Indium-mediated, highly efficient and diastereoselective addition of cyclic secondary allylic bromides to carbonyl compounds

Article abstract of DOI:10.1016/S0040-4020(00)00672-4

Indium-mediated addition of 3-bromocyclohexene and 3-bromocyclooctene to a variety of aromatic aldehydes and cyclohexanone proceeds smoothly with excellent syn diastereoselectivity to produce the corresponding cycloalkenyl substituted homoallylic alcohols in good to high yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00672-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 7595–7599
Indium-Mediated, Highly Efficient and Diastereoselective
Addition of Cyclic Secondary Allylic Bromides to
Carbonyl Compounds
*
Faiz Ahmed Khan and B. Prabhudas
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 18 April 2000; revised 12 July 2000; accepted 27 July 2000
Abstract—Indium-mediated addition of 3-bromocyclohexene and 3-bromocyclooctene to a variety of aromatic aldehydes and cyclo-
hexanone proceeds smoothly with excellent syn diastereoselectivity to produce the corresponding cycloalkenyl substituted homoallylic
alcohols in good to high yields. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Allylic organometallic compounds have been extensively
used for the allylation of carbonyl compounds to obtain
homoallylic alcohols. The regio- and diastereoselectivities
which in many cases involve elaborate procedures and
activation of the metals before use to generate the corre-
sponding cyclic allylic metal reagent. Further, in the case of
certain cyclic 6-membered allylic organometallic reagents
their generation from the corresponding bromide was not
straightforward and furnished poor yields of the desired
product due to the formation of dimeric homocoupling
1
are highly dependent on the metal used, the geometry of the
alkene and the additives (e.g. Lewis acids). In the last few
years, indium has emerged as one of the most attractive
2
metals for allyl group transfer. The regio- and stereo-
7
,8b
selectivities of acyclic allylindium reagents is well studied.
For example, indium mediated addition of crotyl bromide to
carbonyl compounds is g-selective, but the diastereo-
products.
In connection with an ongoing project, we
became interested in developing simpler procedures for
cycloalkenyl group transfer with high stereoselection.
Surprisingly, to the best of our knowledge, indium-mediated
coupling of cycloalkenyl halides to carbonyl compounds
has not been studied so far. We describe herein an efficient
and highly diastereoselective addition of cyclohex-2-enyl-
and cyclooct-2-enyl indium to a variety of aromatic
aldehydes.
3
selectivity is poor (Eq. (1)). Recently, modifications such
4
as addition of lithium alkoxide (ligand tuning) or lantha-
5
nide triflate to the reaction mixture and careful tailoring of
6
reaction conditions have been shown to improve the dia-
stereoselectivity of addition of acyclic allylindium reagents
to carbonyl compounds.
Results and Discussion
The indium-mediated coupling reactions were initially
performed employing 3-bromocyclohexene and a variety
of aromatic aldehydes (Table 1). The reactions were very
clean and were complete within a few hours. The reaction of
benzaldehyde furnished a mixture of syn and anti dia-
stereomers in a ratio of 92:8 (Scheme 1 and entry 1,
Table 1). Cyclohexenylation of an a,b-unsaturated alde-
hyde (entry 2) gave solely 1,2-addition product in excellent
yield and diastereoselectivity. The results summarized in
Table 1 clearly demonstrate that the reactions are equally
efficient with both electron donating as well as electron
withdrawing substituents on the aromatic aldehyde. Poly-
nuclear aromatic (entry 3) together with biphenylic
aldehydes (entry 5) also gave good yields of the product.
It is interesting to note that 9-anthraldehyde (entry 3)
furnished essentially a single diastereomer. The reaction
ꢀ
1†
Cycloalkenes possessing a side chain at the allylic position
and adorned with a hydroxyl group at the homoallylic posi-
tion on the side chain are important intermediates in organic
synthesis. They can be obtained by a coupling reaction
between cyclic allylic organometallic reagents and carbonyl
compounds. Notable among the metals used for such
7
8
9
10
7,11
12
coupling reactions are Sn, Ge, Bi, Ti,
Zn, etc.,
Keywords: indium; diastereoselectivity; homoallyl alcohol.
