Nickel-Catalyzed Reductive Allylation of Aldehydes with Allyl Acetates

Article abstract of DOI:10.1055/s-0040-1705961

Carbonyl allylation reactions constitute an important step in the formation of carbon-carbon reactions, and involve various related reactions that chiefly use allylmetal reagents. This report presents a nickel-catalyzed carbonyl allylation reaction using allyl acetate, which produces homoallyl alcohols in moderate to good yields, as an efficient methodology under reductive coupling conditions.

Full text of DOI:10.1055/s-0040-1705961

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 52, A–F
paper
A
en
H. Suzuki et al.
Paper
Synthesis
Nickel-Catalyzed Reductive Allylation of Aldehydes with Allyl
Acetates
Hiroyuki Suzuki
O
OH
Ni cat.
Zn0
Eiji Yamaguchi*
Akichika Itoh*
+
OAc
- Ni-catalyzed reductive allylation
- allyl acetate employed
Laboratory of Pharmaceutical Synthetic Chemistry,
Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi,
Gifu 501-1196, Japan
- moderate to good yield
yamaguchi@gifu-pu.ac.jp
itoha@gifu-pu.ac.jp
EALeaMikjbiacoYihCrlaaioyimktraoramrheIgytsaauop@ogchofuhgnPcifdhuiian-@rpgmguAi.afauuccte-.hpjupoutir.casacl.jSpynthetic Chemistry, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan
Received: 01.09.2020
a. Carbonyl allylation with stoichiometric allyl metal reagent
Accepted after revision: 01.10.2020
Published online: 02.12.2020
DOI: 10.1055/s-0040-1705961; Art ID: ss-2020-f0470-op
with or without
catalyst
O
OH
+
[M]
R
R
[M] = Si, B, Mg, Li, Sn…
Abstract Carbonyl allylation reactions constitute an important step
in the formation of carbon–carbon reactions, and involve various relat-
ed reactions that chiefly use allylmetal reagents. This report presents a
nickel-catalyzed carbonyl allylation reaction using allyl acetate, which
produces homoallyl alcohols in moderate to good yields, as an efficient
methodology under reductive coupling conditions.
b. Catalytic carbonyl allylation with allyl acetate
O
OH
Ru or Ir cat.
+
OAc
R
R
c. Ni-catalyzed reductive carbonyl arylation
O
OH
X
Ni cat.
Key words reductive allylation, nickel complex, allyl acetate, carbonyl
addition, transition-metal catalysis
+
R
R
d. This work: Ni-catalyzed carbonyl allylation
The formation of carbon–carbon bonds by the addition
of carbon nucleophiles on carbonyl is important for organic
synthesis.1,2 In particular, the allylation of carbonyls using
allylmetal reagents is now universally used and accepted as
one of the most reliable methods for the formation of C–C
bonds.3 This system allows the further possible conversion
of the introduced allylic moiety, due to readily transform-
able double bonds. Consequently, a remarkable method for
carbonyl allylation reactions using allylic metal reagents
has been developed (Scheme 1a).4–6 Generally, the prepara-
tion of allylmetal reagents involves the multistep combina-
tion of an allylic precursor (allyl halide, carbonate, or ace-
tate) with a stoichiometric amount of the organometallic
reagent.7 Although the catalytic allylation of carbonyls with
the in situ transformation of the allylic precursor into an al-
lylmetal reagent has also been developed to avoid the
preparation of a discrete organometallic reagent, unstable
organometallic reagents are required.8 Therefore, there has
been a demand for green and sustainable chemistry with
simple methodology without the use of a preformed
organometallic reagent.
O
OH
Ni cat.
