Decarboxylative reduction of free aliphatic carboxylic acids by photogenerated cation radical

Article abstract of DOI:10.1039/b714526h

The decarboxylation of free carboxylic acids was effected by a photogenerated cation radical of phenanthrene to yield the reduction product in the presence of a thiol, which provides an alternative method to the Barton decarboxylation procedure for aliphatic acids such as N-Boc amino acids. The Royal Society of Chemistry.

Full text of DOI:10.1039/b714526h

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Decarboxylative reduction of free aliphatic carboxylic acids by
photogenerated cation radical{
Yasuharu Yoshimi,* Tatsuya Itou and Minoru Hatanaka*
Received (in Cambridge, UK) 20th September 2007, Accepted 12th October 2007
First published as an Advance Article on the web 17th October 2007
DOI: 10.1039/b714526h
An aqueous acetonitrile solution (CH3CN–H2O = 9 : 1)8
containing phenanthrene (Phen, 10 mM),9 1,4-dicyanobenzene
The decarboxylation of free carboxylic acids was effected by a
photogenerated cation radical of phenanthrene to yield the
(DCB, 10 mM), t-dodecanethiol (RSH, 20 mM), and N-Boc-L-
phenylalanine 1a (10 mM) was irradiated with a 400 W high-
pressure mercury lamp through a Pyrex filter (.300 nm) under an
argon atmosphere for 6 h at room temperature. This resulted in a
decarboxylated product 2a in a 97% yield; further, this reaction
recovered Phen and DCB (.95%) (Table 1, entry 1).
reduction product in the presence of a thiol, which provides an
alternative method to the Barton decarboxylation procedure
for aliphatic acids such as N-Boc amino acids.
The decarboxylative reduction of carboxylic acid is a useful
synthetic transformation. Although several methods have been
reported,1 this reduction has been most effectively performed by
the Barton decarboxylation2 involving the decomposition of the
thiohydroxamic ester into radical fragments by either light or heat
in the presence of a hydrogen donor such as a thiol or tributyltin
hydride (Scheme 1). In addition to the Barton decarboxylation,
carboxylic acids are also known to undergo decarboxylative
reduction via photoinduced electron transfer in the presence of
several electron acceptors such as cyanonaphthalene,3 acridine4
and benzophenone;5 however, the carboxylic acids used in these
cases were limited to aryl and aryloxy acetic acids.
The addition of one equivalent of NaOH to this solution
accelerated the photoreaction in the initial stage (2 h) (entry 2) and
finally produced 2 in a similar or slightly higher yield (yields of 2 in
the presence of 1 equiv. NaOH are given in the parentheses in
Table 1). On the other hand, the addition of HCl (10 mM) resulted
in the recovery of 1 without the formation of 2. Thus, the
Table 1 Decarboxylative reduction of N-Boc amino acids 1a–ia,b
In the course of our study, the photochemical reaction in
water using a photosensitive surfactant yielded a decarboxylated
product, probably via the electron transfer between the photo-
generated cation radical and the carboxylate ion.6 On the basis of
this observation, we undertook to investigate the decarboxylative
reduction of free carboxylic acid in a redox-photosensitized
reaction system7 (Scheme 2).
We now report that the decarboxylation of free carboxylic
acids was effected by the reaction with a photogenerated cation
radical of phenanthrene to yield the reduction product in the
presence of a thiol. The reaction provides an effective method for
the decarboxylative reduction of free aliphatic carboxylic acids,
including N-Boc amino acids, and several naturally occurring
substrates.
Entry
1
Yield of 2c (%)
1
a
a
b
c
d
e
f
g
h
i
97 (97)
26 (51)
78 (74)
78 (86)
83 (87)
56 (44)
78 (82)
45 (64)d
82 (90)
62 (73)
2d
3
4
5
6
7
8
9
10
a
Scheme 1 Barton decarboxylation.
Department of Applied Chemistry and Biotechnology, Graduate School
of Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui, 910-8507,
Japan. E-mail: yoshimi@acbio2.acbio.fukui-u.ac.jp;
Fax: +81-776-27-8747; Tel: +81-776-27-8633
{ Electronic supplementary information (ESI) available: Experimental
section and spectroscopic data. See DOI: 10.1039/b714526h
Photochemical reactions were carried out with 0.6 mmol (10 mM)
b
of 1 for 6 h. 1–Phen–DCB–RSH = 1 : 1 : 1 : 2. The values in