Corresponding author. Tel./fax: ϩ91-512-597436;
e-mail: faiz@iitk.ac.in
*
0
040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00672-4

7
596
F. A. Khan, B. Prabhudas / Tetrahedron 56 (2000) 7595–7599
Table 1. Indium-mediated coupling of cycloalkenyl bromides with aromatic aldehydes
a
1
Based on H NMR integration of proton on carbinol carbon.
b
Yield based on recovered starting material (80% conversion).
conditions are compatible with various substituents, includ-
ing halogens (entries 7–10), on the aromatic ring. The
carboxylic acid group is also tolerated in these reactions
but when it is o-substituted, it gave the corresponding
lactone (entry 11). The coupling reactions were also
performed using 3-bromocyclooctene with a few aromatic
aldehydes under similar conditions in order to check the
generality of the reaction (entries 6, 8, 10, 12, 14 and 16).
Cyclohexenylation in all the cases showed very high syn
selectivity, but cyclooctenylation using 3-bromocyclo-
octene in some cases (entry 6, 16), gave moderate syn
selectivity. Cyclohexenylation of ketones was also
attempted employing cyclohexanone. The reaction was
sluggish and gave only 45% yield of the corresponding
homoallyl alcohol (Eq. (2)).
ꢀ2†
The ratio of syn and anti isomers was unambiguously
assigned in the case of benzaldehyde adducts (Scheme 1)
1
and is based on comparison of H NMR values (400 MHz)

F. A. Khan, B. Prabhudas / Tetrahedron 56 (2000) 7595–7599
7597
Scheme 1.
8
a
with those reported in the literature. The two doublets
corresponding to the protons on carbinol carbon for both
the isomers are well resolved (syn: dˆ4.55 ppm and anti:
was performed on glass coated with silica gel (acme). All
the products were filtered through a short silica gel (acme;
100–200 mesh) column.
1
dˆ4.44 ppm). Another characteristic feature in the H NMR
is the position of the vinylic protons. Both the vinylic
protons of cyclohexenyl moiety are well separated for the
syn isomer, but in the case of anti isomer, they are further
General procedure
(Entry 1): 3-bromocyclohexene (200 mg, 1.24 mmol) was
added dropwise to a stirred suspension of indium metal
(80 mg, 0.7 mmol) in 0.2 ml of DMF under inert
atmosphere at room temperature until all the metal
dissolved. Then a solution of benzaldehyde (53 mg,
0.5 mmol) in 1 ml of DMF was added slowly to the reaction
mixture and stirring was continued at room temperature
until the completion of the starting material (tlc). The reac-
tion mixture was diluted with 5 ml of water and extracted
three times with ether. Combined ether layer was washed
once with brine and dried over Na SO , filtered and concen-
8
a
deshielded and appear at almost identical position. The
same trend is followed in all the cases studied, and we
assigned the ratios based on these consistent values. The
transition-states A and B for the formation of syn and anti
isomers, respectively, satisfactorily explains the observed
results (Scheme 1). The exclusive formation of only one
isomer in the case of 9-anthraldehyde (entry 3), is clearly
elucidated based on the overwhelming steric congestion in
the transition state when the bulky anthryl group occupies
the hindered axial position in the less-favored transition-
state B.
2
4
trated. Silica gel column purification gave the pure product
8
a
in 78% yield. Compound 1 is known.
In summary, we have reported a simple, preparatively useful
indium-mediated coupling of 3-bromocyclohexene and
(E)-1-Cyclohex-2-enyl-3-phenyl-prop-2-en-1-ol (2). Yield:
1
3
-bromocyclooctene with aromatic aldehydes to obtain
95%, obtained as viscous liquid; syn/antiˆ90:10. H NMR:
homoallylic cycloalkenyl alcohol derivatives in good to
excellent yields. High diastereoselectivities are observed
with syn isomer being the major product.
