Synthesis of α,α-dichloroalcohols, α-hydroxyketones and 1-chloro-1-arylalkylene oxides via protonation of acyllithium reagents

Article abstract of DOI:10.1016/S0022-328X(98)00797-9

The protonation of acyllithium reagents generated in situ from alkyllithiums and carbon monoxide in the presence of dichloromethane or dichloroarylmethanes produces α,α-dichloroalcohols in high yields. The reaction produces α-hydroxy-ketones in high yield

Full text of DOI:10.1016/S0022-328X(98)00797-9

Journal of Organometallic Chemistry 572 (1999) 31–36
Synthesis of h,h-dichloroalcohols, h-hydroxyketones and
-chloro-1-arylalkylene oxides via protonation of acyllithium reagents
1
George W. Kabalka *, Nan-Sheng Li, Su Yu
Department of Chemistry, The Uni6ersity of Tennessee, Knox6ille, TN 37996-1600, USA
Department of Radiology, The Uni6ersity of Tennessee, Knox6ille, TN 37996-1600, USA
Received 16 March 1998; received in revised form 5 June 1998
Abstract
The protonation of acyllithium reagents generated in situ from alkyllithiums and carbon monoxide in the presence of
dichloromethane or dichloroarylmethanes produces h,h-dichloroalcohols in high yields. The reaction produces h-hydroxy-ketones
in high yields when the aryl group of dichloroarylmethane contains a strong electron-donating group at the ortho or para position.
The transformation of h,h-dichloro-h-aryl alcohols into 1-chloro-1-arylalkylene oxides is achieved in high yields by using sodium
amide as a base. © 1999 Elsevier Science S.A. All rights reserved.
Keywords: h,h-Dichloroalcohols; h-Hydroxyketone; 1-Chloro-1-arylalkylene oxide; Acyllithium; Carbon monoxide
1
. Introduction
followed by the trapping of the acyl anion with elec-
trophiles [21,22]. This reaction was used successfully in
the synthesis of carbon-11 labelled carboxylic acid
amides [23]. Recently, we found that trialkylboranes
reacted with acyllithium reagents to afford ketones in
modest yields [24]. We also found that acyllithium
reagents could be protonated with dichloromethane
The transformation of organometallic reagents into
useful synthetic intermediates has played an important
role in organic synthesis for many years. One such
transformation is the carbonylation of organometallic
reagents with carbon monoxide. Studies involving acyl-
lithium reagents generated via the carbonylation of
organolithium with carbon monoxide have proven to
be especially productive [1–7]. For example, Seyferth
reported that acyllithium reagents, generated in situ
from an alkyllithium and carbon monoxide, react with
aldehydes [1], ketones [1], esters [8], lactones [9], iso-
cyanates [10], isothiocyanates [10], carbodiimides [11],
carbon disulfide [12], organic disulfides [13], and
trimethylchlorosilanes [14] to give acylated products.
Nudelman found that the acyllithium, generated from
phenyllithium and carbon monoxide, in the presence of
alkyl bromides gave diphenylalkylcarbinols [15,16]. In
addition, attention has been paid to the carbonylation
of lithium alkylamide with carbon monoxide [17–20],
[25], dichloroarylmethane [25], or acetonitrile [26] to
produce h,h-dichloroalcohols or i-hydroxynitriles. h,h-
Dichloroalcohols are important synthetic intermediates,
which can be transformed into substituted
chloroethylene oxides or h-chlorocarbonyl compounds
[
27–31]. The synthesis of h,h-dichloro alcohols is usu-
ally achieved via the reduction of h,h-dichloro ketones
27–29] or by the addition of the dichloromethyl anion
[
to aldehydes or ketones [30,31]. However, no general
method exists for the synthesis of h,h-dichloro-h-aryl
alcohols [32]. We wish to report the details of the
studies on the protonation of acyllithium reagents with
dichlorocompounds. This reaction provides a useful
synthetic method for the preparation of h,h-dichloroal-
cohols, h-hydroxyketones and 1-chloro-1-arylalkylene
oxides.
*
Corresponding author. Tel.: +1 423 9743260; fax: +1 423
9
0
742997; e-mail: kabalka@utk.edu
022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII S0022-328X(98)00797-9

32
G.W. Kabalka et al. / Journal of Organometallic Chemistry 572 (1999) 31–36
The reaction of a stoichiometric quantity of the
dichloro compound (2) with the acyllithium also led to
good yields of the product (Table 1, entries 7, 14, 16,
1
1
8, 20, 22 and 27; Table 2, entries 2, 3, 5, 9, 11, 12 and
3). The reaction is most efficient when R is a primary
1
alkyl group. Acyl anion reagents generated from sec-
ondary or tertiary alkyllithium reagents react with
dichloromethane to give h,h-dichloroalcohols in only
modest yields (Table 1, entries 8–12). The lower yields
observed with secondary and tertiary alkyllithium
reagents may be due to the steric interactions between
the bulkier aldehyde intermediates and the chlorinated
anion, Scheme 3. The reactions of acyl anion reagents
generated from secondary or tertiary alkyllithium with
dichloroarylmethane gave complex results.
