Development of general methods for the synthesis of new substituted allyl bromides as promising alkenylating agents

Article abstract of DOI:10.1134/S1070428014070069

A general procedure has been developed for the synthesis of hitherto unknown substituted allyl bromides. The procedure includes preparation of the corresponding α,β-unsaturated carboxylic acid esters from accessible ketones according to the Horner-Emmons

Full text of DOI:10.1134/S1070428014070069

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 7, pp. 953–959. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © A.I. Moskalenko, V.I. Boev, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 7, pp. 973–978.
Development of General Methods for the Synthesis of New
Substituted Allyl Bromides as Promising Alkenylating Agents
A. I. Moskalenkoa, and V. I. Boevb
a Lipetsk State Pedagogical University, ul. Lenina 42, Lipetsk, 398020 Russia
e-mail: kaf_himii@lspu.lipetsk.ru
b Timiryazev Russian State Agrarian University, Timiryazevskaya ul. 49, Moscow, 127550 Russia
Received December 13, 2013
Abstract—A general procedure has been developed for the synthesis of hitherto unknown substituted allyl
bromides. The procedure includes preparation of the corresponding α,β-unsaturated carboxylic acid esters from
accessible ketones according to the Horner–Emmons reaction, reduction of these esters with diisobutyl-
aluminum hydride to allylic alcohols, and substitution of the hydroxy group by bromine by the action of PBr3.
The E,Z isomer ratio of the synthesized unsaturated compounds ranges from 3:1 to 4:1.
DOI: 10.1134/S1070428014070069
Allyl bromides are versatile synthons that are
widely used in organic synthesis, in particular, as al-
kenylating agents [1] toward various classes of com-
pounds, including amines, alcohols, CH acids, and
organometallics. In many cases, such reactions are key
processes in the preparation of synthetic analogs of
natural compounds [2] and various heterocycles [3, 4]
iteresting as potential biologically active substances.
Therefore, development of general procedures for the
preparation of new allyl bromide derivatives, their
optimization, and ascertainment of their application
scope constitute topical problems of modern organic
chemistry.
Taking into account the necessity of further devel-
oping our studies in the field of reactions with allyl
bromides [5], in the present article we describe a gen-
eral strategy for the synthesis of new substituted allyl
bromide derivatives. As starting compounds we used
commercially accessible ketones Ia–Ik which reacted
with ethyl (diethoxyphosphoryl)acetate under the
Horner–Emmons reaction conditions in anhydrous
THF in the presence of potassium tert-butoxide [6, 7].
As a result, we obtained in good yields the correspond-
ing α,β-unsaturated carboxylic acid esters IIa–IIk as
mixtures of E and Z isomers at a ratio of 4:1 to 3:1
1
(according to the HPLC/MS and H NMR data),
depending on the initial ketone structure (Scheme 1).
The reaction of cyclic ketone Il with ethyl di-
ethoxyphosphorylacetate under analogous conditions
afforded isomeric compounds IIl and IIm; the latter
being formed as a result of migration of the exocyclic
double bond into the piperidine ring (Scheme 2).
In order to enhance stereoselectivity of the reac-
tions under study, ketone If was brought into reaction
with ethyl diethoxyphosphorylacetate under the condi-
tions reported in [8] for the Horner–Emmons reaction
with aldehydes in the presence of methylmagnesium
bromide, which afforded the corresponding unsaturat-
ed carboxylic acid esters with very high stereoselec-
tivity (180:1 in favor of the E isomer). Unfortunately,
the reaction of ketone If under these conditions led to
the formation of a mixture of E and Z isomers at a ratio
of 67:33 (1H NMR), i.e., it was not stereoselective. We
also tried to separate E and Z isomers according to the
Scheme 1.
R'
R'
O
(EtO)2P(O)CH2COOEt, t-BuOK
R
COOEt
R
H
( )n
( )n
+
R
–(EtO)2P(O)OK
( )n
R'
H
COOEt
Ia–Ik
E Isomer
IIa–IIk
Z Isomer
R = Ph (a), 4-FC6H4 (b), 2-ClC6H4 (c), 3-ClC6H4 (d), 4-ClC6H4 (e), 3-CF3C6H4 (f), PhCH2 (g), PhCH2CH2 (h), Me2CHCH2CH2 (i),
Me2C=CH (j), 4-Boc-morpholin-3-yl (k); R′ = Me (a–f, h–k), Et (g); n = 0 (g–k), 1 (a–f).
953

MOSKALENKO, BOEV
954
Scheme 2.
O
(EtO)2P(O)CH2COOEt, t-BuOK
–(EtO)2P(O)OK
COOEt
COOEt
+
N
N
N
Boc
Boc
Boc
Il
IIl
IIm
Boc = t-BuOC(O).
procedure described in [9]. For this purpose, E/Z
isomer mixtures IIf and IIi were subjected to hydrol-
ysis [9], and the resulting carboxylic acids IIIf and IIIi
were separated by recrystallization from methanol on
cooling to –40°C. Pure E isomers of IIIf and IIIi
crystallized from the solution and were isolated in
40–45% yield and used in further syntheses.
EXPERIMENTAL
The IR spectra were recorded from thin films or
KBr pellets on a Specord 75 IR spectrometer. The
1H NMR spectra were measured on a Varian Mercury
Plus-400 instrument at 400 MHz using CDCl3 as sol-
vent and hexamethyldisiloxane as internal reference.