d 1.41–1.68 (m, 3H), 1.75–1.83 (m, 2H), 1.99 (br s, 2H),
2.36–2.43 (m, 1H), 4.14 (t, Jˆ5.6 Hz, 1H, carbinol H of
minor isomer), 4.18 (t, Jˆ6.8 Hz, 1H, carbinol H of major
isomer), 5.64 (dd, Jˆ10.0, 2.2 Hz, 1H), 5.81–5.87 (m, 1H),
6
.21–6.28 (m, 1H), 6.58 (d, Jˆ15.8 Hz, 1H), 7.21–7.39 (m,
1
3
Experimental
5H); C NMR: d 21.08, 24.11, 25.08, 41.59, 75.91, 126.32,
27.40, 127.54, 128.37, 129.65, 130.46, 131.26, 136.61; IR
1
Ϫ1
Melting points were recorded on a JSGW melting point
apparatus and are uncorrected. DMF was dried using
standard procedures. IR spectra were recorded either as a
KBr pellet or neat on a Perkin-Elmer 1320 infrared spectro-
(neat): 3390, 3000, 2910, 1610 cm . Anal. calcd for
C H O: C 84.07, H 8.47; found: C 84.99, H 8.28.
1
5
18
1-Anthracen-9-yl-1-cyclohex-2-enyl-methanol (3). Yield:
1
13
photometer with NaCl optics. H NMR and C NMR
95%, obtained as solid which was crystallized in CH Cl /
2
2
H
1
spectra were recorded on Jeol 400 spectrometer. The
hexane (1:10), mp 96–98ЊC; syn/antiˆone isomer,
samples were dissolved in CDCl , using tetramethyl silane
NMR: d 1.58–1.64 (m, 1H), 1.80–2.05 (m, 4H), 2.22–
2.29 (m, 1H), 2.40 (br s, 1H), 3.28–3.34 (m, 1H), 4.75
(dd, Jˆ10.1, 2.2 Hz, 1H), 5.48–5.53 (m, 1H), 5.89 (d,
Jˆ10.0 Hz, 1H), 7.38–7.45 (m, 4H), 7.92–7.95 (m, 2H),
3
as the internal standard and spectra were given in the d
scale. The syn/anti ratios were determined by the integration
of the peaks derived from the carbinol protons of both the
isomers. Missing signals of the minor isomers are hidden by
signals of the major isomers. CHN analysis was done in
Technische Universit a¨ t Dresden, Sektion Chemie. TLC
1
3
8.34 (s, 1H), 8.60 (br s, 2H); C NMR: d 20.81, 25.19,
26.63, 41.79, 74.16, 124.64, 125.33, 127.81, 128.16,
128.95, 129.19, 129.86, 131.55, 133.64, 133.88; IR (KBr):

7
598
F. A. Khan, B. Prabhudas / Tetrahedron 56 (2000) 7595–7599
Ϫ1
3
400, 3000, 2900 cm . Anal. calcd for C H O: C 87.46,
1.15–1.68 (m, 6H), 1.83–1.89 (m, 1H), 1.97–2.15 (m, 4H),
2.83–2.85 (m, 1H), 4.42 (d, Jˆ7.6 Hz, 1H, carbinol H of
minor isomer), 4.50 (d, Jˆ6.8 Hz, 1H, carbinol H of major
isomer), 5.22 (t, Jˆ10.0 Hz, 1H), 5.56–5.63 (m, 1H), 7.05
2
1
20
H 6.99; found: C 87.09, H 6.68.
1
-Cyclohex-2-enyl-1-(4-methoxy-phenyl)-methanol (4).
Yield: 96%, obtained as solid which was crystallized in
1
3
(d, Jˆ8.0 Hz, 2H), 7.64 (d, Jˆ7.8 Hz, 2H); C NMR: d
23.64, 26.26, 26.69, 29.32, 31.41, 43.17, 77.41 (carbinol C
of major isomer), 78.15 (carbinol C of minor isomer), 92.86,
128.74, 129.84, 130.47, 137.21, 142.94; IR (neat): 3400,
1
CH Cl /hexane (1:10), mp 42–44ЊC; syn/antiˆ90:10, H
2
2
NMR: d 1.42–1.55 (m, 2H), 1.69–1.78 (m, 2H), 1.97 (br
s, 3H), 2.44 (br s, 1H), 3.78 (s, 3H), 4.36 (d, Jˆ7.6 Hz, 1H,
carbinol H of minor isomer), 4.46 (d, Jˆ7.1 Hz, 1H, car-
binol H of major isomer), 5.33 (dd, Jˆ10.1, 2.0 Hz, 1H),
Ϫ1
3000, 2910, 1570, 730 cm . Anal. calcd for C H IO: C
1
5
19
52.65, H 5.60; found: C 52.66, H 5.26.