Scheme 1.
2
. Results and discussion
The reaction of an alkyllithium reagent with carbon
monoxide in the presence of dichloromethane or
dichloroarylmethane generally produces h,h-dichloroal-
cohols, Scheme 1.
The reaction produces h-hydroxyketones when the
aryl group of dichloroarylmethane contains a strong
electron-donating group at the ortho or para position,
Scheme 2.
The syntheses are straightforward. Commercially
available alkyllithium reagents were utilized in this
study. However, as demonstrated by Seyferth for the
nucleophilic acylation of chlorosilane [14], other alkyl-
lithium reagents may be used. The reaction is initiated
by the slow addition of the alkyllithium reagent to a
solution of dichloromethane (or a dichloroarylmethane)
The reaction of n-butyllithium with carbon monoxide
in the presence of p-methyl-phenyldichloromethane
produces
1,1-dichloro-1-(p-methylphenyl)-2-hexanol,
along with a small amount of 1-(p-methylphenyl)-2-hy-
droxy-1-hexanone (Table 1, entries 17 and 18). The
h-hydroxyketone is presumably generated by the hy-
drolysis of the corresponding h,h-dichloro-h-aryl alco-
hols. An electron-donating group at the ortho or para
position of the aryl ring may enhance the hydrolysis of
the corresponding h,h-dichloro-h-aryl alcohols via a
SN1 side reaction.
The reaction presumably occurs via the intermediate
in
a
4:4:1 (by volume) solvent system of
formation of an aldehyde generated by proton abstrac-
tion from the dichloro reagent by the initially formed
acyl anion. The aldehyde then reacts with the chlorine-
stabilized anion as outlined in Scheme 3. The low
temperature (−110°C) is required for the formation of
the intermediate anion and, presumably, minimizes for-
mation of carbene intermediates. The h,h-dichloroalco-
hols are apparently hydrolyzed to generate
THF:Et O:pentane which has been saturated with car-
2
bon monoxide at −110°C. After the alkyllithium addi-
tion, the mixture is stirred at −110°C for 1 h, and the
reaction mixture is then hydrolyzed using saturated
aqueous NH Cl at 0°C. The products are isolated by
4
silica gel column chromatography. The results of the
synthesis of h,h-dichloroalcohols and h-hydroxyketones
are shown in Table 1 and Table 2, respectively.
As shown in the tables, generation of the acyllithium
reagent in the presence of dichloromethane (Table 1,
entry 1) was more efficient than generating the acyl-
lithium prior to the addition of dichloromethane (Table
2
h-hydroxyketones if R is an aryl group with a strong
electron-donating group at the ortho or para position.
h,h-Dichloro-h-aryl alcohols can be transformed into
1
-chloro-1-arylalkylene oxides. Interestingly, no reac-
tion occurred when h,h-dichloro-h-arylalcohols were
treated with sodium hydroxide in DMF or DMSO.
However, using aqueous sodium hydroxide in the pres-
ence of a phase transfer catalyst resulted in a partial
1
, entry 2). In addition, product yields decreased at
higher temperature (Table 1, entry 5). In most cases an
excess dichloro reagent (2) resulted in an increased
product yield; however, a large excess was not required.
Scheme 2.
Scheme 3.

G.W. Kabalka et al. / Journal of Organometallic Chemistry 572 (1999) 31–36
33
Table 1
The synthesis of h,h,-dichloroalcohols
Entrya
Productb
R1
R2
Molar equivalent ratio of 2:1
Yield (%)c
1
2
3a
3a
3a
3a
3a
3a
3a
3b
3b
3c
3c
3c
3d
3d
3e
3e
3f
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
s-Bu
s-Bu
t-Bu
t-Bu
t-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
H
H
H
H
H
H
H
H
H
H
H
H
Ph
Ph
15:1
15:1
6:1
4:1
4:1
2:1
1:1
6:1
4:1
15:1
6:1
4:1
2:1
1:1
2:1
1:1
2:1
1:1
2:1
1:1
2:1
1:1
2:1
6:1
2:1
2:1
1:1
81
58
84
81
59
74
62
23
34
32
40
36
97
89
90
87
74
62
90
80
90
86
90
78
73
99
86
d
3
4
5
e
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
h-naphthyl
h-naphthyl
p-CH C H
p-CH C H
p-ClC H
p-ClC H
p-BrC H
p-BrC H
m-CH OC H
H
H
Ph
Ph
f
3
6
4
4
g
3f
3 6
3g
3g
3h
3h
3i
3j
3j
3k
3k
6
4
4
6
6
4
4
6
3
6
4
n-C H
6
13
13
13
13
n-C H
6
n-C H
6
n-C H
6
a
Acyllithium reagents were generated in the presence of the dichloro compounds at −110°C except where noted. b All new products were
characterized by spectral and elemental analyses. All known compounds were characterized by comparing their spectral and physical properties
c
d
with literature values. Isolated yields based on alkyllithium reagent. Acyllithium reagent was generated prior to the addition of dichloromethane.
