Palladium-catalyzed allylation of tautomerizable heterocycles with alkynes

Article abstract of DOI:10.1039/c7ob01119a

A method for the allylic amidation of tautomerizable heterocycles was developed by a palladium catalyzed allylation reaction with 100% atom economy. A series of structurally diverse N-allylic substituted heterocycles can be synthesized in good yields with high chemo-, regio-, and stereoselectivities under mild conditions.

Full text of DOI:10.1039/c7ob01119a

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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PAPER
Palladium-Catalyzed Allylation of Tautomerizable Heterocycles
with Alkynes
Chuan-Jun Lu,*a Dong-Kai Chen,a Hong Chen,a Hong Wang,a Hongwei Jin,a Xifu Huangb and
Jianrong Gaoa
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A method for the allylic amidation of tautomerizable heterocycles was developed by palladium catalyzed allylation
reaction with 100% atom economy. A series of structurally diverse N-allylic substituted heterocycles can be synthesized in
good yields with high chemo-, regio-, and stereoselectivities under mild conditions.
www.rsc.org/
catalysts.8 We recently described a highly regioselective
palladiumꢀcatalyzed allylation of sulfonyl hydrazides with
arylpropyne derivatives to construct allyl arylsulfones
Introduction
Quinazolinones and related tautomerizable heterocycles are
found as pharmacophores in a large number of drug candidates,
displaying a vast array of biological activities such as
anticancer, antimalarial, antidiabetic, and antihypertensive
activities.1 Consequently, their diverse functionalization is
highly significant. However, as these nucleophiles exist in two
or more tautomeric forms, which in the course of alkylation
compounds.9 We deliberated as to whether this methodology
might be successfully transferred to allylation of
quinazolinones and relevant heterocycles. If this method works,
a stoichiometric amount of leaving group or stoichiometric
amounts of oxidant can be avoided. We report herein a
palladium catalyzed allylic amidation10 of tautomerizable
heterocycles with simple alkynes for the synthesis of linear
allyl heterocycles in good yields with high chemoꢀ, regioꢀ, and
stereoselectivities (Scheme 1, (c)).11
reactions can lead to mixtures of Oꢀ and
Control of chemoꢀselectiv ty is an important consideration as it
Nꢀsubstituted products.
i
poses competitive reaction pathways.2 The palladiumꢀcatalyzed
allylic substitution has been instrumental to obtain structural
diversity via formation of CꢀC and Cꢀhetero bonds.3 However,
to date, very limited examples have been documented accessing
in a regioꢀ and chemoꢀselective fashion of these tautomerizable
heterocycles.4,5 Recently, Cook and coworkers reported an
elegant palladiumꢀcatalyzed regioselective allylation of
quinazolinones and relevant heteroarenes with allyl alcohols.
Previous work
O
X
OH
OH
R
N
N
Pd(PPh3)4
R
+
(a)
(b)
Y
Y
X
N-allylic products
up to 92% yield
OH
O
Excellent
substitution reactions, leading to linear
high yields (Scheme 1, (a)).5a Subsequently, they also reported
regioꢀ and chemoꢀselective palladiumꢀcatalyzed
intermolecular oxidative allylic amidation of tautomerizable
heterocycles with allylbenzene derivatives via allylic CꢀH
N
ꢀselectivity was achieved in these allylic
PdCl2
N
N
Ar
E
ꢀallylated products in
Ar
+
2,6-dimethyl-
benzoquinone
Y
Y
X
N-allylic products
X
a
up to 91% yield
N
ꢀ
Present work
O
N
OH
activation reaction, to afford diverse
for medicinal chemistry applications (Scheme 1, (b)).5b
On the other hand, after the pioneering work by Yamamoto
on the Pd(0)ꢀcatalyzed allylation of methylmalononitrile with
arylpropyne,6 arylpropyne has proved to be an ideal precursor
to form the πꢀallylmetal complex due to its highly atom
economy. A series of
alkynes have been reported to established linear or branched
allylated compounds in the presence of palladium7 or rhodium
Nꢀheterocycles amenable
Ar
[Pd]/L
N
(c)
+ Ar
Me
Y
Acid
Y
X
1
X
3
2
N-allylic products
linear and E-selectivity
100% atom economy
up to 98% yield
Nꢀ, Oꢀ and Cꢀnucleophiles with these
Scheme 1 Different approaches for the allylic alkylation reactions of
tautomerizable heterocycles catalyzed by palladium
Results and discussion
At the beginning of our study, 4ꢀhydroxy quinazoline (4ꢀ
quinazolinone) 1a was chosen as a model substrate with three
distinct tautomerizable nucleophilic centers (ꢀOH and ꢀNH) to
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17e
18f
19g
20h
21i
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
PPh3
PPh3
PPh3
PPh3
PPh3
dioxane
dioxane
dioxane
dioxane
dioxane
80
60
react with 1ꢀphenylꢀ1ꢀpropyne 2a (Table 1). To our delight, in
the presence of 10 mol% Pd(OAc)2 as a catalyst, 24 mol% PPh3
as a ligand and 1.0 equiv. 3ꢀClꢀC6H4CO2H as the additive in
DMSO solvent at 140 C under N2 atmosphere for 12 hours,
48% of amideꢀNH allylation product 3a was isolated as the
72
trace
trace
o
a
Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), 3ꢀClꢀC6H4CO2H (1.0
only regioisomer in excellent chemoꢀ(amideꢀNH), regioꢀ
equiv.), 10 mol% Pd catalyst, 24 mol% ligand in 0.6 mL solvent at 140 oC for
12 h. b isolated yields. c 5 mol% Pd2(dba)3 was used. d 12 mol% ligand was
(linear), and stereoselectivity (
Next, the reaction of 1a with 2a was investigated in the
presence of di erent Pd catalysts. The formation of 3a was
Eꢀproduct) (Table 1, entry 1).
e
f
used. 5 mol% Pd(dba)2, 12 mol% PPh3 was used.
0.4 equiv. 3ꢀClꢀ
C6H4CO2H was used. g 3ꢀFꢀC6H4CO2H was used instead of 3ꢀClꢀC6H4CO2H.
ff
h HOAc was used instead of 3ꢀClꢀC6H4CO2H. TsOH was used instead of 3ꢀ
i
observed with all Pd catalysts with varying yields (entries 2ꢀ6),
however Pd(dba)2 was found to be the best catalyst (entry 2).
