Rhodium-catalyzed cascade reactions: A methylenation-hydroboration homologative process

Article abstract of DOI:10.1016/j.jorganchem.2005.03.058

A very efficient rhodium-catalyzed cascade process allowing the transformation of aldehydes and ketones into their corresponding one or two-carbon homologated alcohol products through a methylenation-hydroboration sequence is reported. Wilkinson's complex is used to catalyze both reactions in a one-pot procedure that does not require the isolation of the alkene intermediate.

Full text of DOI:10.1016/j.jorganchem.2005.03.058

Journal of Organometallic Chemistry 690 (2005) 5198–5205
www.elsevier.com/locate/jorganchem
Rhodium-catalyzed cascade reactions: A
methylenation–hydroboration homologative process
*
´ `
Helene Lebel , Chehla Ladjel
´ ´ ´ ´
Departement de Chimie, Universite de Montreal, P.O. Box, 6128, Station Downtown, Montreal, Qc., Canada H3C 3J7
Received 3 February 2005; received in revised form 22 March 2005; accepted 29 March 2005
Available online 31 May 2005
Abstract
A very efficient rhodium-catalyzed cascade process allowing the transformation of aldehydes and ketones into their correspond-
ing one or two-carbon homologated alcohol products through a methylenation–hydroboration sequence is reported. WilkinsonÕs
complex is used to catalyze both reactions in a one-pot procedure that does not require the isolation of the alkene intermediate.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Rhodium; WilkinsonÔs catalyst; Methylenation; Hydroboration
1. Introduction
toward both carbonyl derivatives and alkenes, to func-
tionalize in situ our methylene unit. In this article, we
present a new rhodium-catalyzed cascade process
involving a methylenation–hydroboration reaction se-
quence, to produce the corresponding organoborane.
This intermediate can be further submitted to an oxida-
tion reaction to produce the corresponding alcohol, or
to a second homologation reaction with either LiCHCl2
or LiCH2Cl [9].
The WilkinsonÕs complex, RhCl(PPh3)3 [1] is well
known to catalyze a variety of reactions with alkenes,
such as hydrogenation [2], hydrosilylation [3], hydro-
formylation [4], and hydroboration reactions [5]. Re-
cently, our group has reported the methylenation of a
variety of carbonyl derivatives catalyzed by WilkinsonÕs
complex in the presence of trimethylsilyldiazomethane,
triphenylphosphine and 2-propanol, producing the cor-
responding terminal alkene in high yield (Eq. 1) [6,7]
N
2
2. Results and discussion
i-PrOH, PPh
2
2
3
R
R
ð1Þ
TMS
H
2.1. Rhodium-catalyzed methylenation–hydroboration
cascade with aliphatic aldehydes
1
1
RhCl(PPh ) (2.5 mol%) / THF
R
O
R
3 3
Moreover, we have shown that multicatalytic processes
including our rhodium-catalyzed methylenation reaction
allowed the formation of various substituted alkenes di-
rectly from alcohols, without the isolation of any inter-
mediate [8]. Another cascade process will consist in
using the dual catalytic activity of WilkinsonÕs complex
The use of WilkinsonÕs complex allows the hydrobo-
ration of alkenes with catecholborane to occur at room
temperature, where heat is required for the uncatalyzed
reaction [5]. We first investigated the rhodium-catalyzed
methylenation–hydroboration cascade with aliphatic
aldehydes by using catecholborane as our hydroborat-
ing agent to produce, after the oxidative work-up, the
corresponding terminal alcohol. Indeed, treatment of
*
Corresponding author. Tel.: +5143435826; fax: +5143432177.
E-mail address: helene.lebel@umontreal.ca (H. Lebel).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.03.058

H. Lebel, C. Ladjel / Journal of Organometallic Chemistry 690 (2005) 5198–5205
5199
hydrocinnamaldehyde (1) with 1.1 equivalent of triphe-
nylphosphine, 2-propanol, and 1.4 equivalent of trim-
ethylsilyldiazomethane in the presence of 3 mol% of
WilkinsonÕs catalyst in THF for two hours, followed
by the addition of catecholborane produced the desired
organoborane after an additional two hours of reaction.
