Enzyme-triggered radical reactions: Another approach for tin-free radical chemistry

Article abstract of DOI:10.2533/chimia.2012.435

The system laccase/mediator/dioxygen is able to trigger radical reactions with radical precursors which are not natural substrates of this enzyme. The radical generation has been accomplished by single electron transfer oxidation of a 1,3-dicarbonyl precursor. The process is exemplified with a radical cascade. Schweizerische Chemische Gesellschaft.

Full text of DOI:10.2533/chimia.2012.435

Organic Free radicals
CHIMIA 2012, 66, No. 6 435
doi:10.2533/chimia.2012.435
Chimia 66 (2012) 435–438 © Schweizerische Chemische Gesellschaft
Enzyme-triggered Radical Reactions:
Another Approach For Tin-free Radical
Chemistry
Ibrahima Cissokhoa, Anne-Marie Farnetb, Elisée Ferréb, Michèle P. Bertranda, Gérard Gilc,
and Stéphane Gastaldi*a
Abstract: The system laccase/mediator/dioxygen is able to trigger radical reactions with radical precursors which
are not natural substrates of this enzyme. The radical generation has been accomplished by single electron
transfer oxidation of a 1,3-dicarbonyl precursor. The process is exemplified with a radical cascade.
Keywords: 1,3-Dicarbonyl compounds · Laccase · Oxidoreductase · Radical mediator · Radical reaction
Over the last few years, our research water or to hydrogen peroxide. In order to depicted in Scheme 2.[8] They act as ‘elec-
group has explored the possibility to avoid the formation of hydrogen peroxide tron shuttles’; after being oxidized by the
broaden the synthetic potential of radical in the reaction medium that might induce enzyme, the oxidized form of the mediator
reactions by combining them with an enzy- side reactions, laccases have been selected oxidizes any substrate that could not enter
matic transformation. This led us to report
the first switchable dynamic kinetic resolu- copper-containing oxidases,[5b,6] the only
Moreover, the wide structural variety
tion (DKR) process allowing the synthesis side-product formed during the redox pro- of oxidized mediators enables the reaction
of either (R)- or (S)-amides from racemic cess is water (Scheme 1). to evolve through oxidation mechanisms
amines depending on the nature of the en- Laccases have a low redox potential that cannot be catalyzed by the enzyme
zyme, lipase or protease.[1] This fruitful (0.5–0.8 V/NHE)[6,7] which explains why alone, and thus to broaden the range of po-
adventure in the world of hydrolases led their natural substrates are mainly elec- tential substrates (Scheme 2). Thus PT and
us to think about the possibility to use an tron-rich phenols.[6a] To extend the scope
ABTS radical cations lead to single elec-
enzyme to initiate radical reactions. The
of applications to non-phenolic substrates, tron transfer (SET) reactions (Fig. 1).[9]
latter can be initiated through a redox re- a redox mediator can be used (Fig. 1). The N-Hydroxy mediator-derived radicals (e.g.
action.[2] This second approach might be
role of mediators in laccase oxidations is HBT, HPI) enable the abstraction of a hy-
for this preliminary study since, with these in the enzymatic pocket.
achieved with the assistance of an oxidore-
ductase. Indeed, numerous redox reaction,
such as oxidation of alcohol, aldehyde or
ketone, hydroxylation of aromatic or non-
activated carbon atoms, can be catalyzed
by isolated enzymes.[3,4] Oxidase, a sub-
class of the oxidoreductases, is constituted
of any enzyme that catalyzes an oxida-
tion–reduction reaction involving molecu-
lar oxygen as the final electron acceptor.[5]
In these reactions, oxygen is reduced to
drogen atom from benzylic positions.[9a,10]
In the present paper, we describe our
recent results on the use of the laccase-me-
diator system to initiate a radical reaction
on radical precursors which are not laccase
classical substrates.
H O
Laccase
Substrate
Substrate
2
ox
O
2
Laccase
ox
SET
oxidative processes that enable
Scheme 1.
the generation of radicals are interesting
Scheme 2.
H O
2
Substrate
Mediator
Mediator
Laccase
ox
ox
Substrate
O
2
Laccase
ox
Fig. 1. Examples of
mediators.