HPLC/MS analyses were obtained on a Surveyor MSQ
Thermo Finnigan instrument (atmospheric pressure
chemical ionization). The progress of reactions was
monitored by TLC on Silufol UV-254 plates using
hexane–ethyl acetate (10:1 or 3:1 by volume) as
eluent.
Ethyl (E/Z)-3-methyl-4-phenylbut-2-enoate (IIa).
Potassium tert-butoxide, 22.4 g (0.2 mol), was added
under stirring and cooling with ice water in an argon
atmosphere to a mixture of 26.8 g (0.2 mol) of
1-phenylpropan-2-one and 44.8 g (0.2 mol) of ethyl
(diethoxyphosphoryl)acetate in 550 mL of anhydrous
THF. The mixture was heated for 2 h under reflux with
stirring (TLC), the solvent was distilled off under
reduced pressure, and the residue was treated with
300 mL of ethyl acetate and 300 mL of 5% aqueous
HCl. The organic phase was separated, washed with
brine, and dried over anhydrous sodium sulfate, the
solvent was distilled off under reduced pressure, and
the residue was purified by column chromatography on
silica gel using hexane–ethyl acetate (10:1) as eluent.
Yield 30.4 g (75%), colorless oily substance, Rf 0.76.
IR spectrum, ν, cm–1: 1712 (C=O), 1652 (C=C).
1H NMR spectrum, δ, ppm: 1.26 t (3H, CH3, J =
7.6 Hz), 1.77 s (0.21·3H, CH3C=C), 2.16 s (0.79·3H,
CH3C=C), 3.42 s (0.77·2H, CH2), 4.02 s (0.23·2H,
CH2), 4.21 q (2H, OCH2, J = 7.6 Hz), 5.69 s (0.8H,
CH=C), 5.78 s (0.2H, CH=C), 7.18–7.28 m (5H,
Harom). Mass spectrum: m/z 205.20 (Irel 100%)
[M + H]+. Found, %: C 76.31; H 7.84. C13H16O2. Cal-
culated, %: C 76.48; H 7.93. M 204.26.
Esters IIa–IIk as E/Z isomer mixtures were
reduced to the corresponding alcohols IVa–IVk in
almost quantitative yield with hydrido(diisobutyl)-
aluminum in anhydrous methylene chloride [10]
1
(Scheme 3). According to the H NMR data, the
isomer ratio did not change in this transformation. The
E isomers of IIIf and IIIi were reduced to alcohols
E-IVf and E-IVi with lithium tetrahydridoaluminate
following the procedure described in [9].
Scheme 3.
R'
R'
(i-Bu)2AlH
R
CH2OH
R
H
( )n
( )n
IIa–IIk
+
H
CH2OH
E Isomer
IVa–IVk Z Isomer
E-IVf, E-IVi
R'
LiAlH4
R
COOH
( )n
H
E-IIIf, E-IIIi
Substituted allyl bromides were synthesized by
treatment of alcohols IVa–IVi with phosphorus(III)
bromide in anhydrous diethyl ether [11, 12]. New allyl
bromide derivatives Va–Vi as mixtures of E and Z
isomers and pure isomers E-Vf and E-Vi were isolated
in 65–95% yield (Scheme 4).
The structure of the newly synthesized compounds
1
was proved by elemental analyses and IR, H NMR,
and mass spectra (see Experimental).
Scheme 4.
Compounds IIb–IIm were synthesized in a similar
R'
R'
way.
PBr3
R
CH2Br
R
H
( )n
( )n
IVa–IVi
+
Ethyl (E/Z)-4-(4-fluorophenyl)-3-methylbut-2-
enoate (IIb). Yield 66%, colorless oily substance. IR
spectrum, ν, cm–1: 1715 (C=O), 1658 (C=C). 1H NMR
H
CH2Br
E Isomer
Va–Vi
Z Isomer
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DEVELOPMENT OF GENERAL METHODS
955
spectrum, δ, ppm: 1.26 t (3H, CH3, J = 7.6 Hz), 1.76 s
(0.25·3H, CH3C=C), 2.17 s (0.75·3H, CH3C=C), 3.39 s
(0.75·2H, CH2), 3.98 s (0.25·2H, CH2), 4.22 q (2H,
OCH2, J = 7.6 Hz), 5.62 s (0.75H, CH=C), 5.77 s
(0.25H, CH=C), 6.88–7.15 m (4H, Harom). Mass spec-
trum: m/z 223.15 (Irel 100%) [M + H]+. Found, %:
C 70.12; H 6.73. C13H15FO2. Calculated, %: C 70.35;
H 6.82. M 222.26.
Ethyl (E/Z)-4-(2-chlorophenyl)-3-methylbut-2-
enoate (IIc). Yield 66%, colorless oily substance. IR
spectrum, ν, cm–1: 1714 (C=O), 1650 (C=C). 1H NMR
spectrum, δ, ppm: 1.26 t (3H, CH3, J = 7.2 Hz), 1.76 s
(0.21·3H, CH3C=C), 2.20 s (0.79·3H, CH3C=C), 3.08 s
(0.22·2H, CH2), 3.58 s (0.78·2H, CH2), 4.16 q (2H,
OCH2, J = 7.2 Hz), 5.57 s (0.77H, CH=C), 5.82 s
(0.23H, CH=C), 7.18–7.30 m (4H, Harom). Mass spec-
trum: m/z 239.11 (Irel 100%) [M + H]+. Found, %:
C 65.26; H 6.44; Cl 14.81. C13H15ClO2. Calculated, %:
C 65.43; H 6.37; Cl 14.92. M 238.71.