5
.74–5.79 (m, 1H), 6.88 (d, Jˆ8.6 Hz, 2H), 7.23 (d,
1
3
Jˆ8.5 Hz, 1H); C NMR: d 20.96, 24.22, 25.17, 42.89,
5.21, 77.05 (carbinol C of major isomer), 77.66 (carbinol
C of minor isomer), 113.50, 127.65, 127.89, 129.92, 135.09,
1-(4-Chloro-phenyl)-1-cyclohex-2-enyl-methanol (9). Yield:
77%, obtained as viscous liquid. syn/antiˆ92:8. Compound
5
1
0
9 is known.
Ϫ1
1
58.81; IR (neat): 3420, 3000, 2900, 1600 cm . Anal.
cacld. for C H O : C 77.03, H 8.31; found: C 77.39, H
1-(4-Chloro-phenyl)-1-cyclooct-2-enyl-methanol
(10).
1
4
18
2
8.69.
Yield: 94%, obtained as viscous liquid. syn/antiˆ88:12,
1
H NMR: d 1.18–1.66 (m, 7H), 1.85–1.90 (m, 1H)1.99–
1
-Biphenyl-4-yl-1-cyclohex-2-enyl-methanol (5). Yield:
2.02 (m, 1H), 2.09–2.16 (m, 2H), 2.84–2.86 (m, 1H), 4.46
(d, Jˆ7.8 Hz, 1H, carbinol H of minor isomer), 4.53 (d,
Jˆ7.1 Hz, 1H, carbinol H of major isomer), 5.22 (dd,
Jˆ10.2, 9.5 Hz, 1H), 5.58–5.60 (m, 1H), 7.23–7.29 (m,
96%, obtained as solid which was crystallized in CH Cl /
2
2
1
hexane (1:10), mp 69–72ЊC; syn/antiˆ91:9, H NMR: d
1
.45–1.60 (m, 2H), 1.69–1.81 (m, 2H), 1.98 (s, 2H), 2.12
1
3
(
br s, 1H), 2.50 (m, 1H), 4.46 (d, Jˆ6.8 Hz, carbinol H of
4H); C NMR: d 25.36, 26.59, 26.70, 29.23, 31.48,
43.25, 77.35 (carbinol C of major isomer), 78.05 (carbinol
C of minor isomer), 128.05, 128.31, 129.88, 130.42, 133.04,
minor isomer), 4.57 (d, Jˆ6.6 Hz, carbinol H of major
isomer), 5.40 (dd, Jˆ10.3, 2.2 Hz, 1H), 5.78–5.85 (m,
1
3
Ϫ1
1
2
H), 7.30–7.43 (m, 5H), 7.54–7.58 (m, 4H); C NMR: d
141.88; IR (neat): 3380, 3000, 2900, 1630, 820 cm . Anal.
0.99, 23.88, 25.17, 42.89, 77.18 (carbinol C of major
calcd for C H ClO: C 71.85, H 7.64; found: C 71.42, H
1
5
19
isomer), 77.78 (carbinol C of minor isomer), 126.82,
7.98.
1
1
26.91, 126.95, 127.13, 127.92, 128.67, 130.29, 140.14,
40.77, 141.90; IR (KBr): 3400, 3000, 1590, 900 cm .
Ϫ1
3-Cyclohex-2-enyl-3H-isobenzofuran-1-one (11). Yield:
1
Anal. calcd for C H O: C 86.32, H 7.63; found: C 86.64,
H 7.98.
