Synthesis of (E)-1-Aryl-1-alkenes via a Novel BF3·OEt2-Catalyzed Aldol-Grob Reaction Sequence

Article abstract of DOI:10.1021/jo9822784

The reactions of aromatic aldehydes with ketones in the presence of various acids were examined. The reactions generate (E)-1-aryl-1-alkenes in the presence of boron trifluoride diethyl etherate in nonnucleophilic solvents.

Full text of DOI:10.1021/jo9822784

J . Org. Chem. 1999, 64, 3157-3161
3157
Syn th esis of (E)-1-Ar yl-1-a lk en es via a Novel BF 3‚OEt2-Ca ta lyzed
Ald ol-Gr ob Rea ction Sequ en ce
George W. Kabalka,* Nan-Sheng Li, David Tejedor, Rama R. Malladi, and Sarah Trotman
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, Tennessee 37996-1600
Received November 17, 1998
The reactions of aromatic aldehydes with ketones in the presence of various acids were examined.
The reactions generate (E)-1-aryl-1-alkenes in the presence of boron trifluoride diethyl etherate in
nonnucleophilic solvents.
Ta ble 1. Rea ction of 5-Non a n on e w ith
2-Ch lor oben za ld eh yd e in th e P r esen ce of Va r iou s Acid s
In tr od u ction
The Aldol condensation has proven to be a very useful
reaction in organic synthesis.1 Recently, a variety of boron
reagents have been developed for carrying out mixed
aldol condensations because of their ability to efficiently
control the stereochemistry of the reaction.2 A â-hydroxy
carbonyl compound is the initial product of the aldol
reaction but it is often transformed into the correspond-
ing R,â-unsaturated derivative via dehydration.3 During
the course of an investigation involving the stereoselec-
tive synthesis of 1,3-diols starting from â-hydroxy-
ketones,4 we discovered an unprecedented boron trifluo-
ride initiated cleavage when the reactions were carried
out in nonetheral solvents. The new reaction resulted in
the formation of (E)-arylalkenes and carboxylic acids5 (eq
1). We then found that a boron trifluoride initiated
Aldol-Grob reaction sequence could be carried out in a
tandem fashion starting from aromatic aldehydes and
ketones6 (eq 2). We now wish to report the results of a
detailed study of this Aldol-Grob reaction sequence.
entrya
acidb
product yieldsc (%)
1
BF3
74
2d
3d
4d
5d
6d
7e
8d
9d
BCl3
BBr3
AlCl3
TiCl4
ZnCl2
trace
trace
30
9
trace
32
<5
trace
p-CH3C6H4SO3H‚H2O
CF3CO2H
C7F15CO2H
a
Reactions carried out in carbon tetrachloride at reflux for 2 h
b
using 10% excess 2-chlorobenzaldehyde. A small excess of BF3
was bubbled into the reaction mixture (entry 1); 3 equiv of acid
added to the reaction mixture (entries 2-9). c Isolated yield of (E)-
d
1-(2-chlorophenyl)-1-pentene. GC/MS analysis revealed unre-
acted starting material. e A 60% yield of R,â-unsaturated ketone
was isolated in this experiment.
Resu lts a n d Discu ssion
The overall sequence is rather remarkable since the
reaction conditions appear to be ideal for a straightfor-
ward dehydration resulting in the formation of R,â-
unsaturated ketones. It would seem that the combination
of a powerful Lewis acid and a nonnucleophilic solvent
is key to this unexpected behavior and, ultimately, to the
success of the reaction.
We examined the effect of various acids on the reaction
sequence in order to ascertain which would be most
efficient. The results are summarized in Table 1. When
* To whom correspondence should be addressed. E-mail: kabalka@
utk.edu. Phone: (423) 974-3260. Fax: (423) 974-2997.
(1) (a) March, J . Advanced Organic Chemistry, 4th ed.; Wiley-
Interscience: New York, 1992; pp 937-945. (b) Nielsen, A. T.;
Houlihan, W. J . Org. React. 1968, 16, 1-438.
(2) (a) Ramachandran, P. V.; Xu, W.-C.; Brown, H. C. Tetrahedron
Lett 1997, 38, 769. (b) Abiko, A.; Liu, J .-F.; Masamune, S. J . Org. Chem.
1996, 61, 2590. (c) Duffy, J . L.; Yoon, T. P.; Evans, D. A. Tetrahedron
Lett. 1995, 36, 9245. (d) Ganesan, K.; Brown, H. C. J . Org. Chem. 1994,
59, 7346.
(3) (a) Fu¨rstner, A.; Langemann, K. J . Org. Chem. 1996, 61, 8746.
(b) Larock, R. C. Comprehensive Organic Transformations; VCH
Publishers: New York, 1989; pp 167-172.