With Pd2(dba)3 or Pd(PPh3)4 as the catalyst, a slightly lower
yield was achieved (entries 3 and 5). Whereas by switching the
palladium catalyst to PdCl2 or PdCl2(PPh3)2, the product 3a was
obtained in poor yield (entries 4 and 6). Subsequent ligand
screening indicated that in the case of the bidentate ligands such
as BINAP, DPPE, DPPB, and DPPF, inferior results were
obtained (entries 7ꢀ10). And the electroꢀrich ligand PCy3 also
was not an efficient one (entry 11). To further improve the
yield, we investigated the solvent effect on this reaction. The
studies revealed that solvent was crucial for this transformation.
It showed that reduced yield was observed in toluene and THF
(entries 12 and 15). However, to our delight, the desired
product was isolated in 82% yield when the reaction was
conducted in DMF (entry 13). And in solvents like dioxane and
DME, the formation of 3a was found to be more optimal, with
dioxane as the solvent to give the highest yield (entries 14 and
16). Moreover, by reducing the amount of catalyst/ligand (entry
17) or acid (entry 18), the reaction can also occur smoothly to
give 3a in 80% and 60% yield, respectively. Finally, with 3ꢀFꢀ
C6H4CO2H as the additive instead of 3ꢀClꢀC6H4CO2H , reduced
yield was achieved (entry 19). While HOAc or TsOH was used,
almost no product 3a could be detected (entries 20ꢀ21).
ClꢀC6H4CO2H.
Table 2 Scope of tautomerizable heterocycles a
O
N
O
N
O
N
Me
Cl
N
Ph
N
Ph
N
Ph
3c, 91%
3b, 88%
3a, 98%
O
O
O
N
N
Ph
N
N
Ph
Ph
N
Ph
N
Me
3d, 75%
3e, 76%
3f, 78%
O
O
N
O
N
Me
N
Ph
Ph
Ph
Ph
Me
3g, 86%
3h, 65%
3i, 89%
O
O
N
O
N
Ph
Table 1 Optimization of reaction conditionsa
N
N
Ph
Me
3j, 83%
3k, 52%
3l, 55%
Ph
Ph
X
Ph
N
O
O
N
O
N
O
O
S
Entry
Catalyst
Ligand
Solvent
Yieldb (%)
3n, X = Cl, 88%
3o, X = F, 75%
3m, 90%
3p, 75%
1
2
3c
Pd(OAc)2
Pd(dba)2
Pd2(dba)3
PdCl2
PPh3
PPh3
PPh3
PPh3
/
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
toluene
DMF
48
72
58
25
64
32
57
38
45
28
30
42
82
98
50
90
a Reaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), 3ꢀClꢀC6H4CO2H (0.3
mmol), Pd(dba)2 (10 mol %), and PPh3 (24 mol%) in dioxane (0.6 mL) at 140
°C for 12ꢀ24 h under N2 atmosphere.
4
5
Pd(PPh3)4
PdCl2(PPh3)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
6
PPh3
BINAP
DPPE
DPPB
DPPF
PCy3
PPh3
PPh3
PPh3
PPh3
PPh3
7d
8d
9d
10d
11
12
13
14
15
16
Under the optimized reaction conditions (Table 1, entry 14),
the scope of substituted quinazolinone was first examined with
phenylpropyne 2a as a standard substrate (Table 2). Di erently
substituted quinazolinones reacted well to produce
3 in high
yields with excellent chemoꢀ, regioꢀ, and stereoselectivities. It
was found that quinazolinones possessing either electronꢀrich
or electronꢀdeficient groups on the phenyl proceeded efficiently
to afford the amidation products in good yields (Table 2, 3b-
3c). Additionally, more hindered 2ꢀsubstituted quinazolinones
dioxane
THF
DME
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can also react with 2a to afford the allylic products but with different aryl substituents. All of the alkynes were coupled with
relatively lower yields (Table 2, 3d-3e). The applicability of to give the corresponding linear allylic products in high
this protocol was further extended to other tautomerizable chemoꢀ and stereoselectivities 3q 3z). With 1ꢀnaphth
heteroarenes. Gratifyingly, ꢀcinnamylation of a variety of substituted alkynes as the substrate, relatively lower yield was
heteroarenes proceeded well with good chemoꢀ, regioꢀ, and achieved 3s). 3ꢀ(Propꢀ1ꢀynꢀ1ꢀyl)thiophene 2i bearing
ꢀheterocycles such as heterocycle group can also be used as the partner to react with
3j) all reacted well with 1a, affording the desired allylic product 3x in 70% yield.
1
(
ꢀ
N
(
a
stereoselectivities. Sixꢀmembered
N
pyrimidine (3f), and pyridines (3g
ꢀ
excellent yields under the optimized conditions. However, for However, when the internal alkyne butꢀ1ꢀynꢀ1ꢀylbenzene 2j
the isoquinolinone (3k) or phthalazinone (3l), relatively lower was employed, no reaction ensued, which may be due to the
yield was afforded. Moreover, fiveꢀmembered tautomerizable large steric hindrance (eqn (1)). This reflects the limitation of
heteroarenes such as benzoxazolinone
benzothiazolinone (3p) can also be used as the partner to react
with the alkyne 2a, affording the allylic amidation products.
(
3m
ꢀ
3o
)
and alkynes in the current method.
Furthermore, terminal alkyne
work as the partner to react with 4ꢀhydroxy quinazoline 1a
4 and phenylallene 5 can also
.
Under the optimized reaction conditions, the reaction proceeded
smoothly to afford amideꢀNH allylation product 3a in 70% and
84% yield respectively (eqn (2) and (3)), suggesting that the
alkyne is capable of undergoing CꢀH activation to allene
Table 3 Substrate scope of alkynesa
through a βꢀHꢀelimination.
A reasonable mechanism for the direct allylic amidation can
be envisioned (Scheme 2). The catalytic cycle is initiated by the
oxidation addition of Pd(0) with 3ꢀClꢀC6H4CO2H (Ar’CO2H) to
generate the hydropalladation intermediate
insertion of alkyne affords vinyl palladium intermediate
The resulting vinyl palladium species would produce allene
intermediate and the active catalyst via ꢀelimination.