78%, obtained as viscous liquid. syn/antiˆ92:8, H NMR:
1
9
20
d 1.41–1.55 (m, 3H), 1.73–1.75 (m, 1H), 1.99–2.02 (m,
2
H), 2.70–2.73 (m, 1H), 5.36 (d, Jˆ10.3 Hz, 1H, carbinol
-Biphenyl-4-yl-1-cyclooct-2-enyl-methanol (6). Yield:
H of minor isomer), 5.47 (d, Jˆ4.9 Hz, 1H, carbinol H of
major isomer), 5.70 (dd, Jˆ10.1, 2.2 Hz, 1H), 5.87–5.91
(m, 1H), 7.49–7.55 (m, 2H), 7.66–7.70 (m, 1H), 7.90 (m,
1H); C NMR: d 20.66, 22.78, 24.75, 39.68, 83.54, 122.29,
125.54, 125.89, 126.54, 128.95, 130.76, 133.70, 148.44,
170.46; IR (neat): 3000, 2900, 1740, 1600 cm . Anal.
calcd for C H O : C 78.48, H 6.59; found: C 78.81, H
6.72.
1
H
1
3
.97 (m, 1H), 4.50 (d, Jˆ7.8 Hz, 1H, carbinol H of minor
Ϫ1
1
3
.30–7.44(m, 5H), 7.54–7.60 (m, 4H); C NMR: d
1
4
14
2
5.45, 26.63, 26.76, 29.30, 31.59, 43.20, 77.78 (carbinol C
of major isomer), 78.59 (carbinol C of minor isomer)
1
26.91, 126.98, 127.00, 127.16, 128.68, 130.19, 130.27,
3-Cyclooct-2-enyl-3H-isobenzofuran-1-one (12). Yield:
1
1
40.25, 140.77, 142.45; IR (neat): 3400, 3000, 2900,
660 cm . Anal. calcd for C H O: C 86.26, H 8.27;
85%, obtained as viscous liquid. syn/antiˆone isomer, H
Ϫ1
1
NMR: d 1.32–1.37 (m, 3H), 1.50–1.67 (m, 5H), 2.04–2.19
(m, 2H), 2.95–3.03 (m, 1H), 5.42 (d, Jˆ5.8 Hz, 1H), 5.55
2
1
24
found: C 87.18, H 8.24.
(
m, 1H), 5.81–5.88 (m, 1H), 7.51–7.54 (m, 2H), 7.64–7.68
13
1
9
1
1
-Cyclohex-2-enyl-1-(4-iodo-phenyl)-methanol (7). Yield:
(m, 1H), 7.89–7.91 (m, 1H); C NMR: d 24.97 (t), 26.53
(2C, t), 29.04 (t), 30.44 (t), 41.09 (d), 83.99 (d), 122.41 (d),
125.47 (d), 126.45 (s), 128.38 (d), 128.98 (d), 132.06 (d),
133.77 (d), 148.99 (s), 170.54 (s); IR (neat): 3000, 2900,
1
4%, obtained as viscous liquid. syn/antiˆ91:9, H NMR: d
.42–1.51 (m, 2H), 1.59–1.64 (m, 1H), 1.67–1.73 (m, 1H),
.96 (m, 2H), 2.29 (s, 1H), 2.39–2.43(m, 1H), 4.34 (d,
Ϫ1
Jˆ6.6 Hz, 1H, carbinol H of minor isomer), 4.47 (d,
Jˆ6.4 Hz, 1H, carbinol H of major isomer), 5.34 (dd,
Jˆ10.2, 2.0 Hz, 1H), 5.77–5.82 (m, 1H), 7.04 (d,
1750, 1600 cm . Anal. calcd for C H O : C 79.31, H
1
6
18
2
7.48; found: C 78.93, H 7.70.
1
3
Jˆ6.5 Hz, 2H), 7.63 (d, Jˆ6.5 Hz, 2H); C NMR: d
1-Cyclohex-2-enyl-1-(3-nitro-phenyl)-methanol (13). Yield:
1
2
0.83, 23.47, 25.05, 42.80, 76.65 (carbinol C of major
97%, obtained as viscous liquid. syn/antiˆ88:12, H NMR:
isomer), 77.30 (carbinol C of minor isomer), 92.61,
d 1.47–1.60 (m, 3H), 1.71–1.74 (m, 1H), 1.98 (br s, 2H),
2.51 (m, 1H), 2.66 (br s, 1H), 4.61 (d, Jˆ6.1 Hz, 1H, car-
binol H of minor isomer), 4.74 (d, Jˆ5.8 Hz, 1H, carbinol H
of major isomer), 5.40 (d, Jˆ10.0 Hz, 1H), 5.85–5.88 (m,
1
3
4
27.50, 128.49, 130.59, 137.11, 142.38; IR (neat): 3400,
Ϫ1
000, 2900, 1580, 720 cm . Anal. calcd for C H IO: C
1
3
15
9.70, H 4.81; found: C 49.52, H 4.35.