(4) Narayana, C.; Reddy, M. R.; Hair, M.; Kabalka, G. W. Tetrahe-
dron Lett. 1997, 38, 7705.
(5) Kabalka, G. W.; Tejedor, D.; Li, N.-S.; Reddy, M. R.; Trotman,
S. Tetrahedron Lett. 1998, 39, 8071.
(6) Kabalka, G. W.; Tejedor, D.; Li, N.-S.; Malladi, R. R.; Trotman,
S. J . Org. Chem. 1998, 63, 6438.
a mixture of 5-nonanone, 2-chlorobenzaldehyde, and a
small excess of BF3 gas was refluxed for 2 h in CCl4, (E)-
1-(2-chlorophenyl)-1-pentene was obtained in 74% yield
(Table 1, entry 1). The reaction also occurred in the
presence of other acids, but the yields were substantially
lower. For example, the use of either AlCl3 or TiCl4
produced (E)-1-(2-chlorophenyl)-1-pentene in 30% (Table
1, entry 4) and 9% (Table 1, entry 5) yields, respectively,
under similar reaction conditions. Interestingly, a strong
protic acid such as p-toluenesulfonic acid monohydrate
10.1021/jo9822784 CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/14/1999

3158 J . Org. Chem., Vol. 64, No. 9, 1999
Kabalka et al.
Ta ble 4. Rea ction of 5-Non a n on e w ith
Ta ble 2. Rea ction of 5-Non a n on e w ith
2-Ch lor oben za ld eh yd e in th e P r esen ce of Va r iou s Bor on
Tr iflu or id e Com p lexes
2-Ch lor oben za ld eh yd e in th e P r esen ce of Va r iou s
Am ou n ts of BF 3‚OEt2
entrya
boron trifluoride complexb
product yieldc (%)
entrya BF3‚OEt2 (molar equiv) reaction time (h) yieldb (%)
1
2
3
4
BF3 gas
BF3‚OEt2
BF3‚THF
BF3‚2CH3CO2H
BF3‚2H2O
BF3‚2PhOH
BF3‚C2H5NH2
84
84
84
78
66
0
1
2
3
4
2.2
1.4
1.0
0.7
0.7
0.7
0.5
0.4
0.4
0.4
0.2
0.1
1
1
1
1
1
2.5
1
1
2.5
4
84
84
88
88
80
84
84
71
78
81
25
4
5
5c
6d
7
6d
7e
0
8
9
10
11
12
a
Reaction carried out in hexane at reflux for 1 h using 10%
excess 2-chlorobenzaldehyde. b A small excess BF3 gas bubbled into
the reaction mixture (entry 1); 2.2 equiv of the BF3 complex was
added to the reaction mixture (entries 2-7). c Isolated yield of (E)-
4
4
d
1-(2-chlorophenyl)-1-pentene. GC/MS analysis revealed acetal-
a
ization of 2-chlorobenzaldehyde with phenol. e GC/MS analysis
revealed unreacted starting material.
All reactions carried out in hexane at reflux using 10% excess
b
2-chlorobenzaldehyde except where noted. Isolated yield of (E)-
1-(2-chlorophenyl)-1-pentene. c In this experiment, 1 molar equiv
d
Ta ble 3. Rea ction of 5-Non a n on e w ith
2-Ch lor oben za ld eh yd e in Va r iou s Solven ts
each of ketone and aldehyde were used. The product was found
to slowly dimerize (evidenced by GC/MS) when the reaction time
was lengthened.
entrya
solvents
product yieldb (%)
1
2
3
CCl4
64
70
68
37
trace
0
the solvent for the remainder of the study and the
reactions were carried out in hexane at reflux in order
to enhance the reaction rate.
hexane
CH2Cl2
toluene
Et2O
4
5c
6c
We then examined the affect of varying the quantity
of BF3‚OEt2 on the reaction. The results are summarized
in Table 4. All experiments were carried out in refluxing
hexane using a 10% excess 2-chlorobenzaldehyde, except
for entry 5 where 1 molar equiv each of ketone and
aldehyde were utilized. An excess of the aldehyde pro-
duced (E)-1-(2-chlorophenyl)-1-pentene in slightly higher
yield (Table 4, entries 4 and 5). Using a 10% excess of
aldehyde, the reactions generally gave (E)-1-(2-chlo-
rophenyl)-1-pentene in 80-88% yield when 0.5-2.2 molar
equiv of BF3‚OEt2 was added. The use of 0.4 molar equiv
of BF3‚OEt2 gave the alkene in 71% yield after 1 h (Table
4, entry 8) but the yields of the product could be increased
slightly by lengthening the reaction time (Table 4, entries
9 and 10). The alkene product was found to slowly
dimerize (evidenced by GC-MS) when the reaction time
was increased significantly (Table 4, entries 4 and 6). In
addition, the reactions were very slow if less than 0.4
molar equiv of BF3‚OEt2 was used. For example, the use
of 0.2 or 0.1 molar equiv of BF3‚OEt2 gave (E)-1-(2-
chlorophenyl)-1-pentene in only 25% and 4% yields,
respectively, even after refluxing for 4 h. We conclude
that 0.5-1.0 molar equiv of BF3‚OEt2 is optimum for the
tandem Aldol-cleavage reaction.
