Preparation and reactions of 2-chloro-3,4-epoxy-1-butene: a convenient route to (Z)-3-chloroallylic alcohols.

Article abstract of DOI:10.1021/jo020079l

Epoxide 2 was prepared from 3,4-dichloro-1-butene (1) by epoxidation with m-CPBA and subsequent dehydrohalogenation of the intermediate dichloroepoxide with molten KOH, affording 2 in 64% overall yield (2 steps). Catalytic CuBr/SMe(2)-mediated S(N)2' addition of sp(2)- or sp(3)-hybridized Grignard reagents to 2-chloro-3,4-epoxy-1-butene (2) afforded (Z)-3-chloroallylic alcohols such as 3 in good yields and with high regio- and stereoselectivity.

Full text of DOI:10.1021/jo020079l

J . Org. Chem. 2002, 67, 3847-3851
3847
P r ep a r a tion a n d Rea ction s of 2-Ch lor o-3,4-ep oxy-1-bu ten e: A
Con ven ien t Rou te to (Z)-3-Ch lor oa llylic Alcoh ols
Douglass F. Taber* and J effrey V. Mitten
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716
taberdf@udel.edu
Received February 1, 2002
Epoxide 2 was prepared from 3,4-dichloro-1-butene (1) by epoxidation with m-CPBA and subsequent
dehydrohalogenation of the intermediate dichloroepoxide with molten KOH, affording 2 in 64%
overall yield (2 steps). Catalytic CuBr/SMe2-mediated SN2′ addition of sp2- or sp3-hybridized Grignard
reagents to 2-chloro-3,4-epoxy-1-butene (2) afforded (Z)-3-chloroallylic alcohols such as 3 in good
yields and with high regio- and stereoselectivity.
In tr od u ction
The marine natural products halichlorine (1) and the
pinnaic acids (2 and 3) are of particular interest to
organic synthesis chemists because of their interesting
biological activities and unique structural frameworks.1
One problem in the synthesis of this class of marine
alkaloids is the preparation of the internal (Z)-chloro-
alkene moieties. The most general method for the prepa-
ration of (Z)-chloroalkenes has been the Pd(II)-mediated
coupling of Grignard or organozinc nucleophiles with 1,1-
dichloro-1-alkenes.2 (Z)-Chloroalkenes have also been
prepared by acid-catalyzed dehydration of ketones in the
presence of acyl halides.3 (Z)-3-Chloroallylic alcohols have
been prepared via the electrophilic addition of CH2O‚
Me2AlCl to alkynes.4 (E)-Chloroalkenes have been pre-
pared by Ru(I)-mediated coupling of alkynes with enones.5
We envisioned that copper-catalyzed SN2′ opening of the
title compound (epoxide 5) would provide a verstatile
entry to (Z)-3-chloroallylic alcohols with high regio- and
stereoselectivity. Herein, we report an improved prepara-
tion of epoxide 5. Copper(I) bromide/dimethyl sulfide
mediated SN2′ opening of epoxide 5 with Grignard
reagents afforded the (Z)-3-chloroallylic alcohols 6 in good
yields and with high regio- and stereoselectivity.
P r ep a r a tion of 2-Ch lor o-3,4-ep oxy-1-bu ten e. Ep-
oxide 5 was prepared (Scheme 1) by epoxidation of the
commercially available dichloroalkene 4. It had been
reported that treatment of the dichloroepoxide (7) with
different bases gave variable yields of the epoxide 5,
accompanied by unreacted starting material and the
other regioisomer.6 After some experimentation, we found
that dropwise addition of 7 to molten potassium hydrox-
ide (neat, 120 °C, bath temperature) under a nitrogen
atmosphere gave clean conversion to epoxide 5 (64%
overall yield from 4).
P r ep a r a tion of (Z)-3-Ch lor oa llylic Alcoh ols. Treat-
ment of the title compound (5) with a solution of 1.0 M
phenylmagnesium bromide (8) in THF afforded (Table
1) a mixture of the 1,4-addition products (Z/ E-9), the 1,2-
addition product (10), and the 1,1-addition product (11)
in a ratio of 2.5:1.0:3.5, respectively, in 70% total yield.
To improve the regioselectivity of this reaction, copper(I)
bromide/dimethyl sulfide catalysis was investigated. By
careful optimization of the reaction conditions, the de-
sired (Z)-3-chloroalkene 9 could be made the dominant
product of the reaction. Changing the reaction solvent
or using other additives in the reaction, including LiBr,
HMPA, or TMSCl as a trapping agent, either had no
effect or adversely affected the desired outcome.
(1) For the structural determination and biological activity of
halichlorine, see: (a) Kuramoto, M.; Tong, C.; Yamada, K.; Chiba, T.;
Hayashi, Y.; Uemura, D. Tetrahedron Lett. 1996, 37, 3867. (b) Arimoto,
H.; Hayakawa, I.; Kuramoto, M.; Uemura, D. Tetrahedron Lett. 1998,
39, 861. (c) Trauner, D.; Churchill, D. G.; Danishefsky, S. J . Helv. Chim.