e
f
g
Experiment was carried out at −78°C. 6% yield of h-hydroxyketone was also isolated. 7% yield of h-hydroxyketone was also isolated.
transformation of h,h-dichloro-h-aryl alcohols into 1-
chloro-1-arylalkylene oxides. The dichloroalcohols are
readily transformed into alkylene oxides by reacting
them with sodium amide in THF as shown in Scheme 4.
The H- and C-NMR spectra of the product alkylene
oxides reveal that only one isomer is produced. Assuming
reagents with dichloro compounds is reported. The
reaction provides a new method for the preparation of
h,h-dichloroalcohols, h-hydroxyketones and 1-chloro-
1-arylalkylene oxides in high yields.
1
13
that this isomer is formed via an internal S 2 reaction
4. Experimental section
N
which proceeds through the lowest energy configuration.
The structure of the epoxides should be that in which the
All reagents and solvents were transferred using tech-
niques designed to eliminate contact with air. All glass-
ware and syringes were oven-dried for 24 h prior to use.
THF and ethyl ether were distilled from sodium ben-
zophenone ketyl. Pentane and dichloromethane were
dried by distillation from calcium hydride. n-Butyl-
lithium (1.6 M in hexane), s-butyllithium (1.3 M in
cyclohexane), t-butyllithium (1.7 M in pentane), n-
hexyllithium (2.0 M in hexane), sodium amide (95%)
and aryl aldehydes were purchased from Aldrich. h,h-
Dichlorotoluene, Aldrich, was dried and purified by
distillation from phosphorus pentoxide. Other h,h-
dichloroarylmethanes were prepared by the reaction of
phosphorus pentachloride with the corresponding aryl
aldehydes according to the literature procedure [33].
1
R group and the chloro substituent are cis.
3. Conclusion
The first example of protonation of alkyl acyllithium
1
13
Scheme 4.
H- and C-NMR spectra were obtained using a

34
G.W. Kabalka et al. / Journal of Organometallic Chemistry 572 (1999) 31–36
Table 2
The synthesis of h-hydroxyketones
Entrya
Productb
R1
Ar
Molar equivalent ratio of 2:1
Yield (%)c
1
2
3
4
5
6
7
8
9
0
1
2
3
4a
4a
4b
4c
4c
4d
4d
4e
4e
4f
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
p-CH OC H
2:1
1:1
1:1
2:1
1:1
2:1
1:1
2:1
1:1
2:1
1:1
1:1
1:1
93
88
81
96
91
31
21
88
72
95
88
77
87
3
6
4
4
p-CH OC H
3
6
p-CH CH OC H
3
2
6
4
p-C H CH OC H
6
5
2
6
4
p-C H CH OC H
6
5
2
6
4
o-CH OC H
3
6
4
4
o-CH OC H
3
6
m,p-(CH O) C H
3
2
6
4
m,p-(CH O) C H
4
3
2
6
1
1
1
1
m,p-(OCH O)C H
2 6
4
4
4f
4g
4h
m,p-(OCH O)C H
2 6
n-C H
p-CH CH OC H
6
13
13
3 2 6 4
n-C H
p-C H CH OC H
6 5 2 6 4
6
a
Acyllithium reagents were generated in the presence of the dichloro compounds at −110°C. b All products were characterized by spectral and
elemental analyses. c Isolated yields based on alkyllithium reagent.
Bruker AC-250 (250 MHz) NMR spectrometer. Ele-
mental analysis were performed by Atlantic Microlab,
Inc. Norcross, GA. HRMS were performed by the
mass spectrometry laboratory at The University of
Tennessee-Knoxville.
