Morita-Baylis-Hillman Reaction of α,β-Unsaturated Ketones with Allylic Acetates by the Combination of Transition-Metal Catalysis and Organomediation

Article abstract of DOI:10.1021/acs.joc.6b00684

An intermolecular Morita-Baylis-Hillman (MBH) reaction of α,β-unsaturated ketones with allylic acetates under the catalysis of 10 mol % of tetrakis(triphenylphosphine)palladium(0) and mediation of tributylphosphine has been developed in the presence of acetic acid, affording the desired α-coupling products. The MBH reaction has the advantages of good tolerance to many functional groups, excellent regioselectivity and E-stereoselectivity, and moderate to good yields.

Full text of DOI:10.1021/acs.joc.6b00684

Brief Communication
pubs.acs.org/joc
Morita−Baylis−Hillman Reaction of α,β-Unsaturated Ketones with
Allylic Acetates by the Combination of Transition-Metal Catalysis and
Organomediation
Ya-Qiong Li,† Hai-Jun Wang,‡ and Zhi-Zhen Huang*,†
†Department of Chemistry, Zhejiang University, Hangzhou 310028, China
‡College of Pharmaceutical Sciences, Qiqihar Medical University, Qiqihar 161006, P. R. China
S
* Supporting Information
ABSTRACT: An intermolecular Morita−Baylis−Hillman
(MBH) reaction of α,β-unsaturated ketones with allylic
acetates under the catalysis of 10 mol % of tetrakis-
(triphenylphosphine)palladium(0) and mediation of tributyl-
phosphine has been developed in the presence of acetic acid,
affording the desired α-coupling products. The MBH reaction
has the advantages of good tolerance to many functional groups, excellent regioselectivity and E-stereoselectivity, and moderate
to good yields.
ketones with allylic acetates by the combination of transition-
he Morita−Baylis−Hillman (MBH) reaction is a very
Timportant carbon−carbon bond-forming reaction to metal catalysis and organomediation.
Initially, aryl vinyl ketone 1a and allylic acetate 2a were
provide densely functionalized organic compounds with
enormous synthetic application.1 This reaction was shown to
be highly efficient in the coupling of activated alkenes at their
α-positions with carbon electrophiles under the influence of
organic compounds mainly by the catalysis of amines or
phosphines. The activated alkenes can be alkyl vinyl ketones,
acrylates, acrylonitrile, vinyl sulfones, acrylamides, allenic esters,
vinyl sulfonates, vinyl phosphonates, acrolein, etc.1a A broad
range of electrophiles, such as aldehydes,1a α-keto esters,1a 1,2-
diketones,1a aldimines,1a α,β-unsaturated carbonyl compounds,2
epoxides,3 and triarylbismuth(V) dichlorides,4 have been
employed in the MBH reaction. In 2005, Krafft and co-workers
revealed an intramolecular MBH reaction of α,β-unsaturated
ketones with saturated alkyl halides to give five- or six-
membered ring enones under the mediation of tertiary
phosphine.5 Until now, the MBH alkylation reaction especially
intermolecular alkylation is still a challenging subject. The
MBH reaction of α,β-unsaturated carbonyl compounds with
allylic halides was developed under organocatalysis or organo-
mediation.6a−d In these cases, most α,β-unsaturated carbonyl
compounds are cyclic α,β-unsaturated ketones6a,b or intra-
molecular MBH reaction occurs via allylic chloride interme-