Acta 2000, 83, 2344. For the structural determination and biological
activity of the pinnaic acids, see: (d) Chou, T.; Kuramoto, M.; Otani,
Y.; Shikano, M.; Yazawa, K.; Uemura, D. Tetrahedron Lett. 1996, 37,
3871. For the synthesis of halichlorine, see: (e) Trauner, D.; Schwarz,
J . B.; Danishefsky, S. J . Angew. Chem., Int. Ed. 1999, 38, 3542. (f)
Trauner, D.; Danishefsky, S. J . Tetrahedron Lett. 1999, 40, 6513. For
approaches to halichlorine and the pinnaic acids, see: (g) Keen, S. P.;
Weinreb, S. M. J . Org. Chem. 1998, 63, 6739. (h) Arimoto, H.; Asano,
S.; Uemura, D. Tetrahedron Lett. 1999, 40, 3583. (i) Lee, S.; Zhao, Z.
Org. Lett. 1999, 1, 681. (j) Koviach, J . L.; Forsyth, C. J . Tetrahedron
Lett. 1999, 40, 8529. (k) Wright, D. L.; Schulte, J . P., II.; Page, M. A.
Org. Lett. 2000, 2, 1847. (l) Shindo, M.; Fukuda, Y.; Shishido, K.
Tetrahedron Lett. 2000, 41, 929. (m) Yakota, W.; Shindo, M.; Shishido,
K. Heterocycles 2001, 54, 871.
(2) Minato, A.; Suzuki, K. J . Am. Chem. Soc. 1987, 109, 1257.
(3) Moughamir, K.; Mezgueldi, B.; Atmani, A.; Mestdagh, H.;
Rolando, C. Tetrahedron Lett. 1998, 39, 59.
(4) Rodini, D. J .; Snider, B. B. Tetrahedron Lett. 1980, 21, 3857.
(5) Trost, B. M.; Pinkerton, A. B. J . Am. Chem. Soc. 1999, 121, 1988.
(6) Hawkins, E. C. E. J . Chem. Soc. 1958, 248.
10.1021/jo020079l CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/07/2002

3848 J . Org. Chem., Vol. 67, No. 11, 2002
Taber and Mitten
Ta ble 1. Effect of Cu X a n d Equ iva len ts on Regioch em istr y a n d Ster eoch em istr y of SN2′ Ad d ition P r od u ct
product distributna
entry
CuX
equiv of CuX
temp (°C)
9
10
11
3.5
yieldb
Z:E ratioa (9)
c
c
c
c
c
c
d
d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Br/SMe2
Br/SMe2
Br/SMe2
Br/SMe2
Br/SMe2
Br/SMe2
Br/SMe2
Br/SMe2
Cld
0.000
0.025
0.050
0.100
0.100
0.200
0.200
1.000
0.200
1.000
0.200
1.000
0.200
0.200
0.200
1.000
0.200
1.000
-40
-40
-40
-40
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
2.5
4.5
6.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
70%
69%
67%
61%
71%
69%
81%
64%
72%
66%
67%
84%
66%
70%
64%
50%
75%
79%
36:1
12:1
26:1
22:1
16:1
17:1
15:1
14:1
12:1
14:1
16:1
15:1
14:1
16:1
13:1
10:1
16:1
11:1
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
trace
10.9
12.1
14.2
16.6
54.1
22.8
37.1
25.2
18.7
22.6
18.4
8.0
Cld
Brd
Brd
Brd,e
Br/PPh3
Id
Id
3.8
21.9
6.4
CNd
CNd
a
b
d
From 1H NMR. Isolated. c Saturated aqueous NH4Cl workup. Aqueous 5% HCl workup. e Dried.
Sch em e 1
chloroalkenes with organometallic reagents yield di- and
trisubstituted alkenes7 and nitriles.8 The chloroalkene
moiety can also be converted to a ketone,9 an R-halo-
ketone,10,11 a vinyl silane,12 an alkene,13 or an alkyne.14
The approach delineated here will make (Z)-3-chloro-
allylic alcohols more readily available for use in organic
synthesis.
Sch em e 2
Exp er im en ta l Section
Gen er a l Meth od s. All air- and moisture-sensitive reactions
were performed under an atmosphere of dry nitrogen. Tetra-
hydrofuran (THF) was distilled from sodium metal/benzo-
phenone ketyl, and methylene chloride (CH2Cl2) was distilled
1
from calcium hydride immediately prior to use. H NMR and
13C NMR spectra were recorded at 400 or 100 MHz, respec-
tively using deuteriochloroform (CDCl3) as solvent with 1% v/v
TMS (tetramethylsilane) ) 0.00 as an internal standard,
unless otherwise specified. 13C multiplicities were determined
with the aid of an APT (attached proton test) pulse sequence,
differentiating the signals for methyl and methine carbons as
down, “d”, from methylene and quaternary carbons as up, “u”.