Ethyl (E/Z)-4-(3-chlorophenyl)-3-methylbut-2-
enoate (IId). Yield 97%, colorless oily substance. IR
spectrum, ν, cm–1: 1716 (C=O), 1652 (C=C). 1H NMR
spectrum, δ, ppm: 1.26 t (3H, CH3, J = 6.8 Hz), 1.76 s
(0.28·3H, CH3C=C), 2.16 s (0.72·3H, CH3C=C), 3.11 s
(0.26·2H, CH2), 3.41 s (0.74·2H, CH2), 4.20 q (2H,
OCH2, J = 6.8 Hz), 5.61 s (0.73H, CH=C), 5.79 s
(0.27H, CH=C), 7.06–7.25 m (4H, Harom). Mass spec-
trum: m/z 239.13 (Irel 100%) [M + H]+. Found, %:
C 65.26; H 6.34; Cl 14.68. C13H15ClO2. Calculated, %:
C 65.43; H 6.37; Cl 14.92. M 238.71.
[M + H]+. Found, %: C 61.73; H 5.58. C14H15F3O2.
Calculated, %: C 61.85; H 5.62. M 272.26.
Ethyl (E/Z)-3-benzylpent-2-enoate (IIg). Yield
77%, colorless oily substance. IR spectrum, ν, cm–1:
1
1712 (C=O), 1649 (C=C). H NMR spectrum, δ, ppm:
1.02 t (3H, CH3, J = 6.0 Hz), 1.26 t (3H, CH3, J =
6.5 Hz), 2.41 q (0.65·2H, CH2C=C, J = 6.0 Hz), 2.58 q
(0.35·2H, CH2C=C, J = 6.0 Hz), 3.46 s (0.33·2H,
CH2), 3.69 s (0.67·2H, CH2), 4.13 q (0.61·2H, OCH2,
J = 6.5 Hz), 4.20 q (0.39·2H, OCH2, J = 6.5 Hz), 5.58 s
(0.58H, CH=C), 5.77 s (0.42H, CH=C), 7.20–7.36 m
(5H, Harom). Mass spectrum: m/z 219.16 (Irel 100%)
[M + H]+. Found, %: C 76.83; H 8.21. C14H18O2. Cal-
culated, %: C 77.06; H 8.34. M 218.29.
Ethyl (E/Z)-3-methyl-5-phenylpent-2-enoate
(IIh). Yield 66%, colorless oily substance. IR spec-
1
trum, ν, cm–1: 1715 (C=O), 1648 (C=C). H NMR
spectrum, δ, ppm: 1.26 t (3H, CH3, J = 5.9 Hz), 1.86 s
(0.26·3H, CH3C=C), 2.22 s (0.74·3H, CH3C=C), 2.46 t
(2H, CH2, J = 7.8 Hz), 2.79 t (0.75·2H, CH2, J =
7.6 Hz), 2.92 t (0.25·2H, CH2, J = 7.6 Hz), 4.18 q (2H,
OCH2, J = 5.9 Hz), 5.72 s (1H, CH=C), 7.19–7.28 m
(5H, Harom). Mass spectrum: m/z 219.19 (Irel 100%)
[M + H]+. Found, %: C 77.13; H 8.43. C14H18O2. Cal-
culated, %: C 77.06; H 8.34. M 218.29.
Ethyl (E/Z)-3,6-dimethylhept-2-enoate (IIi).
Yield 64%, colorless liquid. IR spectrum, ν, cm–1: 1718
(C=O), 1651 (C=C). 1H NMR spectrum, δ, ppm: 0.88–
0.94 m (6H, CH3), 1.26 t (3H, CH3, J = 8.2 Hz), 1.33–
1.39 m (2H, CH2), 1.47–1.60 m (1H, CH), 2.12–
2.16 m (3H, CH3C=C), 2.42 t and 2.64 t (1H each,
CH2C=C, J = 8.9 Hz), 4.15 q (2H, OCH2, J = 8.2 Hz),
5.62 s (0.3H, CH=C), 5.70 s (0.7H, CH=C). Mass
spectrum: m/z 185.22 (Irel 100%) [M + H]+. Found, %:
C 71.56; H 10.83. C11H20O2. Calculated, %: C 71.74;
H 10.96. M 184.28.
Ethyl (E/Z)-3,5-dimethylhexa-2,4-dienoate (IIj).
Yield 46%, colorless liquid. IR spectrum, ν, cm–1: 1709
(C=O); 1656, 1645 (C=C). 1H NMR spectrum, δ, ppm:
1.26 t (3H, CH3, J = 6.1 Hz), 1.71 s (0.45·3H, CH3),
1.80 s (0.55·3H, CH3), 2.09 s (0.41·3H, CH3), 2.22 s
(0.59·3H, CH3), 2.77 s (0.72·3H, CH3C=C), 3.80 s
(0.28·3H, CH3C=C), 4.14 q (2H, OCH2, J = 6.1 Hz),
4.75 s (0.65H, CH=C), 4.82 s (0.35H, CH=C), 5.64 s
(0.35H, C=CH–C=O), 5.74 s (0.65H, C=CH–C=O).
Mass spectrum: m/z 169.25 (Irel 100%) [M + H]+.
Found, %: C 71.34; H 9.48. C10H16O2. Calculated, %:
C 71.45; H 9.67. M 168.23.