+
OAc
R
R
Scheme 1 Carbonyl allylation chemistry
In 1989, Tsuji et al. reported ruthenium-catalyzed car-
bonyl allylation using allyl acetate.9 Their pioneering work
inspired the development of transition-metal-catalyzed
carbonyl allylation reactions without the use of stoichio-
metric amounts of organometallic reagents. Over the past
few decades, the topic of catalytic reactions has been exten-
sively studied, and many methodologies have been pro-
posed (Scheme 1b). Accordingly, Krische et al. developed
iridium-catalyzed carbonyl allylation protocols in which
allyl acetate serves as a precursor to allylmetal nucleo-
philes.10,11 Moreover, Denmark et al. independently devel-
oped a methodology for Ru-catalyzed carbonyl allylation
using allyl acetate.12 These procedures provide simple and
efficient methodologies for the allylation of aliphatic and
aromatic aldehydes.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
H. Suzuki et al.
Paper
Synthesis
Conversely, we have previously developed a reductive
carbonyl addition reaction of aldehydes with aryl halides
catalyzed by a nickel complex (Scheme 1c).13 In the original
report, the aryl halide transforms into a transient nucleop-
hile under Ni catalysis. Driven by the authors’ interest in
carbonyl addition chemistry, the research focused on the
synthesis of homoallyl alcohols by the reaction of carbonyl
with allyl acetate via Ni catalysis. The reported Ni-catalyzed
reductive coupling reactions are now one of the fundamen-
tal approaches toward coupling reactions between two
electrophiles.14 However, the proposal of a methodology for
reductive carbonyl allylation using allyl acetate catalyzed by
Ni complexes is unprecedented. Therefore, this study re-
ports the first example of a Ni-catalyzed reductive carbonyl
allylation reaction of aldehydes with allyl acetate (Scheme
1d).
First, this study examined the reaction of p-tolualde-
hyde (1a) with allyl acetate (2a) (Table 1).15 Various Ni com-
plexes bearing phosphine ligands, such as NiCl2(PPh3)2,
NiCl2(dppp)2, and NiCl2(dppb)2, Ni(ClO4)2·6H2O or
NiCl2(dme)2 with bipyridyl, and Ni complexes bearing ni-
trogen ligands, such as NiCl2(bpy), NiCl2(tBu-bpy), and
NiCl2(MeO-bpy), were screened. The expected allylation re-
action was confirmed to occur at 105 °C in a pressure tube
when aldehyde 1a was treated with allyl acetate (2a) in the
presence of diisopropylamine, benzoic acid, Zn dust, and
sodium iodide in tetrahydrofuran as solvent. The best cata-
lyst for this allylation was the Ni complex bearing bipyridyl,
namely [NiCl2(bpy)2], which provided the desired product
3aa in an isolated yield of 88% (entry 1). Inferior results
were obtained with other metal reductants, which included
Mn, Cr, and Mg (entries 2–4). These metal reductants were
inefficient in supplying the required allylation product. The
use of other amines, such as EtNiPr2 and pyridine, reduced
the reaction efficiency, providing product 3aa in 18% and
31% yield, respectively (entries 5 and 6). The suitable selec-
tion of the acid was critical for this reaction, as no product
formation occurred, with the recovery of the starting mate-
rials, when p-toluenesulfonic acid or trifluoroacetic acid
was used (entries 7 and 8). Solvent screening showed that
the allylation reaction tends to be accelerated by an ethere-
al solvent (entries 9 and 10). Further screening suggested
that both the Ni complex and the Zn reductant are critical
in this reaction (entries 11 and 12).
Table 1 Optimization of Reaction Conditions
NiCl2(bpy) (0.05 equiv)
HNiPr2 (1.25 equiv)
O
OH
BzOH (1.5 equiv)
AcO
Zn0 (3.0 equiv), NaI (0.25 equiv)
THF (1.0 mL), 105 °C, 7 h
p-Tol
H
+
p-Tol
2.0 equiv
0.3 mmol
1a
2a
3aa
Ni complex
tBu
MeO
P
Ni
P
Cl
Cl
N
N
N
N
N
Cl
Cl
Cl
Cl
Cl
Cl
Ni
Ni
Ni
N
NiCl2(PPh3)2: 4%
NiCl2(dppp) : 6%
NiCl2(dppb) : 9%
tBu
MeO
NiCl2(bpy): 94% NiCl2(tBu-bpy): 80% NiCl2(MeO-bpy): 79%
Ni(ClO4)2•6H2O + bpy: 17%
Ni(OAc)2 + bpy: 11%
Entry
Deviation from standard conditions
Yield of 3aa (%)a
1
2
standard conditions
Mn instead of Zn
94 (88)
0
0
3
Cr instead of Zn
4
Mg instead of Zn
0
5
EtNiPr2 instead of HNiPr2
pyridine instead of HNiPr2
PTSA instead of BzOH
TFA instead of BzOH
CPMEb instead of THF
toluene instead of THF
without NiCl2(bpy)
without Zn dust
18
31
0
6
7
8
0
9
63
58
0
10
11
12
0
a Yields were determined by 1H NMR analysis of the crude reaction mixture
using 1,1,2,2-tetrachloroethane as an internal standard. The number in pa-
rentheses is the isolated yield.