The infrared (IR) spectra were determined as neat oils on 4
mm sodium chloride plates, unless otherwise indicated. Mass
spectra (MS) were obtained by chemical ionization (CI) in NH3
or CH4 or by electronic ionization (EI) with an ionizing
potential of 70 eV, unless otherwise indicated. Elemental
analyses were performed by Galbraith Laboratories, Knoxville,
(7) (a) Ratovelomanana, V.; Linstrumelle, G. Synth. Commun. 1984,
14, 179. (b) Ramiandrasoa, P.; Brehon, B.; Thivet, A.; Alami, M.;
Cahiez, G. Tetrahedron Lett. 1997, 38, 2447. (c) Littke, A. F.; Dai, C.
Y.; Fu, G. C. J . Am. Chem. Soc. 2000, 122, 4020. (d) Dai, C. Y.; Fu, G.
C. J . Am. Chem. Soc. 2001, 123, 2719.
(8) Yamamura, K.; Murahashi, S. I. Tetrahedron Lett. 1977, 4429.
(9) (a) Mukaiyama, T.; Imamoto, T.; Kobayashi, S. Chem. Lett. 1973,
261. (b) Mukaiyama, T.; Imamoto, T.; Kobayashi, S. Chem. Lett. 1973,
715. (c) Yoshioka, H.; Takasaki, K.; Kobayashi, M.; Matsumoto, T.
1979, 37, 3489.
(10) Morton, H. E.; Leanna, M. R. Tetrahedron Lett. 1993, 34, 4481.
(11) Griesbaum, K.; Lie, G. O.; Raupp, E. Chem. Ber. 1981, 114,
3273.
(12) Hurdlik, P. F.; Kulkarni, A. K.; J ain, S.; Hurdlik, A. F.
Tetrahedron 1983, 39, 877.
Other Grignard reagents also participated efficiently
in this reaction (Table 2). With these additions, the
products corresponding to 10 and 11 were observed at
most as minor product (<3%, combined).
The alcohols as prepared were sufficiently pure for
most purposes. We found that, for 9, the purity could be
improved by recrystallization of the derived phenyl
urethane 14 (Scheme 2).
Con clu sion
(13) Vanderesse, R.; Brunet, J . J .; Caubere, P. J . Org. Chem. 1981,
46, 1270.
(14) Hatch, L. F.; Chiola, V. J . Am. Chem. Soc. 1951, 73, 360.
Chloroalkenes are useful intermediates for target-
directed synthesis. Pd- and Ni-mediated coupling of

(Z)-3-Chloroallylic Alcohols
Ta ble 2. Exa m p les of Gr ign a r d Ad d ition to
J . Org. Chem., Vol. 67, No. 11, 2002 3849
filtered again to remove solids, which were rinsed again with
chilled (-78 °C) CH2Cl2. The filtrate was then cooled to 0 °C
and neutralized with 125 mL of saturated aqueous NaHCO3
with vigorous stirring to remove residual acid. The organic
layer was then partitioned between Et2O and brine. The
combined organic extract was dried (Na2SO4) and then con-
centrated to a pale yellow oil. The oil was bulb-to-bulb distilled,
bp0.1mm(pot) ) 85 °C, to afford 23.7 g (85% yield) of 1,2-dichloro-
3,4-epoxybutane (7) as a clear colorless liquid (1.3:1 mixture
of diastereomers): 1H NMR (CDCl3) major isomer δ 2.78 (dd,
1H, J ) 2.50 and 4.76 Hz), 2.94 (dd, 1H, J ) 4.08 and 4.75
Hz), 3.28 (ddd, 1H, J ) 2.50 and 4.08 Hz and 7.26 Hz), 3.73
(dt, 1H, 5.3 and 7.26 Hz), 3.89 (d, 2H, J ) 5.3 Hz), minor isomer
δ 2.89 (dd, 1H, J ) 2.50 and 4.75 Hz), 3.00 (dd, 1H, J ) 4.08
and 4.75 Hz), 3.18 (tt, 1H, J ) 2.50 and 4.08 Hz), 3.76 (m,
3H); 13C NMR (u) δ 46.3, 47.8, (d) δ 52.3, 60.1, minor isomer
(u) δ 44.6, 46.8, (d) δ 53.3, 60.7; IR (neat) 3065, 3001, 2956,
1430, 1256 cm-1; MS (CI) m/z 105 ([M - Cl]+, 100), 107 (31);
HRMS calcd for C4H6ClO ([M - Cl]+) 105.0107, found 105.0112.