Ethyl (E/Z)-4-(4-chlorophenyl)-3-methylbut-2-
enoate (IIe). Yield 75%, colorless oily substance. IR
spectrum, ν, cm–1: 1715 (C=O), 1648 (C=C). 1H NMR
spectrum, δ, ppm: 1.26 t (3H, CH3, J = 7.1 Hz), 1.76 s
(0.24·3H, CH3C=C), 2.11 s (0.76·3H, CH3C=C), 3.40 s
(0.77·2H, CH2), 3.94 s (0.23·2H, CH2), 4.19 q (2H,
OCH2, J = 7.1 Hz), 5.68 s (0.78H, CH=C), 5.79 s
(0.22H, CH=C), 7.10 d and 7.28 d (2H each, Harom
,
J = 8.6 Hz). Mass spectrum: m/z 239.09 (Irel 100%)
[M + H]+. Found, %: C 65.36; H 6.28; Cl 15.07.
C13H15ClO2. Calculated, %: C 65.43; H 6.37; Cl 14.92.
M 238.71.
Ethyl (E/Z)-3-methyl-4-[3-(trifluoromethyl)-
phenyl]but-2-enoate (IIf). Yield 68%, colorless oily
substance. IR spectrum, ν, cm–1: 1718 (C=O), 1653
1
(C=C). H NMR spectrum, δ, ppm: 1.26 t (3H, CH3,
J = 6.4 Hz), 1.76 s (0.31·3H, CH3C=C), 2.07 s
(0.69·3H, CH3C=C), 3.18 s (0.3·2H, CH2), 3.49 s
(0.7·2H, CH2), 4.15 q (2H, OCH2, J = 6.4 Hz), 5.70 s
(0.71H, CH=C), 5.81 s (0.29H, CH=S), 7.30–7.53 m
(4H, Harom). Mass spectrum: m/z 273.10 (Irel 100%)
tert-Butyl 2-[(E/Z)-3-ethoxy-1-methyl-3-oxoprop-
1-en-1-yl]morpholine-4-carboxylate (IIk). Yield
74%, colorless oily substance. IR spectrum, ν, cm–1:
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MOSKALENKO, BOEV
956
1716, 1685 (C=O); 1649 (C=C). 1H NMR spectrum, δ,
ppm: 1.26 t (3H, CH3, J = 6.8 Hz), 1.91 s (0.18·3H,
CH3C=C), 2.19 s (0.82·3H, CH3C=C), 2.58–2.73 m
(1H, CHN), 2.81–2.97 m (1H, CHN), 3.46–3.58 m
(2H, CH2N), 3.75–3.97 m (3H, CH2O, CHO), 4.19 q
(2H, OCH2, J = 6.8 Hz), 5.71 s (0.2H, CH=C), 6.00 s
(0.8H, CH=C). Mass spectrum, m/z (Irel, %): 300.25
(4.8) [M + H]+, 243.73 (100) [M – 57 + 2H]+, 200.22
(17.4) [M – 101 + 2H]+. Found, %: C 60.12; H 8.31;
N 4.64. C15H25NO5. Calculated, %: C 60.24; H 8.46;
N 4.75. M 299.36.
tert-Butyl 4-(2-ethoxy-2-oxoethylidene)piperi-
dine-1-carboxylate (IIl). Yield 78%, mp 85–86°C. IR
spectrum, ν, cm–1: 1706, 1684 (C=O); 1643 (C=C).
1H NMR spectrum, δ, ppm: 1.28 t (3H, CH3, J =
6.8 Hz), 1.47 s (9H, t-Bu), 2.25 t (2H, CH2, J =
6.6 Hz), 2.98 t (2H, CH2, J = 6.8 Hz), 3.49 m (4H,
CH2N), 4.16 q (2H, OCH2, J = 6.8 Hz), 5.73 s (1H,
CH=C). Mass spectrum: m/z 170.22 (Irel 100%) [M –
101 + 2H]+. Found, %: C 62.18; H 8.43; N 5.31.
C14H23NO4. Calculated, %: C 62.45; H 8.55; N 5.20.
M 269.28.
Ethyl (1-tert-butoxycarbonyl-1,2,5,6-tetrahydro-
pyridin-4-yl)ethanoate (IIm). Yield 5%, light yellow
oily substance. IR spectrum, ν, cm–1: 1718, 1685
(C=O); 1628 (C=C). 1H NMR spectrum, δ, ppm: 1.27 t
(3H, CH3, J = 7.2 Hz), 1.48 s (9H, t-Bu), 2.13 s (2H,
CH2), 3.03 t (2H, CH2CO), 3.51 t (2H, CH2N, J =
6.8 Hz), 3.88 s (2H, CH2N), 4.15 q (2H, OCH2, J =
7.2 Hz), 5.53 s (1H, CH=C). Mass spectrum:
m/z 170.24 (Irel 100%) [M – 101 + 2H]+. Found, %:
C 62.23; H 8.41; N 5.16. C14H23NO4. Calculated, %:
C 62.45; H 8.55; N 5.20. M 269.28.
3.42 s (0.24·2H, CH2), 4.18 d (0.75·2H, OCH2, J =
12.7 Hz), 4.28 d (0.25·2H, OCH2, J = 12.7 Hz), 5.51 t
(0.75H, CH=C, J = 12.7 Hz), 5.61 t (0.25H, CH=C, J =
12.7 Hz), 7.16–7.32 m (5H, Harom). Mass spectrum:
m/z 145.31 (Irel 100%) [M – 18 + H]+. Found, %:
C 81.26; H 8.48. C11H14O. Calculated, %: C 81.43;
H 8.76. M 162.23.
