Regio- and Stereoselective Nickel-Catalyzed Coupling of Boronic Acids with Allenoates

Article abstract of DOI:10.1055/s-0037-1610023

The Ni(II)-catalyzed cross-coupling of arylboronic acids with allenoates is documented. The high regio- and stereoselectivity of the process enables a wide range of β-aryl β,γ-unsaturated esters to be prepared in good to excellent yields (up to 95%) and high E / Z -selectivity. Additionally, [3+2]-cascade sequence was observed when 2-formylphenylboronic acid was employed.

Full text of DOI:10.1055/s-0037-1610023

SYNTHESIS
0
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–J
special topic
A
en
Y. Liu et al.
Special Topic
Synthesis
Regio- and Stereoselective Nickel-Catalyzed Coupling of Boronic
Acids with Allenoates
Yang Liu
Br
Mario Daka
N
Cl
Marco Bandini*
Ni
Cl
O
N
Dipartimento di Chimica ‘G. Ciamician’–Alma Mater
Studiorum, Università di Bologna, via Selmi 2, 40138
Bologna, Italy
O
Ar
•
R1
(5 mol%)
R2O
Br
R2O
R
+
R
R1
marco.bandini@unibo.it
K2CO3
1,4-dioxane, 90 °C, 5 h
yields up to 95%
22 examples
ArBH(OH)2
Published as part of the Special Topic Modern Coupling
Approaches and their Strategic Applications in Synthesis
Received: 27.03.2018
Accepted after revision: 23.04.2018
Published online: 12.06.2018
ides was obtained in high yields. Accordingly, we envi-
sioned the possibility to extend our protocol to allenotates,8
a well-known family of ‘electronically modified’ allenes
that, to the best of our knowledge, have never been subject-
ed to Ni-assisted condensation with boronic acids. Notably,
the reverse electron perturbation with respect to allenam-
ides (EWG are present instead of EDG) could impact on the
chemo-, regio-, and stereoselectivity. Additionally, previous
examples on transition-metal-catalyzed addition of or-
ganometallic species (i.e., Grignard reagents,9 boronic ac-
ids10) to allenoates clearly emphasized that also the nature
of the metal species substantially contributes to determine
the formation of α,β- or β,γ-unsaturated β-arylated esters
(Scheme 1, a–c).
In order to verify the extension of the Ni-catalysis to
EWG-conjugated allenes, allenoate 1a and phenylboronic
acid (2a) were subjected to an extensive survey of reaction
conditions regarding structure of the nickel catalyst, base,
and temperature. A collection of results is documented in
Table 1 from which some conclusions are drawn.
Interestingly, bis-pyridyl-based complexes Cat1–6/8 (5
mol%) displayed moderate to very good selectivity (yield up
to 95% with Cat3, Table 1, entry 3) towards the formation of
the β-phenyl-β,γ-unsaturated ester 3aa with high stereose-
lectivity and affording the E-isomer in major amount (up to
13:1). In contrast, keto-bridged catalyst Cat7, NHC, and
phosphine-based [Ni(II)] complex analogues failed in pro-
moting the cross-coupling reaction. Interestingly,
[Ni(PPh3)2Cl2] displayed a divergent chemical course deliv-
ering the isomeric conjugate diene isomer 3aa′′ in 50% yield
(entry 9). This finding can be seen as a preliminary indica-
tion that the presence of [Ni(0)] intermediate (more likely
with P-based complexes with respect to pyridyl analogues)
disfavors the cross-coupling process with boronic acids. The
catalyst of election (Cat3) enabled lowering of the catalyst
up to 2.5 mol% with only a slight erosion in chemical yield
DOI: 10.1055/s-0037-1610023; Art ID: ss-2018-c0208-st
Abstract The Ni(II)-catalyzed cross-coupling of arylboronic acids with
allenoates is documented. The high regio- and stereoselectivity of the
process enables a wide range of β-aryl β,γ-unsaturated esters to be pre-
pared in good to excellent yields (up to 95%) and high E/Z-selectivity.
Additionally, [3+2]-cascade sequence was observed when 2-formyl-
phenylboronic acid was employed.
Key words allenoate, boronic acid, catalysis, cross-coupling, nickel,
stereoselection
The impact of nickel catalysis in modern organic syn-
thesis is flourishing with a plethora of applications in diver-
sified research lines such as cross-coupling processes, syn-
thesis of natural/bioactive compounds, asymmetric trans-
formations, and photo-redox methodologies.1 Low cost,
earth abundance, mild reaction conditions, fine-tunability
via ligand modulation, and wide range of easily accessible
oxidation states are some of main features that are contrib-
uting to expand the applicability of nickel catalysis in or-
ganic synthesis.2
In this context, Ni-promoted nucleophilic type cross-
coupling transformations deserve a prominent role.1,3
[Ni(0)] species, mainly based on [Ni(COD)2] precursor, have
traced some landmarks in the field, however, the high sen-
sitivity of these nickel-precatalysts prompted to envision
the applicability of more stable [Ni(II)] precursors in redox-
active as well as redox-neutral C–C and C–X cross-coupling
processes.4
In conjunction with our interest in the transition-metal-
catalyzed functionalization of cumulate π-systems,5 we
have recently documented on the site-selective condensa-
tion of boronic acids6 to N-allenamides under [Ni(bpy)Cl2]
catalysis.7 A wide range of configurationally defined enam-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

B
Y. Liu et al.
Special Topic
Synthesis
The generality of the protocol was further investigated
by subjecting a range of diversely substituted allenoates
1b–i to condensation with 2a (Table 2). Structural varia-
tions on the allenoates were realized on the allenyl unit
(both α- and γ-position with respect to ester group) and at
the alkyloxy group (R2). Substituted (R = alkyl, aryl) and un-
substituted (R = H) allenoates at the γ-position reacted sat-
isfyingly under optimal conditions, delivering the corre-
sponding cross adduct in synthetically useful yields. How-
ever, the stereochemical outcome proved to be dependent
on R. As a matter of fact, with R = linear alkyl chain (i.e., n-
C3H7 and n-C9H19) the corresponding β,γ-unsaturated esters
were isolated with good E-predominance (up to 6:1) re-
gardless the nature of R2 [i.e., BnO, EtO, 3,5-Me2C6H3O]
(90 °C). Interestingly, the employment of mono-substituted
allenes 1b and 1e at the same temperature resulted in a
drop of β,γ/α,β ratio. However, by lowering the reaction
temperature to 40 °C 80:20 chemoselectivity in favor of the
unconjugated compound 3 was observed. Additionally, the
γ-phenyl-substituted allenoate 1i still delivered the β,γ-un-
saturated adduct 3ia in very high yield (85%) but a signifi-
cant erosion in C=C stereoselection was recorded (Table 2,
entry 8). A limitation of the methodology appeared when
the α,γ-disubstituted allene 1h was utilized. Here, the reac-
tion became particular sluggish and the corresponding
cross-coupling compounds was obtained only in traces (en-
try 7). Finally, the methodology proved competent also for
Iron-Copper catalysis (S. Ma)
R
R1
R1
[Fe(III)] or Cu(I)
low temp.