b CPME = cyclopentyl methyl ether.
tions to produce both fluoro- and chloro-containing prod-
ucts 3fa and 3ga in moderate yields, the bromo-substituted
benzaldehyde did not function as a good substrate under
the same conditions.16 Unfortunately, the reactions employ-
ing aldehydes bearing electron-withdrawing groups, such
as the cyano (3i) and nitro groups (3j), resulted in a signifi-
cant reduction in yield. The protocol was successful with 1-
naphthaldehyde (1k), 2-naphthaldehyde (1l), and 2-fur-
aldehyde (1m), affording 3ka, 3la, and 3ma in yields of 60%,
65%, and 62%, respectively.
Next, the investigation assessed the scope of the reac-
tion. A combination of various substituted benzaldehydes 1
with allyl acetate (2a) provided the desired allylation prod-
ucts 3 (Scheme 2). Alkyl (1a–c), unsubstituted (1d), and
alkoxy-substituted (1e) benzaldehydes transformed into
the corresponding homoallyl alcohols 3 under optimal con-
ditions in yields of 66–88%. This method was also successful
with benzaldehydes bearing m- (1b) and o-methyl (1c) sub-
stituents. Although synthetically modifiable halo-substitut-
ed benzaldehydes 1f–h were used under the optimal condi-
Then, to further assess the scope of the substrates, the
same approach was applied to aliphatic aldehydes (Scheme
2). Under optimal conditions, phenylacetaldehyde (1n) pro-
vided a good yield of the corresponding allylation product
3na. When the reaction was performed using 2-phenylpro-
panal (1o) with allyl acetate, the corresponding homoallyl
alcohol was obtained in 52% yield with 71:29 syn diastereo-
selectivity. This finding confirmed that the carbonyl addi-
tion step proceeded through a Felkin–Anh-type addition
model.17 The linear aliphatic-chain aldehyde nonanal (1p)
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–F

C
H. Suzuki et al.
Paper
Synthesis
allyl alcohols 2e and 2f, the reaction efficiency was signifi-
cantly reduced. Surprisingly, a benzyl allyl ether (2g) also
acted as an allyl source under the same reaction conditions.
When the evaluation of substrates for the allylation re-
action was completed, the use of crotyl acetate as allylation
reagent was then investigated. Control experiments were
conducted to identify an intermediate for the reaction.
When the crotylation reactions of aldehyde 1a using the
two possible crotyl donors (E)-but-2-enyl acetate (2h) and
but-3-en-2-yl acetate (2h′) were investigated, good yields of
the same product 4a were obtained with similar diastereo-
selectivities under the optimal conditions (Scheme 4). The
results indicate that the developed reaction is initiated by
the formation of a -allyl Ni complex from the in situ gener-
ated Ni0 species with allyl acetate; the resulting Ni complex
is in equilibrium with the -allyl and the -allyl complex-
es.20 Moreover, the observed diastereoselectivity of the re-
action indicated that possible intermediates such as η1-(E)-
crotyl–Ni and (Z)-crotyl–Ni were in equilibrium under the
catalytic cycle (Scheme 4a vs 4b).14g
NiCl2(bpy) (0.05 equiv)
HNiPr2 (1.25 equiv)
benzoic acid (1.5 equiv)
Zn0 (3.0 equiv), NaI (0.25 equiv)
THF (1.0 mL), 105 °C, 7 h
O
OH
+
AcO
2.0 equiv
2a
R
H
R
0.3 mmol
1
3
aromatic aldehydes
OH
Me
OH
OH
MeO
3aa p-Me 88%
3ba m-Me 68%
3ca o-Me 67%
3da 66%
3ea 85%
OH
OH
OH
X
NC
O2N
3ia 22%a
3ja trace
3fa X = F 48%
3ga X = Cl 39%
3ha X = Br <20%
OH
OH
OH
O
3la 65%a
3ma 62%
3ka 60%a
aliphatic aldehydes
OH
Crotylation of aldehyde with two types of crotyl acetates
O
OH
OH
Me
OH
standard conditions
72%, dr = 56:44
AcO
Me
+
+
Me
p-Tol
1a
H
H
p-Tol
p-Tol
7
2.0 equiv
2h
Me
4a
3na 53%a
3oa 52%a
3pa 65%
dr = 71:29
OH
O
AcO
standard conditions
62%, dr = 59:41
Scheme 2 Evaluation of aldehydes 1. a Reaction performed at 115 °C.