TMS): l 7.79–7.67 (m, 2H), 7.45–7.32 (m, 3H), 4.08
(dd, 1H, J=1.9, J=9.4 Hz), 2.38 (brs, 1H), 1.67–1.17
(m, 6H), 0.84 (t, 3H, J=7.1 Hz). C-NMR (CDCl3):
l 139.8, 129.2, 128.2, 127.3, 97.6, 81.1, 31.2, 28.3,
22.3, 13.8 ppm.
13
All other h,h-dichloroalcohols and h-hydroxyke-
tones were prepared via the procedure outlined for 3d.
Yields of these compounds are indicated in Table 1
and Table 2. The characteristics of these compounds
are as follows:
4
.1. Synthesis of h,h-dichloroalcohols and h-hydroxyke-
tones
4.1.1. The preparation of 1,1-dichloro-1-phenyl-2-hex-
anol (3d) is representati6e
To a three-necked, 250 ml, round bottomed flask
equipped with a magnetic stirrer, glass-enclosed ther-
mocouple probe, and a fritted-glass gas dispersion
tube were added h,h-dichlorotoluene (1.61 g, 10.0
mmol) and 150 ml of a 4:4:1 (by volume) mixture of
THF, diethyl ether, and pentane. The solution was
cooled to −110°C by means of a low temperature
bath. Carbon monoxide was then continuously bub-
bled into the solution. After 30 min of carbon monox-
ide addition, n-butyllithium (5.0 mmol, 3.1 ml of a 1.6
M solution in hexane) was added slowly via syringe
over a period of approximately 45 min. After the
addition was complete, the reaction was stirred at −
4.1.2. 1,1-Dichloro-2-hexanol (3a)
B.p. 82°C/10 mm Hg (lit. [30] b.p. 86°C/12 mm Hg).
1
H-NMR (CDCl /TMS): l 5.70 (d, 1H, J=4.0), 3.86
3
(m, 1H), 2.36 (brs, 1H), 1.87–1.19 (m, 6H), 0.93 (t,
13
3H, J=7.0 Hz); C-NMR (CDCl ): l 76.8, 76.4,
3
32.0, 27.5, 22.5, 13.9 ppm.
4.1.3. 1,1-Dichloro-3-methyl-2-pentanol (3b)
The ratio of the two diastereomers was 65:35, based
1
1
on H-NMR data. H-NMR (CDCl /TMS): l 5.89 (d,
3
0.65H, J=3.5), 5.75 (d, 0.35H, J=6.3), 3.72 (dd,
0.35H, J=6.3, J=4.7), 3.61 (dd, 0.65H, J=3.5, J=
7.1 Hz), 2.42 (brs, 1H), 1.96–1.02 (m, 3H), 1.01–0.83
13
110°C for 1 h and then allowed to warm to 0°C.
(m, 6H); C-NMR (CDCl ): l 80.1, 79.0, 76.1, 75.8,
3
Hydrolysis was achieved by adding saturated aqueous
ammonium chloride (40 ml). The two phases were
separated, and the aqueous phase was extracted with
diethyl ether (3×20 ml). The organic phases were
combined, washed with a saturated NaCl solution (20
37.2, 36.3, 26.3, 24.0, 14.9, 12.6, 11.3, 10.8 ppm. Anal.
Found: C, 42.40; H, 7.09. C H Cl O Calc.: C, 42.13;
H, 7.07.
6
12
2
4.1.4. 1,1-Dichloro-3,3-dimethyl-2-butanol (3c)
ml) and then dried over anhydrous MgSO . The sol-
vent was removed under reduced pressure and the
residue was isolated by silica gel chromatography [hex-
B.p. 55°C/4 mmHg (Lit. [30] b.p. 71–73°C/
4
1
12mmHg). H-NMR (CDCl /TMS):l 6.04 (d, 1H, J=
3
1.6), 3.69 (dd, 1H, J=5.2 J=1.6), 2.66 (d, 1H, J=5.2
13
ane/ethyl acetate=9/1 (v/v) as eluent] to give 3d [32]
Hz), 1.04 (s, 9H); C-NMR (CDCl ): l 83.2, 74.8,
3
1
[
1.2 g, 97% (Table 2, entry 13)]. H-NMR (CDCl /
35.7, 26.4 ppm.
3

G.W. Kabalka et al. / Journal of Organometallic Chemistry 572 (1999) 31–36
35
1
3
4
.1.5. 1,1-Dichloro-1-(1-naphthyl)-2-hexanol (3e)
(t, 3H, J=6.7 Hz); C-NMR (CDCl ): l 139.8, 129.2,
3
1
H-NMR (CDCl /TMS): l 8.75 (d, 1H, J=8.6),
128.2, 127.3, 97.6, 81.1, 31.6, 31.5, 28.9, 26.2, 22.5,
14.0 ppm. Anal. Found: C, 61.19; H, 7.34. C H Cl O
Calc.: C, 61.10; H, 7.32.