Subsequently, reinsertion of hydropalladation intermediate to
allene to form the ꢀallylpalladium intermediate . Finally,
can be captured by the
to afford the desired allylic
A. The following
2
B.
B
C
A
β
A
C
π
D
the palladiumꢀallyl species
tautomerizable heterocycle
D
1
amidation product
3 and regenerated intermediate A.
a Reaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), 3ꢀClꢀC6H4CO2H (0.3
mmol), Pd(dba)2 (10 mol %), and PPh3 (24 mol%) in dioxane (0.6 mL) at 140
°C for 12ꢀ24 h under N2 atmosphere.
Scheme 2. Plausible reaction mechanism
Conclusions
In summary, we have developed a palladium catalyzed allylic
amidation of tautomerizable heterocycles with simple alkynes
for the synthesis of
Nꢀallylation of a variety of heteroarenes in
We then turned to examine the scope of the alkynes for this
reaction and the results are summarized in Table 3. Different
aromatic substituted internal alkynes were subjected to the
allylic amidation reaction. The reactions worked well over
good yields with high chemoꢀ, regioꢀ, and stereoselectivities
under mild conditions. This methodology was found to be
advantageous in terms of substrate scope, functional group
tolerance and with 100% atom economy.
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was added 0.6 mL dry dioxane under N2 atmosphere. The
resulting mixture was then stirred at 140 C until the reaction
was completed (monitored by TLC). The solvent was then
removed under vacuum and the residue was purified by
chromatography on silica, eluting with EtOAc/petroleum ether 1:5
Experimental section
o
Materials and methods
Reactions and manipulations involving organometallic or
moisture sensitive compounds were carried out under dry
nitrogen and glassware heated under oven for two hours prior to
(v/v) to afford the desired product
.
1
use. H and 13C spectra were recorded on Bruker AVANCE III 3-Cinnamylquinazolin-4(3H)-one (3a). 77 mg, 98%, pale yellow
1
solid, m.p. 108ꢀ110°C. H NMR (500 MHz, CDCl3) δ 8.40ꢀ8.33 (m,
1H), 8.11 (s, 1H), 7.78ꢀ7.71 (m, 2H), 7.52 (s, 1H), 7.39ꢀ7.35 (m, 2H),
7.31 (dd, J = 8.1, 6.6 Hz, 2H), 7.26 (d, J = 7.2 Hz, 1H), 6.66 (d, J =
15.9 Hz, 1H), 6.34 (dt, J = 15.8, 6.5 Hz, 1H), 4.79 (dd, J = 6.5, 1.3
Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 160.8, 148.0, 146.1, 135.7,
134.4, 134.2, 128.6, 128.2, 127.4, 126.7, 126.5, 122.7, 122.1, 48.1.
IR (neat) υ (cmꢀ1) 3022, 1677, 1606, 1476, 1367, 1292, 1258, 1167,
782. The recorded NMR spectral data was in agreement with the
known compound.5a
6-Chloro-3-cinnamylquinazolin-4(3H)-one (3b). 78 mg, 88%, off
white solid, m.p. 120ꢀ121°C. 1H NMR (500 MHz, CDCl3) δ 8.28 (d,
J = 1.1 Hz, 1H), 8.14 (s, 1H), 7.68 (d, J = 2.1 Hz, 2H), 7.39ꢀ7.34 (m,
2H), 7.31 (t, J = 7.4 Hz, 2H), 7.28ꢀ7.24 (m, 1H), 6.67 (d, J = 15.9
Hz, 1H), 6.33 (dt, J = 15.8, 6.5 Hz, 1H), 4.78 (dd, J = 6.5, 1.1 Hz,
2H). 13C NMR (125 MHz, CDCl3) δ 159.8, 146.4, 135.6, 134.8,
133.2, 128.9, 128.6, 128.3, 126.6, 126.1, 123.1, 122.3, 48.3. IR (neat)
υ (cmꢀ1) 3060, 2939, 1671, 1605, 1469, 1359, 1320, 1257, 1158. The
recorded NMR spectral data was in agreement with the known
compound.5a
500 MHz using CDCl3 as solvent with TMS as internal
standard. Anhydrous dioxane, THF, toluene were freshly
distilled over Na and stored under nitrogen. Commercial
reagents were used as received without further purification
unless otherwise noticed. Melting points (m.p.) were recorded
on a SGW Melting Point Xꢀ4. IR was recorded on the Thermo
Nicolet 6700. HRMS were recorded on Agilent 6210 TOF
LC/MS mass spectrometer. Column chromatography was
carried out using silica gel (200ꢀ300 mesh).
General procedure for the synthesis of alkynes
The alkynes were synthesized according to the known method.12
A
mixture
of
Pd(PPh3)2Cl2
(5
mol%),
1,4ꢀ
bis(diphenylphosphanyl)butane (10 mol%), 4ꢀiodobenzene (1.1
equiv.), 2ꢀbutynoic acid (1.0 equiv.), DBU (3.0 equiv.), and
DMSO (1.0 M) was stirred at 80 °C for 12 h under N2
3-Cinnamyl-6-methylquinazolin-4(3H)-one (3c). 75 mg, 91%,
white solid, m.p. 125ꢀ127°C. 1H NMR (500 MHz, CDCl3) δ 8.14
(dd, J = 1.2, 0.7 Hz, 1H), 8.08 (s, 1H), 7.62 (dd, J = 19.8, 5.0 Hz,
2H), 7.41ꢀ7.36 (m, 2H), 7.35ꢀ7.30 (m, 2H), 7.27 (t, J = 3.6 Hz, 1H),
6.66 (d, J = 15.9 Hz, 1H), 6.35 (dt, J = 15.9, 6.4 Hz, 1H), 4.80 (dd, J
= 6.4, 1.3 Hz, 2H), 2.52 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
161.0, 146.1, 145.5, 137.7, 135.8, 134.4, 128.7, 128.3, 127.3, 126.7,
126.3, 122.9, 121.9, 48.2, 21.4. IR (neat) υ (cmꢀ1) 3060, 2936, 1666,
1608, 1488, 1360, 1161, 970. HRMS (ESI) m/z calculated for
C18H17N2O [M+H]+ 277.1335, found 277.1334.