In this one-pot procedure, not only is the rhodium
catalyst required for the methylenation reaction, but
also for the hydroboration reaction. At the outset, oxi-
dation with hydrogen peroxide and sodium hydroxide
of the organoborane intermediate led to a disappoint-
ing 62% yield of the corresponding alcohol 2 (Table 1,
entry 1).
It was found that adding dioxane, either with the
catecholborane or with the oxidative reagent further im-
proves the isolated yield (75–79%, entries 4–5) of the de-
sired 4-phenylbutanol (2). The reaction could be also
performed with dioxane as the only solvent, although
it is then necessary to heat the methylenation reaction
to 60 ꢁC (entry 6). Two equivalents of catecholborane
are required, as only 40% conversion is observed in
the presence of 1.5 equivalent and less then 10% conver-
sion with 1.1 equivalent (entries 2–3). We postulate that
catecholborane either reacts or complexes the triphe-
nylphosphine oxide generated from the methylenation
reaction. Both hydrogen peroxide and sodium perbo-
rate [10] could be used as oxidative reagents (entries 5
vs. 7).
as well as a-branched aldehydes (entries 4–15).
Although in most cases, the difference in yields for both
oxidative protocol was not noteworthy, in some cases,
the isolated yields were significantly higher when using
the sodium borate procedure (entries 4–5 and 16–17).
The chemoselectivity of this cascade process is excep-
tional, as both rhodium-catalyzed reactions could distin-
guish between functional groups that differed only by
the substitution. The rhodium-catalyzed hydroboration
is chemoselective for terminal double bonds thus, the tri-
substituted alkene of the diene produced by the methyl-
enation of citronellal (11) stays intact (entries 16–17).
Furthermore, as we can perform chemoselective methyl-
enation of aldehydes over ketones, it is possible to ob-
tain keto alcohol product 14 in good yields (entry 20).
No only the aromatic ketone did not react during the
rhodium-catalyzed methylenation reaction, but was
not reduced during the hydroboration step.
2.2. Rhodium-catalyzed methylenation–hydroboration
cascade with aromatic aldehydes
The regioselectivity of the rhodium-catalyzed hyd-
roboration of aromatic aldehydes typically favors the
corresponding secondary organoborane. The regioselec-
tivity is strongly dependant on the reaction conditions,
including the catalyst and its ligands, as well as the bor-
ane reagent [11]. Under our standard cascade reaction
conditions, using WilkinsonÕs catalyst and catecholbo-
rane, we observed mainly the formation of the second-
ary organoborane but only with a moderate ratio: for
instance the organoborane derived from p-bromobenz-
aldehyde was obtained with a 4:1, branched:linear ratio
(Table 3, entry 1). However, this ratio could be signifi-
cantly improved by using a cationic rhodium complex,
[Rh(COD)2]BF4 in the presence of pinacolborane,
We have extended these one-pot methylenation–hyd-
roboration reaction conditions to a variety of aldehydes
using the two oxidative procedures (Table 2). The corre-
sponding alcohol could be isolated with 63–84% yields,
which are typically similar or higher than the yields ob-
tained for the step-by-step approach, in which the al-
kene intermediate is isolated. The reaction conditions
are compatible with silyl- and benzyl-protected alcohols
Table 1
Optimization of rhodium-catalyzed methylenation hydroboration cascade process of hydrocinnamaldehyde
Entry
Methylenation (solvent, ꢁC)
Hydroboration (RO2 B–H (equiv.)/solvent)
Oxidation
Conv. (yield)a
1
2
3
4
5
THF, 25 ꢁC
THF, 25 ꢁC
THF, 25 ꢁC
THF, 25 ꢁC
THF, 25 ꢁC
2 equiv./THF
H2O2, NaOHaq
H2O2, NaOH
>98% (62%)
<10%
40%
1.1 equiv./dioxane
1.5 equiv./dioxane
2 equiv./dioxane
2 equiv./THF
aq
H2O2, NaOHaq
H2O2, NaOHaq
H2O2, NaOHaq
Dioxane
>98% (79%)
>98% (75%)
6
7
8
Dioxane, 60 ꢁC
THF, 25 ꢁC
THF, 25 ꢁC
2 equiv./dioxane
2 equiv./dioxane
2 equiv./THF
H2O2, NaOHaq
NaBO3aq
NaBO3/dioxane
>98%
>98% (55%)
>98% (70%)
Isolated yields in parentheses.
