The radical-chain addition of aldehydes to alkenes by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst

Article abstract of DOI:10.1039/b107548a

Hydroacylation of simple alkenes with aldehydes via a radical process was successfully achieved by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst. Thus, 5-tridecanone was obtained by the reaction of oct-1-ene with pentanal in the presence of small amounts of NHPI and dibenzoyl peroxide (BPO).

Full text of DOI:10.1039/b107548a

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The radical-chain addition of aldehydes to alkenes by the use of
N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst
Shinya Tsujimoto, Takahiro Iwahama, Satoshi Sakaguchi and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center, Kansai
University, Suita, Osaka 564-8680, Japan. E-mail: ishii@ipcku.kansai-u.ac.jp
Received (in Corvallis, OR, USA) 20th August 2001, Accepted 3rd October 2001
First published as an Advance Article on the web 29th October 2001
Hydroacylation of simple alkenes with aldehydes via a
radical process was successfully achieved by the use of N-
hydroxyphthalimide (NHPI) as a polarity-reversal catalyst.
Thus, 5-tridecanone was obtained by the reaction of oct-
1-ene with pentanal in the presence of small amounts of
NHPI and dibenzoyl peroxide (BPO).
alkanes. In this reaction, we found that the hydrogen atom
attached to the hydroxyimide moiety of NHPI is easily
abstracted by a radical species to generate phthalimide N-oxyl
(PINO) which abstracts the hydrogen atom from alkanes to give
alkyl radicals.6 Therefore, if the adduct radical B in Scheme 1
can abstract the hydrogen atom from NHPI, NHPI is expected to
serve as a polarity-reversal catalyst in analogy with methyl
thioglycolate. The hydrogen atom of the hydroxylimide moiety
adjacent to two carbonyl groups may be easily abstracted by a
nucleophilic radical rather than an electrophilic one, and the
resulting PINO would behave as an electrophilic radical that can
efficiently abstract the aldehydric hydrogen atom. In this paper,
we wish to report the radical-chain hydroacylation of simple
alkenes with aldehydes assisted by NHPI [eqn. (1)].
Intermolecular radical-chain addition of aldehydes to alkenes is
the simplest methodology for the synthesis of long-chain
unsymmetrical ketones, but employment of this method is
usually difficult for the synthesis of simple aliphatic ketones.1–3
The hydroacylation between alkenes and aldehydes via a radical
process involves the following reaction sequences: (i) hydrogen
abstraction from an aldehyde by a radical initiator to form an
acyl radical (A), (ii) addition of the acyl radical to alkene
leading to a b-oxocarbon radical (B), and (iii) abstraction of the
aldehydic hydrogen atom from another aldehyde by B,
generating ketone and acyl radical A (Scheme 1).
In this radical-chain reaction, if the RA is an alkyl or an
electron-donating group (EDG), step (iii) becomes a sluggish
process, since the abstraction of the aldehydic hydrogen atom
by nucleophilic radical B (Nu·) proceeds with difficulty. In
contrast, if the RA is an electron-withdrawing group (EWG), this
step proceeds smoothly because of the ease of aldehydic
hydrogen abstraction by an electrophilic radical B (El·).2 Acyl
radicals, which are nucleophilic in nature, are known to add
more easily to electron-deficient alkenes than normal alkenes.3
As a result, the hydroacylation of simple alkenes with aldehydes
via a radical process proceeds with difficulty. Recently, the
hydroacylation of alkenes, particularly electron-rich alkenes,
with aldehydes has been reported to be achieved by the use of
methyl thioglycolate (HSCH2CO2Me) which acts as a polarity-
reversal catalyst. For instance, the addition of butanal to
isopropenyl acetate using di-tert-butyl hyponitrite (TBHN) as
an initiator and methyl thioglycolate as the polarity-reversal
catalyst at 60 °C produces 1-acetoxyhexan-3-one in good
yield.4,5
(1)
A solution in dry toluene (0.5 mL) containing pentanal (1a)
(6 mmol), oct-1-ene (2a) (2 mmol), NHPI (0.2 mmol) and
dibenzoyl peroxide (BPO) (0.1 mmol) was stirred at 80 °C
under argon. After 12 h, additional BPO (0.1 mmol) in toluene
(0.5 mL) was added to the reaction system and the mixture was
allowed to react at that temperature for 12 h.† The reaction gave
tridecan-5-one (3aa) in 78% yield at 77% conversion (Table 1,
Run 1). In the absence of NHPI, the reaction gave 3aa in lower
conversion and yield (Run 2). This indicates that the NHPI
enhances the chain transfer reaction of step (iii) shown in
Scheme 1.
In a previous paper, we reported that NHPI under dioxygen
serves as an efficient carbon radical generation catalyst from
Table 1 Reaction of pentanal (1a) with oct-1-ene (2a) using various
catalysts in toluene at 80 °C in the presence of BPOa
Run
Catalyst
Conv. (%)
Yield (%)b
1
2
3
4
NHPI
—
77
63
79
72
78
67
72
53
78
48
80
78
65
75
88
58
3F-NHPIc
4Cl-NHPId
NHSIe
NHPI
NHPI
—
5
6f
7g
8g
a Reaction was run as described text. b Based on 1a reacted. c 3F-NHPI =
3-fluoro-N-hydroxyphthalimide. d 4Cl-NHPI = 4-chloro-N-hydroxyphtha-
limide. e NHSI = N-hydroxysuccinimide. f BPO (0.2 mmol) was added at
once at the start of the reaction. g BPO (0.2 mmol) was added over 18 h
using a syringe pump.
Scheme 1
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Chem. Commun., 2001, 2352–2353
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b107548a