The reaction was found to be general for aromatic
aldehydes (Table 5, entries 1-12). The yields were
dependent on the electronic nature of the substituent,
being generally higher in instances where electron-
withdrawing groups were present, a fact attributed to
the stability of the styrenyl products under the reaction
conditions. Chloro-, bromo-, methoxycarbonyl-, carboxyl-,
and trifluoromethyl-substituted benzaldehydes gave the
corresponding alkenes in good to excellent yields (Table
5, entries 3-5, 8, and 10-12). However, the presence of
strong electron-withdrawing groups such as nitro and
cyano led to lower yields of the corresponding alkenes.
These groups presumably destabilize the formation of the
carbocation intermediate and subsequent cleavage reac-
tion, allowing side reactions to compete more effectively.
Indeed, R,â-unsaturated ketone products were isolated
in these cases (Table 5, entries 6, and 7, and 9). The
reactions of benzaldehyde and 4-methylbenzaldehyde
THF
a
Reaction carried out in the presence of 2.2 equiv of BF3‚OEt2
in various solvents at room temperature for 24 h using 10% excess
b
2-chlorobenzaldehyde. Isolated yield of (E)-1-(2-chlorophenyl)-1-
pentene. c Both the starting aldehyde and ketone were recovered.
also produced (E)-1-(2-chlorophenyl)-1-pentene in 32%
yield in addition to the expected R,â-unsaturated ketone
60% (Table 1, entry 7). We conclude that boron trifluoride
is the most effective acid catalyst for the new tandem
condensation-cleavage sequence.
We then examined the reaction of 5-nonanone with
2-chlorobenzaldehyde in the presence of various com-
mercially available complexes of boron trifluoride. The
results are summarized in Table 2. As shown, the aldol-
cleavage reaction can be initiated by complexes of boron
trifluoride with diethyl etherate, tetrahydrofuran, acetic
acid, and water. The complexes produced (E)-1-(2-chlo-
rophenyl)-1-pentene in good to excellent yields (Table 2,
entries 1-5). None of the desired cleavage reaction
occurred when the boron trifluoride-phenol complex
(Table 2, entry 6) was used; only acetal formation
occurred. The boron trifluoride-ethylamine complex was
apparently too stable to initiate the reaction. Both ketone
and aldehyde were recovered unchanged (Table 2, entry
7). Even though a number of boron trifluoride reagents
are effective, boron trifluoride etherate was chosen for
further evaluation for economic reasons.
The BF3‚OEt2-catalyzed reactions of 5-nonanone with
2-chlorobenzaldehyde in various solvents were investi-
gated, and the results are summarized in Table 3. All
the reactions were carried out at room temperature. The
most significant observation is that a nonnucleophilic
solvent is required. A donor solvent such as THF or
diethyl ether inhibits the formation of the product.
Apparently, the Lewis acidity of boron trifluoride is
moderated sufficiently by complexation to donor solvents
to render it ineffective as an aldol catalyst. Although
there is an appreciable difference in the reaction rates,
all of the nonnucleophilic solvents examined in this study
produced (E)-1-(2-chlorophenyl)-1-pentene in good yields.
For safety and economic reasons, hexane was chosen as

BF3‚OEt2-Catalyzed Aldol-Grob Reaction Sequence
J . Org. Chem., Vol. 64, No. 9, 1999 3159
Ta ble 5. Rea ction s of Ar om a tic Ald eh yd es w ith Keton es in th e p r esen ce of BF 3‚OEt2
BF3‚OEt2
(molar equiv)
timec
(h)
yieldd
(%)
entrya
productb
X
R
R′
1
2
3
3a
3b
3c
3d
3e
3fe
3gf
3h
3ig
3j
H
4-CH3
2-Cl
3-Cl
4-Cl
3-NO2
4-NO2
4-Br
4-CN
4-COOME
4-COOH
4-CF3
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Me
Et
Bu
i-Pr
Ph
Pr
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Et
0.4
0.4
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.7
0.7
0.7
0.5
0.5
1.0
1.0
1.5
2.0
4.5
1.5
5.0
3.5
3.5
2.0
1.0
1.0
1.3
4.5
4.5
2.0
21.0
1.0
50
51
88
78
91
41
23
89
13
69
61
78
61
83
87
83
41
62
66
30
4
5c
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
3k
3l
3m
3n
3o
3p
3q
3c
3r
Pr
Pentyl
i-PrCH2
PhCH2
Ph
t-Bu
Me
Pentyl
Bu
3o
a
Reactions carried out in hexane at reflux using 10% excess aldehyde. b The structure of product was confirmed by spectral and elemental
analysis. c Reaction time required to obtain optimum yield. Isolated yields of 3; refer to eq 2. e 34% of the dehydration product isolated.
