A mild and efficient three-component synthesis of secondary and tertiary homoallylic hydrazides

Article abstract of DOI:10.1002/ejoc.201201757

A three-component reaction that involved a carbonyl compound, benzoylhydrazine, allyl bromide, and indium in the presence of readily available Zn(ClO₄)₂·6H₂O was developed for the syntheses of secondary and tertiary homoal

Full text of DOI:10.1002/ejoc.201201757

Job/Unit: O21757
/KAP1
Date: 02-04-13 16:25:19
Pages: 9
FULL PAPER
DOI: 10.1002/ejoc.201201757
A Mild and Efficient Three–Component Synthesis of Secondary and Tertiary
Homoallylic Hydrazides
Bum Seok Lee[a] and Doo Ok Jang*[a]
Keywords: Multicomponent reactions / Allylation / Aldehydes / Ketones / Chemoselectivity / Hydrazides
A three-component reaction that involved a carbonyl com-
pound, benzoylhydrazine, allyl bromide, and indium in the
presence of readily available Zn(ClO4)2·6H2O was developed
for the syntheses of secondary and tertiary homoallylic hy-
drazides. Excellent chemoselectivities and diastereoselectiv-
ies were observed. Aldehydes as well as acyclic and cyclic
ketones were well-suited to the reaction conditions and pro-
vided secondary and tertiary homoallylic hydrazides in ex-
cellent yields.
Introduction
Results and Discussion
4-Fluorobenzaldehyde (1a) was chosen as a model alde-
hyde. First, a one-pot three-component reaction that in-
volved 1a, benzoylhydrazine, allyl bromide, and indium in
MeOH at room temperature was performed (see Table 1,
Entry 1). The reaction afforded the homoallylic amine de-
rivative 2a along with homoallylic alcohol 3a. Because carb-
onyl groups are generally more reactive than hydrazones
towards allylindium reagents, the first challenge was to
achieve chemoselectivity from the allylindium species for
the C=N bond over the C=O bond.[12] To our delight, when
the low-cost, readily available Lewis acid Zn(ClO4)2·6H2O
was used, the reaction afforded 2a in 95% yield without the
accompanying homoallylic alcohol 3a within 3 h at room
temperature (see Table 1, Entry 2). The efficiencies of dif-
ferent additives were screened by treating 1a, benzoylhy-
drazine, allyl bromide, and indium with 1 mol-% of an addi-
tive in MeOH at room temperature. Additives such as
Homoallylic amines are valuable building blocks for the
syntheses of natural products and biologically active com-
pounds, as the C=C bond and amine moieties can be fur-
ther transformed into various functional groups.[1] The ad-
dition of allylmetals to C=N bonds is a general synthetic
strategy for the formation of homoallylic amines.[2–6]
Among the various reported methods for the preparation
of homoallylic amines, one-pot three-component reactions
that involve carbonyl compounds, nitrogen nucleophiles,
and allylmetal reagents are attractive.[7] Despite their wide
scope, these protocols are limited to the syntheses of sec-
ondary homoallylic amine derivatives and are not suitable
for the preparation of tertiary homoallylic amine deriva-
tives. For these compounds, a few examples of procedures
that employ allylsilanes[8] and allylboronates[9] as nucleo-
philes have been reported.
Indium-mediated reactions for the synthesis of homoall-
ylic amines are particularly interesting, as the indium metal
has low toxicity and a high tolerance to moisture and air.[10]
The one-pot addition of allylindium reagents to hydrazones,
which are derived from ketones, for the purpose of synthe-
sizing tertiary homoallylic amine derivatives has not yet
been reported.[11] Herein, we wish to report the first one-
pot three-component α-aminoallylation of carbonyl com-
pounds with benzoylhydrazine, allyl bromide, and indium
in the presence of Zn(ClO4)2·6H2O to afford protected sec-
ondary and tertiary homoallylic amines under mild reaction
conditions.
MgBr2, Sc(OTf)3 (Tf
= trifluoromethylsulfonyl), and
Yb(OTf)3 promoted the reaction to produce the homoall-
ylic amine derivative 2a exclusively in high yields (see
Table 1, Entries 3–5). With In(OTf)3, Mg(ClO4)2, and
ZnCl2, the reaction afforded 2a along with some 3a (see
Table 1, Entries 6–8). SnCl2·2H2O and TiCl3 led to mix-
tures of 2a, 3a, and 4a, which indicated that 4a was not
completely converted into 2a, even after 24 h under the re-
action conditions (see Table 1, Entries 9 and 10). A further
survey of the reaction conditions showed that polar sol-
vents such as MeOH, MeCN, and EtOAc were optimal (see
Table 1, Entries 2, 11, and 12). After prolonged reaction
times, nonpolar solvents such as toluene, chloroform, and
1,2-dichloroethane afforded 4a as the major product (see
Table 1, Entries 15–17). In terms of cost, efficiency, and re-
action times, methanol was the solvent of choice. The reac-
tions depended on the nature of the Lewis acids, which im-
plied that the In(III) species that was generated in situ was
[a] Department of Chemistry, Yonsei University,
Wonju 220-710, Republic of Korea
Fax: +82-33-760-2182
E-mail: dojang@yonsei.ac.kr
Homepage: http://web.yonsei.ac.kr/dojang
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201757.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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B. S. Lee, D. O. Jang
FULL PAPER
less effective than when Lewis acids were employed (see tron-withdrawing group at the sterically hindered ortho po-
Table 1, Entry 1 vs. 2–8).
sition also produced the corresponding protected homoall-
ylic amine derivatives in excellent yields (see Table 2, En-
tries 6 and 7). Furthermore, the reactions with aliphatic al-
dehydes provided the desired product in excellent yields (see
Table 2, Entries 13–16). These results imply that the carb-
onyl group in the substrate becomes a stronger Lewis base
by changing from an electron-poor aromatic substrate to an
electron-rich aromatic substrate. Thus, the catalyst may
bind to the aldehyde, which then increases the rate of reac-
tion with the allylindium instead of the formation of
hydrazones. The reaction of organometallic compounds
with hydrazones, which are derived from aliphatic aldehydes
with an α-hydrogen, can be complicated because of the for-
mation of enamines. Interestingly, the unsaturated aldehyde
cinnamaldehyde gave low chemoselectivity with exclusive
1,2-addition to provide the homoallylic amine derivative in
56% yield along with the homoallylic alcohol in 35% yield
(see Table 2, Entry 17).
Table 1. Screening reaction conditions for the synthesis of 2a.
Entry Catalyst
Time Solvent
[h]
%
%
%
2a[a]
3a[a]
4a[a]
1
2
3
4
5
6
7
8
none
Zn(ClO4)2·6H2O
MgBr2
Sc(OTf)3
Yb(OTf)3
In(OTf)3
Mg(ClO4)2
ZnCl2
SnCl2·2H2O
TiCl3
Zn(ClO4)2·6H2O
Zn(ClO4)2·6H2O
Zn(ClO4)2·6H2O
Zn(ClO4)2·6H2O
Zn(ClO4)2·6H2O
Zn(ClO4)2·6H2O
Zn(ClO4)2·6H2O
6
3
3
4
4
4
4
4
24
24
4
20
10
4
24
24
24
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
CH3CN
EtOAc
THF
60
95
94
93
92
89
74
73
43
32
95
94
84
54
9
35
0
0
0
0
0
0
0
0
0
0
0
0
41
49
0
0
0
Table 2. Synthesis of secondary homoallylic amine derivatives from
various aldehydes.
4
17
19
9
11
0
9
10
11
12
13
14
15
16
17
Entry 1, R
Time [h]
Product
% Yield[a]
0
1
2
3
4
5
6
7
8
1b, C6H5
4
4
4
4
6
3
3
3
4
4
4
4
4
4
4
4
6
2b
2c
95
97
56 (34)
53 (41)
7 (85)
94
96
95
94
94
95
92
95
95
95
93
56 (35)
11
39
0
5
0
1c, p-Et-C6H4
1d, p-MeO-C6H4
1e, p-HO-C6H4
1f, p-(Me)2N-C6H4
1g, o-Br-C6H4
1h, o-F-C6H4
1i, m-F-C6H4
1j, o-Cl-C6H4
1k, m-Cl-C6H4
1l, p-Cl-C6H4
1m, p-NO2-C6H4
1n, PhCH2CH2
1o, heptyl
CH2Cl2
toluene
CHCl3
(CH2Cl)2
0
2d (3b)
2e (3c)
2f (3d)
2g
83
76
83
13
11
2h
[a] Isolated yield.
2i
2j
9
With optimized reaction conditions on hand, we investi-
gated the generality and scope of the synthetic method by
using a range of aromatic and aliphatic aldehydes. The re-
sults are summarized in Table 2. A general trend was ob-
served for different aromatic and aliphatic aldehydes. Reac-
tions with benzaldehyde and p-ethylbenzaldehyde provided
the corresponding homoallylic amine derivatives in excel-
lent yields and with high chemoselectivities (see Table 2,
Entries 1 and 2). Aromatic aldehydes with strong electron-
donating groups gave the desired products in poor yields
and with poor chemoselectivities. With aromatic aldehydes
10
11
12
13
14
15
16
17
2k
2l
2m
2n
2o
1p, iPr
1q, cyclohexyl
1r, (E)-cinnamyl
2p
2q
2r (3e)
[a] Isolated yield.