a
Conversion by GC–MS.

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H. Lebel, C. Ladjel / Journal of Organometallic Chemistry 690 (2005) 5198–5205
Table 2
Rhodium-catalyzed methylenation hydroboration of aliphatic aldehydes
a
Condition A: catecholborane/dioxane; H2O2, NaOH/H2O. Condition B: catecholborane/THF; NaBO3/H2O + dioxane. Condition C: step-by-step
approach with H2O2, NaOH oxidative protocol.
b
Isolated yields.
leading to an 8:1 branched:linear ratio (entry 2). The
methylenation reaction was carried out in dioxane at
50 ꢁC to generate the catalytically active species, pre-
sumably [(Ph3P)Rh(COD)]+, then hydroboration was
performed at room temperature for 12 h. Other styrene
derivatives could be in-situ prepared and converted into
the corresponding branched organoboranes with good
ratios (entries 3–4). It was only with an electron-donat-
ing substituent that the reaction became unselective
leading to a 1.5:1 branched:linear ratio (entry 5).
zation of our cascade procedure was required to account
for the reactivity of ketones towards the methylenation
reaction. Our previous report on methylenation of ke-
tones has shown that an excess of 2-propanol was essen-
tial to perform the reaction with 1 equivalent of
triphenylphosphine [6b]. Typically, 10 equivalents of 2-
propanol was used; however such an excess of alcohol
is not compatible with the hydroboration reaction. Fur-
ther optimization showed that the amount of 2-propa-
nol could be decreased, when using an excess of
triphenylphosphine. Indeed, the methylenation was car-
ried out in the presence of an excess of trimethylsilyldia-
zomethane (2.5 equiv.), 2-propanol (2 equiv.) and
triphenylphosphine (2 equiv.), and with 5 mol% of Wil-
kinsonÕs catalyst in THF at 60 ꢁC. Three equivalents of
catecholborane in dioxane were then added to produce
2.3. Rhodium-catalyzed methylenation–hydroboration
cascade with ketones
In the case of non-symmetrical ketone derivatives,
only the primary organoborane was observed. Optimi-

H. Lebel, C. Ladjel / Journal of Organometallic Chemistry 690 (2005) 5198–5205
5201
Table 3
Rhodium-catalyzed methylenation hydroboration of aromatic aldehydes
Entry
X
Yielda
Ratio B:Lb
1c
2
3
4
5
a
Br
Br
–
4:1
8:1
62%
67%
61%
65%
H
9:1
5:1
Me
OMe
1.5:1
Isolated yields.
Determined by GC–MS.
Reaction was performed using 3 mol% of RhCl(PPh3)3 and 2 equiv. of catecholborane.
b
c
the desired organoborane after 2 h at room temperature.
Oxidation with hydrogen peroxide and sodium hydrox-
ide led to the formation of the desired primary alcohol
with 80–81% yields (Eqs. 2 and 3)
was produced in 64% yield from a 5-steps sequence
whereas aldehyde 21 could be generated with 62% yield,
from a 4-steps sequence indicating that each individual
step was about 90% yield. It is also possible to produce
ð2Þ
ð3Þ
2.4. Rhodium-catalyzed methylenation–hydroboration-
homologation cascade
the two-carbon homologated alcohol product by using
LiCH2Cl generated by lithium–halogen exchange from
bromochloromethane. The homologated organoborane
species is then submitted to oxidation reaction to furnish
the desired alcohol 22 in 60% yield from a 4-steps se-
quence. These two-carbon homologation sequences are
thus particularly efficient, as it is not required to isolate
any intermediate and as the reagent and/or the oxidation
level could be adjusted to furnish the requisite product.