d
f Dehydration product isolated in 49% yield. Dehydration product isolated in 41% yield.
g
Sch em e 1
with 5-nonane were very fast but gave the corresponding
alkenes (3a and 3b) in only 50% yield along with some
dimer product (Table 5, entries 1 and 2). The reaction
conditions were optimized by reducing the reaction time
and the quantity of catalyst, which minimized loss of the
styrenyl products due to polymerization. None of the
desired reaction occurred between 5-nonanone with p-
anisaldehyde or 4-N,N-dimethylaminobenzaldehyde even
in the presence of excess BF3‚OEt2. Presumably, the
methoxy and dimethylamino groups complexed to the
BF3‚OEt2 as evidenced by the formation of a white solid
in these reactions.
produced alkene (3q) in moderate yield (Table 5, entry
17). The reaction of 2-chlorobenzaldehyde with 1-phenyl-
1-pentanone produced alkene (3c) in 62% yield (entry 18)
along with some R,â-unsaturated ketone. The reaction
of 2,2-dimethyl-3-nonanone with 2-chlorobenzaldehyde
slowly generated (E)-1-(2-chlorophenyl)-1-heptene in 66%
yield after refluxing for 21 h (Table 5, entry 19). Methyl
alkyl ketones (entry 20) produced lower yields of â-alkyl-
styrenes since the initial aldol condensation does not
occur exclusively at the methylene group as evidenced
by the formation of hexanoic acid in the reaction of
2-heptanone with 2-chloro-benzaldehyde.
Although a detailed study of the reaction mechanism
The other product in the reactions leading to 3a -l was
pentanoic acid. A 67% isolated yield of pentanoic acid was
obtained from the reaction of 2-chlorobenzaldehyde with
5-nonanone leading to (E)-1-(2-chlorophenyl)-1-pentene
(Table 5, entry 3). A small amount of ethyl pentanoate
was also generated in the BF3‚OEt2-catalyzed reactions.
Nonaromatic aldehydes failed to produce alkene products,
suggesting that a benzylic carbocation intermediate is
involved in the reaction mechanism.
We then examined the reactions of various ketones
with 2-chlorobenzaldehyde in the presence of BF3‚OEt2
(Table 5, entries 13-20). The results reveal that sym-
metrical ketones produced the styrenyl products in high
yields (Table 5, entries 3 and 14-16). The result using
small symmetrical ketones revealed that sterically less
hindered styrenyl products were prone to polymerization
(Table 5, entry 13). The reaction of 1,3-diphenylacetone
has not yet been completed, the consistent formation of
7,8
(E)-alkene products,
as well as the fact that aromatic
aldehydes appear to be required, would point toward the
intermediacy of a carbocation derivative. A reasonable
mechanism would involve the formation of the mixed
aldol followed by the formation and subsequent nonsyn-
chronous ring opening of a lactol as shown in Scheme 1.
The proposed fragmentation is reminiscent of two step
Grob9 fragmentations that have been reported for N-halo-
R-amino acids.10 and cyclobutane hemiacetals11 as well
(7) Control experiments revealed that (Z)-1-phenyl-1-alkenes do not
isomerize to the corresponding E isomers under the reaction conditions.
(8) 8.Isomeric mixtures of syn- and anti-â-aryl-â-hydroxy ketones
consistently yield (E)-alkenes.
(9) Grob, C. A. Angew. Chem., Int. Ed. Engl. 1969, 8, 535.
(10) Armesto, X. L.; Canle, L.; Losada, M.; Santaballa, J . A. J . Org.
Chem. 1994, 59, 4659.