p-Tol
1a
Me
Me
2.0 equiv
2h'
4a
also acted as a good substrate for this allylation reaction,
providing the corresponding product 3pa in 65% yield,
without the formation of any byproducts.18
Scheme 4 Control experiments
Following the investigation into the substrate scope of
aldehydes, the study then examined the variation in allyl
sources 2 (Scheme 3).19 The use of allyl bromide (2b) in-
stead of allyl acetate provided the corresponding product
3aa, although the yield was significantly reduced to 45%.
Additionally, other allyl alcohol-bearing protecting groups
were also investigated. When allyl benzoate (2c) was used
as an allyl reagent for the reaction, 47% yield of homoallyl
alcohol 3aa was produced. With allyl phenyl ether (2d) and
tert-butyldimethylsilyl- and tert-butoxycarbonyl-protected
Based on these experiments and the previously pro-
posed reaction mechanism, a plausible reaction mechanism
(Scheme 5) is presented. The reduction of NiII with Zn0
forms Ni0, and the oxidative addition of allyl acetate forms
-allyl–NiII intermediate I and -allyl–NiII intermediate I′.
The generated I interacts with aldehyde and acid H–X to
form a reactive intermediate II. The 1,2-migratory insertion
of the allyl group into the aldehyde could form an alkoxy–NiII
R
OH
+ Zn(OBz)X
Ni0
H
OAc
O
OH
standard conditions
LG
+
p-Tol
H
p-Tol
2.0 equiv
Zn0
BzO
1a
2
3aa
H
O
NiII
π-allyl-Ni
I
OAc
NiII
OAc
OPh
Br
OBz
AcONi
σ-allyl-Ni
H
III
R
2b
45%
2c
47%
2d
32%
I’
OAc
NiII
H
II
BzOH
O
OTBS
OBoc
OBn
O
BzO
H
+
2e
2f
2g
R
H
R
27%
13%
11%
Scheme 3 Evaluation of allyl sources
Scheme 5 Plausible reaction mechanism
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–F

D
H. Suzuki et al.
Paper
Synthesis
intermediate III. Although there was evidence of trace for-
mation of the corresponding ketone side product, which is
generated by -elimination of the alkoxy–NiII intermediate,
a route for the direct release of the product from II cannot
be excluded. Finally, the catalytic cycle is completed by the
alkoxy exchange reaction of III and the reduction of NiII.21
In summary, this research developed an efficient meth-
odology for the allylation of carbonyl using allyl acetate un-
der conditions of reductive coupling. Further laboratory-
based investigations into the mechanism and the develop-
ment of an asymmetric version of the methodology are cur-
rently underway.
1H NMR (400 MHz, CDCl3):  = 7.26–7.08 (m, 4 H), 5.86–5.76 (m, 1 H),
5.19–5.13 (m, 2 H), 4.71–4.68 (m, 1 H), 2.52–2.46 (m, 2 H), 2.36 (s, 3
H), 2.03 (br s, 1 H).
13C NMR (100 MHz, CDCl3):  = 143.9, 138.2, 134.7, 128.4, 128.4,
126.6, 123.0, 118.5, 73.4, 44.0, 21.6.
1-o-Tolylbut-3-en-1-ol (3ca)24
Yield: 32.6 mg (0.20 mmol, 67%); colorless oil.
TLC (silica gel): Rf = 0.33 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.48 (d, J = 7.8 Hz, 1 H), 7.25–7.12 (m, 3
H), 5.91–5.81 (m, 1 H), 5.21–5.14 (m, 2 H), 4.98 (m, 1 H), 2.54–2.39
(m, 2 H) 2.34 (s, 3 H), 1.96 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 141.9, 134.7, 134.3, 130.3, 127.2,
126.2, 125.1, 118.3, 69.6, 42.6, 19.0.
All dry solvents were obtained from Kanto Kagaku Co., Ltd. and Wako
Pure Chemical Industries, Ltd. Other chemicals used were of reagent
grade and were obtained from Tokyo Kasei Kogyo Co., Ltd., Wako Pure
Chemical Industries, Ltd., Nacalai Tesque, and Sigma Aldrich Co., Ltd.