O
R
N
N
N
N
*Correspondence: Dr. S. Gastaldia
N OH
E-mail: stephane.gastaldi@univ-amu.fr
aAix-Marseille Univ, Institut de Chimie Radicalaire
UMR 7273, Equipe Chimie Moléculaire Organique
13397 Cedex 20, Marseille, France
OH
S
O
HPI
HBT
R= H, Phenothiazine (PT)
bAix-Marseille Univ, Institut Méditerranéen de Biodi-
versité et d’Ecologie UMR CNRS IRD 7263
Equipe Vulnérabilité des Systèmes Microbiens
Faculté des Sciences et Techniques de St Jérôme,
13397, Marseille, Cedex 20, France
R= Et, N-Ethyl-phenothiazine (EPT)
N
HO S
3
S
N
N
N
S
SO H
cAix-Marseille Univ, ISM2 UMR 7313
Equipe Chirosciences, 13397 Cedex 20, Marseille,
France
3
ABTS

436 CHIMIA 2012, 66, No. 6
Organic Free radicals
Scheme 3.
Meldrum
sodium salt
P.p. 504
O
O
EPT
Na
N
S
N
EPT
O
A
O
O
O
P.p. 504, EPT
EPT
+
S
O
EPT
O O
pH 5buffer
Acetone, 30 °C
24 h
O
O
O
O
16%
59%
O O
3
O O
2
Na-1
O
O
O
O
H
pH 5
buffer
S
S
+
-H
alternatives to tin-based methodologies.[11]
Carbon-centered radicals have been
generated from neutral carbonyl deriva-
tives, carbanions, enamines or enolates
by employing, among other oxidants,
Mn(OAc)3,[12] ceric ammonium nitrate
(CAN),[13] copper(ii)[14] or iron(iii)[14a,b,15]
N
equilibrium between both forms enabled
the reaction to proceed.
N
B
2
The formation of 2 might be explained
Scheme 4.
on the grounds of the mechanism proposed
in Scheme 4. After a first electron trans-
fer (ET) step from EPT
to the enzyme,
·+
EPT oxidized Na-1/1 through a second
moiety (6). No transformation occurred in
ET generating radical A. The latter was
complexes. The main drawback of these
the presence of EPT
contrary to the reac-
then trapped by the persistent EPT
tivity previously observed with unsubsti-
·+ (B)[21]
methodologies is that the oxidant is often
used in excess and it is difficult to get rid
which evolved to 2 after deprotonation.
tuted 1,3-dicarbonyl compounds.
The concomitant formation of 3 resulted
of metal traces. This problem may be eas-
On the other hand, when a solution of
from the reaction of EPT
·+ with water. The
6 in toluene was added to the dark blue
ily overcome by the enzymatic approach.
Indeed, laccases enable the use of a catalyt-
ic amount of enzymes since the co-oxidant
of the reaction is dioxygen. Moreover, the
copper atoms in charge of the oxidation
are strongly liganded to the enzyme and
from this point of view the medium can be
considered as metal-free at the end of the
process.
buffered solution of ABTS·+, a slow dis-
coloration of the solution was observed.
structure of 3 was confirmed by compari-
son with an authentic sample produced by
a direct oxidation of EPT with m-CPBA,[22]
ABTS was added by portion until the
in this case the corresponding sulfone was
blue color became persistent (0.6 equiv.).
also produced. The latter was not detected
After consumption of the substrate (TLC
during the enzyme-catalyzed reaction.
monitoring, 3 h), the reaction was stopped
This transformation was applied to
and analyzed. Cyclopropane 7 was char-
other acidic 1,3-dicarbonyl compounds.
Acetylacetone and dimedone led to 4 and 5
acterized as a mixture of two diasteromers
The goal of this preliminary study was
(1:1). Its formation might be explained by
in 58 and 78% yield (Fig. 2) whereas a less
acidic substrate like ethyl cyanoacetate did
to trigger, with a laccase, a radical reaction
from a substrate which is not a classical
the mechanism proposed in Scheme 5. The
α-dicarbonyl radical C, resulting from the
oxidation of 6, added reversibly to the dou-
not undergo any transformation. It must be
enzyme substrate. To reach this goal, it was
underlined that the formation of sulfoxide
3 could not be avoided.
necessary to select a mediator capable to
act as an ‘electron shuttle’, between the
enzyme and the substrate, during the re-
ble bond. Equilibrium was then displaced
by the oxidation of radical D with ABTS·+
This first approach showed that a com-
leading to the benzylic cation E which was
mercially available laccase could be used
action. Thus ABTS and Meldrum’s acid
trapped by a molecule of water to form 7
in 38% yield. This radical-polar crossover
cursor respectively. The strong acidity of
as catalyst to generate a carbon-centered
radical. However, the nature of the couple
were selected as mediator and radical pre-
cascade showed that ABTS was able to act
laccase/mediator had to be optimized in or-
der to preclude any interference of the me-
diator with the fate of the radical species.