diates.6c In general, allylic alcohols and their esters are more
easily available as compared to allylic halides. In 2003, Krische
et al. reported an intramolecular MBH reaction of the
substrates bearing both α,β-unsaturated ketone moieties and
allylic carbonate moieties under palladium catalysis and
phosphine mediation.7 However, to the best of our knowledge,
there is no systematic results on the intermolecular MBH
reaction of α,β-unsaturated carbonyl compounds with allylic
esters. Herein we wish to present our recent results on the
intermolecular MBH reaction of acyclic α,β-unsaturated
chosen as model substrates to explore and optimize their MBH
reaction. When the reaction performed in the presence of
Pd(PPh3)4 (10 mol %) and P(n-Bu)3 (100 mol %) under
nitrogen at 60 °C, we were pleased to find that the desired α-
allylic group substituted aryl vinyl ketone 3aa was formed in
20% yield (entry 1, Table 1). Along with the minor α-allylated
product 3aa, Rauhut−Currier byproduct 4aa was also formed
in 78% yield. We added an equimolecular Brønsted acid,
benzoic acid, to the reaction mixture to quench the generation
of the Rauhut−Currier byproduct (also see Scheme 2).8 As
expected, the amount of Rauhut−Currier byproduct 4aa was
decreased remarkably, and the yield of α-allylated product 3aa
was increased to 50% (entry 2, Table 1). Other palladium
catalysts and other tertiary phosphines or amines were
screened, but none of them gave a better yield for 3aa
(compare entries 3−8 with entry 2, Table 1; also see the
Supporting Information). Then other Brønsted acids were
examined in the MBH reaction, and AcOH proved to be the
most efficient among them (entries 9−11, Table 1). Increasing
the amount of AcOH from 1.0 to 2.0 equiv resulted in
improvement of the yield to 82% (entry 12, Table 1). When the
loading of P(n-Bu)3 was decreased to 50 mol %, the yield of 3aa
was decreased to 37% dramatically. The effect of solvent on this
reaction was also studied, and 1,4-dioxane proved to be best for
the yield of desired 3aa (compare entries 13−15 with entry 12,
Table 1; also see SI). It is noteworthy that, if either Pd(PPh3)4
or P(n-Bu)3 was employed in the MBH reaction, no desired α-
coupling product 3aa was obtained.
Received: March 30, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b00684
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
a
Table 1. Optimization of MBH Reaction of Aryl Vinyl Ketone 1a with Allylic Acetate 2a
b
yield (%)
entry
[Pd]
phosphine
additive
solvent
3aa
4aa
1
Pd(PPh3)4
Pd(PPh3)4
Pd(dba)2
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(t-Bu)3
P(Cyhex)3
PPh3
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
toluene
DME
20
50
39
43
45
78
2
BzOH
BzOH
BzOH
BzOH
BzOH
BzOH
BzOH
p-TSA
PivOH
AcOH
AcOH
AcOH
AcOH
AcOH
45
3
51
4
Pd2(dba)3.CHCl3
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
50
5
53
6
trace
trace
trace
7
trace
8
9
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
P(n-Bu)3
10
11
47
51
40
12
31
16
39
59
c
d
12
82 (37)
60
c
13
c
14
74
c
15
THF
46
a
The mixture of 1a (0.1 mmol), 2a (0.3 mmol), catalyst (10 mol %), phosphine (100 mol %), and additive (1.0 equiv) was stirred in solvent (2 mL)
b
c
d
at 60 °C; under N2 (1 atm) for 24 h. Isolated yield. 2.0 equiv of AcOH. 50 mol % of phosphine.