Reactions of 1a with methallyl bromide, crotyl bromide,
that were substituted with –OH and –OMe groups, the reac- cinnamyl bromide, and prenyl bromide were also investi-
tion produced mixtures of the homoallylic amine derivative gated, and the results are summarized in Table 3. A selectiv-
and homoallylic alcohol in a ratio of approximately 6:4 (see ity for γ-addition and a high chemoselectivity were ob-
Table 2, Entries 3 and 4). In the case of N,NЈ-dimethylanil- served (see Table 3, Entries 1–5). An excellent selectivity for
ine, the corresponding homoallylic alcohol was obtained as anti addition was observed with cinnamyl bromide (see
the major product instead of the homoallylic amine deriva- Table 3, Entry 3). As expected, the γ-addition reaction with
tive (see Table 2, Entry 5). The reaction with aromatic alde- sterically hindered prenyl bromide did not go to comple-
hydes that were substituted with an electron-withdrawing tion, even after 48 h (see Table 3, Entry 4). Using a large
group proceeded smoothly to afford the corresponding excess amount of prenyl bromide and indium resulted in
homoallylic amine derivatives exclusively in high yields (see a shorter reaction time, and the product was produced in
Table 2, Entries 6–12). Aromatic aldehydes with an elec- excellent yield (see Table 3, Entry 5).
2
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Efficient Synthesis of Homoallylic Hydrazides
Table 3. Reaction of 1a with various allyl bromides.
forded the homoallylic alcohols 7 exclusively (see Table 4,
Entries 7–9) and none of the desired tertiary homoallylic
amine derivatives.
Amine 8a was obtained in 85% yield through the N–N
bond cleavage of compound 2a. This reaction was carried
out by treating 2a with SmI2 in MeOH at room temperature
as shown in Scheme 1.[1a]
Entry
R1
R2
R3
Time
[h]
Product
%
Yield[a]
1
H
CH3
Ph
CH3
CH3
H
H
H
CH3
CH3
CH3
H
H
H
H
4
4
6
48
6
2s
2t
93
95
92
81 (12)
94
2[b]
3[c]
4
2u
2v (4a)
2v
5[d]
Scheme 1. N–N bond cleavage of 2a.
[a] Isolated yield. [b] Diastereomeric ratio (anti/syn, 77:23) was ob-
tained by 1H NMR spectroscopic analysis.[13] [c] Diastereomeric ra-
1
tio (anti/syn, 99:1) was obtained by H NMR spectroscopic analy-
sis. [d] Employed 6 equiv. of prenyl bromide and indium.
Conclusions
Next, we extended this method to the synthesis of terti-
ary homoallylic amine derivatives by starting from ketones.
It was previously reported that the one-pot allylation of
hydrazones, which are derived from ketones with allyl-
indium reagents, was unachievable even at 60 °C.[6a] The re-
activities of ketones were examined under the present reac-
tion conditions, and the results are summarized in Table 4.
Interestingly, the one-pot three-component reaction that in-
volved 5a, benzoylhydrazine, allyl bromide, and indium in
the presence of Zn(ClO4)2·6H2O proceeded smoothly even
at room temperature to provide the corresponding tertiary
homoallylic amine derivative 6a in 94% yield (see Table 4,
Entry 1). Other acyclic ketones such as 5b and 5c also led
to the desired products 6b and 6c, respectively, in excellent
yields (see Table 4, Entries 2 and 3). An extension of this
methodology to cyclic ketones 5d, 5e, and 5f resulted in the
corresponding tertiary homoallylic amine derivatives in
high yields (see Table 4, Entries 4–6). However, the reac-
tions with aromatic ketones and α,β-unsaturated ketones af-
In summary, an efficient one-pot, three-component reac-
tion was developed for the synthesis of secondary and terti-
ary homoallylic amine derivatives by treating aldehydes and
ketones, respectively, with benzoylhydrazine, allyl bromide,
and indium in the presence of readily available Zn(ClO4)2·
6H2O. The reaction was general for aldehydes as well as
acyclic and cyclic ketones, which provided tertiary homoall-
ylic amine derivatives, whereas aromatic ketones afforded
homoallylic alcohols.
Experimental Section
General Methods: Unless otherwise specified, the chemicals were
purchased from commercial suppliers and used without further pu-
rification. Column chromatography was performed using silica gel
(230–400 mesh, Merck). TLC was performed on glass sheets pre-
coated with silica gel (Kieselgel 60 PF254, Merck). The melting
points were measured with a Fisher-Johns melting point apparatus.
The 1H and 13C NMR spectroscopic data were recorded with a
Table 4. Synthesis of tertiary homoallylic amine derivatives from
various ketones.
1
Bruker 400 NMR spectrometer that operated at 400 MHz for H
and 100 MHz for 13C nuclei. The spectra were internally referenced
to residual protio solvent signals. Chemical shifts were reported in
parts per million (ppm). IR spectra were recorded with a Perkin–
Elmer 16 PC FTIR spectrometer. Microanalyses were performed
with a CE instrument EA1110 elemental analyzer.
Typical Procedure for the One-Pot Synthesis of Homoallylic Amine
Derivatives: A solution of aldehyde or ketone (1.47 mmol), benzoyl-
hydrazine (200 mg, 1.47 mmol), allyl bromide (533 mg, 2.19 mmol),
and indium powder (506 mg, 2.19 mmol) in the presence of
Zn(ClO4)2·6H2O (6 mg, 1.47ϫ10–2 mmol) in MeOH (7 mL) was
stirred at room temperature until the reaction went to completion.
The solvent was then removed, and the residue was diluted with
CH2Cl2. The resulting solution was washed with 1 m HCl, saturated
aqueous NaHCO3 solution, and brine. The organic layer was dried
with anhydrous MgSO4 and then was evaporated under reduced
pressure. The resulting residue was purified by silica gel column
chromatography to afford the product.
Entry
5
R1, R2
Time Product
[h]
%
Yield[a]
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
5g
5h
5i
CH3CH2, CH3
CH3(CH2)6, CH3
PhCH2CH2, CH3
–(CH2)4–
–(CH2)5–
–(CH2)11–
C6H5, CH3
p-F-C6H4, CH3
(E)-cinnamyl, CH3
4
4
4
4
4
4
5
5
5
6a
6b
6c
6d
6e
6f
7a
7b
7c
94
92
90
92
95
92
96
95
94
[a] Isolated yield.
Eur. J. Org. Chem. 0000, 0–0
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B. S. Lee, D. O. Jang
NЈ-[1-(4-Fluorophenyl)but-3-enyl]benzohydrazide (2a):[6b] Colorless 1 H, =CH2), 5.20 (dd, J = 17.2 Hz, J = 1.4 Hz, 1 H, =CH2), 5.26
FULL PAPER
oil (397 mg, 95% yield); Rf = 0.7 (EtOAc/hexane, 3:7). IR (neat):
(d, J = 6.4 Hz, 1 H, NH), 5.80–5.91 (m, 1 H, –CH=), 6.73 (d, J =
8.8 Hz, 2 H, Ar), 7.31 (m, 2 H, Ar), 7.32 (d, J = 6.4 Hz, 1 H, NH),
7.38 (dd, J = 7.8 Hz, J = 7.4 Hz, 2 H, Ar), 7.47 (dd, J = 7.5 Hz, J
= 7.3 Hz, 1 H, Ar), 7.60 (d, J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.0, 150.2, 135.0, 133.1, 131.7, 129.2,
128.6, 128.5, 117.7, 112.6, 63.4, 40.6, 40.3 ppm.
1
ν = 3275, 1643, 1604, 1224 cm–1. H NMR (400 MHz, CDCl ): δ
˜
3
= 2.37–2.52 (m, 2 H, –CH2–), 4.13 (t, J = 6.8 Hz, 1 H, –CH), 5.08
(dd, J = 18.6 Hz, J = 11.2 Hz, 2 H, =CH2), 5.20 (d, J = 5.3 Hz, 1
H, NH), 5.69–5.80 (m, 1 H, –CH=), 6.99 (t, J = 8.6 Hz, 2 H, Ar),
7.30 (m, 4 H, Ar), 7.45 (dd, J = 7.6 Hz, J = 7.2 Hz, 1 H, Ar), 7.61
(d, J = 7.6 Hz, 2 H, Ar), 7.98 (d, J = 6.3 Hz, 1 H, NH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 167.5, 162.2 (JC,F = 240 Hz), 137.3,
NЈ-[1-(2-Bromophenyl)but-3-enyl]benzohydrazide (2g):[6b] White so-
lid (477 mg, 94% yield); m.p. 76–77 °C. Rf = 0.7 (EtOAc/hexane,
134.3, 132.8, 131.9, 129.4, 129.3, 128.6, 127.0, 118.1, 115.3 (JC,F
=
3:7). IR (neat): ν = 3070, 1633, 1602, 1315 cm–1. 1H NMR
˜
21 Hz), 63.2, 40.3 ppm.
(400 MHz, CDCl3): δ = 2.35–2.55 (m, 2 H, –CH2–), 4.71 (t, J =
5.9 Hz, 1 H, –CH), 5.09 (d, J = 10.2 Hz, 1 H, =CH2), 5.14 (dd, J
= 17.1 Hz, J = 1.2 Hz, 1 H, =CH2), 5.28 (dd, J = 6.4 Hz, J =
2.1 Hz, 1 H, NH), 5.81–5.92 (m, 1 H, –CH=), 7.05 (td, J = 7.8 Hz,
J = 1.6 Hz, 1 H, Ar), 7.27 (t, J = 7.7 Hz, 3 H, Ar), 7.39 (t, J =
13.8 Hz, 1 H, Ar), 7.48 (dd, J = 8.0 Hz, J = 1.1 Hz, 1 H, Ar), 7.60
(d, J = 7.1 Hz, 2 H, Ar), 7.64 (dd, J = 7.8 Hz, J = 1.6 Hz, 1 H,
Ar), 8.16 (d, J = 6.4 Hz, 1 H, NH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.4, 140.7, 134.1, 133.0, 132.8, 131.7, 128.8, 128.5,
127.7, 127.0, 124.6, 118.4, 62.1, 39.3 ppm.