(a)
+
R’MgX
CO2R2
R
•
CO2R2
R’
yields
up to 99%
Palladium catalysis (S. Ma and X. Lu)
Ar
R1
[Pd(0)]
R1
CO2R2
R
+
ArB(OH)2
CO2R2
yields
up to 86%
R
R
•
•
AcOH
(b)
O
OH
[L*Pd(II)]
H
CO2R1
Y
CO2R1
+
Y
B(OH)2
ee up to 84%
R
Ar1
Rhodium catalysis (S. Ma)
[Rh(I)]
H2O
Ar1BH(OH)2
Ar2CHO
+
+
•
CO2Me
(c)
Ar2
O
O
yields up to 59%
Scheme 1 Previous work on the metal-catalyzed condensation of bo-
ronic acids to allenoates
(84%, entry 13). Additionally, the possibility to carry out the
reaction also with the in situ formed complex was verified
(entry 14, 88% yield, 11:1 stereoisomeric ratio). A very brief
survey of inorganic bases elected K2CO3 as the most effi-
cient one. The use of [Cu(L1)Cl] furnished similar 3aa/3aa′
selectivity but in lower extent (53% yield, entry 11), while
[Pd(PPh3)4] under acidic conditions10c resulted in the isola-
tion of the α,β-unsaturated compound 3aa′ (entry 12). Fi-
nally, the impact of the temperature on the kinetics and
stereochemistry of the process was also examined (entries
15 and 16). Here, while at 60 °C the reaction did not pro-
ceed at all, at 110 °C a drop in E/Z ratio with respect to 90 °C
was recorded (5:1 vs 11:1).
The generality of the methodology in term of boronic
acids was then addressed by condensing 1a with a series of
differently substituted compounds 2 (optimal reaction con-
ditions: 1a, 2, Cat3, K2CO3, 5 h, 90 °C, reagent grade 1,4-di-
oxane, Scheme 2). Remarkably, the protocol did not show
any perturbation by varying position and electronic proper-
ties of the substituent on the aromatic ring. EWGs (i.e., NO2,
Br, COMe, CO2Me, and F) and EDGs (i.e., OH, Me, On-Bu,
NMe2, and OMe) were adequately supported providing the
corresponding β,γ-unsaturated ethyl esters 3 in very high
yields (up to 92%) and from moderate to very high E/Z ratio.
Analogously, the 2-naphthylboronic acid (2n) performed
satisfyingly in Ni-catalyzed process (58% yield, E/Z = 4:1). In
contrast, aliphatic c-HexB(OH)2 proved ineffective in the
catalytic process.
R1
Cat3 (5 mol%)
CO2Et
+
R
•
CO2Et
R1B(OH)2
K2CO3, 1,4-dioxane
90 °C, 5 h
3
2
1a
(R = n-Pr)
R
COMe
X
NO2
3ae: 83%
(11:1)
3ac (X = F): 83% (4:1)
3ad (X = Br): 90% (4:1)
3ab: 85%
(9:1)
CO2Et
CO2Et
CO2Et
R
R
R
OnBu
Me
CO2Me
3ag: 89%
(9:1)
3af: 92%
(10:1)
3ah: 89%
(7:1)
CO2Et
CO2Et
CO2Et
R
R
R
X
3ai (X = OH): 52% (11:1)
3aj (X = OMe): 83% (10:1)
3ak (X = CO2Me): 92% (10:1)
3al (X = NO2): 70% (7:1)
3am (X = NMe2): 64% (10:1)
3an: 58%
(4:1)
CO2Et
CO2Et
R
R
Scheme 2 Examining the reaction scope with respect to the phenylbo-
ronic acids
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

C
Y. Liu et al.
Special Topic
Synthesis
the keto-allenyl compound 1f that provided the thermody-
namically more stable enone (E)-3fa in 84% as a single ste-
reoisomer (entry 5).
Interestingly, the use of 2-formylphenylboronic acid
(2p) led to the isolation of the [3+2]-annulated compound
3ap in 63% yield as a single diastereoisomer. Once again, ab-
solute stereospecificity towards the formation of the trans-
C=C bond was observed (Scheme 3).11,12
OH
B(OH)2
CHO
Cat3 (5 mol%)
CO2Et
+
CO2Et
R
•
K2CO3, 1,4-dioxane
90 °C, 5 h
3ap: 63%
1a
(R = n-Pr)
2p
(E/Z 9:1)
R
Scheme 3 Formal [3+2] cycloaddition between the 2-formylphenylbo-
ronic acid (2p) and allenoate 1a
Table 1 Optimization of the Reaction Conditionsa
Ph
Cat (5 mol%)
CO2Et
base, 1,4 diaxane
T, 5 h
CO2Et
+
1a
3aa
PhB(OH)2 (2a)
O
R2
R2
R1
R1
N
N
N
N
N
N
Ni
Ni
Ni
Cl
Cl
Cl
Cl
Cl
Cat8
Cl
Cat1–6
Cat7
3aa'
N+
N
N
N
CO2Et
Ph
L1
CO2Et
3aa''
L2
Entry
Cat (5 mol%)
Base
Temp (°C)
Yield of 3aa (%)b
E/Zc
13:1
1
2
Cat1 (R1 = R2 = H)
K2CO3
90
90
90
90
90
90
90
90
90
90
90
r.t.
90
90
60
110
90
90
52
Cat2 (R1 = H, R2 = t-Bu)
Cat3 (R1 = H, R2 = Br)
Cat4 (R1 = H, R2 = OMe)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
–
82
10:1
11:1
9:1
7:1
13:1
–
3
95
4
65
5
Cat5 (R1 = H, R2 = CO2Me)
Cat6 (R1 = Me, R2 = H)
Cat7
90
6
82
7
traces
73
8
Cat8
11:1
–
9
[Ni(PPh3)2Cl2]
L2/NiCl2(DME)
L1/CuCl
(50, 3aa′′)
traces
53
10
11
12d
13
14e
15f
16
17
18
–
11:1
–
[Pd(PPh3)4]
Cat3 (2.5 mol%)
Cat3 (in situ)
Cat3
(34, 3aa′)
84
K2CO3
K2CO3
K2CO3
K2CO3
11:1
11:1
–
88
traces
85
Cat3
5:1
10:1
–
Cat3
Na2CO3
Cs2CO3
82
Cat3
traces
a All the reactions were carried out under N2 in reagent grade 1,4-dioxane, unless otherwise specified.
b Isolated yield after flash chromatography.
c Determined by 1H NMR analysis and/or GC-MS on the reaction crude.
d In the presence of AcOH (100 mol%).
e Complex made in situ from 4,4′-Br2-bpy and NiCl2(DME).
f Reaction time: 16 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

D
Y. Liu et al.
Special Topic
Synthesis
Table 2 Reaction Scope of Allenoates 1a
tion and consequent cross-coupling event is unlikely. As a
matter of fact, when a mixture of allene/alkyne (~1:1)13 was
employed as the starting material, the reaction rate
dropped significantly and a mixture of inseparable com-
pounds was recorded with most of the alkyne unreacted.
In conclusion, the [Ni(II)]-catalyzed synthesis of β,γ-
unsaturated esters via condensation of boronic acids to
allenoates is presented. Excellent isolated yields were ac-
companied by high levels of chemo-, regio-, and stereose-
lectivity. The robustness of the chemistry, ready availability
of the nickel precatalyst, and relatively mild reaction condi-
tions predict the present cross-coupling type methodology
as a valuable synthetic protocol for the synthesis of added
value organic compounds.
R1
O
R
Cat3
(5 mol%)
O
Ph
O
R2
1
+
R
Ph
R2
R2
K2CO3
1,4-dioxane
90 °C, 5 h
R1
3
(E)-3ba’, (E)-3ea’, (E)-3ga’
PhB(OH)2
2a
Entry
R/R1/R2 (1)
Yield of 3 (%)b
E/Zc
4:1d
1
2
3
4
5
6
7
8
H/H/OBn (1b)
82 (3ba)
89 (3ca)
81 (3da)
90 (3ea)
84 (3fa)
n-Pr/H/OBn (1c)
6:1
9:1
n-Pr/H/3,5-Me2C6H3O (1d)
H/H/3,5-Me2C6H3O (1e)
n-C8H17/H/OEt (1f)
H/H/Ph (1g)
2:1e
6:1
1H NMR spectra were recorded on Varian 400 (400 MHz) spectrome-
ter. Chemical shifts are reported in ppm from TMS with the solvent
resonance as the internal standard (CDCl3: 7.27 ppm). Data are re-
ported as follows: chemical shift, multiplicity (standard abbrevia-
tions), coupling constants (Hz). 13C NMR spectra were recorded on a
Varian 400 (100 MHz) spectrometer with complete proton decou-
pling. Chemical shifts are reported in ppm from TMS with the solvent
as the internal standard (CDCl3: 77.0 ppm). GC-MS spectra were taken
by EI ionization at 70 eV on a Hewlett-Packard 5971 with GC injec-
tion. LC-electrospray ionization mass spectra were obtained with
Agilent Technologies MSD1100 single-quadrupole mass spectrometer.