After the reaction conditions were screened, it can be
concluded that the optimized reaction should be performed
under the catalysis of 10 mol % of Pd(PPh3)4 and 100 mol % of
P(n-Bu)3 with 2.0 equiv of AcOH in 1,4-dioxane at 60 °C
under nitrogen atmosphere. Under the optimized conditions,
we found that various aryl vinyl ketones 1a−l, which bear either
electron-donating or electron-withdrawing groups on the
benzene ring (in 1a−l), were able to undergo the MBH
reaction smoothly with allylic acetate 2a to give the desired α-
allylated products 3aa−la in the yields of 65−82% (entries 1−
12, Table 2). The MBH reaction tolerated a range of functional
groups on the benzene ring in 1a−l, such as fluoro, chloro,
bromo, nitro, trifluoromethyl, and methoxyl. A naphthyl group
instead of a benzene group in aryl vinyl ketone 1m also resulted
in a good yield of 3ma in the MBH reaction (entry 13, Table
2). We also found that 3-aryl allylic acetates 2b−e were also
able to undergo the MBH reaction with vinyl ketone 1a
smoothly to give 5-aryl α-allylated products 3ab−ae in good
yields with high E selectivity (entries 14−17, Table 2). The
MBH reaction of vinyl ketone 1a with 3-aryl allylic acetates
2b−e also has excellent regioselectivity, and no 3-aryl α-
allylated product was observed. Moreover, 2-branched allylic
acetate 2f also performed the MBH reaction with vinyl ketone
1a expediently (entry 18, Table 2). However, when 3-(4-
nitrophenyl)allylic acetate was employed, no desired coupling
product was observed.
obtained when allylic bromide was employed instead of allylic
acetate (eq 2).
On the basis of the literature1a,7,9 and our experimental
results, a plausible mechanism for the MBH allylation reaction
is depicted in Scheme 2. First, aryl vinyl ketone 1 undergoes a
nucleophilic addition with tri(n-butyl)phosphine followed by
protonation with AcOH, generating phosphonium acetate 6,
1
which was determined by H NMR, 13C NMR, 31P NMR, and
MS (see the SI). Then, phosphonium salt 6 may be deprived a
proton slowly by acetate anion to give active intermediate 7.
Intermediate 7 nucleophilically attacks π-allylpalladium com-
plex 8 to generate phosphonium salt 9 with regenerating
palladium(0) for catalytic cycle. Finally, the β-hydrogen
elimination of phosphonium salt 9 leads to the desired α-
allylated product 3 with regenerating tri-n-butylphosphine.
In conclusion, we have developed a intermolecular MBH
reaction of α,β-unsaturated ketones 1 with allylic acetates 2
under the catalysis of 10 mol % of Pd(PPh3)4 and mediation of
P(n-Bu)3 and AcOH, affording the desired α-coupling products
3. The MBH reaction has the advantages of good tolerance to
many functional groups, excellent regioselectivity and E-
stereoselectivity, and moderate to good yields. A plausible
mechanism via phosphonium salt 6 was also proposed. Further
studies on the intermolecular alkylation of the MBH reaction
using Brønsted acid to decrease Rauhut−Currier byproduct are
currently underway.
EXPERIMENTAL SECTION
When alkyl vinyl ketone 1n was employed in the MBH
reaction under the optimized conditions, the coupling product
3nb was also obtained albeit in a lower yield as compared to
that of 3aa−ma (Scheme 1, eq 1). If the acetate group in 2a
was switched to phenoxyl group in allylic phenyl ether 5a, aryl
vinyl ketone 1a was able to perform the MBH reaction readily
with ether 5a, affording the desired α-coupling product 3aa in
moderate yield (eq 2). However, no desired product was
■
Preparation of Aryl Vinyl Ketone 1.10 To a mixture of methyl
aryl ketone (10.0 mmol) and paraformaldehyde (0.90 g, 30.0 mmol) in
THF (20.0 mL) were added diisopropylammonium trifluoroacetate
(2.13 g, 10.0 mmol) and trifluoroacetic acid (0.11 g, 1.0 mmol, 10 mol
%). After the reaction mixture was stirred at reflux for 1 day, the
mixture was cooled to room temperature, and a second addition of
paraformaldehyde (0.90 g, 30.0 mmol) was performed. The reaction
mixture was then stirred at reflux for an additional 1 day. After the
B
DOI: 10.1021/acs.joc.6b00684
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
Table 2. Intermolecular MBH Reaction of Aryl Vinyl
ketones 1 with Allylic Acetates 2 by the Combination of
Transition-Metal Catalysis and Organomediation
Scheme 1. MBH Reactions of Expanded Scope by the
Combination of Transition-Metal Catalysis and
Organomediation
a
Scheme 2. Possible Mechanism for the MBH Reaction of
Aryl Vinyl Ketone 1 with Allylic Acetate 2 by the
Combination of Transition-Metal Catalysis and
Organomediation
mmol) were added. The reaction mixture was stirred at 60 °C for 24 h
under N2. Then, the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (silica gel, ethyl
acetate/petroleum ether = 1/100 as eluent) to give the desired α-
allylic group substituted aryl vinyl ketone 3.