1H NMR, 13C NMR, and 19F NMR spectra were obtained on a JEOL AL
400 instrument at room temperature of samples in CDCl3 as a solvent
(400 MHz for 1H NMR, 100 MHz for 13C NMR). Chemical shifts () are
expressed in parts per million and are internally referenced [ = 0.00
(TMS) for 1H NMR and  = 77.0 (CDCl3) for 13C NMR]. TLC was carried
out on precoated plates of silica gel (Merck, silica gel F-254, 0.5 mm).
Subsequent to elution, plates were visualized using UV radiation (254
nm) of Handy UV lamp SLUV-4 254 nm (AS ONE Co.) Preparative TLC
(PTLC) was carried out on precoated plates of silica gel (Merck, silica
gel F-254, 0.5 mm). Flash column chromatography was performed on
Kanto silica gel 60N (Spherical, Neutral, 40–50 mm) and on a Biotage
Isolera® automated chromatography system using normal phase car-
tridges with YMC*GEL SIL (YMC Co., Ltd., 25 m).
1-Phenylbut-3-en-1ol (3da)24
Yield: 29.3 mg (0.20 mmol, 66%); colorless oil.
TLC (silica gel): Rf = 0.33 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.38–7.27 (m, 5 H), 5.86–5.78 (m, 1 H),
5.20–5.14 (m, 2 H), 4.75 (ddd, J = 8.0, 4.6, 2.9 Hz, 1 H), 2.47–2.57 (m, 2
H).
13C NMR (100 MHz, CDCl3):  = 143.8, 134.4, 128.4, 127.6, 125.8,
118.5, 73.3, 43.9.
1-(4-Methoxyphenyl)but-3-en-1-ol (3ea)24
Yield: 45.4 mg (0.26 mmol, 85%); colorless oil.
TLC (silica gel): Rf = 0.17 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.28 (d, J = 8.7 Hz, 2 H), 6.89 (d, J = 8.7
Hz, 2 H), 5.85–5.75 (m, 1 H), 5.18–5.12 (m, 2 H), 4.69 (t, J = 6.4 Hz, 1
H), 3.81 (s, 3 H), 2.50 (t, J = 6.4 Hz, 2 H), 1.97 (s 1 H).
13C NMR (100 MHz, CDCl3):  = 159.0, 136.0, 134.6 127.1, 118.3, 113.8,
72.9, 55.3, 43.8.
1-p-Tolylbut-3-en-1-ol (3aa); Typical Procedure22
A screw-capped test tube (16.5 cm × 1.5 cm) containing a mixture of
p-tolualdehyde (1a; 35.4 L, 0.3 mmol), allyl acetate (2a; 64.5 L, 0.6
mmol, 2.0 equiv), NiCl2(bpy) (4.3 mg, 0.015 mmol, 0.05 equiv), BzOH
(54.9 mg, 0.45 mmol, 1.5 equiv), NaI (11.2 mg, 0.075 mmol, 0.25
equiv), Zn0 (58.8 mg, 0.9 mmol, 3.0 equiv), and HNiPr2 (52.7 L, 0.375
mmol, 1.25 equiv) in anhydrous THF (1.0 mL) was degassed by freeze–
pump–thaw cycles (3×) and backfilled with argon. The resulting solu-
tion was stirred at 105 °C for 7 h. The solution was filtrated through a
Celite pad, which was washed with chloroform several times, and
concentrated in vacuo. The resulting mixture was purified by flash
column chromatography (silica gel, n-hexane/EtOAc, 10:1) to give
3aa.
1-(4-Fluorophenyl)but-3-en-1-ol (3fa)22
Yield: 23.9 mg (0.14 mmol, 48%); colorless oil.
TLC (silica gel): Rf = 0.17 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.34–7.31 (m, 2 H), 7.05–7.02 (m, 2 H),
5.83–5.75 (m, 1 H), 5.18–5.15 (m 2 H), 4.74–4.71 (m, 1 H), 2.54–2.43
(m, 2 H), 2.05 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 162.1 (d, J = 245.9 Hz), 139.5 (d, J = 2.4
Hz), 134.1, 127.4 (d J = 8.4 Hz), 118.7, 115.2 (d, J = 21. 4 Hz), 72.6, 44.0.