Chromatographic purification was done with 240–400 mesh silica
gel. Elemental analyses were carried out by using a EACE 1110 CHNOS
analyzer. All anhydrous solvents were supplied by Sigma Aldrich in
Sureseal® bottles and used without any further purification. Com-
mercially available chemicals were purchased from Sigma Aldrich,
and used without any further purification. IR spectra were recorded
on a Bruker-alpha spectrophotometer. Melting points were measured
using open glass capillaries in a Bibby Stuart Scientific Melting Point
Apparatus SMP 3 and are calibrated by comparison with literature
values (Aldrich). Allenoate 1a was obtained following a known proce-
dure.
84 (3ga′)
traces (3ha)
85 (3ia)
>95:5f
–
n-Pr/Me/OEt (1h)
Ph/H/OEt (1i)
1:1
a All the reactions were carried out under N2 in reagent grade 1,4-dioxane.
b Isolated yield after flash chromatography.
c Determined by 1H NMR analysis and/or GC-MS on the reaction crude.
d The β,γ-/α,β-conjugated compound is represented, reaction at 40 °C.
e The β,γ-/α,β-conjugated compound is represented.
f The (E)-α,β-unsaturated isomer was obtained exclusively (reaction at
40 °C).
As a speculative mechanism, the reaction process de-
picted in the Scheme 4 is presented. Initially, base-assisted
transmetalation between the arylboronic acid 2 and the
preformed [Ni(II)] complex could lead to the organonickel
intermediate [LNiArCl] that engages the allenoate 1 in a co-
ordinating event (A). Transfer of the aryl group to the cen-
tral carbon of the allenyl unit, anti with respect to R′, would
result in the formal nickel-enolate B. A second molecule of
ArB(OH)2 finally delivers the compound 3 by selective pro-
to-denickelation. The possible allene → alkyne isomeriza-
Allenoates 1b–f,h,i;14 3,5-Dimethylphenyl Buta-2,3-dienoate (1e);
Typical Procedure
A dry two-necked flask was charged with a stirring bar, 3,5-dimethyl-
phenol (1.22 g, 10 mmol), CH2Cl2 (30 mL), and pyridine (1.77 mL, 22
mmol). The mixture was cooled to 0 °C, and bromoacetyl bromide
(0.86 mL, 10 mmol) was added to the mixture slowly. The mixture
was warmed to r.t. and stirred overnight. After the completion of the
reaction (TLC monitoring), the mixture was washed with H2O (2 × 20
mL) and the organic phase was dried (Na2SO4). The solvent was re-
moved and the residue was purified by flash chromatography on sili-
ca gel (c-Hex/EtOAc 10:1) to give 3,5-dimethylphenyl 2-bromoacetate
(2.1 g, 86%) as a colorless oil.
ArB(OH)2 (2)
base
O
LNiArCl
RO
transmetalation
•
LNiCl2
1
R’
[Ni(II)]
H+
proto
Ar
3
O
denickelation
coordination
Cl
O
OR
RO
1’
R’
OR
O
LNi
A dry two-neck flask was charged with PPh3 (786 mg, 3.0 mmol) and
CHCl3 (10 mL). The solution was cooled to 0 °C and the above pre-
pared 3,5-dimethylphenyl 2-bromoacetate (729 mg, 3.0 mmol) was
added. The reaction was warmed to r.t. and stirred overnight. The
mixture was washed with aq 2 N NaOH (2 × 20 mL) and the collected
organic phase was dried (Na2SO4). After removal of solvent under vac-
uum, the intermediate pure ylide was obtained as a white solid (1.20
g, 95%) and used in the next step without further purification.
Ar
R’
•
A
2
NiLCl
OR
ArB(OH)2
R’
insertion
Ar
O
2
3
B
R’
Scheme 4 Tentative mechanistic picture
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

E
Y. Liu et al.
Special Topic
Synthesis
A dry Schlenk tube was charged with a stirring bar, CH2Cl2 (6 mL), the
above prepared ylide (2.0 mmol), and Et3N (305 μL, 2.2 mmol). The
mixture was cooled to 0 °C in ice bath. A solution of acetyl chloride
(2.2 mmol) in CH2Cl2 (2 mL) was added dropwise to the reaction mix-
ture. The mixture was warmed to r.t. and stirred overnight. After the
completion of the reaction (TLC monitoring), most of solvent was re-
moved under vacuum, and Et2O (50 mL) was added to the flask, and
the mixture was stirred for 0.5 h (Caution: longer reaction time may
promote the isomerization of allenoate to the corresponding alkyl es-
ter). The mixture was filtered and the organic phase was concentrat-
ed under vacuum. The residue was purified by flash chromatography
on silica gel (c-Hex/EtOAc 20:1) to give the allenoate 1e; yield: 147
mg (78%); colorless oil; Rf = 0.65 (c-Hex/EtOAc 10:1).
MS (70 eV): m/z (%) = 244 (100).
Anal. Calcd for C14H24O2: C, 74.95; H, 8.45. Found: C, 74.77; H, 8.35.
Ethyl 2-Methylhepta-2,3-dienoate (1h)
Yield: 84 mg (50%); colorless oil; Rf = 0.65 (c-Hex/EtOAc 10:1).
1H NMR (400 MHz, CDCl3): δ = 5.47–5.38 (m, 1 H), 4.22–4.13 (m, 2 H),
2.07 (q, J = 7.0 Hz, 2 H), 1.85 (d, J = 2.9 Hz, 3 H), 1.54–1.38 (m, 2 H),
1.26 (t, J = 7.1 Hz, 3 H), 0.95 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 210.25, 168.22, 95.69, 93.67, 60.87,
30.16, 22.21, 15.37, 14.41, 13.60.
MS (70 eV): m/z (%) = 168 (100).
Anal. Calcd for C10H16O2: C, 71.39; H, 9.59. Found: C, 71.30; H, 9.71.
1H NMR (400 MHz, CDCl3): δ = 6.87 (s, 1 H), 6.75 (s, 2 H), 5.84–5.79
(m, 1 H), 5.34–5.29 (m, 2 H), 2.35–2.30 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 216.69, 164.49, 150.84, 139.39,
127.76, 119.26, 87.94, 79.81, 21.38.
Ethyl 4-Phenylbuta-2,3-dienoate (1i)
Yield: 248 mg (66%); colorless oil; Rf = 0.55 (c-Hex/EtOAc 10:1).
1H NMR (400 MHz, CDCl3): δ = 7.35–7.27 (m, 5 H), 6.62 (d, J = 6.4 Hz, 1
H), 6.02 (d, J = 6.4 Hz, 1 H), 4.28–4.19 (m, 2 H), 1.29 (t, J = 7.1 Hz, 3 H).
MS (70 eV): m/z (%) = 188 (100).
Anal. Calcd for C12H12O2: C, 76.57; H, 6.43. Found: C, 76.41; H, 6.61.