3-Cinnamyl-2-phenylquinazolin-4(3H)-one (3d). 76 mg, 75%,
white solid, m.p. 105ꢀ106°C. 1H NMR (500 MHz, CDCl3) δ 8.39 (d,
J = 7.8 Hz, 1H), 7.81ꢀ7.76 (m, 2H), 7.59ꢀ7.52 (m, 6H), 7.31ꢀ7.26 (m,
4H), 7.26ꢀ7.22 (m, 1H), 6.28ꢀ6.14 (m, 2H), 4.77 (d, J = 5.6 Hz, 2H).
13C NMR (125 MHz, CDCl3) δ 162.1, 156.2, 147.2, 136.1, 135.3,
134.4, 133.5, 130.0, 128.6, 128.0, 127.5, 127.1, 126.8, 126.4, 123.2,
120.9, 47.9. IR (neat) υ (cmꢀ1) 3026, 2924, 2027, 2924, 1677, 1565,
1472, 1125. The recorded NMR spectral data was in agreement with
the known compound.5a
3-Cinnamyl-2-methylquinazolin-4(3H)-one (3e). 63 mg, 76%,
white solid, m.p. 127ꢀ128°C. 1H NMR (500 MHz, CDCl3) δ 8.28 (dd,
J = 8.0, 1.2 Hz, 1H), 7.77ꢀ7.69 (m, 1H), 7.65 (d, J = 7.9 Hz, 1H),
7.48ꢀ7.42 (m, 1H), 7.37ꢀ7.32 (m, 2H), 7.28 (dd, J = 10.2, 4.7 Hz,
2H), 7.23 (d, J = 7.2 Hz, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.29 (dt, J =
16.0, 5.8 Hz, 1H), 4.94ꢀ4.85 (m, 2H), 2.68 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 161.8, 154.3, 147.1, 135.8, 134.3, 132.9, 126.8,
126.45, 126.43, 126.4, 122.6, 120.3, 45.9, 22.9. IR (neat) υ (cmꢀ1)
3054, 2925, 1673, 1602, 1472, 1397, 1339, 1301, 1245. The
recorded NMR spectral data was in agreement with the known
compound.5a
3-Cinnamylpyrimidin-4(3H)-one (3f). 50 mg, 78%, white solid,
m.p. 138ꢀ140°C. 1H NMR (500 MHz, CDCl3) δ 8.17 (s, 1H), 7.89 (d,
J = 6.6 Hz, 1H), 7.38ꢀ7.35 (m, 2H), 7.33ꢀ7.29 (m, 2H), 7.28ꢀ7.25 (m,
1H), 6.63 (d, J = 15.9 Hz, 1H), 6.48 (dd, J = 6.6, 0.8 Hz, 1H), 6.29
(dt, J = 15.8, 6.6 Hz, 1H), 4.69 (dd, J = 6.6, 1.3 Hz, 2H). 13C NMR
(125 MHz, CDCl3) δ 160.6, 153.2, 150.9, 135.5, 135.0, 131.9, 128.5,
128.4, 126.5, 122.0, 115.9, 48.3. IR (neat) υ (cmꢀ1) 3027, 1666,
1595, 1524, 1434, 1201, 1134. The recorded NMR spectral data was
in agreement with the known compound.5a
atmosphere until the reaction was completed (monitored by TLC)
.
The reaction mixture was poured into NH4Cl aq.) and extracted
(
with DCM. The organic phase was dried over MgSO4, and solvents
were removed in vacuo to give a residue, which was purified by flash
column chromatography to give the title compounds. The NMR
spectral data of all the alkynes were in agreement with the
published data.12
1-Methyl-4-(prop-1-yn-1-yl)benzene (2b). 75%, colorless oil. 1H
NMR (500 MHz, CDCl3) δ 7.31 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 7.9
Hz, 2H), 2.35 (s, 3H), 2.06 (s, 3H).
1,3-Dimethyl-5-(prop-1-yn-1-yl)benzene (2c). 62%, colorless oil.
1H NMR (500 MHz, CDCl3) δ 7.06 (s, 2H), 6.94 (s, 1H), 2.30 (s,
6H), 2.07 (s, 3H).
1
1-(Prop-1-yn-1-yl)naphthalene (2d). 56%, colorless oil. H NMR
(500 MHz, CDCl3) δ 8.48 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 8.1 Hz,
1H), 7.85 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 7.1 Hz, 1H), 7.67ꢀ7.62 (m,
1H), 7.60ꢀ7.56 (m, 1H), 7.47 (dd, J = 8.1, 7.3 Hz, 1H), 2.29 (s, 3H).
1-Methoxy-4-(prop-1-yn-1-yl)benzene (2e). 86%, yellow oil. 1H
NMR (500 MHz, CDCl3) δ 7.35 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.8
Hz, 2H), 3.80 (s, 3H), 2.05 (s, 3H).
1-Nitro-4-(prop-1-yn-1-yl)benzene (2f). 70%, yellow solid. 1H
NMR (500 MHz, CDCl3) δ 8.16 (d, J = 8.9 Hz, 2H), 7.52 (d, J = 8.9
Hz, 2H), 2.11 (s, 3H).
1-(prop-1-yn-1-yl)-4-(trifluoromethyl)benzene (2g). 60%,
colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.55 (d,
J = 8.2 Hz,
2H),7.49 (d, J = 8.2 Hz, 2H), 2.09 (s, 3H).
3-(Prop-1-yn-1-yl)thiophene (2i). 68%, colorless oil. 1H NMR
(500 MHz, CDCl3) δ 7.37ꢀ7.35 (m, 1H), 7.26ꢀ7.23 (m, 1H),
7.10ꢀ7.07 (m, 1H), 2.05 (s, 3H).