2-Methylene-1-(4-tolyl)pent-4-en-1-one (3aa): colorless oil (15.3
1
mg, 82% yield); H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0 Hz,
2H), 7.24 (d, J = 8.0 Hz, 2H), 5.95−5.83 (m, 2H), 5.64 (s, 1H), 5.17−
5.09 (m, 2H), 3.22 (d, J = 6.4 Hz, 2H), 2.41 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 197.5, 146.5, 143.0, 135.0, 134.9, 129.8, 128.9, 125.5,
117.1, 36.4, 21.6; HR-MS (EI-TOF) (M+) calcd for C13H14O
186.1045, found 186.1049.
2-Methylene-1-(2-tolyl)pent-4-en-1-one (3ba): colorless oil (13.2
1
mg, 71% yield); H NMR (400 MHz, CDCl3) δ 7.34−7.30 (m, 1H),
7.25−7.17 (m, 3H), 5.97−5.87 (m, 2H), 5.65 (s, 1H), 5.19−5.11 (m,
2H), 3.21 (d, J = 6.8 Hz, 2H), 2.30 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 199.9, 147.8, 138.9, 136.2, 135.1, 130.8, 129.8, 129.7, 127.9,
125.0, 117.1, 34.8, 19.7; HR-MS (EI-TOF) (M+) calcd for C13H14O
186.1045, found 186.1048.
a
The mixture of 1a (0.1 mmol), 2a (0.3 mmol), Pd(PPh3)4 (10 mol
%), P(n-Bu)3 (100 mol %), and AcOH (2.0 equiv) was stirred in
dioxane (2 mL) at 60 °C; under N2 (1 atm) for 24 h. Isolated yield.
b
mixture was cooled, solvent was removed under reduced pressure. The
residue was dissolved in Et2O, and the etheric solution was washed
with 1 N HCl (200 mL), 1 N NaOH (200 mL), and brine (200 mL),
respectively. The organic phase was dried over Na2SO4 and
concentrated under vacuum. The crude product was purified by
column chromatography (silica gel, ethyl acetate/petroleum ether = 1/
200−1/100 as eluent) to give aryl vinyl ketone 1.
General Procedure for the MBH Reaction. To a mixture of aryl
vinyl ketone 1 (0.1 mmol) and AcOH (12.0 mg, 0.2 mmol) in 1,4-
dioxane (2 mL) was added P(n-Bu)3 (20.2 mg, 0.1 mmol, 100 mol %).
After the reaction mixture was stirred at room temperature for 1 min,
Pd(PPh3)4 (11.6 mg, 0.01 mmol, 10 mol %) and allylic acetate 2 (0.3
2-Methylene-1-(3-tolyl)pent-4-en-1-one (3ca): colorless oil (11.9
1
mg, 64% yield); H NMR (400 MHz, CDCl3) δ 7.56−7.53 (m, 2H),
7.36−7.29 (m, 2H), 5.95−5.85 (m, 2H), 5.67 (d, J = 0.8 Hz, 1H),
5.18−5.10 (m, 2H), 3.22 (dt, J = 6.8, 1.0 Hz, 2H), 2.40 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 197.9, 146.5, 138.1, 137.7, 135.0, 133.0,
129.9, 128.0, 126.8, 126.4, 117.1, 36.2, 21.3; HR-MS (EI-TOF) (M+)
calcd for C13H14O 186.1045, found 186.1044.