13C NMR (100 MHz, CDCl3): δ = 214.75, 165.24, 131.33, 128.99,
128.24, 127.65, 98.81, 92.09, 61.28, 14.39.
Benzyl Buta-2,3-dienoate (1b)
MS (70 eV): m/z (%) = 188 (100).
Yield: 296 mg (85%); colorless oil; Rf = 0.65 (c-Hex/EtOAc 10:1).
Anal. Calcd for C12H12O2: C, 76.57; H, 6.43. Found: C, 76.41; H, 6.38.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.32 (m, 5 H), 5.69 (t, J = 6.5 Hz,
1 H), 5.24 (d, J = 6.5 Hz, 2 H), 5.20 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 216.14, 165.66, 136.02, 128.67,
1-Phenylbuta-2,3-dien-1-one (1g)
A dry two-necked flask was charged with DMF/Et2O (6 mL, 1:1),
benzaldehyde (530 mg, 5 mmol), and Zn dust (630 mg, 10 mmol). The
reaction mixture was cooled to 0 °C and propargyl bromide (1.08 mL,
10 mmol, 80% in toluene) was added dropwise. The mixture was
warmed to r.t. and stirred for 24 h when TLC showed the completion
of the reaction. The mixture was filtered, the organic phase concen-
trated under vacuum, and the residue was purified by flash chroma-
tography on silica gel (c-Hex/EtOAc 5:1) to give propargyl 1-phenyl-
but-3-yn-1-ol (613 mg, 84%) as a colorless oil.
128.34, 128.26, 88.00, 79.54, 66.76.
MS (70 eV): m/z (%) = 174 (100).
Anal. Calcd for C11H10O2: C, 75.84; H, 5.79. Found: C, 75.71; H, 5.61.
Benzyl Hepta-2,3-dienoate (1c)
Yield: 302 mg (70%); colorless oil; Rf = 0.70 (c-Hex/EtOAc 10:1).
1H NMR (400 MHz, CDCl3): δ = 7.37 (m, J = 4.3 Hz, 4 H), 7.35–7.31 (m,
1 H), 5.63 (m, J = 7.5, 3.9 Hz, 2 H), 5.18 (d, J = 4.7 Hz, 2 H), 2.15–2.09
(m, 2 H), 1.55–1.44 (m, 2 H), 0.94 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 212.84, 166.23, 136.22, 128.62,
128.24, 128.21, 95.47, 88.11, 66.55, 29.64, 22.14, 13.62.
A dry single-necked flask was charged with CH2Cl2 (6 mL), propargyl
1-phenylbut-3-yn-1-ol (292 mg, 2.0 mmol), followed by 2-iodoxy-
benzoic acid (IBX; 1.68 g, 6.0 mmol). The reaction mixture was stirred
for 20 h at r.t. The mixture was filtered and the organic phase concen-
trated under vacuum. The residue was purified by flash chromatogra-
phy on silica gel (c-Hex/EtOAc 20:1) to give 1g, yield: 225 mg (78%);
colorless oil; Rf = 0.80 (c-Hex/EtOAc 10:1)
MS (70 eV): m/z (%) = 216 (100).
Anal. Calcd for C14H16O2: C, 77.75; H, 7.46. Found: C, 77.61; H, 7.31.
1H NMR (400 MHz, CDCl3): δ = 7.93–7.86 (m, 2 H), 7.58–7.53 (m, 1 H),
7.48–7.42 (m, 2 H), 6.44 (t, J = 6.5 Hz, 1 H), 5.28–5.23 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 217.20, 191.07, 137.59, 132.90,
3,5-Dimethylphenyl Hepta-2,3-dienoate (1d)
Yield: 336 mg (73%); colorless oil; Rf = 0.70 (c-Hex/EtOAc 10:1).
1H NMR (400 MHz, CDCl3): δ = 6.86 (s, 1 H), 6.75 (s, 2 H), 5.75 (m, 1 H),
5.70 (m, 1 H), 2.32 (s, 6 H), 2.17 (ddd, J = 14.4, 7.1, 3.0 Hz, 2 H), 1.57–
1.51 (m, 2 H), 1.00 (t, J = 7.4 Hz, 3 H).
128.79, 128.48, 93.37, 79.33.
MS (70 eV): m/z (%) = 144 (100).
13C NMR (100 MHz, CDCl3): δ = 213.43, 165.02, 150.96, 139.28,
Anal. Calcd for C10H8O: C, 83.31; H, 5.59. Found: C, 83.18; H, 5.40.
127.57, 119.28, 119.06, 95.66, 87.98, 29.61, 22.12, 21.34, 13.62.
Nickel-Catalyzed Coupling of Boronic Acids with Allenoates; Ethyl
MS (70 eV): m/z (%) = 230 (100).
(E)-3-Phenylhept-3-enoate (3aa); Typical Procedure
Anal. Calcd for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.09; H, 7.71.
A flame-dried Schlenk tube, filled with N2, was charged sequentially
with reagent grade 1,4-dioxane (1 mL), [4,4′-dibromobpy-NiCl2] (4.0
mg, 5 mol%), phenylboronic acid (2a; 37 mg, 0.3 mmol, 1.5 equiv), al-
lenoate 1a (30.8 mg, 0.2 mmol, 1.0 equiv), and K2CO3 (55.2 mg, 0.4
mmol, 2.0 equiv). The reaction mixture was then heated at 90 °C for 5
h (complete consumption of the allenoate was monitired by TLC).
Then the solvent was removed under vacuum and the residue puri-
fied via flash chromatography.
Ethyl Dodeca-2,3-dienoate (1f)
Yield: 181 mg (81%); colorless oil; Rf = 0.75 (c-Hex/EtOAc 10:1).
1H NMR (400 MHz, CDCl3): δ = 6.00–5.90 (m, 2 H), 4.55 (m, 2 H), 2.48
(qd, J = 7.1, 3.2 Hz, 2 H), 1.80 (dd, J = 14.8, 7.4 Hz, 2 H), 1.68 (m, 2 H),
1.63 (m, 11 H), 1.24 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 212.44, 166.45, 95.53, 88.37, 60.85,
32.00, 29.47, 29.38, 29.08, 28.88, 27.65, 22.80, 14.40, 14.23.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

F
Y. Liu et al.
Special Topic
Synthesis
Ethyl (E)-3-Phenylhept-3-enoate (3aa)
Ethyl (E)-3-(4-Bromophenyl)hept-3-enoate (3ad)
Yield: 44 mg (95%); colorless oil; Rf = 0.45 (c-Hex/EtOAc 100:1 →
30:1); E/Z = 11:1.
Yield: 56 mg (90%); colorless oil; Rf = 0.75 (c-Hex/EtOAc 10:1); E/Z =
4:1.
IR (neat): 2961, 2934, 2874, 1960, 1713, 1463, 1249, 1154, 1039, 796
1H NMR (400 MHz, CDCl3): δ = 7.43–7.39 (m, 2 H), 7.26–7.22 (m, 2 H),
5.93 (t, J = 7.3 Hz, 1 H), 4.09 (q, J = 7.1 Hz, 2 H), 3.47 (s, 2 H), 2.19 (q, J =
7.4 Hz, 2 H), 1.55–1.45 (m, 2 H), 1.18 (t, J = 7.1 Hz, 3 H), 0.96 (t, J = 7.4
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.33, 141.53, 133.40, 131.45,
131.36, 130.41, 127.81, 120.84, 60.90, 44.57, 36.07, 31.22, 22.67,
14.26, 14.02.
cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.37 (m, 2 H), 7.33–7.28 (m, 2 H),
7.23–7,21 (m, 1 H), 5.95 (t, J = 7.3 Hz, 1 H), 4.10 (q, J = 7.1 Hz, 1 H),
3.52 (s, 1 H), 2.26–2.17 (m, 1 H), 1.57–1.45 (m, 1 H), 1.19 (t, J = 7.1 Hz,
2 H), 0.97 (t, J = 7.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 171.61, 142.57, 132.76, 132.60,
128.38, 126.91, 126.09, 60.79, 36.22, 31.21, 22.75, 14.24, 14.04.
