N-Hydroxyphthalimide-catalyzed radical addition of 1,3-dioxolanes and molecular oxygen to alkenes under ambient conditions: A new route to β-oxycarbonyl compounds

Article abstract of DOI:10.1039/b008418m

A novel catalytic hydroxyacylation of alkenes using 1,3-dioxolanes and molecular oxygen has been developed, and the reaction of 2-methyl-1,3-dioxolane with methyl acrylate under dioxygen atmosphere in the presence of catalytic amounts of NHPI and Co(OAc)₂ produced the corresponding adduct in 81% yield.

Full text of DOI:10.1039/b008418m

N-Hydroxyphthalimide-catalyzed radical addition of 1,3-dioxolanes and
molecular oxygen to alkenes under ambient conditions: a new route to
b-oxycarbonyl compounds
Kazutaka Hirano, 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 Cambridge, UK) 18th October 2000, Accepted 2nd November 2000
First published as an Advance Article on the web
A novel catalytic hydroxyacylation of alkenes using 1,3-di-
oxolanes and molecular oxygen has been developed, and the
reaction of 2-methyl-1,3-dioxolane with methyl acrylate
under dioxygen atmosphere in the presence of catalytic
amounts of NHPI and Co(OAc)2 produced the correspond-
ing adduct in 81% yield.
(2)
Addition of aldehydes to terminal alkenes has received attention
as a method for the synthesis of ketones from aldehydes.1 The
frequently used methodologies are the direct hydroacylation of
alkenes with aldehydes by transition-metal catalysts1 and the
addition of acyl radicals to alkenes bearing electron-with-
drawing substituents such as fumarate by radical initiators.2 If
the concomitant introduction of acyl and hydroxy moieties to
alkenes can be carried out by a cascade reaction, this type of
reaction is referred to as hydroxyacylation and would provide a
novel route to b-oxycarbonyl compounds which constitute
important structural subunits in key intermediates leading to
pharmaceuticals [eqn. (1)].3 Although there is one report on the
hydroxyacylation of alkenes like acrylates with acyl radicals
from aldehydes using dioxygen as a hydroxy source assisted by
a cobalt(II) Schiff-base complex,4 the attempt was not fully
successful due to the decarbonylation from acyl radicals as well
as the reaction of acyl radicals with O2 leading to carboxylic
acids which cause undesired side reactions.
fails to react with O2 could not promote the reaction under O2 at
rt (Run 2).6a,7
From 1,3-dioxolane (1b), the corresponding adduct 3b was
obtained in high yield (82%) (Run 4). The introduction of the
masked formyl group to 2a is promising, since the direct use of
formaldehyde is restricted due to its intractability. These
dioxolane moieties could be easily deprotected upon treatment
under acidic conditions to form the corresponding carbonyl
compounds [eqns. (3) and (4)].
(3)
(4)
(1)
To overcome these drawbacks arising from acyl radicals, we
employed 1,3-dioxolanes, masked aldehydes, as an acyl source
in place of an aldehyde.5 This paper describes the development
of a novel catalytic method leading to b-hydroxy carbonyl
compounds after deprotection under acidic conditions.
Recently, we have shown that N-hydroxyphthalimide (NHPI)
combined with a Co(II) species serves as a catalyst for the
generation of alkyl radicals from alkanes even under ambient
conditions, and that the resulting alkyl radicals are readily
captured by O2 to give oxygenated products.6 In this catalytic
system, phthalimide N-oxyl (PINO) is the active species
abstracting hydrogen atoms from the alkanes.6a This finding
prompted us to study the generation of a,a-dioxaalkyl radicals
from 1,3-dioxolanes and their addition to alkenes using the
NHPI/Co(II)–O2 catalytic system [eqn. (2)].
At the beginning, a mixture of 2-methyl-1,3-dioxolane (1a)
(15 mmol) and methyl acrylate (2a) (3 mmol) was allowed to
react under O2 (1 atm) in the presence of NHPI (5 mol%) and a
small amount of Co(OAc)2 (0.05 mol%) at rt for 3 h (Table 1,
Run 1).† The apparent hydroxyacylation based on the concomi-
tant introduction of a dioxaalkyl radical and a hydroxy group to
2a was achieved to form b-hydroxy ketal (3a) in 81% yield. In
a previous paper, we showed that a Co(III)–dioxygen complex
derived from the Co(II) species and O2 assists the formation of
a PINO radical from the NHPI.6a Accordingly, the Co(III) which
The reaction of 1a or 1b with various alkenes was run under
selected reaction conditions (Table 2). Acrylonitrile (2e) was
found to serve as a good acceptor of 1a and 1b in a similar
manner as 2a, giving cyanohydrin derivatives in good yields.
However, methyl crotonate (2c) bearing a b-methyl group
retarded the hydroxyacylation, probably owing to the steric
hindrance towards attack by an a,a-dioxaalkyl radical on 2c.8
To our surprise, methyl vinyl ketone (5a) reacted with 1a to
afford a cleaved product, 3-(1,3-dioxolan-2-yl)butanoic acid (6)