3
8
7
1
.15–8.09 (d, 1H, J=7.5), 7.91–7.83 (m, 2H), 7.62–
14
20
2
.37 (m, 3H), 4.82 (t, 1H, J=5.7), 2.40 (s, 1H), 1.75–
13
.11 (m, 6H), 0.80 (t, 3H, J=7.1 Hz); C-NMR
(
CDCl ): l 134.9, 134.6, 131.4, 129.5, 129.4, 126.3,
4.1.12. 2-Hydroxy-1-(4-methoxyphenyl)-1-hexanone
3
1
26.2, 125.9, 125.7, 124.2, 98.2, 78.3, 32.3, 28.4, 22.3,
(4a)
1
13.8 ppm. Anal. Found: C, 64.85; H, 6.13. C H Cl O
H-NMR (CDCl /TMS): l 7.91 (d, 2H, J=8.8),
6.97 (d, 2H, J=8.8), 5.09–4.97 (m, 1H), 3.89 (s, 3H),
1
6
18
2
3
Calc.: C, 64.66; H, 6.10.
3
.79 (brs, 1H), 1.96–1.19 (m, 6H), 0.87 (t, 3H, J=7.1
13
4
.1.6. 1,1-Dichloro-1-(4-methylphenyl)-2-hexanol (3f)
Hz); C-NMR (CDCl ): l 200.4, 164.1, 130.8, 126.5,
114.0, 72.6, 55.5, 36.0, 27.1, 22.4, 13.9 ppm. Anal.
Found: C, 70.32; H, 8.22. C H O Calc.: C, 70.24;
3
1
H-NMR (CDCl /TMS): l 7.61 (d, 2H, J=8.3),
3
7
2
3
1
.18 (d, 2H, J=8.3), 4.06 (dd, 1H, J=1.6, J=9.4),
13
18
3
.52 (s, 1H), 2.36 (s, 3H), 1.67–1.18 (m, 6H), 0.84 (t,
H, 8.16.
1
3
H, J=7.1 Hz); C-NMR (CDCl ): l 139.3, 137.0,
3
28.8, 127.1, 97.8, 81.1, 31.2, 28.4, 22.3, 20.9, 13.9
4
.1.13. 2-Hydroxy-1-(4-ethoxyphenyl)-1-hexanone (4b)
ppm. Anal. Found: C, 59.67; H, 6.90. C H Cl O
Calc.: C, 59.78; H, 6.95.
1
1
3
18
2
H-NMR (CDCl /TMS): l 7.89 (d, 2H, J=8.8),
3
6
.95 (d, 2H, J=8.8), 5.07–4.97 (m, 1H), 4.11 (q, 2H,
J=7.0), 3.75–3.42 (brs, 1H), 1.97–1.16 (m, 9H), 0.87
4
.1.7. 1,1-Dichloro-1-(4-chlorophenyl)-2-hexanol (3g)
13
(
t, 3H, J=7.0 Hz); C-NMR (CDCl ): l 200.3, 163.5,
3
1
H-NMR (CDCl /TMS): l 7.68 (d, 2H, J=8.7),
3
1
1
30.8, 126.2, 114.4, 72.6, 63.8, 36.0, 27.0, 22.4, 14.6,
3.8 ppm. Anal. Found: C. 71.26; H, 8.57. C H O
3
7
2
0
1
.36 (d, 2H, J=8.7), 4.05 (dd, 1H, J=1.8, J=7.6),
14
20
.40 (brs, 1H), 1.72–1.43 (m, 2H), 1.43–1.15 (m, 4H),
Calc.: C, 71.16; H, 8.53.
13
.85 (t, 3H, J=7.1 Hz); C-NMR (CDCl ): l 138.4,
3
35.4, 128.8, 128.3, 96.6, 81.0, 31.2, 28.3, 22.3, 13.9
4
.1.14. 2–Hydroxy-1-(4-benzyloxyphenyl)-1-hexanone
ppm. Anal. Found: C, 51.29; H, 5.30. Calc.:
C H Cl O C, 51.18; H, 5.37.
(
4c)
1
2
15
3
1
H-NMR (CDCl /TMS): l 7.90 (d, 2H, J=8.8),
3
7
5
6
2
1
.52–7.30 (m, 5H), 7.04 (d, 2H, J=8.8), 5.14 (s, 2H),
4
.1.8. 1,1-Dichloro-(4-bromophenyl)-2-hexanol (3h)
.06–4.96 (m, 1H), 3.20–3.70 (brs, 1H), 1.94–1.17 (m,
1
H-NMR (CDCl /TMS): l 7.66–7.46 (m, 4H), 4.05
3
13
H), 0.87 (t, 3H, J=7.0 Hz); C-NMR (CDCl ): l
3
(
dd, 1H, J=1.6, J=7.7), 2.40 (brs, 1H), 1.71–1.44 (m,
00.4, 163.2, 135.9, 130.9, 128.7, 128.3, 127.5, 126.6,
14.9, 72.7, 70.2, 36.0, 27.1, 22.5, 13.9 ppm. Anal.