Compounds IVb–IVk were synthesized in a similar
way.
(E/Z)-4-(4-Fluorophenyl)-3-methylbut-2-en-1-ol
(IVb). Yield 98%, colorless oily substance. IR spec-
trum, ν, cm–1: 3415 (OH), 1644 (C=C). 1H NMR spec-
trum, δ, ppm: 1.64 s (0.78·3H, CH3), 1.73 s (0.22·3H,
CH3), 3.28 s (0.79·2H, CH2), 3.44 s (0.21·2H, CH2),
4.20 d (0.79·2H, OCH2, J = 12.8 Hz), 4.26 d (0.21·2H,
OCH2, J = 12.8 Hz), 5.48 t (0.78H, CH=C, J =
12.8 Hz), 5.60 t (0.22H, CH=C, J = 12.8 Hz), 6.97–
7.15 m (4H, Harom). Mass spectrum: m/z 162.98
(Irel 100%) [M – 18 + H]+. Found, %: C 73.21; H 7.18.
C11H13FO. Calculated, %: C 73.36; H 7.32. M 180.22.
(E/Z)-4-(2-Chlorophenyl)-3-methylbut-2-en-1-ol
(IVc). Yield 96%, colorless oily substance. IR spec-
trum, ν, cm–1: 3409 (OH), 1648 (C=C). 1H NMR spec-
trum, δ, ppm: 1.68 s (0.79·3H, CH3), 1.97 s (0.21·3H,
CH3), 3.47 s (0.78·2H, CH2), 3.60 s (0.22·2H, CH2),
4.21 d (0.78·2H, OCH2, J = 11.5 Hz), 4.26 d (0.22·2H,
OCH2, J = 11.5 Hz), 5.36 t (0.78H, CH=C, J =
11.5 Hz), 5.70 t (0.22H, CH=C, J = 11.5 Hz), 7.18–
7.46 m (4H, Harom). Mass spectrum, m/z (Irel, %):
197.42 (6.4) [M + H]+, 181.03 (100) [M – 18 + H]+.
Found, %: C 67.03; H 6.81; Cl 17.86. C11H13ClO. Cal-
culated, %: C 67.24; H 6.75; Cl 18.04. M 196.67.
(E/Z)-4-(3-Chlorophenyl)-3-methylbut-2-en-1-ol
(IVd). Yield 99%, colorless oily substance. IR spec-
trum, ν, cm–1: 3412 (OH), 1650 (C=C). 1H NMR spec-
trum, δ, ppm: 1.68 s (0.74·3H, CH3), 1.98 s (0.26·3H,
CH3), 3.28 s (0.75·2H, CH2), 3.41 s (0.25·2H, CH2),
4.22 d (0.78·2H, OCH2, J = 10.6 Hz), 4.26 d (0.22·2H,
OCH2, J = 10.6 Hz), 5.49 t (0.78H, CH=C, J =
10.6 Hz), 5.63 t (0.22H, CH=C, J = 10.6 Hz), 7.05–
7.26 m (4H, Harom). Mass spectrum: m/z 181.03
(Irel 100%) [M – 18 + H]+. Found, %: C 67.18; H 6.34;
Cl 18.13. C11H13ClO. Calculated, %: C 67.24; H 6.75;
Cl 18.04. M 196.67.
(E/Z)-4-(4-Chlorophenyl)-3-methylbut-2-en-1-ol
(IVe). Yield 98%, colorless oily substance. IR spec-
trum, ν, cm–1: 3412 (OH), 1648 (C=C). 1H NMR spec-
trum, δ, ppm: 1.63 s (0.77·3HH, CH3), 1.71 s (0.23·3H,
CH3), 3.28 s (0.77·2H, CH2), 3.41 s (0.23·2H, CH2),
4.18 d (0.77·2H, OCH2, J = 11.2 Hz), 4.26 d (0.23·2H,
(E/Z)-3-Methyl-4-phenylbut-2-en-1-ol (IVa).
A solution of 30.4 g (0.149 mol) of compound IIa in
450 mL of anhydrous methylene chloride was cooled
to –70°C, 317 mL (0.447 mol) of a 25% solution of
hydrido(diisobutyl)aluminum in hexane was added
under stirring in an argon atmosphere, and the mixture
was stirred for 2 h at room temperature. It was then
cooled to –10°C, 500 mL of 5% aqueous HCl and
500 mL of methylene chloride were added in succes-
sion, the mixture was stirred for 15 min, the organic
phase was separated, and the aqueous phase was
extracted with methylene chloride (2×200 mL). The
extracts were combined with the aqueous phase and
dried over Na2SO4, and the solvent was distilled off
under reduced pressure. Yield 24.1 g (98%), colorless
oily substance. IR spectrum, ν, cm–1: 3408 (OH), 1642
1
(C=C). H NMR spectrum, δ, ppm: 1.69 s (0.75·3H,
CH3), 1.73 s (0.25·3H, CH3), 3.30 s (0.76·2H, CH2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 7 2014

DEVELOPMENT OF GENERAL METHODS
957
C 75.91; H 12.76. C9H18O. Calculated, %: C 76.07;
OCH2, J = 11.2 Hz), 5.47 t (0.77H, CH=C, J =
11.2 Hz), 5.60 t (0.23H, CH=C, J = 11.2 Hz), 7.11 d
and 7.26 d (2H each, Harom, J = 9.1 Hz). Mass spec-
trum: m/z 181.03 (Irel 100%) [M – 18 + H]+. Found, %:
C 67.13; H 6.51; Cl 17.86. C11H13ClO. Calculated, %:
C 67.24; H 6.75; Cl 18.04. M 196.67.
