2Si
353.1937; Found 353.1927.
(Z)-2-chloro-4-((triisopropylsilyl)methylene)thieno[2,3-c]furan-
6(4H)-one (3o): Yellow solid, 20 mg (60% yield), M.p. = 136-138 °C.
Purified by column chromatography (petroleum ether/ethyl
acetate = 25/1, Rf = 0.6). 1H NMR (501 MHz, CDCl3) δ 7.39 (s, 1H),
6.77 (s, 1H), 1.37 (m, 3H), 1.14 (d, J = 7.5 Hz, 18H); 13C{1H} NMR
(101 MHz, CDCl3) δ 166.1, 159.0, 147.1, 131.3, 124.8, 124.3, 111.4,
77.5, 77.4, 77.2, 76.8, 18.6, 10.7; HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C16H24Cl35O2SSi 343.0955; Found: 343.0970. [M + H]+
Calcd for C16H24Cl37O2SSi 345.0925; Found: 343.0916.
(Z)-7-bromo-4-methyl-3-((triisopropylsilyl)methylene)-3,4-
dihydro-1H-furo[3,4-b]indol-1-one (3p): Yellow solid, 28 mg (65%
yield), M.p. = 132-134 °C. Purified by column chromatography
1
(petroleum ether/ethyl acetate = 25/1, Rf = 0.6). H NMR (501
MHz, CDCl3) δ 8.37 (d, J = 1.5 Hz, 1H), 7.47 (dd, J = 8.5, 1.5 Hz, 1H),
7.24 (d, 1H), 6.76 (s, 1H), 3.82 (s, 3H), 1.45 (m, 3H), 1.17 (d, J = 7.5
Hz, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ 170.0, 161.3, 144.7,
137.4, 127.7, 125.9, 124.2, 116.2, 110.9, 105.0, 100.8, 77.5, 77.4,
77.2, 76.8, 30.2, 18.6, 10.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C21H29Br79NO2Si 434.1151; Found 434.1128. [M + H]+ Calcd for
C21H29Br81NO2Si 436.1130; Found 436.1106.
(Z)-7-phenyl-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3k): Yellow solid, 26 mg (70% yield), M.p. = 100-102 °C.
Purified by column chromatography (petroleum ether/ethyl
1
acetate = 25/1, Rf = 0.6). H NMR (501 MHz, CDCl3) δ 8.11 (d, J =
5-methoxy-2-((triisopropylsilyl)ethynyl)benzoic acid (4a)6a: White
solid, 20 mg (62% yield), M.p. = 126-128 °C. Purified by column
0.5 1H), 7.94 (dd, J = 8.0, 1.5 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.63
(d, J = 7.5 Hz, 2H), 7.49 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.5 Hz, 1H),
5.62 (s, 1H), 1.39 (m, 3H), 1.14 (d, J = 7.5 Hz, 18H); 13C{1H} NMR
(101 MHz, CDCl3) δ 167.7, 156.7, 143.9, 139.5, 138, 133.5, 129.3,
128.5, 127.4, 125.8, 123.4, 121.4, 101.3, 77.5, 77.2, 76.8, 19.0,
18.8, 11.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H31O2Si
379.2093; Found 379.2086.
(Z)-6-phenyl-3-((triisopropylsilyl)methylene)isobenzofuran-
1(3H)-one (3l): Yellow solid, 28 mg (75% yield), M.p. = 137-139 °C.
Purified by column chromatography (petroleum ether/ethyl
acetate = 25/1, Rf = 0.6). 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H),
chromatography (petroleum ether/ethyl acetate/AcOH
=
5/1/0.05, Rf = 0.5). 1H NMR (501 MHz, CDCl3) δ 7.63 (d, J = 3.0 Hz,
1H), 7.53 (d, J = 8.5 Hz, 1H), 7.04 (d, J = 8.5, 3.0 Hz, 1H), 3.87 (s,
3H), 1.15 (d, J = 3.5 Hz, 21H). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C19H29O3SiNa 355.1705; Found 355.1685.
5-methyl-2-((triisopropylsilyl)ethynyl)benzoic acid (4b)6a: Yellow
solid, 20 mg (63% yield), M.p. = 153-155 °C. Purified by column
chromatography (petroleum ether/ethyl acetate/AcOH
=
5/1/0.05, Rf = 0.5). 1H NMR (501 MHz, CDCl3) δ 7.93 (s, 1H), 7.51
(d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 2.41 (s, 3H), 1.14 (d, J =
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3.5 Hz, 21H); HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H29O2SiNa 339.1756; Found 339.1739.
4-methyl-2-((triisopropylsilyl)ethynyl)benzoic acid (4c): Yellow
solid, 16 mg (52% yield), M.p. = 132-134 °C. Purified by column
acetate/AcOH = 5/1/0.05, Rf = 0.5). H NMR (501 MHz, CDCl3) δ
8.24 (d, J = 7.5 Hz, 1H), 7.32 (m, 3H), 3.89 (s, 3H), 1.21 (d, J = 5.0
Hz, 21H); HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H29NO2SiNa
378.1865; Found 378.1859.
chromatography (petroleum ether/ethyl acetate/AcOH
=
Scale up synthesis.