this 1,3-dicarbonyl compound enables the
use of the corresponding sodium salt, as
substrate in the buffer aqueous medium re-
first as ‘electron shuttle’ between the lac-
case and the radical precursor and second
as final oxidant. However the modest yield
In spite of the rather disappointing pre-
quired to maintain the enzyme active. The
and the quantity of mediator used in the
liminary results obtained with ABTS, we
process, 0.6 equiv., confirmed previous ob-
commercially available laccase Polyporus
pinsitus 504 (P.p. 504)[16] from Novo
Nordisk was selected so that the method-
ology could easily be reproduced or ex-
tended to other substrates.
decided to reinvestigate its reactivity. The
servations thatABTS might give rise to by-
absence of evolution, when the reaction
products and therefore it was not the best
mediator for a selective reaction.[24]
was performed with 1, did not necessarily
mean that the oxidation of the dicarbonyl
In summary, this preliminary study
compound did not occur. The interesting
showed that the couple laccase/mediator,
When Meldrum’s acid (1) or its sodium
point was that if the oxidation proceeded
with dioxygen as co-oxidant, is a viable
salt (Na-1) was reacted with the radical
·+
[17]
the resulting radical did not react with the
cation of ABTS (ABTS )
(1 equiv.),
alternative to initiate a radical reaction in-
mediator.
With this purpose in mind, Meldrum’s
acid was functionalized with an efficient
internal radical acceptor,[23] i.e. a styrene
generated in the presence of P.p. 504 in a
pH 5 succinate buffer solution, no evolu-
volving a redox process. This new method
of radical generation enables the forma-
tion, at 30 °C, of C–C bond and subsequent
functionalization. This system might be
improved by the design of new mediators
which will not interfere with the radical
tion, like dimerization, was detected and
·+
the dark blue color of ABTS
remained
unchanged. Another mediator, N-ethyl-
phenothiazine (EPT),[18,19]
was used under
the same conditions. The light orange color
cascade. These results will be reported in
due course.
of EPT
·+ became violet instantaneously af-
ter addition of Na-1 before turning again
N
N
light orange at the end of the reaction (24
S
S
h). The analysis of the mixture showed that
Experimental Section
O
O
4
58%
O
5
ylide 2[20] together with sulfoxide 3 were
formed in 59 and 16% yield respectively
78%
O
Solvents are commercially available,
(Scheme 3). The same result was observed
they were used as purchased, without fur-
ther purification. Purifications were per-
starting from 1, showing that at pH 5 the
Fig. 2.

Organic Free radicals
CHIMIA 2012, 66, No. 6 437
Scheme 5.
each time the color turned yellow ABTS
was added by portion (7 x 22 mg) until the
color remained blue. Once the reaction fin-
O
O
O
O
O
O
P.p. 504, ABTS
Ph
O
6
ished (TLC monitoring, 3 h), the diphasic
pH= 5buffer
toluene
30 °C,3h
OH
7
O
O
Ph
ABTS
38%
H O
solution was extracted with AcOEt (3x)
and dried over MgSO4. After concentra-
tion, the crude product was purified by
flash chromatography on silica gel (10/90
to 20/80 AcOEt/pentane) leading to 7 (84
mg, 0.3 mmol, 38%) as a mixture of dia-
steromers, further purification enables the
isolation of pure samples of each isomers
d.r 1:1
2
O
O
O
O
O
O
ABTS
Ph
Ph
O
O
O
Ph
O
O
C
D
E
1
for characterization. Isomer 7a: H NMR