(E/Z)-3-Methyl-4-[3-(trifluoromethyl)phenyl]-
but-2-en-1-ol (IVf). Yield 97%, colorless oily sub-
stance. IR spectrum, ν, cm–1: 3421 (OH), 1651 (C=C).
1H NMR spectrum, δ, ppm: 1.62 s (0.72·3H, CH3),
1.98 s (0.28·3H, CH3), 3.41 s (0.72·2H, CH2), 3.49 s
(0.28·2H, CH2), 4.21 d (0.71·2H, OCH2, J = 12.1 Hz),
4.27 d (0.29·2H, OCH2, J = 12.1 Hz), 5.51 t (0.72H,
CH=C, J = 12.1 Hz), 5.65 t (0.28H, CH=C, J =
12.1 Hz), 7.30–7.52 m (4H, Harom). Mass spectrum:
m/z 212.96 (Irel 100%) [M – 18 + H]+. Found, %:
C 62.48; H 5.63. C12H13F3O. Calculated, %: C 62.64;
H 5.75. M 230.23.
H 12.83. M 142.24.
(2E/Z)-3,5-Dimethylhexa-2,4-dien-1-ol (IVj).
Yield 97%, colorless liquid. IR spectrum, ν, cm–1: 3431
1
(OH); 1652, 1643 (C=C). H NMR spectrum, δ, ppm:
1.64 s (0.45·3H, CH3), 1.66 s (0.55·3H, CH3), 1.76–
1.80 m (3H, CH3), 2.70 s (0.6·3H, CH3), 2.77 s
(0.4·3H, CH3), 4.17 d (0.58·2H, OCH2, J = 9.8 Hz),
4.23 d (0.42·2H, OCH2, J = 9.8 Hz), 4.72 s (0.45H,
CH=C), 4.81 s (0.55H, CH=C), 5.46 t (0.6H,
CH=C–C–O, J = 9.8 Hz), 5.63 t (0.4H, CH=C–C–O,
J = 9.8 Hz). Mass spectrum: m/z 109.45 (Irel 100%)
[M – 18 + H]+. Found, %: C 76.23; H 11.18. C8H14O.
Calculated, %: C 76.16; H 11.24. M 126.20.
tert-Butyl 2-[(E/Z)-3-hydroxyprop-1-en-1-yl]-
morpholine-4-carboxylate (IVk). Yield 81%, color-
less oily substance. IR spectrum, ν, cm–1: 3436 (OH),
1
1686 (C=O), 1648 (C=C). H NMR spectrum, δ, ppm:
1.73 s (0.8·3H, CH3C=C), 1.77 s (0.2·3H, CH3C=C),
2.71 t (1H, CHN, J = 6.5 Hz), 2.94 t (2H, CH2N, J =
6.5 Hz), 3.55 t (1H, CHN, J = 6.5 Hz), 3.74 d (1H,
CHO, J = 6.5 Hz), 3.82–3.98 m (2H, CH2O), 4.22 d
(2H, OCH2, J = 9.1 Hz), 5.60 t (0.18H, CH=C, J =
9.1 Hz), 5.75 t (0.82H, CH=C, J = 9.1 Hz). Mass spec-
trum, m/z (Irel, %): 258.35 (3.2) [M + H]+, 184.20 (100)
[M – 57 – 18 + 2H]+. Found, %: C 59.36; H 8.64;
N 5.78. C12H21NO4. Calculated, %: C 59.24; H 8.76;
N 5.83. M 257.33.
(E/Z)-3-Benzylpent-2-en-1-ol (IVg). Yield 98%,
colorless oily substance. IR spectrum, ν, cm–1: 3408
1
(OH), 1648 (C=C). H NMR spectrum, δ, ppm: 1.00 t
(3H, CH3, J = 6.8 Hz), 2.68 q (0.58·2H, CH2C=C, J =
6.8 Hz), 2.82 q (0.42·2H, CH2C=C, J = 6.8 Hz), 3.33 s
(0.54·2H, CH2), 3.46 s (0.46·2H, CH2), 4.18 d
(0.58·2H, OCH2, J = 9.1 Hz), 4.29 d (0.42·2H, OCH2,
J = 9.1 Hz), 5.41 t (0.59H, CH=C, J = 9.1 Hz), 5.60 t
(0.41H, CH=C, J = 9.1 Hz), 7.15–7.34 m (5H, Harom).
Mass spectrum: m/z 159.27 (Irel 100%) [M – 18 + H]+.
Found, %: C 81.73; H 9.08. C12H16O. Calculated, %:
C 81.83; H 9.16. M 176.26.