There are a number of transformations that can be
performed on the organoborane species, other than the
simple oxidation. For instance, a homologation reaction
could be performed when adding LiCHCl2, before the
oxidative work-up [9]. Indeed the organoborane species
19 initially generated from hydrocinnamaldehyde (1),
could be directly treated with the anion of dichlorometh-
ane (LiCHCl2) to produce the chloro one-carbon
homologated organoborane product (Scheme 1). The
oxidation reaction conditions could be adjusted in such
way that either ester 20 or aldehyde 21 could be directly
obtained without further steps. Corresponding ester 20
3. Conclusion
In conclusion, an efficient cascade process has
been developed to perform
a rhodium-catalyzed

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H. Lebel, C. Ladjel / Journal of Organometallic Chemistry 690 (2005) 5198–5205
Scheme 1. Rhodium-catalyzed methylenation hydroboration homologation process.
methylenation–hydroboration sequence in one single
step. In this process, the WilkinsonÕs complex played a
dual role, as it catalyzed both the methylenation and
the hydroboration reaction. Aliphatic aldehydes and ke-
tones produced the corresponding primary alcohol after
the oxidation step, whereas aromatic aldehydes led to
the formation of the corresponding secondary organ-
oborane species. Furthermore, a second homologation
could be performed in situ on the organoborane species,
before the oxidation step, to lead to a 2-carbons homol-
ogation sequence with high yield. Overall this process
illustrates the power of WilkinsonÕs complex at catalyz-
ing very different type of organic reactions.
One FTIR spectrometer. 1H NMR spectra were re-
corded in CDCl3, on a Brucker Av-400, a Brucker
ARX-400, a Brucker AMX-300, or a Brucker AV-300
spectrometers (400, 400, 300, and 300 MHz, respec-
tively). Chemical shifts are reported in ppm on the d
scale from an internal standard of residual chloroform
(7.27 ppm). Data are reported as follows: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet,
q = quartet, qn = quintet, m = multiplet and br = broad),
coupling constant in Hz, integration. 13C NMR spectra
were recorded in CDCl3, on a Brucker Av-400, a Brucker
ARX-400, a Brucker AMX-300, or a Brucker AV-300
spectrometers (100, 100, 75, and 75 MHz, respectively)
with complete proton decoupling. Chemical shifts are re-
ported in ppm from the central peak of CDCl3 (76.9 ppm)
on the d scale. Mass spectra were obtained on a LC-MSD
TOF Agilent Technologies (ESI) high resolution. Analyt-
ical gas chromatography with mass spectroscopy (GC–
MS) was carried out on a Hewlett–Packard 6890 series
gas chromatograph equipped with a split mode capillary
injector and electron impact mass detector. Unless other-
wise noted, injector and detector temperatures were
250 ꢁC and the carrier gas was hydrogen (2 mL/min) with
a HP-5MS column.
4. Experimental
4.1. General considerations
All the non-aqueous reactions were performed under
an oxygen-free atmosphere of argon. The solvents were
dried using standard method prior to use. RhCl(PPh3)3
is commercially available, but was prepared according
to the literature [1]. 2-propanol was distillated over
calcium hydride. [Rh(COD)2]BF4 was prepared accord-
ing to the literature procedure [12]. The commercial
available aldehydes were purified using standards
methods prior to use. Triphenylphosphine was purchase
from Aldrich Chemical Co. and used without further
purification. Catecholborane and pinacolborane are
commercially available but was prepared according to
the literature procedure [13,14]. Analytical thin layer
chromatography (TLC) was performed using EM
Reagent 0.25 mm silica gel 60-F plates. Flash chroma-
tography was performed using EM Silica Gel 60 (230–
400 mesh) with the indicated solvent system. Infrared
spectra were recorded on a Perkin–Elmer Spectrum
4.2. Catalytic methylenation–hydroboration of aliphatic
aldehydes
To a solution of chlorotris(triphenylphosphine)rho-
dium (0.027 g, 0.030 mmol) and triphenylphosphine
(0.290 g, 1.10 mmol) in THF (10.0 mL) under argon
atmosphere, was added 2-propanol (0.084 mL,
1.10 mmol) followed by the aldehyde (1.00 mmol). To
the resulting red mixture, was added trimethylsilyldia-
zomethane (0.197 mL of a 7.10 M solution, 1.40 mmol).