Typical procedure for the palladium catalyzed allylation of
tautomerizable heterocycles with alkynes
To a mixture of tautomerizable heterocycle 1 (0.30 mmol, 1.0
equiv) and 1ꢀphenylꢀ1ꢀpropyne derivatives
equiv), Pd(dba)2 (0.03 mmol, 10 mol%), PPh3 (0.072 mmol, 24
mol%) and ꢀchlorobenzoic acid (0.3 mmol) in a sealed tube
2 (0.45 mmol, 1.5
m
4 | Org. Biomol. Chem. 2016, 00, 1-3
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Organic & Biomolecular Chemistry
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1-Cinnamylpyridin-2(1H)-one (3g). 55 mg, 86%, pale brown liquid. recorded NMR spectral data was in agreement with the known
1H NMR (500 MHz, CDCl3) δ 7.38ꢀ7.33 (m, 2H), 7.33ꢀ7.30 (m, 2H), compound.5a
7.28 (dd, J = 8.7, 2.1 Hz, 2H), 7.23 (dt, J = 9.4, 4.1 Hz, 1H), 6.61ꢀ 5-Chloro-3-cinnamylbenzo[d]oxazol-2(3H)-one (3n). 75 mg, 88%,
1
6.58 (m, 1H), 6.56 (d, J = 15.9 Hz, 1H), 6.29 (dt, J = 15.9, 6.5 Hz, white solid, m.p. 92ꢀ94°C. H NMR (500 MHz, CDCl3) δ 7.39 (d, J
1H), 6.16 (td, J = 6.7, 1.3 Hz, 1H), 4.70 (dd, J = 6.5, 1.2 Hz, 2H). = 7.2 Hz, 2H), 7.34 (t, J = 7.3 Hz, 2H), 7.29 (s, 1H), 7.14 (d, J = 8.5
13C NMR (125 MHz, CDCl3) δ 162.3, 139.4, 136.9, 135.8, 133.9, Hz, 1H), 7.10 (dd, J = 8.5, 2.0 Hz, 1H), 7.03 (d, J = 1.9 Hz, 1H),
128.4, 128.0, 126.4, 123.5, 120.8, 106.1, 50.5. IR (neat) υ (cmꢀ1) 6.70 (d, J = 15.9 Hz, 1H), 6.23 (dt, J = 15.9, 6.3 Hz, 1H), 4.59 (dd, J
3033, 1669, 1597, 1520, 1450, 1200. The recorded NMR spectral = 6.3, 1.4 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 154.1, 141.0,
data was in agreement with the known compound.5a
135.5, 134.4, 131.8, 129.3, 128.6, 128.3, 126.5, 122.3, 121.0, 110.8,
1-Cinnamyl-3-methylpyridin-2(1H)-one (3h). 44 mg, 65%, pale 109.2, 44.4. IR (neat) υ (cmꢀ1) 3033, 1778, 1607, 1486, 1340, 1254,
brown liquid. 1H NMR (500 MHz, CDCl3) δ 7.40ꢀ7.37 (m, 2H), 7.32 1057. HRMS (ESI) m/z calculated for C18H16ClNNaO2 [M+Na]+
(t, J = 7.5 Hz, 2H), 7.26 (s, 1H), 7.22 (d, J = 6.8 Hz, 2H), 6.60 (d, J 308.0449, found 308.0446.
= 15.8 Hz, 1H), 6.34 (dt, J = 15.9, 6.6 Hz, 1H), 6.13 (t, J = 6.7 Hz, 3-Cinnamyl-5-fluorobenzo[d]oxazol-2(3H)-one (3o). 60 mg, 75%,
1
1H), 4.75 (dd, J = 6.5, 1.0 Hz, 2H), 2.19 (s, 3H). 13C NMR (125 white solid, m.p. 95ꢀ96°C. H NMR (500 MHz, CDCl3) δ 7.40ꢀ7.37
MHz, CDCl3) δ 163.0, 136.8, 136.2, 134.3, 134.0, 130.1, 128.6, (m, 2H), 7.34 (t, J = 7.4 Hz, 2H), 7.31ꢀ7.27 (m, 1H), 7.16 (dd, J =
128.1, 126.6, 124.0, 106.0, 51.0, 17.4. IR (neat) υ (cmꢀ1) 3048, 2912, 8.7, 4.2 Hz, 1H), 6.87ꢀ6.77 (m, 2H), 6.71 (d, J = 15.9 Hz, 1H), 6.24
1647, 1585, 1487, 1180. HRMS (ESI) m/z calculated for C15H16NO (dt, J = 15.9, 6.3 Hz, 1H), 4.61 (dd, J = 6.3, 1.4 Hz, 2H). 13C NMR
[M+H]+ 226.1226, found 226.1231.
(125 MHz, CDCl3) δ 159.5 (d, J = 240.0 Hz), 154.7, 138.6, 135.6,
1-Cinnamyl-4-methylpyridin-2(1H)-one (3i). 60 mg, 89%, pale 134.7, 131.7 (d, J = 12.5 Hz), 128.8, 128.5, 126.7, 121,2, 110.6 (d, J
brown liquid. 1H NMR (500 MHz, CDCl3) δ 7.40ꢀ7.35 (m, 2H), = 10.0 Hz), 108.7 (d, J = 23.8 Hz), 97.6 (d, J = 30.0 Hz), 44.7. IR
7.34ꢀ7.29 (m, 2H), 7.26 (dd, J = 4.8, 3.6 Hz, 1H), 7.21 (d, J = 7.0 Hz, (neat) υ (cmꢀ1) 3062, 1775, 1624, 1489, 1384, 1344, 1253, 1174,
1H), 6.57 (d, J = 15.9 Hz, 1H), 6.42 (s, 1H), 6.31 (dt, J = 15.9, 6.5 1083. HRMS (ESI) m/z calculated for C18H16FNNaO2 [M+Na]+
Hz, 1H), 6.04 (dd, J = 7.0, 1.8 Hz, 1H), 4.70 (dd, J = 6.4, 1.3 Hz, 292.0744, found 292.0732.
2H), 2.19 (d, J = 0.6 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 162.4, 3-Cinnamylbenzo[d]thiazol-2(3H)-one (3p). 60 mg, 75%, pale
151.1, 136.1, 135.8, 133.8, 128.6, 128.0, 126.5, 123.9, 119.4, 108.7, yellow solid, m.p. 46ꢀ47°C. 1H NMR (500 MHz, CDCl3) δ 7.46 (dd,
50.2, 21.2. IR (neat) υ (cmꢀ1) 3058, 3037, 2925, 1649, 1586, 1435, J = 7.8, 1.2 Hz, 1H), 7.38ꢀ7.25 (m, 6H), 7.21ꢀ7.13 (m, 2H), 6.65 (d,
1180. HRMS (ESI) m/z calculated for C15H16NO [M+H]+ 226.1226, J = 15.9 Hz, 1H), 6.26 (dt, J = 15.9, 6.0 Hz, 1H), 4.76 (dd, J = 6.0,
found 226.1233.