1-(3-Methoxyphenyl)-2-methylenepent-4-en-1-one (3da): color-
1
less oil (16.2 mg, 80% yield); H NMR (400 MHz, CDCl3) δ 7.36−
7.28 (m, 3H), 7.09−7.06 (m, 1H), 5.95−5.84 (m, 2H), 5.69 (d, J = 0.8
Hz, 1H), 5.17−5.10 (m, 2H), 3.84 (s, 3H), 3.22−3.21 (d, J = 6.8 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 197.4, 159.5, 146.3, 139.0,
C
DOI: 10.1021/acs.joc.6b00684
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The Journal of Organic Chemistry
Brief Communication
134.9, 129.1, 126.4, 122.2, 118.5, 117.2, 113.9, 55.4, 36.2; HR-MS (EI-
TOF) (M+) calcd for C13H14O2 202.0994, found 202.0998.
1-(4-Methoxyphenyl)-2-methylenepent-4-en-1-one (3ea): color-
(d, J = 7.6 Hz, 2H), 7.37−7.20 (m, 7H), 6.50 (d, J = 16.0 Hz, 1H),
6.32−6.25 (m, 1H), 5.89 (s, 1H), 5.67 (s, 1H), 3.37 (d, J = 6.8 Hz,
2H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 197.5, 146.7,
143.1, 137.4, 134.9, 132.4, 129.8, 128.9, 128.5, 127.2, 126.7, 126.2,
125.8, 35.6, 21.6; HR-MS (EI-TOF) (M+) calcd for C19H18O
262.1358, found 262.1359.
(E)-5-(2-Methoxyphenyl)-2-methylene-1-(4-tolyl)pent-4-en-1-one
(3ac): colorless oil (17.8 mg, 61% yield); 1H NMR (400 MHz,
CDCl3) δ 7.70 (d, J = 8.0 Hz, 2H), 7.42 (dd, J = 7.6, 1.2 Hz, 1H),
7.24−7.16 (m, 3H), 6.91−6.80 (m, 3H), 6.32−6.27 (m, 1H), 5.88 (s,
1H), 5.65 (s, 1H), 3.82 (s, 3H), 3.38 (d, J = 7.2 Hz, 2H), 2.40 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 197.7, 156.4, 146.9, 143.0, 135.0,
1
less oil (15.4 mg, 76% yield); H NMR (400 MHz, CDCl3) δ 7.83−
7.79 (m, 2H), 6.94−6.91 (m, 2H), 5.94−5.84 (m, 1H), 5.77 (d, J = 1.2
Hz, 1H), 5.58 (d, J = 0.8 Hz, 1H), 5.16−5.08 (m, 2H), 3.86 (s, 3H),
3.21 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 196.5, 163.2,
146.5, 135.0, 132.0, 130.1, 124.2, 117.1, 113.5, 55.4, 36.7; HR-MS (EI-
TOF) (M+) calcd for C13H14O2 202.0994, found 202.0993.
2-Methylene-1-phenylpent-4-en-1-one (3fa):11 colorless oil (13.4
1
mg, 78% yield); H NMR (400 MHz, CDCl3) δ 7.76−7.74(m, 2H),
7.55−7.51 (m, 1H), 7.45−7.41 (m, 2H), 5.95−5.85 (m, 2H), 5.67 (d, J
= 0.8 Hz, 1H), 5.18−5.09 (m, 2H), 3.22 (dt, J = 6.8, 1.1 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 197.7, 146.4, 137.7, 135.0, 132.2, 129.5,
128.2, 126.5, 117.2, 36.2; MS (EI) m/z 172.1 (M+), 171.1, 129.1,
128.1, 105.1, 77.1, 51.1, 39.1.
129.8, 128.9, 128.2, 127.3, 127.0, 126.6, 126.4, 125.6, 120.6, 110.9,
55.5, 36.0, 21.6; HR-MS (EI-TOF) (M+) calcd for C20H20O2
292.1463, found 292.1467.