2-Ch lor o-3,4-ep oxy-1-bu ten e
2-Ch lor o-3,4-ep oxy-1-bu ten e (5). In a two-neck 100 mL
round-bottom flask equipped with an addition funnel and a
short-path distillation head was placed 10.5 g of KOH (187.3
mmol), which was melted at 120 °C (bath). Then, 15.0 g of
epoxide 7 (106.4 mmol) was added over 15 min to the molten
KOH with rapid stirring. The desired epoxide (5) flash distilled
into the receiving flask. After complete addition of 7, the bath
temperature was raised to 200 °C. The distillate was then
dried (Na2SO4) and filtered. This afforded 8.34 g (75% yield)
of 2-chloro-3,4-epoxy-1-butene (5) as a clear colorless liquid:
1H NMR (CDCl3) δ 2.89-2.95 (m, 2H), 3.53-3.54 (m, 1H), 5.46
(d, 1H, J ) 1.7 Hz), 5.62 (dd, 1H, J ) 1.2 and 1.7 Hz); 13C
NMR (u) δ 7.4, 115.2, 137.9, (d) δ 52.6; IR (neat) 1730, 1632,
1458, 1394, 1261, 1112, 899 cm-1; MS (CI) m/z 104 (M+, 100),
106 (M+, 40); HRMS calcd for C4H5ClO (M+) 104.0029, found
104.0026.
Gen er a l P r oced u r e. (Z)-3-Ch lor o-4-p h en yl-2-bu ten -1-
ol (9). Epoxide 5 (205 mg, 1.95 mmol) and CuBr/SMe2 (82 mg,
0.40 mmol) were suspended in THF (1.9 mL) and cooled to
-20 °C. Then, dropwise addition of 4.6 mL of 0.5 M phenyl-
magnesium bromide (2.3 mmol in THF) was effected over 1.25
h. The mixture was stirred at -20 °C for an 1 h and then
warmed to room temperature. The reaction mixture was
quenched with 10 mL of 5% aqueous HCl and then partitioned
between Et2O and brine. The combined organic extract was
dried (Na2SO4) and concentrated in vacuo. The residue was
chromatographed to give 9 (298 mg, 86% yield) as a mixture
(Z/E, 16.4:1) as a pale yellow oil: 1H NMR (CDCl3) major
isomer δ 1.84 (bs, exch, 1H), 3.63 (s, 2H), 4.29 (d, 2H, J ) 6.1
Hz), 5.74 (tt, 1H, J ) 1.2 and 6.1 Hz), 7.21-7.34 (m, 5H), minor
isomer δ 1.25 (bs, exch, 1H), 3.74 (s, 2H), 6.00 (t, 1H, J ) 7.4
Hz); 13C NMR (u) δ 45.8, 60.0, 136.0, 136.9, (d) δ 126.3, 127.2,
128.7, 129.3; IR (neat) ν 3334, 3029, 2916, 1660, 1495, 1454,
1071, 1011 cm-1; MS (CI) m/z 200 (M + NH4+, 100), 202 (36);
HRMS calcd for (M+) C10H15NClO 200.0842, found 200.0832;
TLC Rf ) 0.16.
(Z)-3-Ch lor o-4-ph en yl-2-bu ten -1-ol P h en ylu r eth an e (14).
The mixture of 9 (190 mg, 1.04 mmol) was dissolved in CH2Cl2
(10 mL) to which was added pyridine (125 µL, 122.3 mmol)
and phenyl isocyanate (130 µL, 1.2 mmol). The resulting
mixture was stirred vigorously at room temperature. After 4
h, the reaction was complete (TLC). The mixture was quenched
with 10 mL of 5% aqueous HCl and partitioned between Et2O
and brine. The combined organic extract was dried (Na2SO4)
and concentrated in vacuo. The residue was chromatographed
to afford 14 (254 mg, 84% yield) as a white crystalline residue
(mp 63-65 °C). This was recrystallized from PE to afford 239
mg of bright white needles (Z/E, g99:1): 1H NMR (CDCl3) δ
3.66 (s, 2H), 4.83 (d, 2H, J ) 6.2 Hz), 5.75 (t, 1H, J ) 6.2 Hz),
6.64 (bs, exch, 1H), 7.07 (t, 1H, J ) 6.7 Hz), 7.23-7.38 (m,
9H); 13C NMR (u) δ 45.6, 62.0, 136.4, 137.6, 138.0, d: δ 121.7,
123.5, 127.1, 128.6, 129.1; IR (thin film) 3323, 3029, 1708,
1601, 1539, 1445 cm-1; MS (CI) m/z 301 (M+, 95), 302 (M +
H+, 81), 303 (44), 304 (29); HRMS calcd for C17H16NClO2 (M+)
301.0869, found 301.0859. Anal. Calcd for C17H16NClO2: C,
TN. Substances for which C, H, N analyses are not reported
were purified as specified and gave spectroscopic data consist-
ent with being g95% the assigned structure. For column
chromatography, 230-400 mesh 60 Å silica gel was used
following to the procedure of Taber.15 Rf values indicated refer
to thin-layer chromatography (TLC) on 2.5 × 10 cm, 250 µm
analytical plates coated with silica gel GF developed in 20%
MTBE/PE solvent system, unless otherwise indicated. Solvents
are reported as volume/volume mixtures. All glassware was
oven dried and cooled under a dry nitrogen stream im-
mediately prior to use. MTBE is methyl tert-butyl ether; PE
is petroleum ether.