parentheses are for the reactions with 1 equiv. NaOH. 1–NaOH–
Phen–DCB–RSH = 1 : 1 : 1 : 1 : 2. Isolated yield. Irradiation
time was 2 h.
c
d
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Scheme 2 Decarboxylative reduction of free carboxylic acid with the photogenerated cation radical of Phen.
decarboxylation of the carboxylate ion was more efficient than
that of the corresponding carboxylic acid. An examination of the
results summarized in Table 1 indicates that most of the N-Boc
amino acids successfully undergo the decarboxylative reduction in
good to excellent yields. It should be noted that N-Boc-L-glutamic
acid 1g (entry 8) having two carboxyl groups selectively gave the
decarboxylative reduction product of the a-carboxyl group, and an
increased yield of 2g was observed with 1 equiv. NaOH at 2 h,
indicating that the decarboxylation of the a-carboxyl group of 1g
was faster than that of the side chain carboxyl group.
results reveal that the minor process via the corresponding anion
existed in the photoreaction.
Scheme 5 shows a plausible mechanism for this photoreaction.
Initially, a cation radical of Phen and an anion radical of DCB are
formed via electron transfer (ET) between the excited Phen and
DCB (1). The secondary electron transfer from a carboxylate ion,
which is generated by the dissociation of the carboxylic acid in
aqueous solution, to the cation radical of Phen is an exothermic
process; this fact is indicated by the negative DG values (20.34 V)10
calculated by using the oxidation potential of Phen (1.50 V vs.
SCE in acetonitrile)11 and an aliphatic carboxylate ion such as
hexanoate ion (1.16 V vs. SCE in acetonitrile).12 Thus, the cation
radical of Phen can be reduced by carboxylate ions13 to produce
radical 7, which is decarboxylated to form radical 8 (2). The
generated alkyl radical 8 can abstract a hydrogen atom of the thiol
to give the reduction product (3). In addition, the minor process
via ET between the anion radical of DCB and radical 8 to form
anion 9 also yielded the reduction product by protonation (4). In
the absence of the thiol, radical 8 is coupled with the anion radical
of DCB, which undergoes a successive decyanation to yield 6 and
CN2 as reported earlier14 (5).
When other aliphatic acids such as fatty acid 3, acids of steroid 4
and sugar 5 were subjected to this photoreaction, decarboxylative
reduction products were also obtained in moderate yields
(Scheme 3).
Scheme 3 Decarboxylative reduction of 3, 4 and 5.
Next, we examined the behaviour of this photoreaction in the
absence of a hydrogen donor and found that a low yield of the
decarboxylative reduction product 2a was observed along with a
decarboxylative substitution product 6 (Scheme 4). In addition,
a deuterium incorporation experiment using D2O showed that a
deuterated product was obtained in a high d-content (100%). These
Scheme 5 Plausible mechanism.
In conclusion, we found that the decarboxylation of free
aliphatic carboxylic acids such as N-Boc amino acids proceeded by
using the photogenerated cation radical to yield the reduction
product in the presence of the thiol. This photoreaction can be
Scheme 4 Decarboxylative reduction of 1a in the absence of RSH.
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useful for generating carbon-centered radicals derived from
aliphatic carboxylic acids via decarboxylation, and the application
of this photoreaction to intra- and inter-molecular addition to
alkenes is in progress.
This work was supported by (Mitsubishi Chemical
Corporation) Award in Synthetic Organic Chemistry, Japan, and
the Sasagawa Scientific Research Grant from the Japan Science
Society.
8 When dry acetonitrile was used as a solvent a lower yield of 2 was
observed.
Notes and references
9 The use of naphthalene or triphenylene instead of phenanthrene led to a
lower yield of 2.
10 Such calculations often include a Coulomb term, which accounts for the
stabilization of the ion pair; however, this Coulombic stabilization gives
a very low yield of acetonitrile. Thus, the Coulomb term is not
considered in this calculation.
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5246 | Chem. Commun., 2007, 5244–5246
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