(E)-5-(4-Fluorophenyl)-2-methylene-1-(4-tolyl)pent-4-en-1-one
1
(3ad): white solid (19.9 mg, 71% yield); Mp: 72−74 °C; H NMR
1-(4-Fluorophenyl)-2-methylenepent-4-en-1-one (3ga): colorless
1
(400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 2H), 7.33−7.23 (m, 4H),
7.00−6.95 (m, 2H), 6.46 (d, J = 16.0 Hz, 1H), 6.23−6.16 (m, 1H),
5.88 (s, 1H), 5.67 (s, 1H), 3.35 (d, J = 6.8 Hz, 2H), 2.41 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 197.4, 162.1 (d, J = 244.8 Hz), 146.6,
143.1, 134.9, 133.5, 131.2, 129.8, 129.0, 127.6 (d, J = 7.8 Hz), 126.4
(d, J = 2.1 Hz), 125.8, 115.4 (d, J = 21.0 Hz), 35.6, 21.6; HR-MS (EI-
TOF) (M+) calcd for C19H17FO 280.1263, found 280.1262.
oil (13.9 mg, 73% yield); H NMR (400 MHz, CDCl3) δ 7.82−7.79
(m, 2H), 7.14−7.09 (m, 2H), 5.94−5.83 (m, 2H), 5.63 (d, J = 0.8 Hz,
1H), 5.17−5.10 (m, 2H), 3.21 (dt, J = 6.8, 1.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 196.1, 165.5 (d, J = 252.1 Hz,), 146.3, 134.8,
133.8 (d, J = 3.0 Hz), 132.1 (d, J = 8.9 Hz), 125.9, 117.3, 115.3 (d, J =
21.5 Hz), 36.3; HR-MS (EI-TOF) (M+) calcd for C12H11FO
190.0794, found 190.0795.
1-(4-Chlorophenyl)-2-methylenepent-4-en-1-one (3ha): colorless
oil (14.9 mg, 72% yield); H NMR (400 MHz, CDCl3) δ 7.72−7.69
(E)-5-(4-Chlorophenyl)-2-methylene-1-(4-tolyl)pent-4-en-1-one
1
1
(3ae): white solid (22.9 mg, 77% yield); Mp: 76−78 °C; H NMR
(400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 2H), 7.29−7.23 (m, 6H),
6.47 (d, J = 16.8 Hz, 1H), 6.30−6.22 (m, 1H), 5.88 (s, 1H), 5.68 (s,
1H), 3.36 (d, J = 7.2 Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 197.4, 146.4, 143.1, 135.8, 134.9, 132.8, 131.2, 129.7, 129.0,
128.6, 127.5, 127.4, 125.9, 35.6, 21.6; HR-MS (EI-TOF) (M+) calcd
for C19H17ClO 296.0968, found 296.0968.
(E)-4-Methyl-2-methylene-5-phenyl-1-(4-tolyl)pent-4-en-1-one
(3af): colorless oil (13.8 mg, 50% yield); 1H NMR (400 MHz, CDCl3)
δ 7.72 (d, J = 8.0 Hz, 2H), 7.31−7.17 (m, 7H), 6.38 (s, 1H), 5.86 (s,
1H), 5.68 (s, 1H), 3.34 (s, 2H), 2.41 (s, 3H), 1.90 (d, J = 1.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 197.5, 146.3, 143.1, 138.2, 135.8,
(m, 2H), 7.43−7.40 (m, 2H), 5.93−5.83 (m, 2H), 5.65 (d, J = 0.8 Hz,
1H), 5.17−5.10 (m, 2H), 3.21 (dt, J = 6.8, 1.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 196.4, 146.3, 138.7, 136.0, 134.7, 130.9, 128.6,
126.5, 117.4, 36.2; HR-MS (EI-TOF) (M+) calcd for C12H11ClO
206.0498, found 206.0498.