NЈ-(1-Phenylbut-3-enyl)benzohydrazide (2b):[6b] White solid
(371 mg, 95% yield); m.p. 98–99 °C. Rf = 0.7 (EtOAc/hexane, 3:7).
1
IR (neat): ν = 3300, 1635, 1578, 1314 cm–1. H NMR (400 MHz,
˜
CDCl3): δ = 2.39–2.51 (m, 2 H, –CH2–), 4.13 (td, J = 3.0 Hz, J =
2.1 Hz, 1 H, –CH), 5.05 (d, J = 10.1 Hz, 1 H, =CH2), 5.10 (dd, J
= 17.1 Hz, J = 1.3 Hz, 1 H, =CH2), 5.23 (dd, J = 6.7 Hz, J =
2.3 Hz, 1 H, NH), 5.71–5.81 (m, 1 H, –CH=), 7.23–7.34 (m, 7 H,
Ar), 7.41 (td, J = 2.7 Hz, J = 1.1 Hz, 1 H, Ar), 7.58 (d, J = 7.0 Hz,
2 H, Ar), 8.07 (d, J = 6.6 Hz, 1 H, NH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.1, 141.4, 134.3, 132.7, 131.5, 128.4, 128.3, 127.6,
127.5, 126.8, 117.7, 63.7, 40.0 ppm.
NЈ-[1-(2-Fluorophenyl)but-3-enyl]benzohydrazide (2h): Colorless oil
(401 mg, 96% yield); R = 0.7 (EtOAc/hexane, 3:7). IR (neat): ν =
˜
f
NЈ-[1-(4-Ethylphenyl)but-3-enyl]benzohydrazide (2c):[6b] White solid
3282, 1634, 1603, 1229 cm–1. 1H NMR (400 MHz, CDCl3): δ =
2.53 (t, J = 7.3 Hz, 2 H, –CH2–), 4.55 (td, J = 12.4 Hz, J = 6.8 Hz,
1 H, –CH), 5.09 (d, J = 10.2 Hz, 1 H, =CH2), 5.14 (dd, J = 17.1 Hz,
J = 1.3 Hz, 1 H, =CH2), 5.26 (dd, J = 6.7 Hz, J = 2.8 Hz, 1 H,
NH), 5.78–5.88 (m, 1 H, –CH=), 7.01 (dd, J = 9.6 Hz, J = 9.0 Hz,
1 H, Ar), 7.13 (dd, J = 7.6 Hz, J = 7.2 Hz, 1 H, Ar), 7.20–7.26 (m,
1 H, Ar), 7.34 (dd, J = 7.8 Hz, J = 7.4 Hz, 2 H, Ar), 7.45 (dd, J =
7.6 Hz, J = 7.2 Hz, 1 H, Ar), 7.52 (td, J = 7.4 Hz, J = 1.5 Hz, 1
H, Ar), 7.61 (d, J = 7.5 Hz, 2 H, Ar), 7.80 (d, J = 6.6 Hz, 1 H,
(419 mg, 97% yield); m.p. 63–64 °C. Rf = 0.7 (EtOAc/hexane, 3:7).
1
IR (neat): ν = 3272, 1641 cm–1. H NMR (400 MHz, CDCl ): δ =
˜
3
1.21 (t, J = 3.0 Hz, J = 2.1 Hz, 3 H, –CH3), 2.41–2.54 (m, 2 H,
–CH2–), 2.61 (d, J = 7.6 Hz, 2 H, –CH2–), 4.11 (t, J = 7.0 Hz, 1
H, –CH), 5.06 (d, J = 10.0 Hz, 1 H, =CH2), 5.13 (dd, J = 17.1 Hz,
J = 1.2 Hz, 1 H, =CH2), 5.24 (s, 1 H, NH), 5.75–5.80 (m, 1 H,
–CH=), 7.14 (d, J = 8.0 Hz, 2 H, Ar), 7.25 (d, J = 8.0 Hz, 2 H,
Ar), 7.31 (dd, J = 7.8 Hz, J = 7.4 Hz, 2 H, Ar), 7.42 (dd, J =
7.5 Hz, J = 7.3 Hz, 1 H, Ar), 7.59 (d, J = 7.2 Hz, 2 H, Ar), 7.81
(s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.3, 143.5,
138.8, 134.8, 133.0, 131.7, 128.5, 128.0, 127.8, 127.1, 117.7, 63.7,
40.2, 28.5, 15.5 ppm.
NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.3, 161.2 (JC,F
240 Hz), 160.0, 134.2, 132.8, 131.8, 129.0, 128.9, 128.6, 128.5,
126.9, 124.3, 118.2, 115.6 (JC,F 22 Hz), 57.1, 39.0 ppm.
=
=
C17H17FN2O (284.33): calcd. C 71.81, H 6.03, N 9.85; found C
71.90, H 6.08, N 9.70.
NЈ-[1-(4-Methoxyphenyl)but-3-enyl]benzohydrazide (2d):[6b] White
solid (244 mg, 56% yield); m.p. 167–168 °C. Rf = 0.7 (EtOAc/hex-
NЈ-[1-(3-Fluorophenyl)but-3-enyl]benzohydrazide (2i): White solid
(397 mg, 95% yield); m.p. 55–56 °C. Rf = 0.7 (EtOAc/hexane, 3:7).
ane, 3:7). IR (neat): ν = 3271, 1640, 1613, 1248 cm–1. 1H NMR
˜
IR (neat): ν = 3294, 1632 cm–1. H NMR (400 MHz, CDCl ): δ =
(400 MHz, CDCl3): δ = 2.41–2.55 (m, 2 H, –CH2–), 3.78 (s, 3 H,
–CH3), 4.10 (td, J = 7.2 Hz, J = 1.8 Hz, 1 H, –CH), 5.08 (d, J =
10.2 Hz, 1 H, =CH2), 5.14 (d, J = 17.1 Hz, 1 H, =CH2), 5.22 (dd,
J = 6.8 Hz, J = 2.0 Hz, 1 H, NH), 5.77–5.83 (m, 1 H, –CH=), 6.86
(d, J = 8.8 Hz, 2 H, Ar), 7.27 (d, J = 8.8 Hz, 2 H, Ar), 7.35 (t, J
= 7.7 Hz, 2 H, Ar), 7.46 (t, J = 7.4 Hz, 1 H, Ar), 7.59 (d, J =
7.3 Hz, 2 H, Ar), 7.68 (d, J = 6.8 Hz, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.3, 159.0, 134.7, 133.5, 133.0, 132.7,
128.9, 128.5, 127.0, 117.7, 113.8, 63.3, 55.2, 40.1 ppm.
1
˜
3
2.38–2.51 (m, 2 H, –CH2–), 4.16 (t, J = 6.5 Hz, 1 H, –CH), 5.08
(d, J = 10.5 Hz, 1 H, =CH2), 5.12 (d, J = 18.9 Hz, 1 H, =CH2),
5.21 (dd, J = 6.5 Hz, J = 1.8 Hz, 1 H, NH), 5.72–5.82 (m, 1 H,
–CH=), 6.93 (td, J = 8.4 Hz, J = 2.5 Hz, 1 H, Ar), 7.12 (dd, J =
8.1 Hz, J = 7.1 Hz, 1 H, Ar), 7.25 (dd, J = 7.8 Hz, J = 5.7 Hz, 1
H, Ar), 7.33 (dd, J = 7.7 Hz, J = 7.6 Hz, 2 H, Ar), 7.44 (dd, J =
7.6 Hz, J = 7.2 Hz, 1 H, Ar), 7.61 (d, J = 7.8 Hz, 2 H, Ar), 8.03
(d, J = 6.5 Hz, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ =
167.6, 163.0 (JC,F = 240 Hz), 144.6, 144.5, 134.1, 132.7, 131.8,
130.0, 130.0, 129.9, 128.6, 127.0, 123.6, 118.2, 114.5 (JC,F = 21 Hz),
114.4 (JC,F = 21 Hz), 114.3, 63.5, 40.3 ppm. C17H17FN2O (284.33):
calcd. C 71.81, H 6.03, N 9.85; found C 71.78, H 6.11, N 9.80.