(CDCl3): 7.32–7.42 (m, 5H), 4.84 (d, J =
9.6, 1H), 2.60 (q, J = 9.2, 1H), 2.13 (m,
2H), 1.98 (s, 3H), 1.78 (s, 3H). 13C NMR
(CDCl ): 168.1 (Cester), 166.5 (C ), 142.1
(C )3, 129.0 (CH ), 128.6est(eCr Harom.),
12a6ro.m0. (CHarom.), 1a0ro5m..9 (O-C-O), 71.7
(-CH-O), 45.5 (-CH-C), 29.4 (-C-), 27.8
(CH3), 27.7 (CH3), 25.5 (CH2). Isomer 7b:
1H NMR (CDCl ): 7.35 (m, 5H), 4.85 (d, J
= 8.4, 1H), 2.723(q, J = 8.4, 2H), 2.13 (m,
2H), 1.98 (s, 3H), 1.78 (s, 3H).13C NMR
(CDCl3):167.8(-C=Oester), 166.5(C=Oester),
141.8 (-C=arom.), 129.1 (=CH ), 128.9
(=CHarom.), 126.7 (CHarom.), 105a.r3om(.O-C-O),
71.6 (-CH-O), 44.7 (-CH-C), 28.5 (-C-),
5-(10-Ethyl-10H-phenothiazin-5-
ylidene)-2,2-dimethyl-1,3-dioxane-
4,6-dione (2)
formed on Macherey Nagel silica gel 60 A
(70–230 mesh). Analytical thin layer chro-
matography was performed on pre-coated
silica gel plates. Visualization was accom-
plished by UV (254 nm) and with phos-
phomolybdic acid in ethanol. 1H NMR, 13C
NMR spectra were recorded at 400 MHz
and 100 MHz, respectively. Chemical
shifts (δ) are reported in ppm. Signals
due to residual undeuteriated solvent (1H
NMR) or to the solvent (13C NMR) served
as the internal standards: CDCl3 (7.26 ppm
and 77.0 ppm). Multiplicity is indicated by
one or more of the following symbols: s
(singlet), d (doublet), t (triplet), q (quartet),
1H NMR (CDCl3): 7.60 (dd, J = 6.4 and
1.6, 2H), 7.50 (ddd, J = 8.7, 7.2 and 1.6,
2H), 7.22 (d, J = 8.3, 2H), 7.11 (broad t, J =
8.0, 2H), 4.26 (q, J = 7.2, 2H), 1.53 (s, 6H),
1.56 (t, J = 7.2, 3H). 13C NMR (CDCl3):
163.0 (C=Oester), 142.9 (Carom), 133.2
(CH ), 130.7 (CHarom), 122.4 (CH ),
115.a4rom (CH ), 106.8 (Carom), 1a0ro3m.2
(O-C-O), 60a.r4om(C=S), 40.0 (CH2-N), 26.1
(2xCH ), 12.9 (CH ). HRMS ([M+Na]+,
ESI): 3m/z calcd 3 for C H19NO4SNa:
392.0927. Found: 392.0921.20
28.0 (-CH -), 27.5 (CH ), 26.5 (CH ).
m (multiplet), br (broad). The lists of cou-
2
HRMS ([M+NH4]+, ESI)3: m/z calcd f3or
3-(10-Ethyl-10H-phenothiazin-5-
ylidene)pentane-2,4-dione (4)
pling constants (J) correspond to the order
C15H20NO5: 294.1336. Found: 294.1341.
of multiplicity assignment and are reported
1H NMR (CDCl ): 7.43 (td, J = 7.2
13
in Hertz (Hz). APT was used for C spec-
3
Acknowledgements
and 1.4, 2H), 7.38 (dd J = 7.8 and 1.2,
2H), 7.13 (m superimposed, 2H), 7.04 (t,
J = 7.3, 2H), 4.22 (q, J = 7.1, 2H), 2.47
(s, 6H), 1.52 (t, J = 7.1, 3H). 13C NMR
tra assignment.
Gift of laccase from Polyporus pinsitus
(P.p. 504) from Novo Nordisk is gratefully
acknowledged.
Enzyme Assay
The crude laccase from Polyporus pin-
(CDCl ): 189.7 (C=O), 142.0 (Carom), 132.0
(CH 3), 128.5 (CHarom), 121.8 (CH ),
114.a8rom(CHarom), 110.3 (Carom), 97.8 (Ca=roSm),
43.2 (CH2-N), 29.7 (2xCH3), 12.6 (CH3).
HRMS ([M+H]+, ESI): m/z calcd for
C19H20NO2S: 326.1209. Found: 326.1208.
situs (P.p. 504) from Novo Nordisk (170
mg) was diluted in 2 mL of pH 5 succi-
nate buffer (0.2 M) and corresponds to
P.p. 504 enzymatic extract in the follow-
ing. Enzyme activity (1.93 μm/min/mg)
was measured by monitoring the oxidation
of syringaldazine[25] to the corresponding
Received: February 21, 2012
[1] a) S. Gastaldi, S. Escoubet, N. Vanthuyne, G.
Gil, M. P. Bertrand, Org. Lett. 2007, 9, 837;
b) L. El Blidi, M. Nechab, N. Vanthuyne, S.
Gastaldi, M. P. Bertrand, G. Gil, J. Org. Chem.
2009, 74, 2901; c) L. El Blidi, N. Vanthuyne, D.