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Table 2 Hydroacylation of alkenes with aldehydes catalyzed by NHPIa
Run
Aldehyde Alkene
Conv. (%) Product
Yield (%)
1
1a
1a
1a
1a
1a
1b
1c
1c
2b
2b
2c
2d
2e
2a
2a
2a
91
91
90
> 99
> 99
58
3ab
3ab
3ac
3ad
3ae
3ba
3ca
3ca
67
80
73
53
92
73
90
83
2b
3
4
5
6
7
8c
30
33
a See Table 1a. b Chlorobenzene was used as a solvent. c Reaction condition
was 90 °C.
Several NHPI derivatives and N-hydroxysuccinimide (NHSI)
were examined as catalysts (Runs 3 to 5). Among them,
3-fluoro- N-hydroxyphthalimide (3F-NHPI) gave the best result
(Run 3). When the radical initiator BPO (0.2 mmol) was added
in one portion, 3aa was formed in slightly lower yield (Run 6).
It was found that the gradual addition of BPO (0.2 mmol) in
toluene (0.5 mL) using a syringe-pump over a period of 18 h
afforded 3ab in higher yield (88%) in 72% conversion (Run
7).
Scheme 2
In conclusion, we have developed a facile catalytic method
for hydroacylation of alkenes using NHPI which acts as a
polarity-reversal catalyst. Further extension of this method is
now underway.
On the basis of these results, the reactions of various
aldehydes with alkenes were run under the same conditions as
Run 1 in Table 1 (Table 2). Diethyl allylmalonate (2b) and
norbornene (2c) were reacted with 1a giving the corresponding
adducts, 3ab and 3ac, respectively, in good yields (Runs 1–3).
a,b-Unsaturated ketone, 2d, afforded the 1,4-adduct 3ad in
slightly lower yield.‡ 5-Norbornene-2,3-dicarboxylic anhy-
dride (2e) resulted in adduct 3ae in high selectivity (Run 5).§
The reaction of benzaldehyde (1c) with 2a produced 1-phenyl-
octan-2-one (3ca) in high selectivity, although the conversion
was not high (30%) (Run 7). Treatment of 2-methylpentanal
(1d) with 2a catalyzed by NHPI gave the corresponding
coupling product 3da (8%) and 4-methyldodecane (4) (42%)
[eqn. (2)]. It is reported that the isoamylacyl radical was easily
decarbonylated to an isoamyl radical and CO.7 Therefore, 4
would be produced by the addition of an isoamyl radical, which
is generated by decarbonylation of 1c, to 2a.
This work was partly supported by a Grant-in-Aid for
Scientific Research (S) (No. 13853008) from Japan Society for
the Promotion of Science (JSPS).
Notes and references
† A typical procedure for reaction of pentanal 1a with oct-1-ene 2a. To a
solution in dry toluene (0.5 mL) containing pentanal (1a) (6 mmol) were
added oct-1-ene (2a) (2 mmol), NHPI (0.2 mmol) and dibenzoyl peroxide
(BPO) (0.1 mmol) and the reaction mixture was stirred at 80 °C under argon.
After 6 h, additional BPO (0.1 mmol) in toluene (0.5 mL) was added to the
reaction system and allowed to react under stirring at that temperature for
12 h. The reaction was quenched with wet diethyl ether, and products were
isolated by column chromatography on silica gel (n-hexane–AcOEt = 7+1)
affording tridecan-5-one (3aa) (238 mg, 60% yield) as a colorless liquid.
‡ Spectral data for 3ad. 1H NMR d 3.34–3.22 (m, 1H), 2.69–1.93 (m, 8H),
1.64–1.53 (m, 2H), 1.39–1.26 (m, 2H), 0.91 (t, J = 7.3 Hz, 3H); 13C NMR
d 216.6, 210.7, 47.4, 41.1, 39.9, 37.3, 25.8, 25.4, 22.1, 13.6.
§ Spectral data for 3ae. 1H NMR d 4.09–3.41 (m, 2H), 2.99–2.87 (m, 2H),
2.62–2.39 (m, 4H), 2.07–2.02 (m, 1H), 1.74–1.48 (m, 4H), 1.36–1.23 (m,
2H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR d 209.1, 171.6, 171.4, 49.3, 49.1,
48.1, 42.6, 41.0, 39.8, 39.6, 27.6, 25.6, 22.1, 13.6.
(2)
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A possible reaction path for the NHPI-catalyzed hydro-
acylation of alkenes with aldehydes is shown in Scheme 2. The
reaction may be initiated by the hydrogen atom abstraction from
aldehyde by the radical initiator (In·), giving an acyl radical C
which then adds to an alkene to afford a b-oxocarbon radical D.
The resulting radical D having a nucleophilic character abstracts
the hydrogen atom from NHPI leading to ketone and PINO. The
abstraction of the hydrogen atom from aldehyde by the PINO
forms the acyl radical C and NHPI. An alternative formation of
PINO from NHPI and radical initiator (In·) may also be
possible.
Chem. Commun., 2001, 2352–2353
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