NЈ-[1-(4-Hydroxyphenyl)but-3-enyl]benzohydrazide (2e):[6b] Off-
white solid (110 mg, 53% yield); m.p. 88–90 °C. Rf = 0.7 (EtOAc/
hexane, 3:7). IR (neat): ν = 3236, 1627, 1596, 1252 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 2.41–2.54 (m, 2 H, –CH2–), 4.07 (dd, J =
7.2 Hz, J = 6.8 Hz, 1 H, –CH), 5.06 (d, J = 10.2 Hz, 1 H, =CH2),
5.12 (d, J = 17.1 Hz, 1 H, =CH2), 5.26 (br. s, 1 H, NH), 5.72–5.82
(m, 1 H, –CH=), 6.82 (d, J = 8.0 Hz, 2 H, Ar), 7.19 (d, J = 8.4 Hz,
2 H, Ar), 7.35 (dd, J = 8.0 Hz, J = 7.6 Hz, 2 H, Ar), 7.46 (t, J =
7.2 Hz, 1 H, Ar), 7.59 (d, J = 7.6 Hz, 2 H, Ar), 7.72 (br. s, 1 H,
NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.1, 155.2, 134.6,
133.7, 132.9 131.8, 129.0, 128.7, 126.8, 118.0, 115.4, 63.5, 40.4 ppm.
NЈ-[1-(2–Chlorophenyl)but-3-enyl]benzohydrazide (2j): White solid
(414 mg, 94% yield); m.p. 80–81 °C. Rf = 0.7 (EtOAc/hexane, 3:7).
1
IR (neat): ν = 3260, 1627 cm–1. H NMR (400 MHz, CDCl ): δ =
˜
3
2.37–2.55 (m, 2 H, –CH2–), 4.75 (t, J = 7.6 Hz, 1 H, –CH), 5.08
(d, J = 10.2 Hz, 1 H, =CH2), 5.13 (d, J = 17.2 Hz, 1 H, =CH2),
5.28 (dd, J = 6.5 Hz, J = 2.3 Hz, 1 H, NH), 5.79–5.90 (m, 1 H,
–CH=), 7.13 (td, J = 7.6 Hz, J = 1.2 Hz, 1 H, Ar), 7.20–7.30 (m,
4 H, Ar), 7.39 (dd, J = 7.6 Hz, J = 7.2 Hz, 1 H, Ar), 7.64 (d, J =
7.7 Hz, 1 H, Ar), 7.60 (d, J = 7.4 Hz, 2 H, Ar), 8.20 (d, J = 6.5 Hz,
1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.3, 139.2,
134.2, 134.1, 132.8, 131.7, 129.7, 128.6, 128.4, 128.2, 127.1, 126.9,
NЈ-{1-[4-(Dimethylamino)phenyl]but-3-enyl}benzohydrazide (2f):[5a]
1
Colorless oil (32 mg, 7% yield); Rf = 0.7 (EtOAc/hexane, 3:7). H
NMR (400 MHz, CDCl3): δ = 2.46–2.57 (m, 2 H, –CH2–), 2.96 (s,
6 H, –CH3), 4.07 (t, J = 7.0 Hz, 1 H, –CH), 5.12 (d, J = 10.1 Hz,
4
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Job/Unit: O21757
/KAP1
Date: 02-04-13 16:25:19
Pages: 9
Efficient Synthesis of Homoallylic Hydrazides
118.3 59.6, 39.2 ppm. C17H17ClN2O (300.79): calcd. C 67.88, H
5.70, N 9.31; found C 67.85, H 5.76, N 9.28.
0.96 (dd, J = 6.9 Hz, J = 3.9 Hz, 6 H, –CH3), 1.85–1.93 (m, 1 H,
–CH–), 2.07–2.15 (m, 1 H, –CH2–), 2.24–2.30 (m, 1 H, –CH2–),
2.86–2.89 (m, 1 H, –CH–), 4.98 (dd, J = 6.3 Hz, J = 2.5 Hz, 1 H,
NH), 5.10 (d, J = 10.1 Hz, 1 H, =CH2), 5.16 (dd, J = 17.1 Hz, J
= 1.3 Hz, 1 H, =CH2), 5.86–5.97 (m, 1 H, –CH=), 7.40 (dd, J =
7.7 Hz, J = 7.2 Hz, 2 H, Ar), 7.46–7.50 (m, 1 H, Ar), 7.75 (d, J =
7.1 Hz, 2 H, Ar), 8.02 (d, J = 6.1 Hz, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.1, 136.4, 133.0, 131.7, 128.6, 126.9,
117.0, 64.4, 33.8, 29.4, 18.7, 17.6 ppm.
NЈ-[1-(3–Chlorophenyl)but-3-enyl]benzohydrazide (2k):[6b] Off-white
solid (414 mg, 94% yield); m.p. 65–66 °C. Rf = 0.7 (EtOAc/hexane,
3:7). IR (neat): ν = 3286, 1631, 1601, 1313 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 2.39–2.52 (m, 2 H, –CH2–), 4.14 (t, J =
6.5 Hz, 1 H, –CH), 5.10 (d, J = 10.6 Hz, 1 H, =CH2), 5.14 (d, J =
18.2 Hz, 1 H, =CH2), 5.20 (d, J = 6.5 Hz, 1 H, NH), 5.73–5.83 (m,
1 H, –CH=), 7.21–7.24 (m, 3 H, Ar), 7.32–7.47 (m, 4 H, Ar), 7.60
(d, J = 7.8 Hz, 2 H, Ar), 7.82 (d, J = 6.5 Hz, 1 H, NH) ppm. 13C NЈ-(1–Cyclohexylbut-3-enyl)benzohydrazide (2q):[5a] White solid
NMR (100 MHz, CDCl3): δ = 167.6, 144.0, 134.4, 134.0, 132.7,
(372 mg, 93% yield); m.p. 115–116 °C. Rf = 0.7 (EtOAc/hexane,
131.8, 129.7, 128.6, 127.8, 127.8, 127.0, 126.2, 118.3, 63.5, 3:7). IR (neat): ν = 3301, 1626, 1546, 1311 cm–1. 1H NMR
˜
40.3 ppm.
(400 MHz, CDCl3): δ = 1.04–1.27 (m, 5 H, –CH2–), 1.48–1.55 (m,
1 H, –CH–), 1.65–1.81 (m, 5 H, –CH2–), 2.12–2.19 (m, 1 H,
–CH2–), 2.27–2.33 (m, 1 H, –CH2–), 2.82–2.86 (m, 1 H, –CH), 4.99
(br. s, 1 H, NH), 5.09 (d, J = 10.2 Hz, 1 H, =CH2), 5.13 (dd, J =
17.2 Hz, J = 1.2 Hz, 1 H, =CH2), 5.86–5.96 (m, 1 H, –CH=), 7.39
(dd, J = 7.6 Hz, J = 7.2 Hz, 2 H, Ar), 7.48 (dd, J = 7.4 Hz, J =
7.3 Hz, 1 H, Ar), 7.75 (d, J = 7.2 Hz, 2 H, Ar), 8.07 (br. s, 1 H,
NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.1, 136.6, 133.0,
131.6, 128.5, 127.0, 116.8, 64.3, 40.0, 34.6, 29.1, 28.5, 26.7,
26.6 ppm.
NЈ-[1-(4–Chlorophenyl)but-3-enyl]benzohydrazide (2l):[6b] White so-
lid (419 mg, 95% yield); m.p. 114–115 °C. Rf = 0.7 (EtOAc/hexane,
3:7). IR (neat): ν = 3269, 1643, 1313 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 2.39–2.52 (m, 2 H, –CH2–), 4.15 (dd, J = 7.2 Hz, J =
6.8 Hz, 1 H, –CH), 5.10 (d, J = 8.7 Hz, 1 H, =CH2), 5.14 (d, J =
17.8 Hz, 1 H, =CH2), 5.20 (d, J = 5.4 Hz, 1 H, NH), 5.73–5.83 (m,
1 H, –CH=), 7.29 (m, 4 H, Ar), 7.36 (dd, J = 8.0 Hz, J = 7.6 Hz,
2 H, Ar), 7.42 (dd, J = 7.6 Hz, J = 7.2 Hz, 1 H, Ar), 7.58 (d, J =
7.6 Hz, 2 H, Ar), 7.64 (d, J = 6.0 Hz, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.5, 140.2, 134.1, 133.3, 132.8, 131.9,
129.1, 128.7, 128.6, 127.0, 118.3, 63.3, 40.3 ppm.
(E)-NЈ-(1-Phenylhexa-1,5-dien-3-yl)benzohydrazide (2r):[5a] Off-
white solid (240 mg, 56% yield); m.p. 83–84 °C. Rf = 0.7 (EtOAc/
hexane, 3:7). IR (neat): ν = 3247, 1630, 1602, 1333 cm–1. 1H NMR
˜
NЈ-[1-(4-Nitrophenyl)but-3-enyl]benzohydrazide (2m):[6b] Yellow oil
(400 MHz, CDCl3): δ = 2.41 (t, J = 6.8 Hz, 2 H, –CH2–), 3.72–
3.77 (m, 1 H, –CH), 5.10 (dd, J = 6.8 Hz, J = 2.3 Hz, 1 H, NH),
5.15 (d, J = 10.2 Hz, 1 H, =CH2), 5.21 (dd, J = 17.1 Hz, J = 1.5 Hz,
1 H, =CH2), 5.85–5.95 (m, 1 H, –CH=), 6.12 (dd, J = 15.9 Hz, J
= 8.5 Hz, 1 H, –CH=), 6.56 (d, J = 15.9 Hz, 1 H, –CH=), 7.24 (dd,
J = 7.1 Hz, J = 6.9 Hz, 1 H, Ar), 7.31 (t, J = 7.4 Hz, 2 H, Ar),
7.39 (dd, J = 13.4 Hz, J = 7.5 Hz, 4 H, Ar), 7.47–7.50 (m, 1 H,
Ar), 7.67–7.72 (m, 3 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ
= 167.5, 136.7, 134.4, 133.1, 133.0 128.7, 127.7, 127.1, 126.5, 118.0,
62.6, 38.4 ppm.