1-(4-Bromophenyl)-2-methylenepent-4-en-1-one (3ia): yellow oil
1
(16.6 mg, 66% yield); H NMR (400 MHz, CDCl3) δ 7.64−7.57 (m,
4H), 5.93−5.83 (m, 2H), 5.65 (s, 1H), 5.17−5.11 (m, 2H), 3.21 (d, J
= 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 196.5, 146.2, 136.4,
134.7, 131.5, 131.0, 127.2, 126.6, 117.4, 36.1; HR-MS (EI-TOF) (M+)
calcd for C12H11BrO 249.9993, found 249.9995.
134.9, 129.8, 129.0, 128.8, 128.1, 127.8, 126.2, 125.8, 42.9, 21.6, 17.9;
HR-MS (EI-TOF) (M+) calcd for C20H20O 276.1514, found 276.1517.
(E)-4-Methylene-7-phenylhept-6-en-3-one (3nb): colorless oil (8.0
2-Methylene-1-(3-nitrophenyl)pent-4-en-1-one (3ja): colorless oil
(15.0 mg, 69% yield); 1H NMR (400 MHz, CDCl3) δ 8.56 (t, J = 1.8
Hz, 1H), 8.40 (ddd, J = 8.4, 2.2, 1.0 Hz, 1H), 8.08 (dt, J = 7.6, 1.2 Hz,
1H), 7.67 (t, J = 8.0 Hz, 1H), 6.03 (t, J = 1.4 Hz, 1H), 5.96−5.85 (m,
1H), 5.72 (s, 1H), 5.21−5.14 (m, 2H), 3.25 (d, J = 6.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 195.1, 148.0, 145.9, 139.2, 134.9, 134.3,
129.6, 128.1, 126.5, 124.2, 117.8, 35.9; HR-MS (EI-TOF) (M+) calcd
for C12H11NO3 217.0739, found 217.0742.
2-Methylene-1-(4-nitrophenyl)pent-4-en-1-one (3ka): colorless oil
(17.4 mg, 80% yield); 1H NMR (400 MHz, CDCl3) δ 8.30 (dt, J = 8.8,
2.1 Hz, 2H), 7.86 (dt, J = 9.2, 2.0 Hz, 2H), 6.04 (t, J = 1.4 Hz, 1H),
5.95−5.85 (m, 1H), 5.71 (s, 1H), 5.20−5.14 (m, 2H), 3.24 (dt, J = 6.8,
1.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 195.7, 149.7, 146.2,
143.1, 134.4, 130.1, 128.8, 123.5, 117.7, 35.7; HR-MS (EI-TOF) (M+)
calcd for C12H11NO3 217.0739, found 217.0742.
1
mg, 40% yield); H NMR (400 MHz, CDCl3) δ 7.36−7.18 (m, 5H),
6.42 (d, J = 15.6 Hz, 1H), 6.25−6.17 (m, 1H), 6.06 (s, 1H), 5.80 (s,
1H), 3.18 (d, J = 7.2 Hz, 2H), 2.74 (q, J = 7.3 Hz, 2H), 1.11 (t, J = 7.4
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 201.9, 147.1, 137.4, 132.0,
128.5, 127.3, 127.2, 126.1, 124.5, 34.3, 30.9, 8.4; HR-MS (EI-TOF)
(M+) calcd for C14H16O 200.1201, found 200.1202.
2-Methylene-1,5-di-4-tolylpentane-1,5-dione (4aa):12 white solid
(22.8 mg, 78% yield); 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.0
Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.26−7.22 (m, 4H), 5.90 (s, 1H),
5.63 (s, 1H), 3.20 (t, J = 7.2 Hz, 2H), 2.89 (t, J = 7.2 Hz, 2H), 2.41 (s,
3H), 2.40 (s, 3H); MS (EI) m/z 292.1 (M+), 277.1, 264.1, 173.1,
119.0, 91.0, 65.0.