MS (70 eV): m/z (%) = 310 (100).
MS (70 eV): m/z (%) = 232 (100).
Anal. Calcd for C15H19BrO2: C, 57.89; H, 6.15. Found: C, 57.55; H, 6.00.
Anal. Calcd for C15H20O2: C, 77.55; H, 8.68. Found: C, 77.51; H, 8.45.
(Z)-3ad
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.63 (t, J = 7.4 Hz, 1
H), 4.08–4.02 (q, J = 7.1 Hz, 2 H), 3.31 (s, 2 H), 1.95 (q, J = 7.4 Hz, 2 H),
1.36 (dq, J = 14.6, 7.4 Hz, 2 H), 1.17–1.13 (m, 3 H), 0.84 (t, J = 7.4 Hz, 3
H).
Ethyl (E)-3-(4-Nitrophenyl)hept-3-enoate (3ab)
Yield: 47 mg (85%); colorless oil; Rf = 0.45 (c-Hex/EtOAc 20:1); E/Z =
9:1.
IR (neat): 2960, 2932, 2872, 1731, 1526, 1347, 1154, 1157, 736, 683
cm–1
.
Ethyl (E)-3-(4-Acetylphenyl)hept-3-enoate (3ae)
1H NMR (400 MHz, CDCl3): δ = 8.18–8.14 (m, 2 H), 7.54–7.50 (m, 2 H),
6.11 (t, J = 7.3 Hz, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.53 (s, 2 H), 2.25 (q, J =
7.4 Hz, 2 H), 1.58–1.48 (m, 2 H), 1.20 (t, J = 7.1 Hz, 3 H), 0.98 (t, J = 7.4
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 170.92, 149.10, 136.69, 131.45,
129.65, 126.76, 123.79, 61.12, 35.86, 31.38, 22.53, 14.25, 14.01.
Yield: 45 mg (83%); colorless oil; Rf = 0.35 (c-Hex/EtOAc 10:1);
E/Z =11:1.
1H NMR (400 MHz, CDCl3): δ = 7.91–7.87 (m, 2 H), 7.48–7.43 (m, 2 H),
6.06 (t, J = 7.3 Hz, 1 H), 4.09 (q, J = 7.1 Hz, 2 H), 3.52 (s, 2 H), 2.58 (s, 3
H), 2.23 (q, J = 7.4 Hz, 2 H), 1.57–1.46 (m, 2 H), 1.18 (t, J = 7.1 Hz, 3 H),
0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 197.73, 171.21, 147.22, 135.63,
135.01, 132.04, 128.61, 126.14, 60.94, 35.90, 31.30, 26.68, 22.62,
14.24, 14.01.
MS (70 eV): m/z (%) = 277 (100).
Anal. Calcd for C15H19NO4: C, 64.97; H, 6.91. Found: C, 64.81; H, 6.77.
(Z)-3ab
MS (70 eV): m/z (%) = 274 (100).
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.74 (t, J = 7.5 Hz, 1
H), 3.37 (d, J = 0.8 Hz, 2 H), 1.96 (dd, J = 14.8, 7.4 Hz, 2 H), 1.15 (t, J =
7.1 Hz, 3 H), 0.85 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 146.74, 134.68,
123.55.
Anal. Calcd for C17H22O3: C, 74.42; H, 8.08. Found: C, 74.25; H, 7.97.
(Z)-3ae
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.68 (t, J = 7.4 Hz, 1
H), 4.07–4.00 (m, 2 H), 3.35 (s, 2 H), 2.59 (s, 3 H), 1.96 (dd, J = 14.8, 7.4
Hz, 2 H), 1.37 (dd, J = 14.8, 7.4 Hz, 2 H), 1.14 (t, J = 7.1 Hz, 3 H), 0.84 (t,
J = 7.4 Hz, 3 H).
Ethyl (E)-3-(4-Fluorophenyl)hept-3-enoate (3ac)
Yield: 42 mg (83%); colorless oil; Rf = 0.70 (c-Hex/EtOAc 10:1), E/Z =
4:1.
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 128.92, 128.33.
1H NMR (400 MHz, CDCl3): δ = 7.33 (m, 2 H), 6.99 (m, 2 H), 5.87 (t, J =
7.3 Hz, 1 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.48 (s, 2 H), 2.19 (q, J = 7.3 Hz, 2
H), 1.51 (dt, J = 14.8, 7.4 Hz, 2 H), 1.18 (t, J = 7.1 Hz, 3 H), 0.97 (t, J = 7.4
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.42, 162.05 (d, J = 244.0 Hz),
138.72 (d, J = 3.0 Hz), 132.72, 131.80, 127.70 (d, J = 8.0 Hz), 115.12 (d,
J = 22.0 Hz), 60.83, 36.35, 31.17, 22.73, 14.23, 14.00.
Methyl (E)-4-(1-Ethoxy-1-oxohept-3-en-3-yl)benzoate (3af)
Yield: 53 mg (92%); colorless oil; Rf = 0.45 (c-Hex/EtOAc 10:1);
E/Z =10:1.
1H NMR (400 MHz, CDCl3): δ = 7.99–7.95 (m, 2 H), 7.43 (d, J = 8.6 Hz, 2
H), 6.05 (t, J = 7.3 Hz, 1 H), 4.09 (q, J = 7.1 Hz, 2 H), 3.90 (s, 3 H), 3.52 (s,
2 H), 2.22 (q, J = 7.4 Hz, 2 H), 1.57–1.46 (m, 2 H), 1.17 (t, J = 7.1 Hz, 3
H), 1.13 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.23, 167.08, 147.06, 134.79,
132.10, 129.77, 128.53, 125.97, 60.91, 52.11, 35.95, 31.28, 22.62,
14.22, 14.01.
MS (70 eV): m/z (%) = 250 (100).
Anal. Calcd for C15H19FO2: C, 71.98; H, 7.65. Found: C, 71.69; H, 7.40.
(Z)-3ac
MS (70 eV): m/z (%) = 290 (100).
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.62 (t, J = 7.5 Hz, 1
H), 4.05 (q, J = 7.1 Hz, 2 H), 3.31 (s, 2 H), 1.95 (q, J = 7.4 Hz, 2 H), 1.36
(dt, J = 10.6, 5.4 Hz, 2 H), 1.17–1.13 (m, 3 H), 0.84 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 171.66, 163.06,
132.25 (d, J = 9.0 Hz), 130.24 (d, J = 8.0 Hz), 115.16, 114.95.
Anal. Calcd for C17H22O4: C, 70.32; H, 7.64. Found: C, 70.21; H, 7.51.
(Z)-3af
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.67 (t, J = 7.4 Hz, 1
H), 4.07–4.00 (m, 2 H), 3.90 (s, 3 H), 3.34 (s, 1 H), 1.95 (dd, J = 14.8, 7.4
Hz, 2 H), 1.36 (dd, J = 14.7, 7.4 Hz, 2 H), 0.83 (t, J = 7.4 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

G
Y. Liu et al.
Special Topic
Synthesis
Ethyl (E)-3-(4-Butoxyphenyl)hept-3-enoate (3ag)
(Z)-3ai
Yield: 54 mg (89%); colorless oil; Rf = 0.70 (c-Hex/EtOAc 10:1); E/Z =
9:1.