1,2-Dich lor o-3,4-ep oxybu ta n e (7). To a stirring slurry of
123.6 g (500 mmol) of 70% m-CPBA in 200 mL of CH2Cl2 at
ambient temperature was added 21.7 mL (200 mmol) of 3,4-
dichloro-1-butene (4) over 5 min. Stirring was continued until
TLC showed the dichloroalkene to be consumed (72 h). The
reaction mixture was then cooled to 0 °C and filtered to remove
solids, which were rinsed with an additional 50 mL of chilled
(-78 °C) CH2Cl2. The filtrate was concentrated in vacuo and
(15) Taber, D. F. J . Org. Chem. 1982, 47, 1351.

3850 J . Org. Chem., Vol. 67, No. 11, 2002
Taber and Mitten
67.66; H, 5.34; N, 4.64. Found: C, 67.37; H, 5.37; N, 4.64.
TLC: Rf ) 0.51; Rf (10% MTBE/PE) ) 0.25. Mp: 74-75 °C.
(Z)-3-Ch lor o-4-(4-m eth oxyp h en yl)-2-bu ten -1-ol (13a ).
By a procedure similar to that for 9, epoxide 5 (200 mg, 1.9
mmol) and CuBr/SMe2 (81 mg, 0.39 mmol) were suspended in
THF (1.9 mL) and cooled to -20 °C. Then, dropwise addition
of 4.6 mL of 0.5 M (4-methoxyphenyl)magnesium bromide (2.3
mmol in THF) was effected over 1.25 h. The mixture was
stirred at -20 °C for 1 h and then warmed to room temper-
ature. The reaction mixture was quenched with 10 mL of 5%
aqueous HCl and then partitioned between Et2O and brine.
The combined organic extract was dried (Na2SO4) and con-
centrated in vacuo. The residue was chromatographed to give
13a (360 mg, 89% yield) as a mixture (Z/E, 11.1:1) as a pale
green oil: 1H NMR (CDCl3) major isomer δ 1.87 (bs, exch, 1H),
3.57 (s, 2H), 3.79 (s, 3H), 4.29 (d, 2H, J ) 6.2 Hz), 5.72 (tt,
1H, J ) 1.0 and 6.2 Hz), 6.86 (dq, 2H, 2.1 and 8.6 Hz), 7.14
(dq, 2H, 2.1 and 8.6 Hz), minor isomer δ 1.21 (bs, exch, 1H),
3.68 (s, 3H), 5.98 (t, 1H, J ) 7.4 Hz); 13C NMR (u) δ 44.7, 59.8,
128.7, 136.1, 158.5, (d) δ 55.2, 113.8, 125.7, 130.0; IR (neat)
3354, 2908, 1611, 1513, 1248, 1035 cm-1; MS (CI) 212 (M+,
100), 214 (31); HRMS calcd for C11H13ClO2 212.0604, found
212.0598; TLC Rf ) 0.16.
and cooled to -20 °C. Then, dropwise addition of 4.6 mL of
0.5 M isopropylmagnesium bromide (2.3 mmol in THF) was
effected over 1.25 h to give 13e (214 mg, 76% yield) as a
mixture (Z/ E, 22.1:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 0.91 (d, 6H, J ) 6.5 Hz), 1.57 (bs, exch, 1H),
2.01 (h, 1H, J ) 6.5 Hz), 2.19 (d, 2H, J ) 7.1 Hz), 4.31 (d, 2H,
J ) 6.2 Hz), 5.71 (t, 1H, J ) 6.2 Hz), minor isomer δ 2.26 (d,
2H, J ) 7.2 Hz), 5.92 (t, 3H, J ) 7.2 Hz); 13C NMR (u) δ 48.7,
60.0, 136.7, (d) δ 22.0, 26.0, 125.7; IR (neat) 3318, 2957, 1661
cm-1; MS (EI) m/z 148 (M+, 100), 150 (32); HRMS Calcd for
C7H13ClO (M+) 148.0655, found 148.0653; TLC Rf ) 0.19.