1.6 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 169.8, 137.0, 136.0,
1-Cinnamyl-5-methylpyridin-2(1H)-one (3j). 56 mg, 83%, yellow 133.5, 128.7, 128.1, 126.6, 126.4, 123.3, 122.7, 122.1, 111.16, 44.6.
1
liquid. H NMR (500 MHz, CDCl3) δ 7.38 (d, J = 7.2 Hz, 2H), 7.31 IR (neat) υ (cmꢀ1) 3054, 3023, 2921, 1648, 1590, 1470, 1327, 1181.
(dd, J =8.2, 6.8 Hz, 2H), 7.26 (d, J = 7.2 Hz, 1H), 7.20 (dd, J = 9.2, The recorded NMR spectral data was in agreement with the known
2.5 Hz, 1H), 7.09 (d, J = 0.7 Hz, 1H), 6.61ꢀ6.55 (m, 2H), 6.31 (dt, J compound.5a
= 15.9, 6.5Hz, 1H), 4.70 (dd, J = 6.5, 1.3 Hz, 2H), 2.07 (s, 3H). 13C 3-(3-(p-Tolyl)allyl)quinazolin-4(3H)-one (3q). 68 mg, 82%, pale
NMR (125 MHz, CDCl3) δ 161.74, 142.13, 136.04, 134.32, 133.79, yellow solid, m.p. 127ꢀ128°C. 1H NMR (500 MHz, CDCl3) δ 8.34 (d,
128.58, 128.02, 126.54, 123.87, 120.60, 115.26, 50.55, 17.07. IR J = 7.9 Hz, 1H), 8.16 (s, 1H), 7.75 (q, J = 7.9 Hz, 2H), 7.51 (t, J =
(neat) υ (cmꢀ1) 3029, 1660, 1580, 1514, 1424, 1154. The recorded 6.4 Hz, 1H), 7.26 (d, J = 7.9 Hz, 2H), 7.11 (d, J = 7.8 Hz, 2H), 6.64
NMR spectral data was in agreement with the known compound.5b
(d, J = 15.8 Hz, 1H), 6.29 (dt, J = 15.7, 6.5 Hz, 1H), 4.77 (d, J = 6.4
2-Cinnamylisoquinolin-1(2H)-one (3k). 41 mg, 52%, yellow solid, Hz, 2H), 2.32 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 160.8, 147.8,
m.p. 78ꢀ81°C. 1H NMR (500 MHz, CDCl3) δ 8.51ꢀ8.46 (m, 1H), 146.3, 138.1, 134.4, 134.2, 132.9, 129.2, 127.2, 126.7, 126.4, 122.0,
7.66 (ddd, J = 8.2, 5.5, 1.3 Hz, 1H), 7.56ꢀ7.49 (m, 2H), 7.39 (dd, J = 121.5, 48.2, 21.1. IR (neat) υ (cmꢀ1) 3017, 2937, 1679, 1610, 1472,
5.2, 3.5 Hz, 2H), 7.33ꢀ7.30 (m, 2H), 7.26 (ddd, J = 12.0, 4.9, 3.1 Hz, 1365, 1252, 1159. The recorded NMR spectral data was in
1H), 7.14 (d, J = 7.4 Hz, 1H), 6.62 (d, J = 15.9 Hz, 1H), 6.54 (d, J = agreement with the known compound.5b
7.3 Hz, 1H), 6.37 (dt, J = 15.9, 6.4 Hz, 1H), 4.82 (dd, J = 6.4, 1.4 Hz, 3-(3-(3,5-Dimethylphenyl)allyl)quinazolin-4(3H)-one (3r). 66 mg,
2H). 13C NMR (125 MHz, CDCl3) δ 162.0, 137.0, 136.2, 133.6, 76%, white solid, m.p. 127ꢀ129°C. 1H NMR (500 MHz, CDCl3) δ
132.2, 131.0, 128.6, 128.0, 126.9, 126.5, 126.3, 125.9, 124.1, 106.4, 8.35 (d, J = 8.1 Hz, 1H), 8.15 (s, 1H), 7.81ꢀ7.66 (m, 2H), 7.52 (d, J =
50.3. IR (neat) υ (cmꢀ1) 3060, 2926, 1646, 1597, 1366, 1290, 1179, 8.0 Hz, 1H), 7.00 (s, 2H), 6.90 (s, 1H), 6.61 (d, J = 15.8 Hz, 1H),
1079. HRMS (ESI) m/z calculated for C18H16NO [M+H]+ 262.1226, 6.33 (dt, J = 15.8, 6.5 Hz, 1H), 4.78 (d, J = 6.5 Hz, 2H), 2.28 (s, 6H).
found 262.1219.
13C NMR (125 MHz, CDCl3) δ 160.8, 147.8, 146.3, 138.0, 135.6,
2-Cinnamylphthalazin-1(2H)-one (3l). 43 mg, 55%, white solid, 134.7, 134.3, 129.9, 127.3, 126.7, 124.4, 122.2, 122.0, 48.2, 21.1. IR
1
m.p. 64ꢀ65°C. H NMR (500 MHz, CDCl3) δ 8.47 (dd, J = 7.5, 1.1 (neat) υ (cmꢀ1) 3011, 2916, 1665, 1610, 1473, 1370, 1160. HRMS
Hz, 1H), 8.20 (s, 1H), 7.84ꢀ7.76 (m, 2H), 7.72ꢀ7.69 (m, 1H), 7.41ꢀ (ESI) m/z calculated for C19H18N2O [M+H]+ 291.1492, found
7.37 (m, 2H), 7.30 (dd, J = 10.3, 4.8 Hz, 2H), 7.23 (ddd, J = 7.3, 3.7, 291.1491.