1-(4-Chlorophenyl)but-3-en-1-ol (3ga)22
Yield: 21.3 mg (0.12 mmol, 39%); colorless oil.
TLC (silica gel): Rf = 0.17 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.34–7.29 (m, 4 H), 5.84–5.73 (m, 1 H),
5.19–5.15 (m, 2 H), 4.75–4.71 (m, 2 H), 2.55–2.42 (m, 2 H), 2.05 (d, J =
3.2 Hz, 1 H).
Yield: 42.8 mg (0.26 mmol, 88%); colorless oil.
TLC (silica gel): Rf = 0.33 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.26 (d, J = 7.3 Hz, 2 H), 7.16 (d, J = 7.8
Hz, 2 H), 5.87–5.76 (m, 1 H), 5.19–5.12 (m, 2 H), 4.71 (t, J = 6.4 Hz, 3
H), 2.52–2.49 (m, 2 H), 2.35 (s, 3 H), 1.97 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 140.9, 137.2, 134.6, 129.1, 125.8,
118.3, 73.2, 43.8, 21.1.
13C NMR (100 MHz, CDCl3):  = 142.3, 134.0, 133.2, 128.5, 127.2,
118.9, 72.5, 43.9.
1-m-Tolylbut-3-en-1-ol (3ba)23
4-(1-Hydroxybut-3-enyl)benzonitrile (3ia)22
Yield: 11.4 mg (0.07 mmol, 22%); colorless oil.
TLC (silica gel): Rf = 0.10 (n-hexane/EtOAc, 10:1).
Yield: 33.1 mg (0.20 mmol, 68%); colorless oil.
TLC (silica gel): Rf = 0.33 (n-hexane/EtOAc, 10:1).
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H. Suzuki et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 7.61 (d, J = 8.0 Hz, 2 H), 7.48 (d, J = 8.0
Hz, 2 H), 5.82–5.74 (m, 1 H), 5.21–5.17 (m, 2 H), 4.83–4.80 (m, 1 H),
2.57–2.41 (m, 2 H), 2.15 (s, 1 H).
TLC (silica gel): Rf = 0.50 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 5.87–5.80 (m, 1 H), 5.16–5.11 (m, 2 H),
3.67–3.61 (m, 1 H), 2.34–2.12 (m, 2 H), 1.63 (s, 1 H), 1.50–1.27 (m, 14
H), 0.88 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 149.0, 133.3, 132.3, 126.5, 119.6,
118.8, 111.2, 72.3, 43.9.
13C NMR (100 MHz, CDCl3):  = 134.9, 118.0, 70.7, 41.9, 36.8, 31.9,
29.64, 29.55, 29.2, 25.6, 22.7, 14.1.
1-(1-Naphthyl)but-3-en-1-ol (3ka)25
2-Methyl-1-p-tolylbut-3-en-1-ol (4a)28
Yield: 49.7 mg (0.18 mmol, 66%); colorless oil.
TLC (silica gel): Rf = 0.33 (n-hexane/EtOAc, 10:1).
Yield: 38.0 mg (0.22 mmol, 72%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.08 (d, J = 8.0 Hz, 1 H), 7.88 (d J = 7.8
Hz, 1 H), 7.79 (d, J = 8.2 Hz, 1 H), 7.68 (d, J = 7.3 Hz, 1 H), 7.55–7.47 (m,
3 H), 5.99–5.89 (m, 1 H), 5.56–5.54 (m, 1 H), 5.26–5.18 (m, 2 H), 2.80–
2.57 (m, 2 H), 2.16 (br s, 1 H).
13C NMR (100 MHz, CDCl3):  = 139.4, 134.8, 133.8, 130.2, 129.0,
128.0, 126.1, 125.5, 125.4, 123.0, 122.8, 118.4, 69.9, 42.8.
TLC (silica gel): Rf = 0.50 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.24–7.14 (m, 4 H, syn and anti), 5.86–
5.71 (m, 1 H, syn and anti), 5.23–5.17 (m, 2 H, syn), 5.08–5.03 (m, 1.6
H, anti), 4.58 (m, 1 H, syn), 4.32 (m, 0.8 H, anti), 2.62–2.54 (m, 1 H,
syn), 2.52–2.44 (m, 0.8 H, anti), 2.35 (s, 3 H), 2.09 (d, J = 2.7 Hz, 0.8 H,
anti), 1.86 (d, J = 3.6 Hz, 1 H, syn), 1.01 (d, J = 6.8 Hz, 3 H, syn), 0.86 (d,
J = 6.4 Hz, 2.4 H, anti).