3160 J . Org. Chem., Vol. 64, No. 9, 1999
Kabalka et al.
with into ether (3 × 10 mL), analyzed by GC/MS, and purified
by silica gel chromatography (hexane as eluent). The reaction
was repeated using CCl4, CH2Cl2, toluene, Et2O, and THF. The
results are summarized in Table 3.
as the acid-catalyzed fragmentation of â-hydroxyac-
etals.12,13 Grob fragmentations have been reported in
numerous syntheses including the preparation of medium-
sized carbocycles,14 hormones,15 pharmaceuticals,16 and
carbohydrates.17
Rea ction s of 5-Non a n on e w ith 2-Ch lor oben za ld eh yd e
in th e P r esen ce of Va r iou s Qu a n tities of BF 3‚OEt2. To
the mixture of 5-nonanone (2.5 mmol) and 2-chlorobenzalde-
hyde (2.75 mmol) in hexane (5 mL) were added various
quantities of BF3‚OEt2 (0.1-2.2 molar equiv). The reaction
mixture was stirred at reflux for 1-4 h and then cooled to room
temperature and quenched with water (5 mL). The product
(E)-1-(2-chlorophenyl)-1-pentene was extracted into ether (3
× 10 mL), analyzed by GC/MS, and purified by flash silica gel
chromatography using hexane as eluent. The results are
presented in Table 4.
Syn th esis of (E)-1-(2-Ch lor op h en yl)-1-p en ten e (3c).
Typ ica l P r oced u r e. BF3‚OEt2 (1.8 mmol) was added via
syringe to a mixture of 5-nonanone (2.5 mmol), 2-chloroben-
zaldehyde (2.75 mmol), and hexane (5 mL). The reaction
mixture was stirred at reflux for 1 h and then quenched with
water (5 mL), extracted with ether (3 × 10 mL), analyzed via
GC/MS, and purified by flash chromatography (silica gel using
hexane as eluent) to yield 0.40 g (88%) of (E)-1-(2-chloro-
phenyl)-1-pentene:19 1H NMR (CDCl3/TMS) δ 7.50 (dd, 1H, J
) 7.6, 1.9), 7.32 (dd, 1H, J ) 7.6, 1.6), 7.24-7.08 (m, 2H), 6.75
(d, 1H, J ) 15.8), 6.20 (dt, 1H, J ) 15.8, 7.0), 2.28-2.19 (m,
2H), 1.59-1.44 (m, 2H), 0.97 (t, 3H, J ) 7.4); 13C NMR (CDCl3)
δ 136.0, 132.5, 129.6, 127.8, 126.7, 126.6, 126.2, 35.2, 22.4, 13.7;
GC/MS (EI) m/z 180 (M+).
Con clu sion
The reaction of ketones with aromatic aldehydes in the
presence of boron trifluoride diethyl etherate in non-
nucleophilic solvent produces (E)-1-arylalkenes. Several
features of this reaction make it synthetically useful: (1)
The starting materials are readily available and inex-
pensive. (2) The reaction is stereoselective, and the yields
of (E)-alkenes are moderate to excellent. (3) The reaction
conditions tolerate a variety of functional groups. (4) The
reaction provides a useful alternative to Wittig, Heck,
Peterson, and related reactions.18
Exp er im en ta l Section
All reactions were carried out under an argon atmosphere.
All glassware and syringes were oven-dried. Hexane, dichlo-
romethane, and toluene were distilled over calcium hydride.
THF and diethyl ether were distilled from sodium benzophe-
none ketyl. All other materials were obtained from commercial
suppliers and used as received. 1H NMR and 13C NMR data
were recorded on a 250 MHz spectrometer. J values are given
in Hz. Elemental analyses were performed by Atlantic Micro-
labs, Norcross, GA.
Rea ction s of 5-Non a n on e w ith 2-Ch lor oben za ld eh yd e
in t h e P r esen ce of Va r iou s Acid s. To a mixture of
5-nonanone (2.5 mmol) and 2-chlorobenzaldehyde (2.75 mmol)
in carbon tetrachloride (5 mL) was introduced a small excess
of BF3 gas or a 3-fold excess of acid (∼7.5 mmol). After the
reaction was stirred at reflux for 2 h, the mixture was
quenched with water (5 mL). The product (E)-1-(2-chlorophe-
nyl)-1-pentene was extracted into ether (3 × 10 mL), analyzed
by GC/MS, and isolated by flash chromatography (silica gel
using hexane as eluent). The results are summarized in Table
1.
All other (E)-1-aryl-1-alkenes were prepared via the proce-
dure outlined for 3c. Yields of these reactions and the reaction
conditions are summarized in Table 3. The physical and
spectral characteristics of the products are as follows:
(E)-1-P h en yl-1-p en ten e (3a ):20 1H NMR (CDCl3/TMS) δ
7.33 B 7.14 (m, 5H), 6.29 (d, 1H, J ) 15.9), 6.18 (dt, 1H, J )
15.9, 6.7), 2.20 B 2.11 (m, 2H), 1.55 B 1.40 (m, 2H), 0.94 (t,
13
3H, J ) 7.4); C NMR (CDCl3) δ 138.0, 130.9, 120.0, 128.4,
126.7, 125.9, 35.1, 22.6, 13.7; GC/MS (EI) m/z 146 (M+).