(420 mg, 92% yield); R = 0.7 (EtOAc/hexane, 3:7). IR (neat): ν =
˜
f
3299, 1631, 1515, 1341 cm–1. 1H NMR (400 MHz, CDCl3): δ =
2.44–2.57 (m, 2 H, –CH2–), 4.35 (dd, J = 7.2 Hz, J = 6.4 Hz, 1
H, –CH), 5.16 (d, J = 10.1 Hz, 1 H, =CH2), 5.18 (dd, J = 10.2 Hz,
J = 1.4 Hz, 1 H, =CH2), 5.23 (d, J = 6.3 Hz, 1 H, NH), 5.77–5.87
(m, 1 H, –CH=), 7.37–7.43 (m, 3 H, Ar), 7.49 (dt, J = 7.5 Hz, J =
1.1 Hz, 1 H, Ar), 7.56–7.61 (m, 4 H, Ar), 8.20 (d, J = 8.7 Hz, 1 H,
NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.7, 149.6, 147.4,
133.3, 132.4, 132.1, 128.7, 128.6, 126.9, 123.8, 119.0, 63.4,
40.4 ppm.
NЈ-[1-(4-Fluorophenyl)-3-methylbut-3-enyl]benzohydrazide
(2s):
NЈ-(1-Phenylhex-5-en-3-yl)benzohydrazide (2n):[6b] Colorless oil
White solid (416 mg, 95% yield); m.p. 118–119 °C. Rf = 0.7
(398 mg, 92% yield); R = 0.7 (EtOAc/hexane, 3:7). IR (neat): ν =
˜
f
(EtOAc/hexane, 3:7). IR (neat): ν = 3286, 1628, 1603, 1219 cm–1.
˜
3281, 1639, 1602, 1313 cm–1. 1H NMR (400 MHz, CDCl3): δ =
1.69–1.85 (m, 2 H, –CH2–), 2.19–2.34 (m, 2 H, –CH2–), 2.64–2.76
(m, 2 H, –CH2–), 3.04–3.10 (m, 1 H, –CH), 4.91–5.08 (m, 1 H,
NH), 5.09 (d, J = 9.6 Hz, 1 H, =CH2), 5.13 (dd, J = 17.0 Hz, J =
1.3 Hz, 1 H, =CH2), 5.81–5.91 (m, 1 H, –CH=), 7.13–7.19 (m, 3
H, Ar), 7.24 (dd, J = 7.6 Hz, J = 2.4 Hz, 2 H, Ar), 7.36 (dd, J =
8.0 Hz, J = 7.2 Hz, 2 H, Ar), 7.46 (dd, J = 7.6 Hz, J = 7.2 Hz, 1
H, Ar), 7.71 (d, J = 7.2 Hz, 2 H, Ar), 8.12 (s, 1 H, NH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 167.6, 142.2, 135.3, 133.0, 131.8,
128.7, 128.5, 128.4, 127.1, 125.9, 117.6, 59.2, 37.4, 34.3, 32.0 ppm.
1H NMR (400 MHz, CDCl3): δ = 1.84 (s, 3 H, –CH3), 2.27–2.32
(m, 1 H, –CH2–), 2.44–2.50 (m, 1 H, –CH2–), 4.27–4.31 (ddd, J =
8.88 Hz, J = 5.4 Hz, J = 1.8 Hz, 1 H, –CH–), 4.88 (d, J = 6.4 Hz,
2 H, =CH2), 5.21 (dd, J = 6.8 Hz, J = 2.0 Hz, 1 H, NH), 6.99 (dd,
J = 8.8 Hz, J = 8.4 Hz, 2 H, Ar), 7.31–7.36 (m, 4 H, Ar), 7.43–
7.56 (m, 1 H, Ar), 7.57 (d, J = 7.2 Hz, 2 H, Ar), 7.70 (d, J = 6.4 Hz,
1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.5, 163.4
(JC,F = 240 Hz), 142.0, 137.9, 132.9, 131.8, 129.2, 128.6, 126.9,
115.4 (JC,F = 22 Hz), 61.0, 45.0, 22.1 ppm. C18H19FN2O (298.36):
calcd. C 72.46, H 6.42, N 9.39; found C 72.09, H 6.47, N 9.31.
NЈ-(Undec-1-en-4-yl)benzohydrazide (2o):[6b] Colorless oil (402 mg,
NЈ-[1-(4-Fluorophenyl)-2-methylbut-3-enyl]benzohydrazide (2t):[13] A
mixture of diastereomers (anti/syn, 77:23) and a white solid
(407 mg, 93% yield); m.p. 124–125 °C. Rf = 0.7 (EtOAc/hexane,
95% yield); R = 0.7 (EtOAc/hexane, 3:7). IR (neat): ν = 3282,
˜
f
1634, 1603, 1314 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.87 (dd,
3 H, –CH3), 1.27–1.51 (m, 12 H, –CH2–), 2.16–2.31 (m, 2 H,
–CH2–), 2.99–3.03 (m, 1 H, –CH), 5.01 (br. s, 1 H, NH), 5.10 (d,
J = 9.2 Hz, 1 H, =CH2), 5.13 (dd, J = 17.8 Hz, J = 1.7 Hz, 1 H,
=CH2), 5.83–5.94 (m, 1 H, –CH=), 7.42 (dt, J = 7.7 Hz, J = 1.6 Hz,
2 H, Ar), 7.50 (dt, J = 7.6 Hz, J = 7.6 Hz, 1 H, Ar), 7.75 (d, J =
7.0 Hz, 2 H, Ar), 8.02 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.1, 135.2, 132.7, 131.4, 128.2, 126.8, 116.8, 59.2,
37.2, 32.3, 31.5, 29.6 29.0, 25.5, 22.4, 13.8 ppm.
3:7). IR (neat): ν = 3280, 1632, 1220 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 0.76 (d, J = 6.8 Hz, 2.3 H, –CH3), 1.04 (d, J = 6.8 Hz,
0.7 H, –CH3), 2.35–2.45 (m, 0.8 H, –CH–), 2.57–2.45 (m, 0.2 H,
–CH–), 3.81 (d, J = 9.5 Hz, 0.8 H, –CH–), 4.06 (d, J = 5.6 Hz, 0.2
H, –CH–), 4.96–5.02 (m, 0.5 H, =CH2), 5.18–5.28 (m, 1.5 H,
=CH2), 5.32 (d, J = 6.0 Hz, 1 H, NH), 5.72–5.80 (m, 0.2 H,
=CH–), 5.85–5.94 (m, 0.8 H, =CH–), 6.95–7.01 (m, 2 H, Ar), 7.27–
7.34 (m, 4 H, Ar), 7.42–7.46 (m, 1 H, Ar), 7.53–7.57 (m, 2 H, Ar),
7.67 (d, J = 6.1 Hz, 0.8 H, NH), 7.82 (d, J = 5.5 Hz, 0.2 H,
NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.3, 167.2, 162.2
(JC,F = 240 Hz), 141.2, 139.7, 136.5, 132.9, 132.8, 131.7, 130.1,
NЈ-(2-Methylhex-5-en-3-yl)benzohydrazide (2p):[5a] White solid
(324 mg, 95% yield); m.p. 75–76 °C. Rf = 0.7 (EtOAc/hexane, 3:7).
1
IR (neat): ν = 3232, 1630 cm–1. H NMR (400 MHz, CDCl ): δ =
˜
3
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O21757
/KAP1
Date: 02-04-13 16:25:19
Pages: 9
B. S. Lee, D. O. Jang
FULL PAPER
130.0, 128.6, 126.7, 126.9, 116.7, 115.2 (JC,F = 22 Hz), 115.0 (JC,F
= 21 Hz), 68.1, 67.9, 44.0, 41.9, 17.7, 15.6 ppm.
7.16 (d, J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3):
δ = 150.2, 135.4, 129.3, 127.8, 116.6, 112.4, 83.4, 56.3, 42.5,
40.6 ppm.