Gas evolution was observed and the resulting mixture

H. Lebel, C. Ladjel / Journal of Organometallic Chemistry 690 (2005) 5198–5205
5203
was stirred at room temperature. When the methylena-
4.6. Catalytic methylenation–hydroboration of ketones
tion is completed by TLC analysis, catecholborane
(0.210 mL, 2.00 mmol) was slowly added and the reac-
tion was stirred at room temperature. When the hydrob-
oration was completed by TLC analysis, the resulting
organoborane was oxidized following method A or B.
To a solution of chlorotris(triphenylphosphine)rho-
dium (0.027 g, 0.030 mmol) and triphenylphosphine
(0.520 g, 2.00 mmol) in THF (10.0 mL) under argon ato-
mosphere, was added 2-propanol (0.150 mL, 2.00 mmol)
followed by the ketone (1.00 mmol). The resulting mix-
ture was heated at 60 ꢁC and trimethylsilyldiazomethane
(0.280 mL of a 7.10 M solution, 2.00 mmol) was added
dropwise. When the reaction is completed by TLC analy-
sis, the mixture is allowed to cool to room temperature
and catecholborane (0.319 mL, 3.00 mmol) was added.
When the hydroboration is completed by TLC, the result-
ing organoborane was oxidized following method A.
4.3. Oxidation method A: H2O2/NaOH
When the hydroboration is completed by TLC anal-
ysis, the flask was opened to air and dioxane (3.0 mL)
was added; the reaction mixture was then cooled to
0 ꢁC. A solution of NaOH (3.0 mL of a 2.0 M solution,
6.00 mmol) was added followed by H2O2 (3.00 mL of a
35% solution, 36.0 mmol). The reaction mixture was
warmed to room temperature and stirred under air
atmosphere for another 3 h. The mixture was then ex-
tracted with ethyl ether (2 · 10 ml), and the combined
organic layers were washed with saturated solutions of
NH4Cl (10 mL), NaHCO3 (10 mL) and brine (10 mL).
The organic layer was dried over MgSO4 and the solvent
was removed under reduced pressure. The crude alcohol
was purified by flash chromatography on silica gel.
4.7. Catalytic methylenation–hydroboration–
homologation
To a solution of chlorotris(triphenylphosphine)rho-
dium (0.013 g, 0.015 mmol) and triphenylphosphine
(0.144 g, 0.550 mmol) in THF (5.00 mL) under argon
atomosphere, was added 2-propanol (0.042 mL,
0.55 mmol) followed by the hydrocinnamaldehyde
(0.670 mg, 0.500 mmol). To the resulting red mixture,
was added trimethylsilyldiazomethane (0.098 mL of a
7.10 M solution, 0.700 mmol). Gas evolution was ob-
served and the resulting mixture was stirred at room
temperature. When the reaction is completed by TLC
analysis, pinacolborane (0.145 mL, 1.00 mmol) was
slowly added and the reaction was stirred at room tem-
perature. When the hydroboration was completed by
TLC analysis, the volume was reduced to roughly
2 mL under reduced pressure. LiCHCl2 (1.00 mmol)
was generated by the dropwise addition of n-BuLi
(0.470 mL of a 2.10 M solution in hexane, 1.00 mmol)
to a mixture of dichloromethane (0.500 mL, 7.80 mmol)
in THF (3.50 mL) at ꢀ100 ꢁC. The solution was stirred
for 10 min before the addition of the organoborane.