(Z)-3-Ch lor o-6-m eth yl-2-h ep ten -1-ol (13f). By a proce-
dure similar to that for 9, epoxide 5 (204 mg, 1.9 mmol) and
CuBr/SMe2 (83 mg, 0.40 mmol) were suspended in THF (1.9
mL) and cooled to -20 °C. Then, dropwise addition of 4.6 mL
of 0.5 M isobutylmagnesium bromide (2.3 mmol in THF) was
effected over 1.25 h. The mixture was stirred at -20 °C for 1
h and then warmed to room temperature. The reaction mixture
was quenched with 10 mL of 5% aqueous HCl and then
partitioned between Et2O and brine. The combined organic
extract was dried (Na2SO4) and concentrated in vacuo. The
residue was chromatographed to give 13f (240 mg, 78% yield)
as a mixture (Z/E, 18.0:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 0.91 (d, 6H, J ) 6.6 Hz), 1.45 (q, 2H, J ) 6.8
Hz), 1.55 (h, 1H, J ) 6.6 Hz), 1.78 (bs, exch, 1H), 2.34 (t, 2H,
J ) 0.6 and 6.8 Hz), 4.29 (d, 2H, J ) 6.2 Hz), 5.72 (tt, 1H, J
) 1.0 and 6.2 Hz), minor isomer δ 2.39 (t, 2H, J ) 7.5 Hz),
4.15 (d, 2H, J ) 7.5 Hz), 5.98 (t, 1H, J ) 7.5 Hz); 13C NMR (u)
δ 36.3, 37.3, 59.8, 137.7, (d) δ 22.4, 27.1, 124.0; IR (neat) 3323,
1662, 1468, 1007 cm-1; MS (EI) m/z 161 ([M - H]+, 100), 163
(33); HRMS calcd for C8H14ClO ([M - H]+) 161.0733, found
161.0726; TLC Rf ) 0.30.
(Z)-3-Ch lor o-7-m eth yl-2-octen -1-ol (13g). By a procedure
similar to that for 9, epoxide 5 (204 mg, 1.9 mmol) and CuBr/
SMe2 (82 mg, 0.40 mmol) were suspended in THF (1.9 mL)
and cooled to -20 °C. Then, dropwise addition of 4.6 mL of
0.5 M phenylmagnesium bromide (2.3 mmol in THF) was
effected over 1.5 h to give 13g (269 mg, 80% yield) as a mixture
(Z/E, 15.2:1) as a pale yellow oil: 1H NMR (CDCl3) major
isomer δ 0.88 (d, 6H, J ) 6.7 Hz), 1.17 (q, 2H, J ) 7.3 Hz),
1.52-1.60 (m, 3H), 2.32 (t, 2H, 7.3 Hz), 4.30 (d, 2H, J ) 6.2
Hz), 5.72 (tt, 1H, J ) 0.9 and 6.2 Hz), minor isomer δ 1.03 (d,
6H, J ) 6.7 Hz), 2.37 (t, 2H, J ) 7.4 Hz), 4.15 (t, 2H, J ) 7.4
Hz), 5.86 (t, 1H, J ) 7.4 Hz); 13C NMR (u) δ 25.0, 37.8, 39.6,
59.8, 137.4, (d) δ 22.5, 27.7, 124.2; IR (neat) 3322, 2955, 1662,
1468, 1016 cm-1; MS (EI) m/z 176 (M+, 100), 178 (32); HRMS
calcd for C9H17ClO (M+) 176.0968, found 176.0972; TLC Rf )
0.27.
(Z)-3-Ch lor o-2,6-h ep ta d ien -1-ol (13h ). By a procedure
similar to that for 9, epoxide 5 (200 mg, 1.9 mmol) and CuBr/
SMe2 (78 mg, 0.38 mmol) were suspended in THF (1.9 mL)
and cooled to -20 °C. Then, dropwise addition of 4.6 mL of
0.5 M phenylmagnesium bromide (2.3 mmol in THF) was
effected over 1.25 h to give 13h (201 mg, 72% yield) as a
mixture (Z/E, 7.0:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 1.49 (bs, exch, 1H), 2.32-2.36 (m, 2H), 2.42-
2.46 (m, 2H), 4.30 (d, 2H, J ) 6.2 Hz), 5.00-5.03 (m, 1H), 5.07
(ddt, 1H, J ) 1.6, 1.7, and 17.1 Hz), 5.75 (tt, 1H, J ) 1.0 and
6.2 Hz), 5.79 (ddt, 1H, J ) 6.7, 10.3, and 17.1 Hz), minor isomer
δ 1.23 (bs, exch, 1H), 4.09 (d, 2H, J ) 7.4 Hz), 5.86 (t, 1H, J )
7.4 Hz); 13C NMR (u) δ 31.3, 38.7, 59.8, 115.7, 136.4, (d) δ 124.9,
136.6; IR (neat) 3332,1661, 1642 cm-1; MS (CI) m/z 145 ([M -
H]+), 147 (34); HRMS calcd for C7H10ClO ([M - H]+) 145.0420,
found 145.0415; TLC Rf ) 0.25.