NЈ-[1-(4-Fluorophenyl)-2-phenylbut-3-enyl]benzohydrazide (2u): Col-
orless oil (492 mg, 93% yield); Rf = 0.7 (EtOAc/hexane, 3:7). IR
(E)-1-Phenylhexa-1,5-dien-3-ol (3e):[14] Colorless oil (217 mg, 85%
(neat): ν = 3281, 1634, 1603, 1224 cm–1. 1H NMR (400 MHz,
yield); R = 0.3 (EtOAc/hexane, 3:7). IR (neat): ν = 3368, 1641,
˜
f
˜
1599 cm–1. H NMR (400 MHz, CDCl3): δ = 1.94 (s, J = 3.4 Hz,
1
CDCl3): δ = 3.57–3.59 (dd, J = 9.5 Hz, J = 8.4 Hz, 1 H, –CH–),
4.49 (dd, J = 10.0 Hz, J = 1.7 Hz, 1 H, –CH–), 4.72 (d, J = 17.0 Hz,
1 H, =CH2), 4.88 (d, J = 10.9 Hz, 1 H, =CH2), 4.92 (dd, J = 6.7 Hz,
J = 1.8 Hz, 1 H, NH), 5.70–5.79 (dt, J = 17.3 Hz, J = 2.3 Hz, 1 H,
=CH), 7.01 (t, J = 8.6 Hz, 2 H, Ar), 7.14 (d, J = 6.6 Hz, 1 H, NH),
7.27–7.36 (m, 5 H, Ar), 7.38–7.44 (m, 7 H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.2, 162.3 (JC,F = 240 Hz), 140.3, 138.2,
136.1, 136.0, 132.7, 131.8, 130.3, 130.2, 129.0, 128.6, 127.4, 126.8,
116.8, 115.3 (JC,F = 21 Hz), 67.1, 56.1 ppm. C23H21FN2O (360.43):
calcd. C 76.64, H 5.87, N 7.77; found C 76.32, H 6.01, N 7.58.
1 H, -OH), 2.34–2.47 (m, 2 H, –CH2–), 4.30 (m, 1 H, –CH–), 5.14
(d, J = 3.4 Hz, 1 H, =CH2), 5.18 (dd, J = 12.4 Hz, J = 1.4 Hz, 1
H, =CH2), 5.80–5.90 (m, 1 H, =CH), 6.23 (dd, J = 15.9 Hz, J =
6.3 Hz, 1 H, =CH), 6.59 (d, J = 15.9 Hz, 1 H, =CH), 7.23 (dd, J
= 7.2 Hz, J = 6.8 Hz, 1 H, Ar), 7.30 (dd, J = 7.6 Hz, J = 7.2 Hz,
2 H, Ar), 7.37 (d, J = 7.6 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 136.7, 134.1, 131.6, 130.4, 128.6, 127.7, 126.5, 118.5,
71.7, 42.0 ppm.
NЈ-(3-Methylhex-5-en-3-yl)benzohydrazide (6a): Colorless oil
(160 mg, 94% yield); R = 0.7 (EtOAc/hexane, 3:7). IR (neat): ν =
˜
f
NЈ-[1-(4-Fluorophenyl)-2,2-dimethylbut-3-enyl]benzohydrazide (2v):
White solid (431 mg, 94% yield); m.p. 139–140 °C. Rf = 0.7
3282, 2969, 1635, 1603 cm–1. 1H NMR (400 MHz, CDCl3): δ =
0.91 (t, J = 7.5 Hz, 3 H, –CH3), 1.04 (s, 3 H, –CH3), 1.39–1.53 (m,
2 H, –CH2–), 2.14–2.27 (m, 2 H, –CH2–), 4.87 (br. s, 1 H, –NH),
5.07 (s, 1 H, =CH2), 5.10 (d, J = 5.8 Hz, 1 H, =CH2), 5.85–5.96
(m, 1 H, =CH), 7.36 (t, J = 7.7 Hz, 2 H, Ar), 7.34 (t, J = 7.5 Hz,
1 H, Ar), 7.73 (d, J = 7.7 Hz, 2 H, Ar), 8.00 (br. s, 1 H, NH) ppm.
13C NMR (100 MHz, CDCl3): δ = 167.2, 134.6, 133.0, 131.6, 128.5,
127.0, 117.6, 59.7, 42.1, 30.1, 22.3, 8.1 ppm. C14H20N2O (232.32):
calcd. C 72.38, H 8.68, N 12.06; found C 71.86, H 8.80, N 11.84.
(EtOAc/hexane, 3:7). IR (neat): ν = 3280, 1633, 1603, 1219 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 0.96 (s, 3 H, –CH3), 1.02 (s, 3
H, –CH3), 3.98 (d, 1 H, –CH–), 5.16 (dd, J = 17.4 Hz, J = 0.9 Hz,
1 H, =CH2), 5.23 (dd, J = 10.7 Hz, J = 0.9 Hz, 1 H, =CH2), 5.23
(dd, J = 10.7 Hz, J = 0.9 Hz, 1 H, NH), 6.11 (dd, J = 17.4 Hz, J
= 10.7 Hz, 1 H, –CH=), 7.03 (t, J = 8.7 Hz, 2 H, Ar), 7.13 (d, J =
6.8 Hz, 1 H, NH), 7.32–7.38 (m, 4 H, Ar), 7.43–7.49 (m, 3 H,
Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.1, 162.2 (JC,F
=
NЈ-(4-Methylundec-1-en-4-yl)benzohydrazide (6b): Colorless oil
240 Hz), 145.5, 134.6, 132.9, 131.7, 130.9, 130.8, 128.6, 126.8, 114.6
(JC,F = 21 Hz), 113.7, 71.1, 40.6, 26.5, 19.8 ppm. C19H21FN2O
(312.39): calcd. C 73.05, H 6.78, N 8.97; found C 73.02, H 6.81, N
8.95.
(203 mg, 92% yield); R = 0.7 (EtOAc/hexane, 3:7). IR (neat): ν =
˜
f
3282, 2929, 1635, 1603 cm–1. 1H NMR (400 MHz, CDCl3): δ =
0.88 (t, J = 6.9 Hz, 3 H, –CH3), 1.08 (s, 3 H, –CH3), 1.28–1.46 (m,
12 H, –CH2–), 2.17–2.27 (m, 2 H, –CH2–), 5.00 (br. s, 1 H, –NH),
5.10 (s, 1 H, =CH2), 5.13 (d, J = 4.8 Hz, 1 H, =CH2), 5.88–5.98
(m, 1 H, =CH), 7.42 (t, J = 7.7 Hz, 2 H, Ar), 7.34–7.51 (m, 2 H,
Ar), 7.74 (d, J = 7.1 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.1, 134.7, 133.0, 131.6, 128.6, 126.9, 117.6, 59.7,
42.6, 37.9, 31.8, 30.3, 29.3, 23.7, 22.8, 22.7, 14.1 ppm. C19H30N2O
(302.46): calcd. C 75.45, H 10.00, N 9.26; found C 75.40, H 10.05,
N 9.18.
1-(4-Fluorophenyl)but-3-en-1-ol (3a):[14] Colorless oil (55 mg, 39%
yield); Rf = 0.3 (EtOAc/hexane, 3:7). 1H NMR (400 MHz, CDCl3):
δ = 2.44 (td, J = 7.0 Hz, J = 1.0 Hz, 2 H, –CH2–), 2.55 (d, J =
2.8 Hz, 1 H, OH), 4.64 (td, J = 6.4 Hz, J = 3.1 Hz, 1 H, –CH–),
5.08 (m, 1 H, =CH2), 5.11–5.12 (m, 1 H, =CH2), 5.18–5.79 (m, 1
H, =CH), 6.99 (t, J = 8.7 Hz, 2 H, Ar), 7.26 (dd, J = 8.5 Hz, J =
5.5 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 162.2
(JC,F = 240 Hz), 139.6, 134.2, 127.5, 124.4, 118.6, 115.2 (JC,F
=
NЈ-(3-Methyl-1-phenylhex-5-en-3-yl)benzohydrazide (6c): Colorless
21 Hz), 72.7, 43.9 ppm.
oil (204 mg, 90% yield); Rf = 0.7 (EtOAc/hexane, 3:7). IR (neat):
1-(4-Methoxyphenyl)but-3-en-1-ol (3b):[14] Colorless oil (89 mg,
1
ν = 3281, 2974, 1634, 1603 cm–1. H NMR (400 MHz, CDCl ): δ
˜
3
34% yield); R = 0.3 (EtOAc/hexane, 3:7). IR (neat): ν = 3401,
˜
f
= 1.16 (s, 3 H, –CH3), 1.70–1.80 (m, 2 H, –CH2–), 2.24–2.34 (m, 2
H, –CH2–), 2.72 (t, 2 H, –CH2–), 5.07 (br. s, 1 H, NH), 5.13 (s, 1
H, =CH2), 5.16 (d, J = 7.2 Hz, 1 H, =CH2), 5.90–6.00 (m, 1 H,
=CH), 7.14–7.20 (m, 3 H, Ar), 7.26 (t, J = 7.4 Hz, 2 H, Ar), 7.39
(t, J = 7.8 Hz, 2 H, Ar), 7.44–7.49 (m, 2 H, Ar), 7.69 (d, J = 7.2 Hz,
2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.3, 142.7,
134.4, 132.9, 131.7, 128.7, 128.5, 126.9, 125.8, 118.1, 59.7, 42.8,
39.8, 30.1, 23.0 ppm. C20H24N2O (308.42): calcd. C 77.89, H 7.84,
N 9.08; found C 77.84, H 7.78, N 8.93.
1612, 1604, 1513 cm–1. H NMR (400 MHz, CDCl3): δ = 2.24 (d,
1
J = 3.20 Hz, 1 H, OH), 2.47 (t, J = 6.8 Hz, 2 H, –CH2–), 3.78 (s,
3 H, OCH3), 4.64 (td, J = 6.48 Hz, J = 3.1 Hz, 1 H, –CH–), 5.09
(m, 2 H, =CH2), 5.86–5.82 (m, 1 H, =CH), 6.86 (d, J = 8.8 Hz, 2
H, Ar), 7.25 (d, J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.0, 136.2, 134.7, 127.1, 118.0, 113.8, 55.3, 43.7 ppm.