13
2
H), 1.44–1.17 (m, 4H), 0.85 (t, 3H, J=7.1 Hz); C-
NMR (CDCl ): l 138.9, 131.3, 129.1, 123.7, 96.6, 81.0,
3
Found: 76.59; H, 7.51. C H O Calc.: C, 76.48; H,
19
22
3
3
4
1.2, 28.3, 22.3, 13.8 ppm. Anal. Found: C, 44.34; H,
.60. C H BrCl O Calc.: C, 44.20; H, 4.64.
7
.43.
1
2
15
2
4
(4d)
.1.15. 2-Hydroxy-1-(2-methoxyphenyl)-1-hexanone
4
.1.9. 1,1-Dichloro-1-(3-methoxyphenyl)-2-hexanol (3i)
1
H-NMR (CDCl /TMS): l 7.35–7.27 (m, 3H),
3
1
H-NMR (CDCl /TMS): l 7.84–7.77 (m, 1H),
3
6
2
.94–6.85 (m, 1H), 4.08 (d, 1H, J=9.0), 3.83 (s, 3H),
.49–2.38 (brs, 1H), 1.69–1.17 (m, 6H), 0.85 (t, 3H,
7
.58–7.47 (m, 1H), 7.09–6.93 (m, 2H), 5.16–5.05 (m,
1
3
1H), 3.91 (s, 3H), 3.88–3.78 (m, 1H), 1.94–1.15 (m,
J=7.1 Hz); C-NMR (CDCl ): l 159.3, 141.3, 129.3,
1
1
3
13
6
2
5
2
H), 0.86 (t, 3H, J=7.0 Hz); C-NMR (CDCl ): l
03.5, 158.6, 134.5, 131.0, 124.4, 120.9, 111.6, 76.6,
5.4, 34.1, 27.6, 22.4, 13.8 ppm. HRMS, Found:
19.5, 114.4, 113.6, 97.3, 81.0, 55.4, 31.2, 28.4, 22.3,
3.9 ppm. Anal. Found: C, 56.49; H, 6.58.
3
C H Cl O Calc.: C, 56.33; H. 6.55.
1
3
18
2
2
+
21.1180. C H O (M–H ) Calc.: 221.1178.
13
17
3
4
.1.10. 1,1-Dichloro-2-octanol (3j) [34]
1
4.1.16. 2-Hydroxy-1-(3,4-dimethoxyphenyl)-1-hexanone
H-NMR (CDCl /TMS): l 5.70 (d, 1H, J=4.2),
3
(
4e)
3
0
7
.95–3.80 (m, 1H), 2.60 (brs, 1H), 1.83–1.15 (m, 8H),
1
13
H-NMR (CDCl /TMS): l 7.58–7.38 (m, 2H), 6.93
.89 (t, 3H, J=6.5 Hz); C-NMR (CDCl ):l 76.8,
3
3
(
(
d, 1H, J=8.8), 5.12–4.95 (m, 1H), 3.97 (s, 3H), 3.95
6.3, 32.2, 31.6, 29.0, 25.3, 22.5, 14.0 ppm.
s, 3H), 3.63–3.36 (brs, 1H), 1.96–1.17 (m, 6H), 0.88
13
4.1.11. 1,1-Dichloro-1-phenyl-2-octanol (3k)
(t, 3H, J=6.9 Hz); C-NMR (CDCl /TMS): l 200.5,
3
1
H-NMR (CDCl /TMS): l 7.78–7.69 (m, 2H),
153.9, 149.3, 126.6, 123.1, 110.6, 110.1, 72.5, 56.05,
55.96, 36.2, 27.0, 22.4, 13.8 ppm. Anal. Found: C,
66.52; H, 7.87. C H O Calc.: C, 66.65; H, 7.99.
3
7.45–7.32 (m, 3H). 4.07 (dd, J=6.0, J=4.0), 2.50
(
brs, 1H), 1.67–1.47 (m, 2H), 1.47–1.13 (m, 8H), 0.85
14
20
4

36
G.W. Kabalka et al. / Journal of Organometallic Chemistry 572 (1999) 31–36
4.1.17. 2-Hydroxy-1-(3,4-methylenedioxyphenyl)-1-hex-
Acknowledgements
anone (4f)
1
H-NMR (CDCl /TMS): l 7.51 (dd, 1H, J=1.5,
We wish to thank the Department of Energy and the
Robert H. Cole Foundation for support of this research.