2-Methylene-1-(4-(trifluoromethyl)phenyl)pent-4-en-1-one (3la):
colorless oil (15.6 mg, 65% yield); H NMR (400 MHz, CDCl3) δ
Phosphonium Acetate 6. To a mixture of aryl vinyl ketone 1a
(14.6 mg, 0.1 mmol) and AcOH (12.0 mg, 0.2 mmol) in 1,4-dioxane
(2 mL) was added P(n-Bu)3 (20.2 mg, 0.1 mmol). After the reaction
mixture was stirred at room temperature for 1 min, the solvent was
evaporated under reduced pressure. The residue was purified by
column chromatography (silica gel, ethyl acetate/methanol = 3/1 as
eluent) to give the desired phosphonium acetate 6.
Tributyl(3-oxo-3-(4-tolyl)propyl)phosphonium acetate (6): Color-
less oil (38.8 mg, 95% yield); 1H NMR (400 MHz, CDCl3) δ 7.98 (d,
J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 3.76−3.68 (m, 2H), 2.76−
2.70 (m, 2H), 2.43−2.36 (m, 9H), 2.00 (s, 3H), 1.53−1.51 (m, 12H),
0.96 (t, J = 6.6 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ 197.7 (d, J =
6.5 Hz), 176.1, 145.1, 132.9, 129.6, 128.7, 31.6 (d, J = 4.1 Hz), 24.0 (d,
J = 15.7 Hz), 23.8 (d, J = 4.6 Hz), 23.2, 21.8, 19.2 (d, J = 47.2 Hz),
13.9 (d, J = 51.4 Hz), 13.4; 31P NMR (162 MHz, CDCl3) δ 34.6 (s);
MS-ESI m/z 349.3 [M − OAc]+. Because phosphonium acetate 6
decomposes gradually, it is not pure enough for elemental analysis
although it is pure enough for NMR.
1
7.82 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 5.98 (s, 1H), 5.95−
5.85 (m, 1H), 5.69 (s, 1H), 5.19−5.13 (m, 2H), 3.23 (d, J = 6.8 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 196.5, 146.2, 140.9, 134.6, 133.5
(q, J = 32.5 Hz), 129.6, 128.0, 125.3 (q, J = 3.7 Hz), 123.7 (q, J =
270.9 Hz), 117.5, 35.8; HR-MS (EI-TOF) (M+) calcd for C13H11F3O
240.0762, found 240.0764.
2-Methylene-1-(naphthalen-2-yl)pent-4-en-1-one (3ma): color-
1
less oil (19.1 mg, 86% yield); H NMR (400 MHz, CDCl3) δ 8.26
(s, 1H), 7.93−7.85 (m, 4H), 7.60−7.51 (m, 2H), 6.00−5.90 (m, 2H),
5.73 (d, J = 0.8 Hz, 1H), 5.22−5.12 (m, 2H), 3.28 (d, J = 6.8 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 197.7, 146.6, 135.2, 135.0, 134.9,
132.3, 131.1, 129.4, 128.2, 128.1, 127.8, 126.8, 126.2, 125.5, 117.3,
36.4; HR-MS (EI-TOF) (M+) calcd for C16H14O 222.1045, found
222.1042.
(E)-2-Methylene-5-phenyl-1-(4-tolyl)pent-4-en-1-one (3ab): col-
1
orless oil (21.5 mg, 82% yield); H NMR (400 MHz, CDCl3) δ 7.70
D
DOI: 10.1021/acs.joc.6b00684
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00684.
Optimization of reaction conditions and H NMR, 13C
1
NMR, and HRMS spectra for new products (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: huangzhizhen@zju.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (No. 21372195) and MOST of China
(973 program 2011CB808600) is gratefully acknowledged.
REFERENCES
■
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DOI: 10.1021/acs.joc.6b00684
J. Org. Chem. XXXX, XXX, XXX−XXX