5/1/0.05, Rf = 0.5). 1H NMR (501 MHz, CDCl3) δ 8.00 (d, J = 8.0 Hz,
1H), 7.42 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 2.39 (s, 3H), 1.15 (d, J =
3.0 Hz, 18H), 1.10 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3)
δ 181.2, 169.7, 143.4, 135.6, 131.7, 129.5, 128.6, 123.7, 105, 98.7,
21.5, 18.9, 11.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H29O2SiNa 339.1756; Found 339.1739.
A mixture of 1a (4 mmol, 0.54 g), Pd(OAc)2 (10 mol %) , alkynyl
bromide (2 equiv), N-Ac-Val-OH (30 mol %), AgOAc (2 equiv) and
Na2HPO4 (1.5 equiv), t-AmylOH (40 mL) in a 150 mL glass vial was
heated at 80 °C for 12 h under an air atmosphere. The reaction
mixture was cooled to room temperature and concentrated under
a reduced pressure. The resulting residue was purified by column
chromatography on silica gel to give the corresponding product 3a
(78%, 0.93 g).
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2-((triisopropylsilyl)ethynyl)benzoic acid (4e)6a: White solid. 17
mg (58% yield), M.p. = 132-134 °C. Purified by column
chromatography (petroleum ether/ethyl acetate/AcOH
=
ASSOCIATED CONTENT
Supporting Information
5/1/0.05, Rf = 0.5). 1H NMR (501 MHz, CDCl3) δ 8.11 (d, J = 8.0 Hz,
1H), 7.63 (d, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.43 (t, J = 7.5
Hz, 1H), 1.17 – 1.14 (d, J = 4.0 Hz, 21H). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C18H27O2SiNa 325.1600; Found 325.1593.
The Supporting Information is available free of charge on the ACS
Publications website http://pubs.acs.org.
Control experiments, kinetic study, 1H and 13C NMR spectra of all
new & known compounds (PDF).
4-(tert-butyl)-2-((triisopropylsilyl)ethynyl)benzoic acid (4f):
Yellow solid. 17 mg (46% yield), M.p. = 132-134 °C. Purified by
column chromatography (petroleum ether/ethyl acetate/AcOH =
5/1/0.05, Rf = 0.5). 1H NMR (501 MHz, CDCl3) δ 8.04 (d, J = 8.0 Hz,
1H), 7.58 (s, 1H), 7.44 (d, J = 8.0 Hz, 1H), 1.34 (s, 9H), 1.16 (d, J =
3.5 Hz, 18H), 1.10 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3)
δ 168.1, 156.4, 131.8, 131.7, 128.7, 126.3, 123.0, 105.5, 99.2, 35.2,
31.2, 18.9, 11.6; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C22H34O2SiNa 381.2226; Found 381.2201.
AUTHOR INFORMATION
Corresponding Author
*E-mail: liuyuejin@hubu.edu.cn.
*E-mail: zmh@mailbox.gxnu.edu.cn.
4-((triisopropylsilyl)ethynyl)-[1,1'-biphenyl]-3-carboxylic
acid
ORCID
(4h): White solid. 16 mg (43% yield), M.p. = 132-134 °C. Purified
by column chromatography (petroleum ether/ethyl acetate/AcOH
= 5/1/0.05, Rf = 0.5). 1H NMR (501 MHz, CDCl3) δ 8.35 (s, 1H), 7.74
(d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 7.0 Hz, 2H),
7.47 (t, J = 7.5 Hz, 2H), 7.39 (t, J = 7.0 Hz, 1H), 1.16 (d, J = 4.0 Hz,
18H), 1.10 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
168.0, 141.8, 139.3, 135.4, 131.8, 130.9, 130.2, 129.3, 128.5,
127.3, 121.9, 104.8, 100.7, 18.9, 11.6; HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C24H30O2SiNa 401.1913; Found 401.1902.
Yue-Jin Liu: 0000-0003-4226-0890
Ming-Hua Zeng: 0000-0002-7227-7688
Notes
There are no conflicts to declare.
ACKNOWLEDGMENT
This work was supported by the Natural Science Foundation
of Hubei Province (No. 2018CFB156), the NSF of Hubei
Province innovation group project (No. 2017CFA006), the
Program of Ministry of Education Key Laboratory for the
Synthesis and Application of Organic Functional Molecules
(No. KLSAOFM1702), the National Science Foundation for
Distinguished Young Scholars of China (No. 21525101), and
Hubei University are gratefully acknowledged.
3-((triisopropylsilyl)ethynyl)-2-naphthoic acid (4i): White solid.
20 mg (56% yield), M.p. = 94-96 °C. Purified by column
chromatography (petroleum ether/ethyl acetate/AcOH
=
1
5/1/0.05, Rf = 0.5). H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 8.14
(s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.59 (m, 2H),
1.19 (d, J = 2.8 Hz, 21H); 13C{1H} NMR (101 MHz, CDCl3) δ 168.3,
135.4, 134.8, 133.7, 132.2, 129.5, 129.5, 128.1, 127.7, 127.6,
118.89, 105.3, 98.4, 18.9, 11.7; HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C22H28O2SiNa 375.1756; Found 375.1742.
REFERENCES
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