1H NMR (400 MHz, CDCl3): δ = 7.30 (d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.8
Hz, 2 H), 5.86 (t, J = 7.3 Hz, 1 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.95 (t, J = 6.5
Hz, 2 H), 3.48 (s, 2 H), 2.19 (q, J = 7.3 Hz, 2 H), 1.76 (m, 2 H), 1.56–1.42
(m, 4 H), 1.19 (t, J = 7.1 Hz, 3 H), 0.99–0.95 (m, 6 H).
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.59 (t, J = 7.4 Hz, 1
H), 4.08–4.03 (q, J = 7.1 Hz, 2 H), 3.32 (s, 2 H), 1.98 (dd, J = 14.7, 7.4 Hz,
2 H), 1.39–1.32 (m, 2 H), 1.15 (t, J = 7.1 Hz, 3 H), 0.84 (t, J = 7.4 Hz, 3
H).
Ethyl (E)-3-(3-Methoxyphenyl)hept-3-enoate (3aj)
13C NMR (100 MHz, CDCl3): δ = 171.70, 158.32, 134.95, 132.06,
131.05, 127.11, 114.36, 67.82, 60.73, 36.29, 31.49, 31.18, 22.85, 19.39,
14.26, 14.03, 13.98.
Yield: 44 mg (83%); colorless oil; Rf = 0.65 (c-Hex/EtOAc 10:1); E/Z =
11:1.
IR (neat): 2958, 2932, 2871, 2835, 1731, 1598, 1149, 1034, 778, 695
cm–1
.
MS (70 eV): m/z (%) = 304 (100).
1H NMR (400 MHz, CDCl3): δ = 7.22 (t, J = 7.9 Hz, 1 H), 6.99–6.95 (m, 1
H), 6.95–6.92 (m, 1 H), 6.78 (ddd, J = 8.1, 2.5, 0.7 Hz, 1 H), 5.96 (t, J =
7.3 Hz, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.81 (s, 3 H), 3.50 (s, 2 H), 2.20 (q,
J = 7.3 Hz, 2 H), 1.56–1.45 (m, 2 H), 1.19 (t, J = 7.1 Hz, 3 H), 0.97 (t, J =
7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.54, 159.69, 144.19, 132.92,
132.55, 129.31, 118.68, 112.33, 112.05, 60.79, 55.33, 36.32, 31.19,
22.73, 14.26, 14.02.
Anal. Calcd for C19H28O3: C, 74.96; H, 9.27. Found: C, 74.77; H, 9.15.
(Z)-3ag
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.60–5.54 (m, 1 H),
4.05 (dd, J = 14.3, 7.1 Hz, 2 H), 3.31 (s, 2 H), 2.00 (dd, J = 14.7, 7.3 Hz, 2
H), 0.85 (t, J = 7.4 Hz, 3 H).
Ethyl (E)-3-(p-Tolyl)hept-3-enoate (3ah)
MS (70 eV): m/z (%) = 262 (100).
Yield: 44 mg (89%); colorless oil; Rf = 0.70 (c-Hex/EtOAc 10:1); E/Z =
Anal. Calcd for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.02; H, 8.21.
7:1.
1H NMR (400 MHz, CDCl3): δ = 7.27 (t, J = 5.5 Hz, 2 H), 7.11 (d, J = 8.0
Hz, 2 H), 5.92 (t, J = 7.3 Hz, 1 H), 4.10 (q, J = 7.1 Hz, 2 H), 3.50 (s, 2 H),
3.32 (s, 2 H), 2.33 (s, 3 H), 2.20 (q, J = 7.3 Hz, 2 H), 1.55–1.45 (m, 2 H),
1.19 (t, J = 7.1 Hz, 3 H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.65, 139.72, 136.56, 132.44,
131.92, 129.07, 125.96, 60.74, 36.23, 31.18, 22.80, 21.15, 14.26, 14.03.
(Z)-3aj
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.60 (t, J = 7.3 Hz, 1
H), 4.06 (dd, J = 14.3, 7.2 Hz, 2 H), 3.80 (s, 3 H), 3.32 (d, J = 0.7 Hz, 2 H),
2.00 (dd, J = 14.7, 7.4 Hz, 2 H), 1.37 (dt, J = 14.0, 7.1 Hz, 2 H), 1.16 (t, J =
7.1 Hz, 3 H), 0.86 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 132.31, 129.14,
121.09, 114.34.
MS (70 eV): m/z (%) = 246 (100).
Anal. Calcd for C16H22O2: C, 78.01; H, 9.00. Found: C, 77.87; H, 8.45.
Methyl (E)-3-(1-Ethoxy-1-oxohept-3-en-3-yl)benzoate (3ak)
(Z)-3ah
Yield: 54 mg (93%); colorless oil; Rf = 0.70 (c-Hex/EtOAc 10:1); E/Z =
10:1.
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.59 (t, J = 7.3 Hz, 1
H), 4.08–4.03 (m, 2 H), 3.32 (s, 2 H), 2.34 (s, 2 H), 1.99 (dd, J = 14.7, 7.4
Hz, 2 H), 1.40–1.35 (m, 3 H), 0.85 (t, J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 1.5 Hz, 1 H), 7.89 (dd, J = 7.7,
1.1 Hz, 1 H), 7.59–7.54 (m, 1 H), 7.37 (t, J = 7.7 Hz, 1 H), 5.99 (t, J = 7.3
Hz, 1 H), 4.09 (q, J = 7.1 Hz, 2 H), 3.52 (s, 2 H), 2.22 (q, J = 7.4 Hz, 2 H),
1.57–1.45 (m, 2 H), 1.18 (t, J = 7.1 Hz, 3 H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.28, 167.26, 142.91, 133.86,
131.97, 130.66, 130.28, 128.46, 128.04, 127.31, 60.87, 52.21, 36.11,
31.23, 22.67, 14.22, 14.02.
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 128.85, 128.48.
Ethyl (E)-3-(3-Hydroxyphenyl)hept-3-enoate (3ai)
Yield: 26 mg (52%); colorless oil; Rf = 0.40 (c-Hex/EtOAc 10:1); E/Z =
11:1.
IR (neat): 3392, 2960, 2932, 2872, 1701, 1581, 1446, 1295, 1196,
MS (70 eV): m/z (%) = 290 (100).
1157, 1026, 783, 695 cm–1
.
Anal. Calcd for C17H22O4: C, 70.32; H, 7.64. Found: C, 77.45; H, 7.80.
1H NMR (400 MHz, CDCl3): δ = 7.15 (t, J = 7.9 Hz, 1 H), 6.93 (dd, J = 7.8,
0.6 Hz, 1 H), 6.87–6.84 (m, 1 H), 6.73–6.66 (m, 1 H), 5.94 (t, J = 7.3 Hz,
1 H), 5.34 (s, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.49 (s, 2 H), 2.19 (q, J = 7.3
Hz, 2 H), 1.55–1.44 (m, 2 H), 1.19 (t, J = 7.1 Hz, 3 H), 0.96 (t, J = 7.4 Hz,
3 H).
13C NMR (100 MHz, CDCl3): δ = 171.95, 155.78, 144.27, 133.01,
132.20, 129.55, 118.55, 113.99, 113.22, 60.99, 36.25, 31.17, 22.71,
14.23, 14.02.
(Z)-3ak
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.66 (t, J = 7.3 Hz, 1
H), 4.06–4.00 (m, 2 H), 3.35 (s, 2 H), 1.94 (dd, J = 14.7, 7.4 Hz, 2 H),
1.37 (td, J = 14.8, 7.4 Hz, 2 H), 1.14 (t, J = 7.2 Hz, 3 H), 0.84 (t, J = 7.4 Hz,
3 H).
Ethyl (E)-3-(3-Nitrophenyl)hept-3-enoate (3al)
MS (70 eV): m/z (%) = 248 (100).
Yield: 39 mg (70%); colorless oil; Rf = 0.40 (c-Hex/EtOAc 10:1); E/Z =
7:1.
Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C, 77.55; H, 8.12.
1H NMR (400 MHz, CDCl3): δ = 8.24 (t, J = 1.9 Hz, 1 H), 8.10–8.05 (m, 1
H), 7.70 (ddd, J = 7.8, 1.7, 1.0 Hz, 1 H), 7.47 (t, J = 8.0 Hz, 1 H), 6.05 (t, J
= 7.3 Hz, 1 H), 4.11 (q, J = 7.1 Hz, 2 H), 3.54 (s, 2 H), 2.24 (q, J = 7.4 Hz,
2 H), 1.58–1.47 (m, 2 H), 1.23–1.18 (m, 3 H), 1.15 (t, J = 7.1 Hz, 1 H),
0.98 (t, J = 7.4 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

H
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Special Topic
Synthesis
13C NMR (100 MHz, CDCl3): δ = 170.95, 148.50, 144.30, 135.52,
132.15, 131.05, 129.29, 121.73, 121.06, 61.10, 35.96, 31.27, 22.56,
14.23, 14.01.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.41 (m, 2 H), 7.40–7.37 (m, 1 H),
7.36–7.29 (m, 5 H), 7.23 (m, 2 H), 5.56 (s, 1 H), 5.25 (s, 1 H), 5.10 (s, 2
H), 3.59 (s, 2 H).
MS (70 eV): m/z (%) = 277 (100).
13C NMR (100 MHz, CDCl3): δ = 180.67, 156.47, 140.89, 135.87,
128.59, 128.54, 128.25, 128.17, 127.93, 125.96, 116.55, 66.67, 41.42.
Anal. Calcd for C15H19NO4: C, 64.97; H, 6.91. Found: C, 64.85; H, 6.75.
MS (70 eV): m/z (%) = 252 (100).
(Z)-3al
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.74 (t, J = 7.4 Hz, 1
H), 4.06 (dd, J = 15.2, 8.0 Hz, 2 H), 3.37 (s, 2 H), 1.95 (dd, J = 14.7, 7.4
Hz, 2 H), 1.39 (dd, J = 15.5, 8.1 Hz, 3 H), 0.85 (t, J = 7.4 Hz, 3 H).
(E)-3ba′
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 6.22 (d, J = 1.2 Hz,
1 H), 5.22 (s, 2 H), 2.62 (d, J = 1.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 135.05, 134.54,
123.65, 122.03.
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 171.24, 166.69,
142.21, 139.81, 136.41, 129.21, 128.69, 128.63, 128.36, 126.43,
116.87, 65.89, 27.04.
Ethyl (E)-3-[3-(Dimethylamino)phenyl]hept-3-enoate (3am)
Benzyl (E)-3-Phenylhept-3-enoate (3ca)
Yield: 18 mg (64%); colorless oil; Rf = 0.30 (c-Hex/EtOAc 10:1); E/Z =
10:1.
Yield: 52 mg (89%); colorless oil; Rf = 0.60 (c-Hex/EtOAc 10:1); E/Z =
6:1.
1H NMR (400 MHz, CDCl3): δ = 7.17 (t, J = 7.9 Hz, 1 H), 6.79–6.74 (m, 2
H), 6.64 (dd, J = 8.3, 2.4 Hz, 1 H), 5.95 (t, J = 7.3 Hz, 1 H), 4.11 (q, J = 7.1
Hz, 2 H), 3.51 (s, 2 H), 2.95 (s, 6 H), 2.21 (q, J = 7.3 Hz, 2 H), 1.56–1.46
(m, 2 H), 1.20 (t, J = 7.1 Hz, 3 H), 0.97 (t, J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.40–7.37 (m, 2 H), 7.32 (m, 5 H), 7.24
(m, 3 H), 5.97 (t, J = 7.3 Hz, 1 H), 5.10 (s, 2 H), 3.60 (s, 2 H), 2.21 (q, J =
7.4 Hz, 2 H), 1.56–1.45 (m, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.76, 150.80, 143.65, 133.34,
132.27, 128.97, 114.94, 111.58, 110.78, 60.72, 40.85, 36.59, 31.22,
22.79, 14.29, 14.05.
13C NMR (100 MHz, CDCl3): δ = 171.37, 142.46, 136.04, 132.93,
132.48, 128.57, 128.43, 128.19, 128.13, 126.97, 126.15, 66.57, 36.18,
31.23, 22.74, 14.01.
MS (70 eV): m/z (%) = 275 (100).
MS (70 eV): m/z (%) = 294 (100).
Anal. Calcd for C17H25NO2: C, 72.84; H, 8.56. Found: C, 72.32; H, 8.32.
Anal. Calcd for C20H22O2: C, 81.60; H, 7.53. Found: C, 81.38; H, 7.39.
(Z)-3am
(Z)-3ca
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 3.33 (s, 2 H), 2.94
(s, 6 H).
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 131.63, 128.79,
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.64 (t, J = 7.3 Hz, 1
H), 5.05 (s, 2 H), 3.42 (d, J = 0.7 Hz, 2 H), 1.99 (q, J = 7.4 Hz, 2 H), 1.37
(m, 2 H), 0.85 (t, J = 7.4 Hz, 3 H).
117.10, 113.04, 111.29.
3,5-Dimethylphenyl (E)-3-Phenylhept-3-enoate (3da)
Yield: 50 mg (81%); colorless oil; Rf = 0.60 (c-Hex/EtOAc 10:1); E/Z =
Ethyl (E)-3-(Naphthalen-2-yl)hept-3-enoate (3an)
9:1.
Yield: 18 mg (64%); colorless oil; Rf = 0.45 (c-Hex/EtOAc 10:1); E/Z =
4:1.
1H NMR (400 MHz, CDCl3): δ = 7.47–7.46 (m, 2 H), 7.36–7.34 (m, 2 H),
7.29–7.25 (m, 1 H), 6.83 (s, 1 H), 6.57 (s, 2 H), 6.03 (t, J = 7.3 Hz, 1 H),
3.76 (s, 2 H), 2.35–2.32 (m, 2 H), 2.29 (s, 6 H), 1.63–1.52 (m, 2 H), 1.02
(t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 170.19, 150.85, 142.47, 139.26,
133.15, 132.43, 128.49, 127.57, 127.08, 126.29, 119.10, 36.45, 31.31,
22.78, 21.29, 14.04.
1H NMR (400 MHz, CDCl3): δ = 7.82–7.77 (m, 3 H), 7.72–7.64 (m, 1 H),
7.60–7.53 (m, 1 H), 7.50–7.40 (m, 2 H), 6.11 (t, J = 7.3 Hz, 1 H), 4.11 (q,
J = 7.1 Hz, 2 H), 3.63 (s, 2 H), 2.28 (q, J = 7.3 Hz, 2 H), 1.56 (dd, J = 14.8,
7.4 Hz, 2 H), 1.19 (t, J = 7.1 Hz, 3 H), 1.05–0.97 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.60, 139.84, 133.37, 132.62,
128.69, 128.57, 128.22, 127.92, 127.61, 126.16, 125.70, 124.76,
124.59, 60.83, 36.27, 31.36, 22.81, 14.28, 14.08.
MS (70 eV): m/z (%) = 308 (100).
MS (70 eV): m/z (%) = 282 (100).
Anal. Calcd for C21H24O2: C, 81.78; H, 7.84. Found: C, 81.66; H, 7.65.
Anal. Calcd for C19H22O2: C, 80.82; H, 7.85. Found: C, 80.59; H, 7.61.
(Z)-3da
Colorless oil; Rf = 0.55 (c-Hex/EtOAc 20:1).