1.1 Hz, 1H), 6.72 (d, J = 15.9 Hz, 1H), 6.47 (dt, J = 15.8, 6.6 Hz, 3-(3-(Naphthalen-1-yl)allyl)quinazolin-4(3H)-one (3s). 42 mg,
1H), 5.02 (dd, J = 6.6, 1.2 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 45%, pale brown solid, m.p. 119ꢀ121°C. 1H NMR (500 MHz, CDCl3)
159.2, 138.0, 136.5, 133.7, 133.1, 131.7, 129.7, 128.5, 128.0, 127.7, δ 8.41ꢀ8.37 (m, 1H), 8.28 (s, 1H), 8.08 (d, J = 8.3 Hz, 1H), 7.88ꢀ7.84
126.7, 126.5, 126.0, 123.7, 53.2. IR (neat) υ (cmꢀ1) 3055, 3022, (m, 1H), 7.82ꢀ7.77 (m, 3H), 7.61ꢀ7.48 (m, 5H), 7.45 (d, J = 7.8 Hz,
2933, 1643, 1589, 1494, 1448, 1327, 1290. The recorded NMR 1H), 6.39 (dt, J = 15.5, 6.5 Hz, 1H), 4.94 (dd, J = 6.5, 1.3 Hz, 2H).
spectral data was in agreement with the known compound.5a
13C NMR (125 MHz, CDCl3) δ 160.9, 147.8, 146.4, 134.4, 133.5,
3-Cinnamylbenzo[d]oxazol-2(3H)-one (3m). 67 mg, 90%, light 132.1, 131.0, 128.6, 127.5, 127.3, 126.9, 126.3, 125.9, 125.5, 124.3,
1
brown solid, m.p. 100ꢀ102 . H NMR (500 MHz, CDCl3) δ 7.40ꢀ 123.5, 122.1, 48.5. IR (neat) υ (cmꢀ1) 3008, 2926, 1667, 1612, 1516,
7.37 (m, 2H), 7.36ꢀ7.32 (m, 2H), 7.29 (dt, J = 4.2, 1.6 Hz, 1H), 7.26ꢀ 1477, 1378, 1248, 1120. The recorded NMR spectral data was in
7.22 (m, 1H), 7.19ꢀ7.12 (m, 2H), 7.06ꢀ7.03 (m, 1H), 6.71 (d, J = agreement with the known compound.5b
15.9 Hz, 1H), 6.27 (dt, J = 15.9, 6.2 Hz, 1H), 4.64 (dd, J = 6.2, 1.5 3-(3-(4-Methoxyphenyl)allyl)quinazolin-4(3H)-one (3t). 72 mg,
Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 154.3, 142.67, 135.7, 134.1, 82%, white solid, m.p. 122ꢀ124°C. 1H NMR (500 MHz, CDCl3) δ
128.61, 128.2, 126.5, 123.8, 122.5, 121.7, 110.0, 108.9, 44.3. IR 8.34 (dd, J = 8.0, 1.0 Hz, 1H), 8.14 (s, 1H), 7.82ꢀ7.69 (m, 2H), 7.54ꢀ
(neat) υ (cmꢀ1) 3027, 2922, 1747, 1616, 1484, 1349, 1237, 1150. The 7.50 (m, 1H), 7.31 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 6.63
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(d, J = 15.8 Hz, 1H), 6.20 (dt, J = 15.8, 6.6 Hz, 1H), 4.77 (dd, J =
6.6, 1.3 Hz, 2H), 3.80 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 160.9,
159.7, 148.0, 146.3, 134.3, 134.1, 128.5, 127.9, 127.4, 127.3, 126.8,
122.1, 120.4, 114.0, 55.2, 48.3. IR (neat) υ (cmꢀ1) 3002, 2924, 1666,
1602, 1512, 1243, 1030, 768. The recorded NMR spectral data was
in agreement with the known compound.5b
Acknowledgements
Financial support from the National Natural Science
Foundation of China (21402175) is acknowledged.
3-(3-(4-Nitrophenyl)allyl)quinazolin-4(3H)-one
(3u). 52 mg,
Notes and references
1
56%, yellow solid, m.p. 170ꢀ172°C. H NMR (500 MHz, CDCl3) δ
8.35 (dd, J = 8.0, 1.2 Hz, 1H), 8.20ꢀ8.15 (m, 2H), 8.11 (s, 1H), 7.83ꢀ
7.72 (m, 2H), 7.55 (ddd, J = 8.2, 7.2, 1.3 Hz, 1H), 7.51 (d, J = 8.8
Hz, 2H), 6.69 (d, J = 16.0 Hz, 1H), 6.54 (dt, J = 15.9, 6.1 Hz, 1H),
4.85 (dd, J = 6.1, 1.3 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 160.9,
148.1, 147.4, 146.0, 142.1, 134.5, 131.9, 127.8, 127.6, 127.2, 126.8,
124.0, 122.1, 48.0. IR (neat) υ (cmꢀ1) 2941, 1675, 1612, 1513, 1347,
1109. HRMS (ESI) m/z calculated for C17H13N3NaO3 [M+Na]+
330.0849, found 330.0845.
3-(3-(4-(Trifluoromethyl)phenyl)allyl)quinazolin-4(3H)-one (3v).
51 mg, 51%, pale yellow solid, m.p.123ꢀ125oC. 1H NMR (500 MHz,
CDCl3) δ 8.36 (dd, J = 8.0, 1.2 Hz, 1H), 8.17 (s, 1H), 7.83ꢀ7.75 (m,
2H), 7.58 (d, J = 8.2 Hz, 3H), 7.48 (d, J = 8.2 Hz, 2H), 6.69 (d, J =
15.9 Hz, 1H), 6.46 (dt, J = 15.9, 6.3 Hz, 1H), 4.84 (dd, J = 6.3, 1.1
Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 160.9, 147.9, 146.3, 139.2,
134.5, 132.9, 130.0, 127.6, 127.3, 126.8, 126.7, 125.7, 125.5, 122.1,
48.1. IR (neat) υ (cmꢀ1) 2951, 1655, 1611, 1487, 1371, 1121. The
recorded NMR spectral data was in agreement with the known
compound.5b
1
(a) J. H. Chan, D. P. Baccanari, R. L. Tansik, C. M. Boytos, S. K.
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Anti-diabetic: M. S. Malamas and J. Millen, J. Med. Chem.,
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Fukuda, R. H. Du Bus and P. J. Baker, J. Antibiot. 1985, 38
,
1003; (g) A. H. Hunt, J. S. Mynderse, S. K. Samlaska, D. S.
Fukuda, G. M. Maciak, H. A. Kirst, J. L. Occolowitz, J. K.