4-(1-Hydroxybut-3-enyl)phenol (3c):[15] Colorless oil (99 mg, 41%
yield); R = 0.3 (EtOAc/hexane, 3:7). IR (neat): ν = 3337, 1640,
˜
f
1614, 1515, 1236 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.41–2.52
(m, 2 H, –CH2–), 2.95 (br. s, 1 H, OH), 4.61 (dd, J = 6.8 Hz, J =
6.4 Hz, 1 H, –CH–), 5.05–5.11 (m, 2 H, =CH2), 5.66–5.76 (m, 1 H,
=CH), 6.71 (d, J = 8.4 Hz, 2 H, Ar), 7.11 (d, J = 8.4 Hz, 2 H,
Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.4, 135.1, 134.4,
127.5, 118.4, 115.5, 73.6, 43.3 ppm.
NЈ-(1-Allylcyclopentyl)benzohydrazide (6d): Off-yellow solid
(165 mg, 92% yield); m.p. 69–70 °C. Rf = 0.7 (EtOAc/hexane, 3:7).
1
IR (neat): ν = 3304, 2955, 1630, 1578 cm–1. H NMR (400 MHz,
˜
CDCl3): δ = 1.50–1.75 (m, 8 H, –CH2–), 2.31 (d, J = 7.2 Hz, 2 H, –
CH2–), 4.89 (br. s, 1 H, NH), 5.08 (s, 1 H, =CH2), 5.12 (d, J =
8.0 Hz, 1 H, =CH2), 5.93–6.01 (m, 1 H, =CH), 7.38 (t, J = 7.6 Hz,
2 H, Ar), 7.46 (t, J = 7.3 Hz, 1 H, Ar), 7.73 (d, J = 7.4 Hz, 2 H,
Ar), 8.02 (br. s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ
= 167.2, 135.5, 132.9, 131.6, 128.6, 126.9, 117.5, 69.1, 42.8, 35.1,
24.5 ppm. C15H20N2O (244.34): calcd. C 73.74, H 8.25, N 11.47;
found C 73.79, H 8.28, N 11.38.
1-[4-(Dimethylamino)phenyl]but-3-en-1-ol (3d):[16] Yellow oil
(239 mg, 85% yield); R = 0.3 (EtOAc/hexane, 3:7). IR (neat): ν =
˜
f
1615, 1521, 1348 cm–1. 1H NMR (400 MHz, CDCl3): δ = 2.36–2.43
(m, 1 H, –CH2–), 2.54–2.62 (m, 2 H, –CH2–), 2.94 (s, 6 H, OCH3),
4.07 (dd, J = 6.1 Hz, J = 1.2 Hz, 1 H, –CH–), 5.00 (dq, J = 10.2 Hz,
J = 1.0 Hz, 1 H, =CH2), 5.05 (dq, J = 17.2 Hz, J = 1.6 Hz, 1 H,
=CH2), 5.74–5.80 (m, 1 H, =CH), 6.67 (d, J = 8.2 Hz, 2 H, Ar),
NЈ-(1-Allylcyclohexyl)benzohydrazide (6e): White solid (360 mg,
95% yield); m.p. 71–72 °C. Rf = 0.7 (EtOAc/hexane, 3:7). IR (neat):
6
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Job/Unit: O21757
/KAP1
Date: 02-04-13 16:25:19
Pages: 9
Efficient Synthesis of Homoallylic Hydrazides
1
ν = 3300, 2929, 1637, 1578 cm–1. H NMR (400 MHz, CDCl ): δ
˜
3
Acknowledgments
= 1.35–1.46 (m, 8 H, –CH2–), 1.62 (d, J = 5.2 Hz, 2 H, –CH2–),
2.22 (d, J = 7.3 Hz, 2 H, –CH2–), 5.00 (br. s, 1 H, NH), 5.05 (s, 1
H, =CH2), 5.09 (d, J = 5.1 Hz, 1 H, =CH2), 5.91–6.02 (m, 1 H,
=CH), 7.30 (t, J = 7.6 Hz, 2 H, Ar), 7.40 (t, J = 7.2 Hz, 1 H, Ar),
7.72 (d, J = 8.1 Hz, 2 H, Ar), 8.27 (br. s, 1 H, NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.2, 134.7, 133.0, 131.4, 128.4, 127.0,
117.3, 58.8, 41.1, 33.4, 25.7, 21.9 ppm. C16H22N2O (258.36): calcd.
C 74.38, H 8.58, N 10.84; found C 74.28, H 8.67, N 10.95.
This work was supported by the Korean Government (Korean Re-
search Foundation Grant number KRF-2011-0021279).
[1]
For recent applications of homoallylic amines, see: a) F. Piao,
M. K. Mishra, D. O. Jang, Tetrahedron 2012, 68, 7050; b) M.
Morgen, S. Bretzke, P. Li, D. Menche, Org. Lett. 2010, 12,
4494; c) E. Airiau, N. Girard, M. Pizzeti, J. Salvadori, M. Tad-
dei, A. Mann, J. Org. Chem. 2010, 75, 8670; d) C. Denhez, J.-
L. Vasse, D. Harakat, J. Szymoniak, Tetrahedron: Asymmetry
2007, 18, 424; e) J. E. Kropf, I. C. Meigh, M. W. P. Bebbington,
S. M. Weinreb, J. Org. Chem. 2006, 71, 2046; f) M. K. Pandey,
A. Bisai, A. Pandey, V. K. Singh, Tetrahedron Lett. 2005, 46,
5039.
NЈ-(1-Allylcyclododecyl)benzohydrazide (6f): White solid (239 mg,
95% yield); m.p. 95–96 °C. Rf = 0.7 (EtOAc/hexane, 3:7). IR (neat):
1
ν = 3260, 2939, 1667, 1579 cm–1. H NMR (400 MHz, CDCl ): δ
˜
3
= 1.37–1.55 (m, 22 H, –CH2–), 2.19 (d, J = 7.2 Hz, 2 H, –CH2–),
5.10–5.19 (m, 3 H, NH, =CH2), 6.08–6.18 (m, 1 H, =CH), 7.32 (br.
s, 1 H, NH), 7.43 (t, J = 7.7 Hz, 2 H, Ar), 7.50 (t, J = 7.2 Hz, 1
H, Ar), 7.72 (d, J = 7.1 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 166.3, 135.5, 133.1, 131.6, 128.7, 126.8, 117.2, 62.3,
41.6, 31.1, 26.1, 22.7, 22.2, 19.1 ppm. C22H34N2O (342.52): calcd.
C 77.14, H 10.01, N 8.18; found C 76.81, H 10.08, N 8.05.
[2]
[3]
For reviews, see: a) S. Kobayashi, M. Sugiura, C. Ogawa, Adv.
Synth. Catal. 2004, 346, 1023; b) C. O. Puentes, V. J. Kouznet-
sov, J. Heterocycl. Chem. 2002, 39, 595; c) S. Kobayashi, H.
Ishitani, Chem. Rev. 1999, 99, 1069.
For allylsilane, see: a) K. K. Pasunooti, M. L. Leow, S. Vedach-
alam, B. K. Gorityala, X.-W. Liu, Tetrahedron Lett. 2009, 50,
2979; b) G. Smitha, B. Miriyala, J. S. Williamson, Synlett 2005,
839; c) P. Phukan, J. Org. Chem. 2004, 69, 4005; d) T. Ollevier,
T. Ba, Tetrahedron Lett. 2003, 44, 9003; e) M. Billet, P. Klotz,
A. Mann, Tetrahedron Lett. 2001, 42, 631; f) L. Niimi, K. Ser-
ita, S. Hiraoka, T. Yokozawa, Tetrahedron Lett. 2000, 41, 7075;
g) S. J. Veenstra, P. Schmid, Tetrahedron Lett. 1997, 38, 997.
For allyltin, see: a) A. V. Narsaiah, J. K. Kumar, P. Narsimha,
Synthesis 2010, 1609; b) P. Thirupathi, S. S. Kim, Tetrahedron
2009, 65, 5168; c) B. Das, K. Laxminarayana, B. Ravikanth, B.
Ramarao, Tetrahedron Lett. 2006, 47, 9103; d) T. Akiyama, J.
Iwai, Y. Onuma, H. Kagoshima, Chem. Commun. 1999, 2191.
For allylborane, see: a) U. Schneider, I.-H. Chen, S. Kobayashi,
Org. Lett. 2008, 10, 737; b) S. Kobayashi, K. Hirano, M. Sugi-
ura, Chem. Commun. 2005, 104; c) M. Sugiura, K. Hirano, S.
Kobayashi, J. Am. Chem. Soc. 2004, 126, 7182.