1
H), 7.48–7.52 (m, 1H), 7.66–7.68 (m, 1H), 8.08–8.11
13
1
-Cyclooct-2-enyl-1-(4-iodo-phenyl)-methanol (8). Yield:
(m,1H), 8.19 (s, 1H); C NMR: d 20.78, 23.10, 24.97,
1
98%, obtained as viscous liquid. syn/antiˆ95:5, H NMR: d
42.75, 75.97 (carbinol C of major isomer), 76.70 (carbinol

F. A. Khan, B. Prabhudas / Tetrahedron 56 (2000) 7595–7599
7599
Ϫ1
C of minor isomer), 121.29, 122.09, 126.93, 128.90, 131.32,
3400, 2850, 1580, 1220 cm ; Anal. calc. For C H O : C
18 26 4
1
1
32.54, 144.94, 147.98; IR (neat): 3400, 3010, 1510,
70.56, H 8.55; found: C 70.24, H 8.36.
Ϫ1
340 cm . Anal. calcd for C H NO : C 66.93, H 6.48,
1
3
15
3
0
N 6.00; found: C 66.35, H 6.04, N 6.09.
Bicyclohexyl-2 -en-1-ol (17). Yield: 45%, obtained as
1
3
viscous liquid. Compound 17 is known.
1
-Cyclooct-2-enyl-1-(3-nitro-phenyl)-methanol (14). Yield:
1
8
0%, obtained as viscous liquid. syn/antiˆ88:12, H NMR:
d 1.22–1.71 (m, 7H), 1.84–1.89 (m, 1H), 2.0–2.03 (m, 1H),
Acknowledgements
2
(
.09–2.15 (m, 1H), 2.35 (br s, 1H), 2.89–2.91 (m, 1H), 4.68
d, Jˆ6.8 Hz, 1H, carbinol H of minor isomer), 4.71 (d,
Jˆ6.8 Hz, 1H, carbinol H of major isomer), 5.24–5.29
This work was supported by the Department of Science and
Technology, New Delhi, India. We thank Dr Reinhold
Zimmer, T. U. Dresden, Germany, for providing analytical
data for some of our compounds. B. P. thanks CSIR, New
Delhi, for a research fellowship.
(
m, 1H), 5.56–5.67 (m, 1H), 7.50 (dd, Jˆ8.0, 7.8 Hz, 1H),
3
7
.67 (d, Jˆ7.6 Hz, 1H), 8.10–8.12 (m, 1H), 8.20 (br s, 1H);
C NMR: d 25.28, 26.67 (2C), 29.16, 31.18, 43.47, 76.93,
21.71, 122.44, 129.26, 129.29, 131.23. 132.85, 145.67,
1
1
1
Ϫ1
48.14; IR (neat): 3380, 3000, 2900, 1520, 1450 cm .
Anal. calcd for C H NO : C 68.94, H 7.33, N 5.36;
found: C 68.01, H 7.38, N 5.14.
1
5
19
3
References
1
-Cyclohex-2-enyl-1-(3,4,5-trimethoxy-phenyl)-methanol
1. Reviews: (a) Yamamoto,Y.; Asao, N. Chem. Rev. 1993, 93,
2207. (b) Roush, W. R. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 2,
Chapter 1.
(
15). Yield: 98%, obtained as solid which was crystallized
in CH Cl /hexane (1:10), mp 82–83ЊC; syn/antiˆ87:13, H
1
2
2
NMR: d 1.48–1.57 (m, 2H), 1.70–1.80 (m, 2H), 1.99 (s,
2
4
2. Reviews: (a) Cintas, P. Synlett 1995, 1087. (b) Chan, T.-H.;
Isaac, M. B. Pure Appl. Chem. 1996, 68, 919. (c) Marshall, J. A.
Chemtract.—Org. Chem. 1997, 10, 481. (d) Hashmi, A. S. K.