(E)-1-(4-Meth ylph en yl)-1-pen ten e (3b):21 1H NMR (CDCl3/
TMS) δ 7.22 (d, 2H, J ) 8.1), 7.07 (d, 2H, J ) 8.1), 6.34 (d,
1H, J ) 15.8), 6.14 (dt, 1H, J ) 15.8, 6.8), 2.30 (s, 3H), 2.20 B
2.11 (m, 2H), 1.54 B 1.40 (m, 2H), 0.94 (t, 3H, J ) 7.3); 13C
NMR (CDCl3) δ 136.3, 135.2, 129.8, 129.7, 129.1, 125.3, 35.1,
22.6, 21.1, 13.7; GC/MS (EI) m/z 160 (M+).
Rea ction s of 5-Non a n on e w ith 2-Ch lor oben za ld eh yd e
in th e P r esen ce of Va r iou s Bor on Tr iflu or id e Com -
p lexes. To a dry 25 mL round-bottom flask were added
5-nonanone (2.5 mmol), 2-chlorobenzaldehyde (2.75 mmol),
hexane (5 mL), and a small excess of BF3 gas or BF3‚complex
(5.5 mmol). The reaction mixture was stirred at reflux for 1 h
and then quenched with water (5 mL). The product (E)-1-(2-
chlorophenyl)-1-pentene was extracted into ether (3 × 10 mL),
analyzed by GC/MS, and purified by silica gel chromatography
(hexane as eluent). The results are presented in Table 2.
Rea ction s of 5-Non a n on e w ith 2-Ch lor oben za ld eh yd e
in th e P r esen ce of BF 3‚OEt2 in Va r iou s Solven ts. To a
dry 25 mL round-bottom flask were added 5-nonanone (2.5
mL), 2-chlorobenzaldehyde (2.75 mmol), hexane (5 mL), and
BF3‚OEt2 (5.5 mmol). The reaction mixture was stirred at room
temperature for 24 h and then quenched with water (5 mL).
The product (E)-1-(2-chlorophenyl)-1-pentene was extracted
(E)-1-(3-Ch lor oph en yl)-1-pen ten e (3d):22 1H NMR (CDCl3/
TMS) δ 7.31 (s, 1H), 7.19-7.11 (m, 3h), 6.34 (d, 1H, J ) 15.9),
6.24 (dt, 1H, J ) 15.9, 6.2), 2.21-2.13 (m, 2H), 1.52-1.41 (m,
2H), 0.93 (t, 3H, J ) 7.3); 13C NMR (CDCl3) δ 139.8, 134.4,
132.6, 129.6, 128.7, 126.6, 125.8, 124.1, 35.0, 22.4, 13.7; GC/
MS (EI) m/z 180 (M+).
(E)-1-(4-Ch lor oph en yl)-1-pen ten e (3e)21,23 1H NMR (CDCl3/
TMS) δ 7.23 (s, 4H), 6.32 (d, 1H, J ) 16.0), 6.18 (dt, 1H, J )
16.0, 6.6), 2.21-2.12 (m, 2H), 1.55-1.41 (m, 2H), 0.94 (t, 3H,
J ) 7.3); 13C NMR (CDCl3) δ 136.4, 131.7, 130.0, 128.7, 128.5,
127.1, 35.0, 22.4, 13.7; GC/Ms (EI) m/z 180 (M+).
(E)-1-(3-Nitr op h en yl)-1-p en ten e (3f): 1H NMR (CDCl3/
TMS) δ 8.17 (t, 1H, J ) 1.9), 8.03-7.99 (m, 1H), 7.64-7.60
(m, 1H), 7.43 (t, 1H, J ) 8.0), 6.44 (d, 1H, J ) 15.3), 6.40-
6.30 (m, 1H), 2.27-2.19 (m, 2H), 1.60-1.45 (m, 2H), 0.97 (t,
3H, J ) 7.4); 13C NMR (CDCl3) δ 148.5, 139.7, 134.4, 131.7,
129.2, 127.8, 121.3, 120.4, 35.0, 22.2, 13.6; GC/MS (EI) m/z
191 (M+). Anal. Calcd. for C11H13NO2: C, 69.09; H, 6.85; N,
7.32. Found: C, 68.84; H, 6.84; N, 7.11.
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8523.
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Lett. 1996, 37, 5817.
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Press: New York; 1996.
(E)-1-(4-Nitr op h en yl)-1-p en ten e (3g): 1H NMR (CDCl3/
TMS) δ 8.12 (d, 2H, J ) 8.9), 7.45 (d, 2H, J ) 8.9), 6.45-6.42
(19) Hubert, A. J . J . Chem. Soc. C 1967, 235.