(Z)-3-Ch lor o-6-m eth yl-2,6-h ep ta d ien -1-ol (13i). By a
procedure similar to that for 9, epoxide 5 (202 mg, 1.9 mmol)
and CuBr/SMe2 (83 mg, 0.40 mmol) were suspended in THF
(1.9 mL) and cooled to -20 °C. Then, dropwise addition of 4.6
mL of 0.5 M phenylmagnesium bromide (2.3 mmol in THF)
was effected over 1.25 h to give 13i (226 mg, 74% yield) as a
mixture (Z/E, 6.5:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 1.50 (bs, exch, 1H), 1.73 (s, 3H), 2.27 (t, 2H, J
) 7.6 Hz), 2.48 (t, 2H, J ) 7.6 Hz), 4.30 (d, 2H, J ) 6.1 Hz),
4.70 (t, 1H, J ) 0.9 Hz), 4.79 (t, 1H, J ) 0.9 Hz), 5.74 (tt, 1H,
J ) 1.0 and 6.1 Hz), minor isomer δ 1.26 (bs, exch, 1H), 1.76
(Z)-3-Ch lor o-6-p h en yl-2-h exen -1-ol (13b). By a procedure
similar to that for 9, epoxide 5 (203 mg, 1.9 mmol) and CuBr/
SMe2 (82 mg, 0.40 mmol) were suspended in THF (1.9 mL)
and cooled to -20 °C. Then, dropwise addition of 4.6 mL of
0.5 M (phenylethyl)magnesium bromide (2.3 mmol in THF)
was effected over 1.5 h to give 13b (329 mg, 82% yield) as a
mixture (Z/E, 16.3:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 1.58 (bs, exch, 1H), 1.87-1.95 (m, 2H), 2.37 (t,
2H, J ) 7.3 Hz), 2.62 (t, 2H, J ) 7.7 Hz), 4.29 (d, 2H, J ) 6.1
Hz), 5.72 (tt, 1H, 0.9 and 6.1 Hz), 7.17-7.34 (m, 5H), minor
isomer δ 1.25 (bs, exch, 1H), 2.46 (t, 2H, J ) 7.4 Hz), 4.04 (d,
2H, J ) 7.4 Hz), 5.86 (t, 1H, J ) 7.4 Hz); 13C NMR (u) δ 28.7,
34.6, 38.7, 59.7, 136.7, 141.6, (d) δ 124.8, 125.9, 126.4, 128.4,
128.5, 129.0; IR (neat) 3342, 3027, 2942, 1661, 1454, 1028 cm-1
MS (CI) m/z 228 (M + NH4+, 100), 230 (32); HRMS calcd for
12H19NClO (M + NH4+) 228.1155, found 228.1153; TLC Rf )
0.23.
(Z)-3-Ch lor o-7-p h en yl-2-h ep ten -1-ol (13c). By a proce-
;
C
dure similar to that for 9, epoxide 5 (205 mg, 2.0 mmol) and
CuBr/SMe2 (81 mg, 0.39 mmol) were suspended in THF (1.9
mL) and cooled to -20 °C. Then, dropwise addition of 4.6 mL
of 0.5 M (phenylpropyl)magnesium bromide (2.3 mmol in THF)
was effected over 1.25 h to give 13c (327 mg, 77% yield) as a
mixture (Z/E, 20.1:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 1.58-1.65 (m, 4H), 1.88 (bs, exch, 1H), 2.33-
2.37 (m, 2H), 2.60-2.64 (m, 2H), 4.26 (d, 2H, J ) 6.2 Hz), 5.69
(tt, 1H, J ) 0.9 and 6.2 Hz), 7.16-7.30 (m, 5H), minor isomer
δ 4.10 (d, 2H, J ) 7.3 Hz), 5.83 (t, 1H, J ) 7.3 Hz); 13C NMR
(u) δ 26.7, 30.3, 35.6, 39.1, 59.7, 136.9, 142.2, (d) δ 124.5, 125.7,
128.3; IR (neat) 3334, 1661, 1503, 1496 cm-1; MS (CI) m/z 242
(M + NH4+, 100), 244 (31); HRMS calcd for C13H21NClO (M +
NH4+) 242.1311, found 242.1300; TLC Rf ) 0.24.
(Z)-3-Ch lor o-4-cycloh exyl-2-bu ten -1-ol (13d ). By a pro-
cedure similar to that for 9, epoxide 5 (203 mg, 1.9 mmol) and
CuBr/SMe2 (83 mg, 0.40 mmol) were suspended in THF (1.9
mL) and cooled to -20 °C. Then, dropwise addition of 4.6 mL
of 0.5 M phenylmagnesium bromide (2.3 mmol in THF) was
effected over 1.5 h to give 13d (264 mg, 74% yield) as a mixture
(Z/E, 23.5:1) as a pale yellow oil: 1H NMR (CDCl3) major
isomer δ 0.79-0.87 (m, 2H), 1.04-1.26 (m, 3H), 1.57-1.68 (m,
6H), 2.01 (bs, exch, 1H), 2.16 (d, 2H, J ) 6.5 Hz), 4.25 (d, 2H,
J ) 6.2 Hz), 5.64 (t, 1H, J ) 6.2 Hz), minor isomer δ 4.08 (d,
2H, J ) 7.4 Hz), 5.84 (t, 1H, J ) 7.4 Hz); 13C NMR (u) δ 26.0,
26.3, 32.5, 47.1, 59.7, 135.7, (d) δ 34.9, 125.5; IR (neat) 3327,
+
1660, 1089, 1061, 1013 cm-1; MS (CI) m/z 206 (M + NH4
100), 208 (33); HRMS calcd for C10H21NClO (M + NH4
,
+
)
206.1312, found 206.1301; MS (EI) m/z 188 (M+, 100), 190 (32);
HRMS calcd for C10H17ClO (M+) 188.0968, found 188.0962;
TLC Rf ) 0.30.