For allylindium, see: a) J. C. González-Gómez, M. Medjahdi,
F. Foubelo, M. Yus, J. Org. Chem. 2010, 75, 6308; b) S. J. Kim,
D. O. Jang, J. Am. Chem. Soc. 2010, 132, 12168; c) D. Samanta,
R. B. Kargbo, G. R. Cook, J. Org. Chem. 2009, 74, 7183; d)
R. B. Kargbo, G. R. Cook, Curr. Org. Chem. 2007, 11, 1287;
e) R. Kargbo, Y. Takahashi, S. Bhor, G. R. Cook, G. C. Lloyd-
Jones, I. R. Shepperson, J. Am. Chem. Soc. 2007, 129, 3846; f)
K. L. Tan, E. N. Jacobsen, Angew. Chem. 2007, 119, 1337; An-
gew. Chem. Int. Ed. 2007, 46, 1315; g) T. Vilaivan, C. Winota-
pan, V. Banphavivhit, T. Sinada, Y. Ohfune, J. Org. Chem.
2005, 70, 3464; h) F. Foubelo, M. Yus, Tetrahedron: Asymmetry
2004, 15, 3823; i) G. R. Cook, B. C. Maity, R. Kargbo, Org.
Lett. 2004, 6, 1741; j) I. R. Cooper, R. Grigg, W. S. MacLach-
lan, V. Sridharan, M. Thornton-Pett, Tetrahedron Lett. 2003,
44, 403.
2-Phenylpent-4-en-2-ol (7a): Colorless oil (228 mg, 96% yield); Rf
= 0.3 (EtOAc/hexane, 3:7). IR (neat): ν = 3435, 1639, 1602,
˜
1446 cm–1. H NMR (400 MHz, CDCl3): δ = 1.49 (s, 3 H, –CH3),
1
2.42–2.63 (m, 3 H, –CH2-, OH), 5.02 (d, J = 0.9 Hz, 1 H, =CH2),
5.06 (d, J = 8.1 Hz, 1 H, =CH2), 5.55–5.65 (m, 1 H, =CH), 7.17
(t, J = 7.3 Hz, 1 H, Ar), 7.29 (t, J = 7.9 Hz, 2 H, Ar), 7.39 (d, J =
8.8 Hz, 2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.8,
134.0, 128.2, 126.7, 125.0, 119.1, 73.8, 48.6, 29.7 ppm. C11H14O
(162.23): calcd. C 81.44, H 8.70; found C 80.95, H 8.57.
[4]
2-(4-Fluorophenyl)pent-4-en-2-ol (7b): Colorless oil (125 mg, 95%
yield); R = 0.3 (EtOAc/hexane, 3:7). IR (neat): ν = 3435, 1639,
[5]
[6]
˜
f
1602, 1510 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.52 (s, 3 H,
–CH3), 2.45–2.50 (dd, J = 13.7 Hz, J = 8.2 Hz, 1 H, –CH2–), 2.60–
2.65 (dd, J = 13.8 Hz, J = 6.6 Hz, 1 H, –CH2–), 5.10 (d, J =
12.2 Hz, 2 H, =CH2), 5.55–5.66 (m, 1 H, =CH), 6.96–7.02 (m, 2
H, Ar), 7.36–7.41 (m, 2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3):
δ = 161.6 (JC,F = 243 Hz), 143.4, 133.5, 126.6, 119.6, 114.8 (JC,F
21 Hz), 73.4, 48.6, 29.9 ppm. C11H13FO (180.22): calcd. C 73.31,
H 7.27; found C 73.63, H 7.08.
=
(E)-3-Methyl-1-phenylhexa-1,5-dien-3-ol (7c): Colorless oil (129 mg,
94% yield); R = 0.3 (EtOAc/hexane, 3:7). IR (neat): ν = 3401,
˜
f
1639, 1598, 1494 cm–1. H NMR (400 MHz, CDCl3): δ = 1.34 (s,
1
3 H, –CH3), 2.39–2.42 (m, 3 H, –CH2-, OH), 5.09 (d, J = 5.2 Hz,
1 H, =CH2), 5.13 (s, 1 H, =CH2), 5.76–5.87 (m, 1 H, =CH), 6.25
(d, J = 16.1 Hz, 1 H, =CH), 6.56 (d, J = 16.1 Hz, 1 H, =CH), 7.16–
7.20 (m, 1 H, Ar), 7.26 (t, J = 7.5 Hz, 2 H, Ar), 7.33 (d, J = 7.2 Hz,
2 H, Ar) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.1, 136.4,
133.8, 128.7, 127.5, 126.6, 119.1 72.5, 47.5, 27.9 ppm. C13H16O
(188.27): calcd. C 82.94, H 8.57; found C 82.73, H 8.18.
[7]
[8]
a) A. J. von Wangelin, H. Neumann, D. Gördes, S. Klaus, D.
Strübing, M. Beller, Chem. Eur. J. 2003, 9, 4286; b) A.
Dömling, I. Ugi, Angew. Chem. 2000, 112, 3300; Angew. Chem.
Int. Ed. 2000, 39, 3168.
For allylsilanes, see: a) E. Prusov, M. E. Maier, Tetrahedron
2007, 63, 10486; b) Q.-Y. Song, B.-L. Yang, S.-K. Tian, J. Org.
Chem. 2007, 72, 5407; c) N. R. Perl, J. L. Leighton, Org. Lett.
2007, 9, 3699; d) R. Berger, K. Duff, J. L. Leighton, J. Am.
Chem. Soc. 2004, 126, 5686; e) C. Ogawa, M. Sugiura, S. Ko-
bayashi, J. Org. Chem. 2002, 67, 5359.
General Procedure for N–N Bond Cleavage of Hydrazides:[1a] Hy-
drazide (0.6 mmol) was dissolved in MeOH (1 mL) and treated
with SmI2 [0.1 m in tetrahydrofuran (THF), 18 mL, 1.8 mmol] at
room temperature for 4 h under argon. After the reaction went to
completion, the mixture was diluted with CH2Cl2. The resulting
solution was washed with distilled water and then dried with anhy-
drous MgSO4. After filtration and evaporation of the solvent, the
residue was passed through a short silica gel column to obtain the
product.
[9]
For allylboronates, see: a) S. Pramanik, P. Ghorai, Chem. Com-
mun. 2012, 48, 1820; b) B. Dhudshia, J. Tiburcio, A. N. Thad-
ani, Chem. Commun. 2005, 5551.
[10]
For reviews, see: a) Z.-L. Shen, S.-Y. Wang, Y.-K. Chok, Y.-H.
Xu, T.-P. Loh, Chem. Rev. 2013, 113, 271; b) V. Nair, S. Ros,
N. C. Jayan, B. S. Pillai, Tetrahedron 2004, 60, 1959; c) J. Pod-
lech, T. C. Maier, Synthesis 2003, 633; d) B. C. Ranu, Eur. J.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the H and 13C NMR spectra.
1
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7

Job/Unit: O21757
/KAP1
Date: 02-04-13 16:25:19
Pages: 9
B. S. Lee, D. O. Jang
FULL PAPER
Org. Chem. 2000, 2347; e) K. K. Chauhan, C. G. Frost, J.
Chem. Soc. Perkin Trans. 1 2000, 3015.
[11] For reactions with preformed imines at high temperature, see:
J. A. Sirvent, F. F. Foubelo, M. Yus, Chem. Commun. 2012, 48,
2543.
d) S. Yamasaki, K. Fujii, R. Wada, M. Kanai, M. Shibasaki,
J. Am. Chem. Soc. 2002, 124, 6536; e) S. Kobayashi, S. Nagay-
ama, J. Am. Chem. Soc. 1997, 119, 10049.
[13] S. Kobayashi, R. Hirabayashi, J. Am. Chem. Soc. 1999, 121,
6943.
[12] a) S. M. Capps, T. P. Clarke, J. P. H. Charmant, H. A. F.
Hoppe, G. C. Lloyd-Jones, M. Murry, T. M. Peakman, R. A.
[14] B. K. Bhuyan, A. J. Borah, K. K. Senapati, P. Phukan, Tetrahe-
dron Lett. 2011, 52, 2649.
Stentifold, K. E. Walsh, P. A. Worthington, Eur. J. Org. Chem. [15] Z. Du, T. Li, F. Wang, W. Zhou, J.-X. Wang, Synth. Commun.
2000, 963; b) H. A. Hoppe, G. C. Lloyd-Jones, M. Murry,
T. M. Peakman, K. E. Walsh, Angew. Chem. 1998, 110, 1653;
Angew. Chem. Int. Ed. 1998, 37, 1545; c) S. Araki, H. Ito, N.
Katsumura, Y. Butsugan, J. Organomet. Chem. 1989, 369, 291;
2011, 41, 1664.
[16] S. E. Denmark, S. T. Nguyen, Org. Lett. 2009, 11, 781.
Received: December 29, 2012
Published Online: ᭿
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O21757
/KAP1
Date: 02-04-13 16:25:19
Pages: 9
Efficient Synthesis of Homoallylic Hydrazides
Multicomponent Reaction
A three-component reaction that involved
a carbonyl compound, benzoylhydrazine,
allyl bromide, and indium in the presence
of readily available Zn(ClO4)2·6H2O pro-
vided secondary and tertiary homoallylic
hydrazides in high yields with excellent
chemoselectivities and diastereoselectivies.
B. S. Lee, D. O. Jang* ...................... 1–9
A Mild and Efficient Three–Component
Synthesis of Secondary and Tertiary
Homoallylic Hydrazides
Keywords: Multicomponent reactions
/
Allylation / Aldehydes / Ketones / Chemo-
selectivity / Hydrazides
Eur. J. Org. Chem. 0000, 0–0
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