ZnCl2 (0.50 mL of a 1.0 M solution in Et2O, 0.50 mmol)
was then added. The reaction was warm up to room
temperature overnight. The volatiles were then removed
under a vigorous flow of argon. The residue was
quenched with 2 mL of saturated NH4Cl solution, ex-
tracted with light petroleum ether (4 · 10 mL), dried
over MgSO4, filtered and concentrated in vacuo. The
residue was then oxidized following method C or D.
4.4. Oxidation method B: NaBO3
When the hydroboration is completed by TLC anal-
ysis, the flask was opened to air and dioxane (3.0 mL)
followed by water (3.0 mL) and sodium perborate
(0.240 g, 3.00 mmol) were added sequentially to the
flask; The reaction mixture was maintained at room
temperature for 3 h with vigorous stirring under air
atmosphere. The two phases were separated, and the
aqueous layer was extracted with ether (3 · 5 mL). The
combined organic layers were washed with brine
(10 mL) and dried with MgSO4. The solvent was re-
moved under reduced pressure. The crude alcohol was
purified by flash chromatography.
4.5. Catalytic methylenation–hydroboration of aromatic
aldehydes
To a solution of [Rh(COD)2]BF4 (0.012 g, 0.030 mmol)
and triphenylphosphine (0.290 g, 1.10 mmol) in dioxane
(10.0 mL) under argon atmosphere, was added 2-propa-
nol (0.084 mL, 1.10 mmol) followed by the aldehyde
(1.00 mmol). The mixture was heated at 50 ꢁC and trim-
ethylsilyldiazomethane (0.197 mL of a 7.10 M solution,
1.40 mmol) was added. When the reaction is completed
by TLC analysis, the mixture was allowed to cool to room
temperature and pinacolborane (0.290 mL, 2.00 mmol)
was added dropwise. The reaction mixture was then stir-
red over night. The solvent was removed under reduced
pressure, the crude organoborane was purified by flash
chromatography. The ratio branched/linear of the boro-
nate ester was obtained by GC/MS.
4.8. Oxidation method C: synthesis of 5-phenylpentanoic
acid methyl ester (20) [15]
The residue obtained from 4.7 was dissolved in t-
BuOH (10 mL) and amylene (2.0 mL). A solution
(20 mL) of NaClO2 (0.600 g, 6.00 mmol) and K2HPO4
(0.920 g, 7.20 mmol) was prepared; 10 mL of this solu-
tion were added and the reaction was stirred for 24 h,
under air atmosphere. The other 10 mL were added

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H. Lebel, C. Ladjel / Journal of Organometallic Chemistry 690 (2005) 5198–5205
and the reaction was stirred for another 72 h. The vola-
tiles were removed in vacuo, and the resulting aqueous
residue was extracted with ether (3 · 10 mL) and ethyl
acetate (3 · 10 mL). The combined organic extracts were
washed with water (2 · 15 mL) and then extracted with
saturated aqueous NaHCO3 (2 · 15 mL). The combined
basic aqueous layers were then slowly acidified to pH 2
with concentrated HCl. The aqueous solution was ex-
tracted with ethyl acetate (4 · 25 mL). The organic ex-
tracts were then combined, washed with water (10 mL)
and brine (10 mL), dried over MgSO4, and concentrated
in vacuo. The resulting white solid was dissolved in
CH2Cl2 (2 mL) and diazomethane (1.07 mL of a
0.70 M solution in ether, 0.75 mmol) was added drop-
wise. The mixture was stirred at room temperature for
1 h. The solvent was evaporated and the crude product
was purified by flash chromatography (10% ethyl ace-
tate/hexane) to produce 0.061 g (64% yield) of the de-
sired ester. Rf 0.32 (10% ethyl acetate/hexane); 1H
NMR (400 MHz, CDCl3) d 7.33–7.28 (m, 2H), 7.22–
7.19 (m, 3H), 3.69 (s, 3H), 2.66 (t, J = 5 Hz, 2H), 2.36
(t, J = 10 Hz, 2H), 1.72–1.67 (m, 4H); 13C NMR
(100 MHz, CDCl3) d 174.4, 142.5, 128.8, 128.7, 126.2,
51.9, 36.0, 34.4, 31.3, 25.0.