(Z)-3-Ch lor o-5-m eth yl-2-h exen -1-ol (13e). By a procedure
similar to that for 9, epoxide 5 (203 mg, 1.9 mmol) and CuBr/
SMe2 (83 mg, 0.40 mmol) were suspended in THF (1.9 mL)

(Z)-3-Chloroallylic Alcohols
J . Org. Chem., Vol. 67, No. 11, 2002 3851
(s, 3H), 4.11 (d, 2H, J ) 7.5 Hz), 5.89 (t, 1H, J ) 7.5 Hz); 13C
NMR (u) δ 35.8, 38.1, 60.2, 111.3, 137.2, 144.4, (d) δ 22.8, 125.1;
IR (neat) ν 3331, 2936, 1651, 1445, 1375, 1105, 1016, 891, 646
cm-1; MS (EI) m/z 160 (M+, 100), 162 (31); HRMS calcd for
C8H13ClO (M+) 160.0655, found 160.0663; TLC Rf ) 0.25.
(Z)-3-Ch lor o-2,7-octa d ien -1-ol (13j). By a procedure simi-
lar to that for 9, epoxide 5 (200 mg, 1.9 mmol) and CuBr/SMe2
(78 mg, 0.38 mmol) were suspended in THF (1.9 mL) and
cooled to -20 °C. Then, dropwise addition of 4.6 mL of 0.5 M
phenylmagnesium bromide (2.3 mmol in THF) was effected
over 1.25 h to give 13j (266 mg, 87% yield) as a mixture (Z/E,
13.8:1) as a pale yellow oil: 1H NMR (CDCl3) major isomer δ
1.56 (bs, exch, 1H), 1.64 (p, 2H, J ) 7.4 Hz), 2.03 (dtt, 2H, J
) 1.3, 6.7, and 7.4 Hz), 2.33 (t, 2H, J ) 7.4 Hz), 4.28 (d, 2H,
J ) 6.2 Hz), 4.97-5.00 (m, 1H), 5.04 (ddt, 1H, J ) 1.7, 1.7,
and 17.2 Hz), 5.71 (tt, 1H, J ) 0.9 and 6.2 Hz), 5.77 (ddt, 1H,
6.7, 10.2, and 17.2 Hz), minor isomer δ 1.25 (bs, exch, 1H),
2.41 (t, 2H, J ) 7.4 Hz), 4.14 (d, 2H, J ) 7.4 Hz); 13C NMR (u)
δ 26.2, 32.5, 38.6, 59.7, 115.1, 136.9; (d) δ 124.6, 137.9; IR
(neat) 3316, 2935, 1661, 1642, 1433 cm-1; MS (EI) m/z 160
(M+, 100), 162 (31); HRMS calcd for C8H13ClO (M+) 160.0655,
found 160.0654; TLC Rf ) 0.26.
effected over 1.25 h to give 13k (402 mg, 76% yield) as a
mixture (Z/E, 14.5:1) as a pale yellow oil: 1H NMR (CDCl3)
major isomer δ 0.88 (t, 3H, J ) 6.8 Hz), 1.26 (s, 22H), 1.55
(bs, exch, 1H), 2.32 (t, 2H, J ) 7.4 Hz), 4.29 (d, 2H, J ) 6.2
Hz), 5.72 (t, 1H, J ) 6.2 Hz), minor isomer δ 2.36 (t, 2H, J )
7.4 Hz), 4.13 (d, 2H, J ) 7.4 Hz), t, 1H, J ) 7.4 Hz); 13C NMR
(u) δ 22.92, 27.38, 28.80, 29.56, 29.58, 29.74, 29.85, 29.87,
29.90, 32.14, 39.59, 60.04, 137.77, (d) δ 14.37, 124.41; IR (neat)
3320, 1661, 1466 cm-1; MS (EI) m/z 274 (M+, 100), 276 (31);
HRMS calcd for C16H31ClO (M+) 274.2063, found 274.2072;
TLC Rf ) 0.22.
Ack n ow led gm en t . We thank the NIH (Grant
GM60287) and the University of Delaware for support
of this work. J .V.M. gives special thanks to both Dr.
Steve Bai and J ohn Dykins for help with 2D-NMR
experiments and MS analyses, respectively, and Dr.
Pierre H. Storck for aid with spectroscopic interpreta-
tion.
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C spectra
for all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
(Z)-3-Ch lor o-2-h exa d ecen -1-ol (13k ). By a procedure
similar to that for 9, epoxide 5 (200 mg, 1.9 mmol) and CuBr/
SMe2 (78 mg, 0.38 mmol) were suspended in THF (1.9 mL)
and cooled to -20 °C. Then, dropwise addition of 4.6 mL of
0.5 M phenylmagnesium bromide (2.3 mmol in THF) was
J O020079L