3
J=8.2), 7.40 (d, 1H, J=1.5), 6.89 (d, 1H, J=8.2), 6.07
s, 2H), 5.02–4.92 (m, 1H), 3.70–3.26 (brs, 1H), 1.94–
.16 (m, 6H), 0.87 (t, 3H, J=7.0 Hz); C-NMR (CDCl ):
(
1
1
3
3
l 200.5, 152.4, 148.3, 128.2, 124.8, 108.2, 106.9, 102.0,
References
7
6
2.7, 36.0, 27.0, 22.4, 13.8 ppm. Anal. Found: C, 66.16; H,
.79. C H O Calc.: C, 66.09; H, 6.83.
[1] D. Seyferth, R.M. Weinstein, R.C. Hui, W.-L. Wang, C.M.
Archer, J. Org. Chem. 57 (1992) 5620 and references cited
therein.
1
3
16
4
4
.1.18. 2-Hydroxy-1-(4-ethoxyphenyl)-1-octanone (4g)
1
[2] A. Orita, M. Fukudome, K. Ohe, S. Murai, J. Org. Chem. 59
H-NMR (CDCl /TMS): l 7.89 (d, 2H, J=8.8), 6.95
3
(
1994) 477 and references cited therein.
(
3
d, 2H, J=8.8), 5.07–4.97 (m, 1H), 4.11 (q, 2H, J=7.0),
.75 (brs. 1H), 1.97–1.16 (m, 13H), 0.85 (t, 3H, J=7.0
[
3] D. Seyferth, R.M. Weinstein, W.-L. Wang, R.C. Hui, C.M.
Archer, Isr. J. Chem. 24 (1984) 167.
1
3
Hz); C-NMR (CDCl ): l 200.4, 163.5, 130.8, 126.2,
[4] D. Seyferth, R.C. Hui, R.M. Weinstein, W.-L. Wang, Nova Acta
Leopold. 59 (1985) 335. D. Seyferth, R.C. Hui, R.M. Weinstein,
W.-L. Wang Chem. Abstr. 108 (1988) 6056t.
3
114.5, 72.7, 63.8, 36.3, 31.6, 29.0, 24.9, 22.5, 14.6, 14.0
ppm. Anal. Found: C, 72.79; H, 9.25. C H O Calc.: C,
1
6
24
3
[
[
5] C. Narayana, M. Periasamy, Synthesis (1985) 253.
6] B.J. Wakefield, Organolithium Methods, Academic Press, Lon-
don, 1988, pp. 95–97.
72.69; H, 9.15.
4
2
.1.19. 4.1.19.
[
[
7] R.C. Hui, D. Seyferth, Org. Synth. 69 (1990) 114.
8] D. Seyferth, R.M. Weinstein, R.C. Hui, W.-L. Wang, C.M.
Archer, J. Org. Chem. 56 (1991) 5768.
-Hydroxy-1-(4-benzyloxyphenyl)-1-octanone (4h)
1
H-NMR (CDCl /TMS): l 7.90 (d, 2H, J=9.0),
3
7
5
.49–7.29 (m, 5H), 7.04 (d, 2H, J=9.0), 5.15 (s, 2H),
.05–4.97 (m, 1H), 1.93–1.13 (m, 10H), 0.85 (t, 3H,
[9] R.M. Weinstein, W.-L. Wang, D. Seyferth, J. Org. Chem. 48
1983) 3367.
[10] D. Seyferth, R.C. Hui, Tetrahedron Lett. 25 (1984) 5251.
(
1
3
J=6.5 Hz); C-NMR (CDCl ): l 200.4, 163.2, 135.9,
3
[
[
[
11] D. Seyferth, R.C. Hui, J. Org. Chem. 50 (1985) 1985.
12] D. Seyferth, R.C. Hui, Tetrahedron Lett. 25 (1984) 2623.
13] D. Seyferth, R.C. Hui, Organometallics 3 (1984) 327.
1
3
8
30.9, 128.7, 128.3, 127.5, 126.6, 114.9, 72.7, 70.2, 36.3,
1.6, 29.0 24.9, 22.5, 14.0 ppm. Anal. Found: C, 77.18; H,
.05. C H O Calc.: C, 77.27; H, 8.03.
2
1
26
3
[14] D. Seyferth, R.M. Weinstein, J. Am. Chem. Soc. 104 (1982)
534.
[15] N.S. Nudelman, A.A. Vitale, J. Org. Chem. 46 (1981) 4625.