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BF3‚OEt2-Catalyzed Aldol-Grob Reaction Sequence
J . Org. Chem., Vol. 64, No. 9, 1999 3161
(m, 2H), 2.28-2.20 (m, 2H), 1.60-1.43 (m, 2H), 0.97 (t, 3H, J
) 7.3); 13C NMR (CDCl3) δ 146.3, 144.3, 136.3, 128.1, 126.2,
123.8, 35.1, 22.0, 13.6; GC/MS (EI) m/z 191 (M+). Anal. Calcd.
for C11H13NO2; C, 69.09; H, 6.85; N, 7.32. Found: C, 68.99; H,
6.87; N, 7.32.
(E)-1-(2-Ch lor op h en yl)-1-bu ten e (3n ): 1H NMR (CDCl3/
TMS)δ 7.46 (d, 1H, J ) 7.6), 7.29 (d, 1H, J ) 7.6), 7.20-7.00
(m, 2H), 6.75 (d, 1H, J ) 15.7), 6.21 (dt, 1H, J ) 15.7, 6.5),
2.33-2.14 (m, 2H), 1.09 (dt, 3H, J ) 7.4, 2.1); 13C NMR (CDCl3)
δ 135.9, 135.4, 132.5, 129.5, 127.7, 126.6, 126.5, 125.1, 26.2,
13.4; GC/MS (E1) m/z 166 (M+). Anal. Calcd for C10H11Cl: C,
72.07; H, 6.65. Found: C, 72.35; H, 6.71.
(E)-1-(2-Ch lor op h en yl)-1-h exen e (3o): 1H NMR (CDCl3-
TMS) δ 7.47 (d, 1H, J ) 7.67), 7.30 (d, 1H, J ) 7.8), 7.18-7.07
(m, 2H), 6.75 (d, 1H, J ) 15.9), 6.18 (dt, 1H, J ) 15.9,7.0),
2.27-2.18 (m, 2H), 1.49-1.31 (m, 4H), 0.92 (t, 3H, J ) 6.8);
13C NMR (CDCl3) δ 136.0, 134.1, 132.5, 129.5, 126.7, 126.6,
126.0, 32.9, 31.4, 22.3, 13.9; GC/MS (EI) m/z 194 (M+). Anal.
Calcd for C12H15Cl: C, 74.03; H, 7.75. Found: C, 74.13; H, 7.77.
(E)-1-(4-Br om op h en yl)-1-p en t en e (3h ):24,25 1H NMR
(CDCl3/TMS) δ 7.35 (d, 2H, J ) 8.5), 7.13 (d, 2H, J ) 8.5),
6.26 (d, 1H, J ) 16.0), 6.15 (dt, 1H, J ) 16.0, 6.4), 2.17-2.09
(m, 2H), 1.53-1.38 (m, 2H), 0.93 (t, 3H, J ) 7.4); 13C NMR
(CDCl3) δ 136.8, 131.7, 131.4, 128.7, 127.4, 120.3, 35.0, 22.4,
13.7; GC/MS (EI) m/z 224 (M+).
(E)-1-(4-Cya n op h en yl)-1-p en ten e (3i):25 1H NMR (CDCl3/
TMS) δ 7.56 (d, 2H, J ) 8.5), 7.40 (d, 2H, J ) 8.25), 6.42-6.33
(m, 2H), 2.31-2.16 (m, 2H), 1.60-1.40 (m, 2H), 0.96 (t, 3H, J
) 7.3); 13C NMR (CDCl3) δ 142.3, 135.3, 132.2, 128.5, 126.3,
119.1, 109.8, 35.1, 22.1, 13.8; (GC/MS (EI) m/z 171 (M+).
(E)-1-(4-Ca r bom eth oxyp h en yl)-1-p en ten e (3j): 1H NMR
(CDCl3/TMS) δ 7.94 (d, 2H, J - 8.4); 7.34 (d, 2H, J - 8.4),
6.43-6.23 (m, 2H), 3.86 (s, 3H), 2.23-2.10 (m, 2H), 1.57-1.38
(m, 2H), 0.94 (t, 3H, J ) 7.3); 13C NMR (CDCl3/TMS) δ 166.6,
142.2, 133.6, 129.6, 129.0, 128.0, 125.5, 51.6, 35.0, 22.1, 13.5;
GC/MS (EI) m/z 204 (M+). Anal. Calcd for C13H16O2: C, 76.44;
H, 7.90. Found: C, 76.42; H, 7.92.