[(E/Z)-4-Bromo-2-methylbut-2-en-1-yl]benzene
(Va). A solution of 24.4 g (0.151 mol) of compound
IVa in 450 mL of anhydrous diethyl ether was cooled
to –15°C, 20.4 g (0.075 mol) of PBr3 was added under
stirring, the mixture was stirred for 3 h at 0°C and
cooled to –15°C, 400 mL of water and 400 mL of ethyl
acetate–hexane (1:10 by volume) were added, and the
mixture was stirred for 15 min. The organic phase was
separated, the aqueous phase was treated with ethyl
acetate–hexane (1:10 by volume; 2×200 mL), the
extracts were combined with the organic phase,
washed with an aqueous solution of sodium hydrogen
carbonate and brine, and dried over Na2SO4, and the
solvent was distilled off under reduced pressure. Yield
31.9 g (94%), colorless liquid. IR spectrum:
ν 1638 cm–1 (C=C). 1H NMR spectrum, δ, ppm: 1.69 s
(0.75·3H, CH3), 1.71 s (0.25·3H, CH3), 3.37 s
(0.73·2H, CH2), 3.48 s (0.27·2H, CH2), 4.03 d
(0.73·2H, CH2Br, J = 8.4 Hz), 4.13 d (0.27·2H, CH2Br,
J = 8.4 Hz), 5.63 t (0.75H, CH=C, J = 8.4 Hz), 5.71 t
(0.25H, CH=C, J = 8.4 Hz), 7.15–7.32 m (5H, Harom).
Mass spectrum: m/z 145.35 (Irel 100)% [M – 80]+.
Found, %: C 58.56; H 5.73; Br 35.28. C11H13Br. Cal-
culated, %: C 58.74; H 5.86; Br 35.57. M 225.12.
(E/Z)-3-Methyl-5-phenylpent-2-en-1-ol (IVh).
Yield 99%, colorless oily substance. IR spectrum, ν,
1
cm–1: 3416 (OH), 1647 (C=C). H NMR spectrum, δ,
ppm: 1.72 s (0.73·3H, CH3C=C), 1.81 s (0.27·3H,
CH3C=C), 2.31–2.42 m (2H, CH2), 2.70–2.79 m (2H,
CH2), 3.89 t (0.26·2H, OCH2, J = 8.7 Hz), 4.16 t
(0.74·2H, OCH2, J = 8.7 Hz), 5.42 t (1H, CH=C, J =
8.7 Hz), 7.15–7.32 m (5H, Harom). Mass spectrum:
m/z 159.22 (Irel 100%) [M – 18 + H]+. Found, %:
C 81.54; H 9.21. C12H16O. Calculated, %: C 81.83;
H 9.16. M 176.26.
(E/Z)-3,6-Dimethylhept-2-en-1-ol (IVi). Yield
98%, colorless liquid. IR spectrum, ν, cm–1: 3428
1
(OH), 1646 (C=C). H NMR spectrum, δ, ppm: 0.90 s
(6H, CH3), 1.23–1.31 m (2H, CH2), 1.50–1.58 m (1H,
CH), 1.68 s (0.7·3H, CH3C=C), 1.74 s (0.3·3H,
CH3C=C), 2.02 t (0.7·2H, CH2, J = 5.8 Hz), 2.08 t
(0.3·2H, CH2, J = 5.8 Hz), 4.12 d (2H, OCH2, J =
6.7 Hz), 5.42 t (1H, CH=C, J = 6.7 Hz). Mass spec-
trum: m/z 125.38 (Irel 100%) [M – 18 + H]+. Found, %:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 7 2014

MOSKALENKO, BOEV
Compounds Vb–Vi were synthesized in a similar (0.28·3H, CH3), 3.40 s (0.72·2H, CH2), 3.55 s
958
way.
(0.28·2H, CH2), 4.01 d (0.72·2H, CH2Br, J = 8.9 Hz),
4.15 d (0.28·2H, CH2Br, J = 8.9 Hz), 5.62 t (0.72H,
CH=C, J = 8.9 Hz), 5.76 t (0.28H, CH=C, J = 8.9 Hz),
7.26–7.52 m (4H, Harom). Mass spectrum: m/z 213.05
(Irel 100%) [M – 80]+. Found, %: C 49.05; H 4.26.
C12H12BrF3. Calculated, %: C 49.26; H 4.17.
M 293.12.
1-[(E/Z)-4-Bromo-2-methylbut-2-en-1-yl]-4-
fluorobenzene (Vb). Yield 83%, colorless liquid. IR
spectrum: ν 1646 cm–1 (C=C). H NMR spectrum, δ,
1
ppm: 1.70 s (3H, CH3), 3.28 s (0.78·2H, CH2), 3.47 s
(0.22·2H, CH2), 4.03 d (0.78·2H, CH2Br, J = 8.6 Hz),
4.11 d (0.22·2H, CH2Br, J = 8.6 Hz), 5.61 t (0.8H,
CH=C, J = 8.6 Hz), 5.71 t (0.2H, CH=C, J = 8.6 Hz),
6.95–7.15 m (4H, Harom). Mass spectrum: m/z 163.04
(Irel 100%) [M – 80]+. Found, %: C 54.18; H 4.87.
C11H12BrF. Calculated, %: C 54.36; H 5.05. M 243.12.
[(E/Z)-4-Bromo-2-ethylbut-2-en-1-yl]benzene
(Vg). Yield 79%, colorless liquid. IR spectrum:
1
ν 1649 cm–1 (C=C). H NMR spectrum, δ, ppm: 0.90–
1.10 m (3H, CH3), 2.62–2.71 m (0.46·2H, CH2C=C),
2.81–2.88 m (0.54·2H, CH2C=C), 3.39 s (0.54·2H,
CH2), 3.51 s (0.46·2H, CH2), 4.05 d (0.58·2H, CH2Br,
J = 9.6 Hz), 4.13 d (0.42·2H, CH2Br, J = 9.6 Hz),
5.51 t (0.56H, CH=C, J = 9.6 Hz), 5.72 t (0.44H,
CH=C, J = 9.6 Hz), 7.18–7.31 m (5H, Harom). Mass
spectrum: m/z 159.16 (Irel 100%) [M – 80]+. Found, %:
C 60.21; H 6.14; Br 33.28. C12H15Br. Calculated, %:
C 60.34; H 6.35; Br 33.46. M 239.15.