J. Prakt. Chem. Chem. Zeit. 1998, 340, 84. (e) Li, C.-J.; Chan,
T.-H. Tetrahedron 1999, 55, 11149.
3. Araki, S.; Ito, H.; Butsugan, Y. J. Org. Chem. 1988, 53, 1831.
4. Reetz, M. T.; Haning, H. J. Organomet. Chem. 1997, 541, 117.
5. Diana, S.-C. H.; Sim, K.-Y.; Loh, T.-P. Synlett 1996, 263.
6. Lloyd-Jones, G. C.; Russel, T. Synlett 1998, 903.
Jˆ6.8 Hz, 1H, carbinol H of major isomer), 5.36 (dd,
Jˆ10.2, 2.2 Hz, 1H), 5.81 (m, 1H), 6.55 (s, 2H);
NMR: d 20.97, 23.97, 25.12, 42.88, 55.96, 60.76, 77.53
carbinol C of major isomer), 78.00 (carbinol C of minor
isomer), 103.34, 127.90, 130.18, 136.91, 138.70, 152.97; IR
(
(KBr): 3300, 2800, 1580, 1100 cm . Anal. calcd for
C H O : C 69.04, H 7.97; found: C 69.18, H 8.27.
7
. Hikichi, S.; Gao, Y.; Sato, F. Tetrahedron Lett. 1997, 38, 2867.
1
-Cyclooct-2-enyl-1-(3,4,5-trimethoxy-phenyl)-methanol
8. (a) Young, D.; Kitching, W. Aus. J. Chem. 1985, 38, 1767.
(b) Yadav, V. K. Syn. Commun. 1990, 20, 1023. (c) Isaacs, N. S.;
Marshall, R. L.; Young, D. J. Tetrahedron Lett. 1992, 33, 3023.
(d) Miyake, H.; Yamamura, K. Chem. Lett. 1992, 2221.
9. Hashimoto, Y.; Kagoshima, H.; Saigo, K. Tetrahedron Lett.
1994, 35, 4805.
10. Ren, P.-D.; Shao, D.; Dong, T.-W. Synth. Commun. 1997, 27,
2569.
11. Kobayashi, Y.; Umeyama, K.; Sato, F. J. Chem. Soc., Chem.
Commun. 1984, 621.
12. (a) Killinger, T. A.; Boughton, N. A.; Runge, T. A.; Wolinsky,
J. J. Organomet. Chem. 1977, 124, 131. (b) Millot, N.; Knochel, P.
Tetrahedron Lett. 1999, 40, 7779.
13. Takaki, K.; Kusudo, T.; Uebori, S.; Nishiyama, T.; Kamata,
T.; Yokoyama, M.; Takehira, K.; Makioka, Y.; Fujiwara, Y. J. Org.
Chem. 1998, 63, 4299.
(16). Yield: 61%, obtained as viscous liquid. syn/
1
antiˆ76:24, H NMR: d 1.12–2.17 (m, 11H), 2.87 (m,
H), 3.81 (s, 6H, OMe of minor isomer), 3.82 (s, 3H,
OMe of minor isomer), 3.83 (s, 6H, OMe of major isomer),
1
3
.85 (s, 3H, OMe of major isomer), 4.39 (d, Jˆ8.1 Hz, 1H,
carbinol H of minor isomer), 4.48 (d, Jˆ7.1 Hz, 1H, car-
binol H of major isomer), 5.26 (t, Jˆ10.5 Hz, 1H, olefinic H
of major isomer), 5.49 (t, Jˆ9.0 Hz, 1H, olefinic H of minor
isomer), 5.59 (dt, Jˆ8.3, 8.9 Hz, olefinic H of major
isomer), 5.85 (dt, Jˆ8.5, 9.5 Hz, olefinic H of minor
isomer), 6.53 (s, 2H, aromatic H of major isomer), 6.56 (s,
1
3
2
2
H, aromatic H of minor isomer); C NMR: d 25.40, 26.64,
6.77, 29.29, 31.56, 43.14, 56.06, 60.78, 78.22 (carbinol C
of major isomer), 79.11 (carbinol C of minor isomer),
03.66, 130.07, 130.26, 130.95, 139.15, 153.00; IR (neat):
1