(E)-1-(2-Ch lor oph en yl)-3-m eth yl-1-bu ten e (3p): 1H NMR
(CDCl3/TMS) δ 7.43 (d, 1H, J ) 7.7), 7.26 (d, 1H, J ) 7.6),
7.10-7.01 (m, 2H), 6.72 (d, 1H, J ) 15.9), 6.12 (dt, 1H, J )
15.9, 6.9), 2.48-2.44 (m, 1H), 1.07 (d, 6H, J ) 6.7); 13C NMR
(CDCl3) δ 140.6, 136.0, 132.7, 129.5, 127.7, 126.6, 126.5, 123.3,
31.8, 22.3; GC/MS (E1) m/z 180 (M+). Anal. Calcd for C11H13
-
Cl: C, 73.13; H, 7.25. Found: C, 73.36; H, 7.18.
(E)-1-P h en yl-2-(2-ch lor op h en yl)eth en e (3q):26 1H NMR
(CDCl3/TMS) δ 7.65 (d, 1H, J ) 7.6), 7.58-7.45 (m, 3H), 7.39-
7.11 (m, 6H), 7.05 (d, 1H, J ) 16.3); 13C NMR (CDCl3) δ 137.0,
135.4, 133.4, 131.2, 129.8, 128.7, 128.5, 128.0, 126.8, 126.4,
124.7; GC/MS (E1) m/z 214 (M+).
(E)-1-(2-Ch lor op h en yl)-1-h ep ten e (3r ): 1H NMR (CDCl3/
TMS) δ 7.50 (dd, 1H, J ) 7.5, 1.6), 7.32 (dd, 1H, J ) 7.7, 1.5),
7.28-7.00 (m, 2H), 6.75 (d, 1H, J ) 15.8), 6.21 (dt, 1H, J )
15.8, 6.9), 2.32-2.11 (m, 2H), 1.59-1.16 (m, 6H), 0.91 (t, 3H,
J ) 6.8); 13C NMR (CDCl3) δ 136.0, 134.2, 132.5, 129.6, 127.7,
126.7, 126.6, 126.0, 33.2, 31.4, 28.9, 14.0; GC/MS (El) m/z 208
(M+). Anal. Calcd for C13H17Cl: C, 74.81; H, 8.21. Found: C,
74.53; H, 8.19.
(E)-1-(4-Ca r b oxylp h en yl)-1-p en t en e (3k ): 1H NMR
(CDCl3/TMS) δ 12.30 (brs, 1H), 8.04 (d, 2H, J ) 8.3), 7.42 (d,
2H, J ) 8.3), 6.50-6.30 (m, 2H), 2.30-2.10 (m, 2H), 1.60-
1.40 (m, 2H), 0.97 (t, 3H, J ) 7.3); 13C NMR (CDCl3/TMS) δ
172.1, 143.4, 134.5, 130.5, 129.1, 127.3, 125.8, 35.2, 22.3, 13.7;
GC/MS (EI) m/z 190 (M+). Anal. Calcd for C12H14O2: C, 75.76;
H, 7.42. Found: C, 75.51; H, 7.51.
(E)-1-(4-Tr iflu or om eth ylph en yl)-1-pen ten e (3l): 1H NMR
(CDCl3/TMS) δ 7.51 (d, 2H, J ) 8.3), 7.39 (d, 2H, J ) 8.3),
6.40 (d, 1H, J ) 16.0), 6.20 (dt, 1H, J ) 16.0, 6.2), 2.24-2.16
(m, 2H), 1.57-1.43 (m, 2H), 0.95 (t, 3H, J ) 7.3); 13C NMR
(CDCl3) δ 141.5, 133.8, 128.8, 126.0, 125.4, 125.4, 35.1, 22.4,
13.7; GC/MS (EI) m/z 214 (M+). Anal. Calcd for C12H13F3: C,
67.28; H, 6.12. Found: C, 67.39; H, 6.05.
(E)-1-(2-Ch lor oph en yl)-1-pr open e (3m ):25 1H NMR (CDCl3/
TMS) δ 7.46 (dd, 1H, J ) 7.6, 1.7), 7.31 (dd, 1H, J ) 7.6, 1.4),
7.22-7.03 (m, 2H), 6.77 (d, 1H, J ) 15.7) 6.20 (dt, 1H, J )
15.7, 6.7), 1.91 (dd, 3H, J ) 6.7, 1.6); 13C NMR (CDCl3/TMS)
δ 135.9, 132.3, 129.5, 128.6, 127.7, 127.3, 126.7, 126.5, 18.7;
GC/MS (EI) m/z 152 (M+).
Ack n ow led gm en t. We wish to thank the Depart-
ment of Energy and the Robert H. Cole Foundation for
their support of this research. We wish to thank
Professor Scott Denmark for his insightful comments.
J O9822784
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