1-[(E/Z)-4-Bromo-2-methylbut-2-en-1-yl]-2-
chlorobenzene (Vc). Yield 82%, colorless liquid. IR
spectrum: ν 1648 cm–1 (C=C). H NMR spectrum, δ,
1
ppm: 1.70 s (0.22·3H, CH3), 1.74 s (0.78·3H, CH3),
3.50 s (0.78·2H, CH2), 3.62 s (0.22·2H, CH2), 4.02 d
(0.75·2H, CH2Br, J = 9.6 Hz), 4.12 d (0.25·2H, CH2Br,
J = 9.6 Hz), 5.49 t (0.78H, CH=C, J = 9.6 Hz), 5.75 t
(0.22H, CH=C, J = 9.6 Hz), 7.15–7.37 m (4H, Harom).
Mass spectrum: m/z 181.01 (Irel 100%) [M – 80]+.
Found, %: C 50.83; H 4.68. C11H12BrCl. Calculated,
%: C 50.96; H 4.74. M 259.57.
[(E/Z)-5-Bromo-3-methylpent-2-en-1-yl]benzene
(Vh). Yield 92%, colorless liquid. IR spectrum:
ν 1648 cm–1 (C=C). 1H NMR spectrum, δ, ppm: 1.75 s
(0.73·3H, CH3C=C), 1.77 s (0.27·3H, CH3C=C), 2.30 t
(0.72·2H, CH2, J = 5.8 Hz), 2.44 t (0.28·2H, CH2, J =
5.8 Hz), 2.78 t (2H, CH2C=C, J = 5.8 Hz), 3.80 d
(0.27·2H, CH2Br, J = 9.0 Hz), 4.00 d (0.73·2H, CH2Br,
J = 9.0 Hz), 5.51 t (1H, CH=C, J = 9.0 Hz), 7.10–
7.30 m (5H, Harom). Mass spectrum: m/z 159.24
(Irel 100%) [M – 80]+. Found, %: C 60.18; H 6.47;
Br 33.24. C12H15Br. Calculated, %: C 60.34; H 6.35;
Br 33.46. M 239.15.
1-[(E/Z)-4-Bromo-2-methylbut-2-en-1-yl]-3-
chlorobenzene (Vd). Yield 65%, colorless liquid. IR
spectrum: ν 1649 cm–1 (C=C). H NMR spectrum, δ,
1
ppm: 1.67 s (0.76·3H, CH3), 1.70 s (0.24·3H, CH3),
3.28 s (0.76·2H, CH2), 3.42 s (0.24·2H, CH2), 4.02 d
(0.74·2H, CH2Br, J = 9.4 Hz), 4.12 d (0.26·2H, CH2Br,
J = 9.4 Hz), 5.63 t (0.78H, CH=C, J = 9.4 Hz), 5.74 t
(0.22H, CH=C, J = 9.4 Hz), 7.03–7.24 m (4H, Harom).
Mass spectrum: m/z 181.16 (Irel 100%) [M – 80]+.
Found, %: C 50.71; H 4.86. C11H12BrCl. Calculated,
%: C 50.96; H 4.74. M 259.57.
(E/Z)-1-Bromo-3,6-dimethylhept-2-ene (Vi).
Yield 68%, colorless liquid. IR spectrum: ν 1645 cm–1
1
(C=C). H NMR spectrum, δ, ppm: 0.87–0.95 m (6H,
1-[(E/Z)-4-Bromo-3-methylbut-2-en-1-yl]-4-
chlorobenzene (Ve). Yield 94%, colorless liquid. IR
CH3), 1.27–1.35 m (2H, CH2), 1.49–1.61 m (1H, CH),
1.73 s (0.68·3H, CH3C=C), 1.76 s (0.32·3H, CH3C=C),
2.05 t (0.7·2H, CH2, J = 6.4 Hz), 2.12 t (0.3·2H, CH2,
J = 6.4 Hz), 4.02 d (2H, CH2Br, J = 11.2 Hz), 5.51 t
(1H, CH=C, J = 11.2 Hz). Mass spectrum: m/z 125.41
(Irel 100%) [M – 80]+. Found, %: C 52.63; H 8.26;
Br 38.85. C9H17Br. Calculated, %: C 52.76; H 8.43;
Br 39.04. M 205.14.
spectrum: ν 1650 cm–1 (C=C). H NMR spectrum, δ,
1
ppm: 1.65 s (0.77·3H, CH3), 1.68 s (0.23·3H, CH3),
3.26 s (0.77·2H, CH2), 3.40 s (0.23·2H, CH2), 4.01 d
(0.7·2H, CH2Br, J = 9.4 Hz), 4.11 d (0.3·2H, CH2Br,
J = 9.4 Hz), 5.61 t (0.78H, CH=C, J = 9.4 Hz), 5.71 t
(0.22H, CH=C, J = 9.4 Hz), 7.08 d and 7.26 d (2H,
H
arom, J = 8.2 Hz). Mass spectrum: m/z 181.00
(Irel 100%) [M – 80]+. Found, %: C 50.69; H 4.86.
C11H12BrCl. Calculated, %: C 50.96; H 4.74.
M 259.57.
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1
spectrum, δ, ppm: 1.69 s (0.72·3H, CH3), 1.73 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 7 2014

DEVELOPMENT OF GENERAL METHODS
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