5
4
1
.1.20. Synthesis of
[
[
[
16] A.A. Vitale, F. Doctorovich, N.S. Nudelman, J. Organomet.
Chem. 332 (1987) 9.
17] J.J.P. Furlong, E.S. Lewkowicz, N.S. Nudelman, J. Chem. Soc.
Perkin Trans. 2 (1990) 1461.
-chloro-1-(4-chlorophenyl)-1-hexylene oxide (5a)
To a solution of 1,1-dichloro-1-(4-chlorophenyl)-2-
hexanol (3g) (100 mg, 0.357 mmol) in dry THF (2 ml) at
°C, was added under argon, sodium amide (300 mg, 7.7
0
18] N.S. Nudelman, E.S. Lewkowicz,. Synthesis (1990) 917.
mmol). The mixture is stirred at room temperature for 2
h. TLC analysis showed no starting material alcohol
remained. The reaction was quenched with saturated
aqueous NH Cl (1 ml) and H O (2 ml). The product was
[19] N.S. Nudelman, D. Perez, J. Org. Chem. 48 (1983) 133.
[20] D.G. Perez, N.S. Nudelman, J. Org. Chem. 53 (1983) 408.
[
[
[
21] V. Rautenstauch, M. Joyeux, Angew. Chem. Int. Ed. Engl. 18
1979) 83.
22] V. Rautenstauch, F. Delay, Angew. Chem. Int. Ed. Engl. 19
1980) 736.
23] M.R. Kilbourn, P.A. Jerabek, M.J. Welch, J. Chem. Soc. Chem.
Commun. (1983) 861.
(
4
2
extracted into ether (3×10 ml) and dried over anhydrous
(
MgSO . The solution was evaporated to give 5a, 79 mg
4
1
(
90% yield). H-NMR (CDCl /TMS): l 7.43 (d, 2H,
3
J=8.6), 7.34 (d, 2H, J=8.6), 2.95 (t, 1H, J=6.0),
.00–1.86 (m, 2H) 1.62–1.34 (m, 4H), 0.96 (t, 3H, J=7.1
[24] G.W. Kabalka, J.T. Gotsick, R.D. Pace, N.-S. Li, Organometal-
lics 13 (1994) 5163.
2
1
3
[
[
[
[
[
25] G.W. Kabalka, N.-S. Li, S. Yu, Organometallics 14 (1995) 1565.
26] N.S. Li, S. Yu, G.W. Kabalka, J. Org. Chem. 60 (1995) 5973.
27] N.D. Kimpe, B.D. Corte, Tetrahedron 48 (1992) 7345.
28] J. Gralak, J.-Y Valnot, Org. Prep. Proced. Int. 11 (1979) 107.
29] P. Duhamet, L. Duhamel, J. Gralak, Bull. Soc. Chim. Fr. (1970)
Hz); C-NMR (CCl ): l 137.8, 135.0, 128.6, 127.2, 81.3,
3
6
2
7.2, 28.9, 27.9, 22.4, 13.9 ppm. HRMS, Found:
44.0420. C H Cl O (M) Calc.: 244.0422.
1
2
14
2
4.1.21. Synthesis of 1-chloro-1-phenyl-1-octylene oxide
3
641.
(
5b)
Compound 5b was prepared according to the proce-
[30] J. Villieras, C. Bacquet, J.F. Normant, J. Organomet. Chem. 97
(1975) 325.
[31] H. Normant, J. Organomet. Chem. 100 (1975) 189.
1
dure outlined for 5a. Yield: 96%. H-NMR (CDCl /
TMS): l 7.54–7.29 (m, 5H), 2.98 (t, 1H, J=6.0),
2
3
[
32] 1,1-Dichloro-1-phenyl-2-hexanol was prepared by cathodic addi-
tion of h,h,h-trichlorotoluene to pentanal in only 25% yield. M.
Steinger, H.J. Schaefer, Bull. Chem. Soc. Jpn. 61 (1988) 125.
.00–1.87 (m, 2H), 1.63–1.20 (m, 8H), 0.90 (t, 3H, J=6.6
1
3
Hz); C-NMR (CDCl ): l 139.2, 128.9, 128.4, 125.7,
3
[33] D.E. Armstrong, D.H. Richardson, J. Chem. Soc. (1933) 496.
8
2.0, 67.0, 31.6, 29.3, 29.0, 25.8, 22.5, 14.9 ppm. HRMS,
[
34] T. Kaffmann, R. Fobker, M. Wensing, Angew. Chem. Int. Ed.
Engl. 27 (1988) 943.
Found: 238.1140. C H ClO (M) Calc.: 238.1124.
.
1
4
19