(Z)-3an
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.71 (t, J = 7.3 Hz, 1
H), 4.05 (q, J = 7.1 Hz, 2 H), 3.44 (s, 2 H), 2.03 (dd, J = 14.7, 7.4 Hz, 2 H),
1.40 (m, J = 14.8, 7.4 Hz, 2 H), 1.13 (t, J = 7.1 Hz, 3 H), 0.85 (t, J = 7.4 Hz,
3 H).
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.04 (t, J = 7.7 Hz, 1
H), 3.53 (s, 2 H).
3,5-Dimethylphenyl 3-Phenylbut-3-enoate (3ea)
Yield: 48 mg (90%); colorless oil; Rf = 0.55 c-Hex/EtOAc 10:1);
3ea/3ea′ = 2:1.
Benzyl 3-Phenylbut-3-enoate (3ba)
Yield: 41 mg (82%); colorless oil; Rf = 0.55 (c-Hex/EtOAc 10:1); E/Z =
4:1.
1H NMR (400 MHz, CDCl3): δ = 7.53 (m, 1 H), 7.44–7.31 (m, 3 H), 6.84
(d, J = 0.6 Hz, 1 H), 6.79 (s, 1 H), 6.57 (s, 2 H), 5.62 (s, 1 H), 5.37 (d, J =
0.8 Hz, 1 H), 3.75 (d, J = 0.9 Hz, 2 H), 2.28 (s, 6 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

I
Y. Liu et al.
Special Topic
Synthesis
13C NMR (100 MHz, CDCl3): δ = 170.05, 150.75, 142.14, 139.30,
Ethyl (E)-1-Butylidene-3-hydroxy-2,3-dihydro-1H-indene-2-car-
128.72, 128.61, 128.03, 127.66, 126.08, 119.06, 116.67, 41.58, 21.38.
boxylate (3ap)
Yield: 29 mg (63%); colorless oil; Rf = 0.36 (c-Hex/EtOAc 10:1); E/Z =
MS (70 eV): m/z (%) = 266 (100).
6:1.
(E)-3ea′
1H NMR (400 MHz, CDCl3): δ = 7.46 (dd, J = 5.0, 3.8 Hz, 1 H), 7.44–7.40
(m, 1 H), 7.30–7.26 (m, 2 H), 6.08 (td, J = 7.6, 1.8 Hz, 1 H), 5.42 (dd, J =
11.3, 7.5 Hz, 1 H), 4.23–4.20 (m, 1 H), 4.17 (dd, J = 14.3, 7.1 Hz, 2 H),
3.05 (d, J = 11.4 Hz, 1 H), 2.29–2.20 (m, 2 H), 1.53–1.43 (m, 2 H), 1.26
(t, J = 7.1 Hz, 3 H), 0.97 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.77, 144.98, 139.85, 136.54,
128.93, 128.49, 124.72, 124.56, 120.08, 74.93, 61.18, 53.03, 31.74,
22.73, 14.31, 14.06.
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 6.89 (d, J = 0.5 Hz,
1 H), 6.38 (d, J = 1.2 Hz, 1 H), 2.66 (d, J = 1.2 Hz, 3 H), 2.35 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ (diagnostic signals) = 165.47, 158.32,
150.72, 140.88, 139.92, 139.32, 129.46, 127.52, 126.52, 119.47,
116.36, 21.30, 18.33.
Ethyl (E)-3-Phenyldodec-3-enoate (3fa)
MS (70 eV): m/z (%) = 260 (100).
Yield: 51 mg (84%); colorless oil; Rf = 0.75 (c-Hex/EtOAc 10:1); E/Z =
7:1.
Anal. Calcd for C16H20O3: C, 73.82; H, 7.74. Found: C, 73.65; H, 7.55.
IR (neat): 3023, 2956, 2853, 1734, 1463, 1151, 1033, 757, 696 cm–1
.
(Z)-3ap
1H NMR (400 MHz, CDCl3): δ = 7.42–7.36 (m, 2 H), 7.31 (t, J = 7.7 Hz, 2
H), 7.24–7.20 (m, 1 H), 5.95 (t, J = 7.3 Hz, 1 H), 4.11 (q, J = 7.1 Hz, 2 H),
3.51 (s, 2 H), 2.23 (q, J = 7.3 Hz, 2 H), 1.53–1.44 (m, 2 H), 1.40–1.29 (m,
10 H), 1.21–1.15 (t, J = 7.1 Hz, 3 H), 0.90 (t, J = 6.8 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.79 (t, J = 6.6 Hz, 1
H), 5.34 (dd, J = 10.8, 7.0 Hz, 1 H), 3.97 (dd, J = 7.0, 1.2 Hz, 1 H), 3.52 (d,
J = 10.8 Hz, 1 H), 2.44 (dd, J = 14.7, 7.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 171.58, 142.62, 132.99, 132.45,
128.37, 126.89, 126.11, 60.77, 36.25, 32.03, 29.66 (2C), 29.57, 29.56,
29.43, 29.21, 22.81, 14.24.
Funding Information
MS (70 eV): m/z (%) = 302 (100).
Acknowledgment is made to University of Bologna for financial sup-
port. Y.L. thanks Chinese Scholarship Council No. 201609120008 for
Anal. Calcd for C20H20O2: C, 79.42; H, 10.00. Found: C, 79.21; H, 9.78.
funding support.
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(Z)-3fa
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 5.62 (t, J = 7.3 Hz, 1
H), 4.05 (q, J = 7.1 Hz, 2 H), 3.34 (s, 2 H), 2.00 (q, J = 7.3 Hz, 2 H).
Supporting Information
Supporting information for this article is available online at
(E)-1,3-Diphenylbut-2-en-1-one (3ga)
https://doi.org/10.1055/s-0037-1610023.
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Yield: 37 mg (84%); colorless oil; Rf = 0.75 (c-Hex/EtOAc 10:1).
1H NMR (400 MHz, CDCl3): δ = 8.03–7.97 (m, 2 H), 7.60–7.53 (m, 3 H),
7.48 (dd, J = 8.1, 6.7 Hz, 2 H), 7.43–7.40 (m, 2 H), 7.18–7.16 (m, 1 H),
2.60 (d, J = 1.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3) : δ = 192.01, 155.20, 142.95, 139.53,
132.67, 129.26, 128.75, 128.69, 128.42, 126.64, 122.28, 19.04.
References
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Anal. Calcd for C16H14O2: C, 86.45; H, 6.35. Found: C, 86.29; H, 6.22.
Ehyl (E)-3,4-Diphenylbut-3-enoate (3ia)
Yield: 45 mg (85%); colorless oil; Rf = 0.75 (c-Hex/EtOAc 10:1); E/Z =
1:1.
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1H NMR (400 MHz, CDCl3): δ = 7.52–7.49 (m, 1 H), 7.40–7.21 (m, 9 H),
7.03 (s, 1 H), 4.09 (q, J = 7.1 Hz, 2 H), 3.71 (s, 2 H), 1.15 (t, J = 7.1 Hz, 3
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140.16, 137.59, 136.83, 135.42, 134.86, 131.34, 130.49, 129.29,
128.89, 128.81, 128.65, 128.58, 128.55, 128.01, 127.70, 127.45,
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(Z)-3ia
1H NMR (400 MHz, CDCl3): δ (diagnostic signals) = 6.59 (s, 1 H), 3.50
(d, J = 0.9 Hz, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

J
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Special Topic
Synthesis
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1
(11) Structure elucidation of 2ap was carried out by H NMR analy-
sis.
(12) Attempts to extend the intramolecural annulation to a three-
component approach involving allenoate/boronic acid/aldehyde
failed.
(13) The inseparable allenoate/alkyne mixture is easily obtainable
by a prolonged reaction time in the synthesis of compound 1.
(14) Characterization of 1a gave data similar to that in the literature:
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J