in 83% yield along with 3-(1,3-dioxolan-2-yl)butylaldehyde (7)
Table 1 Reaction of 1a–c with methyl acrylate (2a)a
NHPI/
mol%
Co(II)/
mol%
Run
1a–c
t/h
Yield (%)b
1
1a
1a
1a
1b
1c
5
5
—
10
5
0.05
0.05
0.05
0.1
3
3
3
2
14
81
n.d.
1
82
76
2c
3
4d
5
0.1
a 2a (3 mmol) was allowed to react with 1a–c (15 mmol) in the presence of
NHPI and Co(OAc)2 under atmospheric oxygen at rt. b GC yield.
c Co(acac)3 was used. d 1b (30 mmol) was used.
DOI: 10.1039/b008418m
Chem. Commun., 2000, 2457–2458
This journal is © The Royal Society of Chemistry 2000
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Table 2 Reaction of 1a–b with various alkenes under ambient con-
ditionsa
Scheme 2
converted into 3a through the hydrogen abstraction from either
NHPI or 1a.10
Although it seems rather hazardous to make an accurate
assessment about the reaction path for the formation of 6 from
1a and methyl vinyl ketone 5a, we can make two proposals
which seem to agree with the experimental results. It is probable
that an a-hydroperoxyketone V derived from 1a and 5a might
decompose into aldehyde 7 via formation of a hydroxydiox-
etane VI (Scheme 2). This type of reaction through the
hydroxydioxetane is shown in the autoxidation of ketones like
diisopropyl ketone.11 However, an alternative proposal is also
possible, viz. the hydroperoxide V is subject to the redox
decomposition to generate an alkoxy radical intermediate VII
which then is converted into 7 via b-scission.
(4%) [eqn. (5)]. The carboxylic acid 6 is considered to be
formed via the further oxidation of aldehyde 7.9
In conclusion, we have developed a novel method for the
introduction of both a masked acyl or formyl group and a
hydroxy or keto function to a double bond of alkenes. Further
work on the extension of this method is actively underway.
This work was partly supported by the Japan Society for the
Promotion of Science under the Research for the Future
program JSPS.
(5)
Notes and references
† A typical procedure for reaction of 2-methyl-1,3-dioxolane 1a with methyl
acrylate 2a: To a solution of 1a (15 mmol), NHPI (0.15 mmol) and
Co(OAc)2 (0.0015 mmol) in a two-necked flask, equipped with a balloon
filled with O2 (1 atm), was added 2a (3 mmol). The mixture was vigorously
stirred at rt for 3 h. The recovery of unreacted 1a under a reduced pressure
followed by flash chromatography on silica gel (n-hexane–AcOEt = 1+2)
afforded methyl 2-hydroxy-4-(1,3-dioxolan-2-yl)valerate (3a) (462 mg,
81% yield) as a colorless liquid.
A plausible reaction path for the apparent hydroxyacylation
of 2a with 1a under dioxygen is shown in Scheme 1. The
reaction may be initiated by the hydrogen atom abstraction from
NHPI by the action of the Co(III)–dioxygen complex, giving
PINO which then abstracts the dioxolane hydrogen of the 1a to
form an dioxolane radical I. The I radical having a highly
nucleophilic character seems to readily add to 2a, yielding a
radical species II. Under the conditions in which O2 is present
in the reaction system, the resulting radical II is rapidly trapped
by O2 to give a hydroperoxide III. It is well-known that
hydroperoxides like III are subjected to redox decomposition
by Co ions to form an alkoxyl radical IV which is eventually
1 Recent review: C.-H. Jun, J.-B. Hong and D.-Y. Lee, Synlett, 1999, 1,
1.
2 M. Tracy and Jr. Patrick, J. Org. Chem., 1952, 17, 1009.
3 M. Braun, Angew. Chem., Int. Ed. Engl., 1987, 26, 24; C. H. Heathcock,
Comprehensive Carbanion Chemistry, ed. E. Buncel and T. Durst,
Elsevier, Amsterdam, 1984, Chap. 4.
4 T. Punniyamurthy, B. Bhatia and J. Iqbal, J. Org. Chem., 1994, 59,
850.
5 The use of dioxolanes as masked aldehydes has been extensively
studied: H.-S. Dang and B. P. Roberts, Tetrahedron Lett., 1999, 40,
8929; A. Gross, L. Fensterbank, S. Bogen, R. Thouvenot and M.
Malacria, Tetrahedron, 1997, 53, 13797.
6 (a) Y. Yoshino, Y. Hayashi, T. Iwahama, S. Sakaguchi and Y. Ishii,
J. Org. Chem., 1997, 62, 6810; (b) S. Sakaguchi, T. Takase, T. Iwahama
and Y. Ishii, Chem. Commun., 1998, 2037, and references therein.
7 E. C. Niederhoffer, J. H. Timmons and A. E. Martell, Chem. Rev., 1984,
84, 137.
8 B. Giese, Angew. Chem., Int. Ed. Engl., 1983, 22, 753.
9 We have reported that aldehydes are readily oxidized to corresponding
carboxylic acids with dioxygen by the NHPI–Co(OAc)2 system under
ambient conditions: T. Iwahama, Y. Yoshino, T. Keitoku, S. Sakaguchi
and Y. Ishii, J. Org. Chem., 2000, in print.
10 R. A. Sheldon and J. K. Kochi, Metal-Catalyzed Oxidation of Organic
Compounds, Academic Press, New York, 1981.
Scheme 1 Proposed reaction path for the radical addition of 1a to 2a under
dioxygen in the presence of NHPI and Co(OAc)2.
11 W. Adam, The Chemistry of Peroxide, ed. S. Patai, John Wiley & Sons,
New York, 1983, p. 830.
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Chem. Commun., 2000, 2457–2458