Swartzendruber and N. D. Jones, J. Antibiot. 1988, 41, 771;
(h) C. A. Martinez, D. R. Yazbeck and J. Tao, Tetrahedron
2004, 60, 759.
2
3
(a) H. Liu, S.-B. Ko, H. Josien and D. P. Curran, Tetrahedron
Lett., 1995, 36, 8917; (b) D. Conreaux, E. Bossharth, N.
Monteiro, P. Desbordes and G. Balme, Tetrahedron Lett.,
2005, 46, 7917; (c) Y.-Q. Fang, M. M. Bio, K. B. Hansen, M. S.
Potter and A. Clausen, J. Am. Chem. Soc., 2010, 132, 15525;
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15380.
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3-(3-(3-Chlorophenyl)allyl)quinazolin-4(3H)-one (3w). 71 mg,
1
80%, white solid, m.p. 131ꢀ133°C. H NMR (500 MHz, CDCl3) δ
8.35 (dd, J = 8.0, 1.2 Hz, 1H), 8.13 (s, 1H), 7.81ꢀ7.73 (m, 2H), 7.56ꢀ
7.52 (m, 1H), 7.36 (s, 1H), 7.23 (s, 3H), 6.60 (d, J = 15.9 Hz, 1H),
6.37 (dt, J = 15.9, 6.3 Hz, 1H), 4.80 (dd, J = 6.3, 1.2 Hz, 2H). 13C
NMR (125 MHz, CDCl3) δ 160.8, 148.0, 146.1, 137.6, 134.6, 134.4,
133.0, 129.8, 128.2, 127.5, 127.4, 126.8, 126.6, 124.8, 124.4, 122.1,
48.1. IR (neat) υ (cmꢀ1) 3048, 2940, 1670, 1611, 1473, 1362, 1159,
771. HRMS (ESI) m/z calculated for C17H13ClN2NaO [M+Na]+
319.0609, found 319.0605.
,
,
2921; (b) B. M. Trost, M. R. Machacek and A. Aponick, Acc.
Chem. Res., 2006, 39, 747.
4
5
(a) A. Ashoorzadeh, Glenn Archibald and V. Caprio,
Tetrahedron, 2009, 65, 4671; (b) G. Liu, C. Liu, C. Ji, L. Sun,
X Liu, Q. Wen and S. Xu, Asian J. Chem., 2013, 25, 9853.
(a) D. Kumar, S. R. Vemula and G. R. Cook, Green Chem.,
2015, 17, 4300; (b) S. R. Vemula, D. Kumar and G. R. Cook,
3-(3-(Thiophen-3-yl)allyl)quinazolin-4(3H)-one (3x). 56 mg, 70%,
1
light yellow solid, m.p. 104ꢀ106°C. H NMR (500 MHz, CDCl3) δ
8.35 (dd, J = 8.0, 0.9 Hz, 1H), 8.15 (s, 1H), 7.80ꢀ7.74 (m, 2H), 7.55ꢀ
7.52 (m, 1H), 7.28ꢀ7.27 (m, 1H), 7.21ꢀ7.19 (m, 2H), 6.70 (d, J =
15.8 Hz, 1H), 6.20 (dt, J = 15.8, 6.5 Hz, 1H), 4.77 (dd, J = 6.5, 1.2
Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 160.9, 147.9, 146.3, 138.4,
134.4, 128.7, 127.4, 127.3, 126.8, 126.4, 124.9, 123.4, 122.5 122.1,
48.2. IR (neat) υ (cmꢀ1) 3102, 2924, 1686, 1606, 1470, 1359, 1161,
768. HRMS (ESI) m/z calculated for C15H12N2NaOS [M+Na]+
291.0563, found 291.0574.
ACS Catal., 2016, 6, 5295.
I. Kadota, A. Shibuya, Y. S. Gyoung and Y. Yamamoto, J. Am.
Chem. Soc., 1998, 120, 10262.
6
7
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6-Chloro-3-(3-(3,5-dimethylphenyl)allyl)quinazolin-4(3H)-one
(3y). 64 mg, 66%, white solid, m.p. 117ꢀ119°C. 1H NMR (500 MHz,
CDCl3) δ 8.30 (dd, J = 2.0, 0.6 Hz, 1H), 8.13 (s, 1H), 7.73ꢀ7.65 (m,
2H), 7.00 (s, 2H), 6.91 (s, 1H), 6.62 (d, J = 15.8 Hz, 1H), 6.31 (dt, J
= 15.8, 6.6 Hz, 1H), 4.77 (dd, J = 6.6, 1.2 Hz, 2H), 2.29 (s, 6H). 13
C
NMR (125 MHz, CDCl3) δ 159.8, 146.4, 138.1, 135.5, 135.1, 134.7,
133.2, 130.0, 129.0, 126.1, 124.5, 123.1, 121.9, 48.4, 21.2. IR (neat)
υ (cmꢀ1) 2922, 1673, 1605, 1469, 1361, 1252. HRMS (ESI) m/z
calculated for C19H18ClN2O [M+H]+ 325.1101, found 325.1102.
3-(3-(3,5-Dimethylphenyl)allyl)benzo[d]oxazol-2(3H)-one (3z). 71
1
mg, 85%, white solid, m.p. 91ꢀ92°C. H NMR (500 MHz, CDCl3) δ
7.24 (dd, J = 7.7, 1.0 Hz, 1H), 7.15 (dqd, J = 15.3, 7.7, 1.3 Hz, 2H),
7.09ꢀ7.04 (m, 1H), 7.02 (s, 2H), 6.94 (s, 1H), 6.66 (d, J = 15.9 Hz,
1H), 6.25 (dt, J = 15.8, 6.3 Hz, 1H), 4.63 (dd, J = 6.3, 1.4 Hz, 2H),
2.32 (s, 6H). 13C NMR (125 MHz, CDCl3) δ 154.3, 142.6, 138.1,
135.6, 134.3, 129.9, 124.4, 123.8, 122.4, 121.2, 109.9, 108.9, 44.4,
21.1. IR (neat) υ (cmꢀ1) 2915, 1757, 1467, 1369, 1238, 1021. HRMS
(ESI) m/z calculated for C18H18NO2 [M+H]+ 280.1332, found
280.1342.
6 | Org. Biomol. Chem. 2016, 00, 1-3
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