solution 7.10 M, 0.700 mmol). Gas evolution was ob-
served and the resulting mixture was stirred at room
temperature. When the reaction is completed by TLC
analysis, pinacolborane (0.145 mL, 1.00 mmol) was
slowly added and the reaction was stirred at room tem-
perature. When the reaction is completed by TLC anal-
ysis, the volume was reduced to roughly 2 mL under
reduced pressure. Bromochloromethane (0.350 mL,
0.550 mmol) was then added and the reaction solution
was cooled to ꢀ78 ꢁC; n-BuLi (0.260 mL of a 2.10 M
solution in hexane, 0.55 mmol) was added dropwise.
The reaction was warmed to ambient temperature over
night. The volatiles were removed under a flow of argon.
The residue was quenched with 5 mL of saturated
NH4Cl, extracted with light petroleum (4 · 10 mL) dried
over MgSO4, filtered, and concentrated in vacuo. The
residue was then submitted to oxidation following the
method A. The crude alcohol was purified by flash chro-
matography (30% ethyl acetate/hexane) to give 0.051 g
1
(60% yield). H NMR (300 MHz, CDCl3) d 7.34–7.29
(m, 2H), 7.23–7.19 (m, 3H), 3.67 (t, J = 6.5 Hz, 2H),
2.67 (t, J = 8 Hz, 2H), 1.75–1.59 (m, 5H), 1.49–1.30
(m, 2H); 13C NMR (75 MHz, CDCl3) d 143.0, 128.8,
128.7, 126.1, 63.3, 36.3, 33.1, 31.7, 25.9.
4.9. Oxidation method D: synthesis of 5-phenylpentanal
(21) [16]
Acknowledgments
This research was supported by NSERC (Canada),
the Canadian Foundation for Innovation, Boehringer
The residue obtained from 4.7 was then dissolved in
THF (5 mL). Sodium perborate (0.120 g, 1.50 mmol)
was added to the flask followed by 5 mL of water and
a solution of NaOH (0.25 mL of a 2 M solution,
0.50 mmol). The mixture was stirred at room tempera-
ture, under air atmosphere, over night. The mixture
was then extracted with ethyl ether (4 · 10 mL). The
combined organic layers were washed with brine
(20 mL), dried over MgSO4 and evaporated in vacuo.
The crude product was purified by flash chromatogra-
phy (10% ethyl acetate/hexane) to produce 0.048 g
(62% yield) of the desired aldehyde. Rf 0.27 (10% ethyl
acetate/hexane). 1H NMR (400 MHz, CDCl3) d 9.78
(s, 1H), 7.32–7.28 (m, 2H). 7.22–7.18 (m, 3H), 2.66 (t,
J = 6 Hz, 2H), 2.48 (t, J = 8 Hz, 2H), 1.79–1.64 (m,
4H). 13C NMR (100 MHz, CDCl3) d 202.2, 141.6.
128.03, 128.0, 125.5, 43.4, 35.3, 30.5, 21.3.
´
Ingelheim (Canada) Ltee, Merck Frosst Canada and
´ ´
the Universite de Montreal.
Appendix A. Supplementary data
Characterization data for compounds 2, 4, 6, 8, 10,
12, 14, 16 and 18. Supplementary data associated with
this article can be found, in the online version, at
doi:10.1016/j.jorganchem.2005.03.058.
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(b) J.A. Osborn, F.H. Jardine, J.F. Young, G. Wilkinson, J.
Chem. Soc. A (1966) 1711–1732;
4.10. Catalytic methylenation–hydroboration–
homologation: synthesis of 5-phenyl-1-pentanol (22)
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