1-(2-Naphthyl)but-3-en-1-ol (3la)25
13C NMR (100 MHz, CDCl3):  (anti) = 140.8, 139.6, 137.3, 128.9, 126.8,
116.7, 77.7, 46.3, 21.1, 14.1;  (syn) = 140.4, 139.4, 137.0, 128.8, 126.4,
115.4, 77.2, 44.6, 21.1, 16.6.
Yield: 53.8 mg (0.20 mmol, 65%); colorless oil.
TLC (silica gel): Rf = 0.20 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.85–7.71 (m, 4 H), 7.50–7.45 (m, 3 H),
5.88–5.80 (m, 1 H), 5.21–5.15 (m 2 H), 4.93–4.90 (m, 1 H), 2.60–2.58
(m, 2 H), 2.14 (s 1 H).
Funding Information
13C NMR (100 MHz, CDCl3):  = 141.2, 134.3, 133.2, 133.0, 128.2,
127.9, 127.8, 126.1, 125.8, 124.5, 123.9, 118.6, 73.3, 43.7.
The work was financially supported by the OGAWA Science and Tech-
nology Foundation (EY) and a Ministry of Education, Culture, Sports,
Science, and Technology (MEXT) Grant-in-Aid for Young Scientists
1-(2-Furyl)but-3-en-1-ol (3ma)22
(Grant Number 18K14871) (to E.Y.).
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Yield: 25.7 mg (0.19 mmol, 62%); colorless oil.
TLC (silica gel): Rf = 0.20 (n-hexane/EtOAc, 10:1).
Supporting Information
1H NMR (400 MHz, CDCl3):  = 7.38 (m, 1 H), 6.35–6.33 (m, 1 H), 6.27–
6.26 (m, 1 H), 5.87–5.77 (m, 1 H), 5.21–5.14 (m, 2 H), 4.78–4.74 (m, 1
H), 2.65–2.61 (m, 2 H), 2.02 (m, 1 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1705961. Su
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ortingInformatio
n
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ortingInformatio
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13C NMR (100 MHz, CDCl3):  = 155,9 142.0, 133.7, 118.7, 110.1, 106.1,
66.9, 40.1.
References
1-Phenylpent-4-en-2-ol (3na)26
(1) Comprehensive Organic Synthesis, 2nd ed., Vol. 1 and 2; Knochel,
P.; Molander, G. A., Ed.; Elsevier: Oxford, 2014.
Yield: 25.8 mg (0.17 mmol, 53%); colorless oil.
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Asao, N. Chem. Rev. 1993, 93, 2207. (b) Li, C.-J. Chem. Rev. 1993,
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TLC (silica gel): Rf = 0.33 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.37–7.22 (m, 5 H), 5.95–5.83 (m, 1 H),
5.18–5.15 (m, 2 H), 3.89 (m, 1 H), 2.85–2.71 (m, 2 H), 2.36–2.20 (m, 2
H), 1.68 (d, J = 2.3 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 138.4, 134.7, 129.4, 128.5, 126.5,
118.2, 71.7, 43.3, 41.2.
2-Phenylhex-5-en-3-ol (3oa)26
52 % yield, 27.5 mg, 0.16 mmol, colorless oil.
TLC (silica gel): Rf = 0.40 (n-hexane/EtOAc, 10:1).
1H NMR (400 MHz, CDCl3):  = 7.37–7.20 (m, 5 H), 5.95–5.75 (m, 1 H),
5.16–5.08 (m, 2 H), 3.77–3.71 (m 2 H), 2.84–2.75 (m, 1 H), 2.23–1.99
(m, 2 H), 1.68 (m, 1 H) (mixture of diastereomers).
13C NMR (100 MHz, CDCl3):  = 144.5, 143.4, 135.2, 135.1, 128.6,
128.6, 128.5, 127.9, 126.8, 126.6, 118.3, 117.9, 75.1, 75.0, 45.7, 45.5,
39.6, 39.1, 17.8, 16.5 (mixture of diastereomers).
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Dodec-1-en-4-ol (3pa)27
Yield: 35.9 mg (0.20 mmol, 65%); colorless oil.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–F

F
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–F