Siri, S. Gastaldi, M. P. Bertrand, G. Gil, Org.
Biomol. Chem. 2010, 8, 4165; d) F. Poulhès, N.
Vanthuyne, M. P. Bertrand, S. Gastaldi, G. Gil,
J. Org. Chem. 2011, 76, 7281.
[2] Y. Kita, M. Matsugi, in ‘Radical in Organic
Synthesis’, Eds. P. Renaud, M. Sibi, Wiley-
VCH: Weinheim, 2001, Vol. 1, pp 1–10.
[3] For a recent review on oxidoreductases, see: D.
Monti, G. Ottolina, G. Carrea, S. Riva, Chem.
Rev. 2011, 111, 4111 and references cited
therein.
M
quinone (ε = 65 000 M–1cm–1) at 525 nm
2-(10-Ethyl-10H-phenothiazin-5-
ylidene)-5,5-dimethylcyclohexane-
1,3-dione (5)
in succinate buffer 0.1 M, pH 4.0 on a spec-
trophotometer Uvikon XL. One unit (U) of
laccase activity is defined as the amount of
enzyme that oxidizes 1 µmol of the sub-
strate per minute per g.
1H NMR (CDCl ): 7.44 (m superim-
posed, 4H), 7.17 (d, J3= 8.9, 2H), 7.04 (t, J =
7.3, 2H), 4.29 (q, J = 7.1, 2H), 2.26 (s, 4H),
1.55 (t, J = 7.1, 3H), 0,96 (s, 6H).13C NMR
(CDCl ): 191.1 (C=O), 142.5 (Carom), 132.4
(CH 3), 130.0 (CHarom), 121.8 (CH ),
114.a7rom(CH ), 107.9 (C ), 99.5 (Ca=roSm),
General Procedure for Ylide
Synthesis
[4] For a review on enzyme-mediated oxidation,
To 10-ethylphenothiazine
[18] (91.2 mg,
see: F. Hollmann, I. W. C. E Arends, K. Buehler,
A. Schallmey, B. Buehler, Green Chem. 2011,
13, 226.
arom
43.5 (CH2-N), 31.0 (CH2a)ro,m29.0 (C), 28.2
0.4 mmol) in a mixture of acetone (3.2 mL)
and pH 5 succinate buffer (32 mL) at 30 °C
was added P.p. 504 enzymatic extract (100
(2xCH3), 12.6 (CH3). HRMS ([M+H]+,
[5] For reviews on oxidases see: a) E. I. Solomon,
A. J. Augustine, J. Yoon, Dalton Trans. 2008,
ESI): m/z calcd for C22H24NO2S: 366.1522.
Found: 366.1521.
µl). The solution was stirred 30 min before
3921; b) E. I. Solomon, U. M. Sundaram, T.
E. Machonkin, Chem. Rev. 1996, 96, 2563;
c) S. Fetzner, R. A. Steiner, Appl. Microbiol.
Biotechnol. 2010, 86, 791.
addition of 1.3-dicarbonyl compound (0.4
mmol).After 24 h stirring, the reaction me-
dium was extracted with CH Cl2 (3x), the
combined organic phases we2re dried over
MgSO4. After concentration, the crude
product was purified by flash chromatog-
raphy on silica gel (5/95 to 100/0 AcOEt/
pentane) leading to the title compound.
Cyclization of 6
To ABTS (22.1 mg, 0,04 mmol) in pH
[6] a) P. Baldrian, FEMS Microbiol. Rev. 2006, 30,
5 succinate buffer (32 mL) at 30 °C were
added P.p. 504 enzymatic extract (400
µL), the color of the solution becomes
215; b) H. Claus, Micron 2004, 35, 93; c) A. M.
Mayer, R. C. Staples, Phytochemistry 2002, 60,
551. For a review on applications of laccases,
see: S. Rodriguez Couto, J. L. Toca Herrera,
Biotech. Adv. 2006, 24, 500.
dark blue. Then (E)-2,2-dimethyl-5-(3’-
phenylallyl)-1,3-dioxane-4-6-dione[23]
[7] F. Xu, W. Shin, S. H. Brown, J. A. Wahleithner,
(209 mg, 0.8 mmol) in toluene (20 mL)
U. M. Sundaram, E. I. Solomon, Biochim.
was added. The solution was stirred and
Biophys. Acta 1996, 1292, 303.

438 CHIMIA 2012, 66, No. 6
Organic Free radicals
[8] a) R. Bourbonnais, D. Leech, M. G. Paice,
Biochim. Biophys. Acta 1998, 1379, 381; b)
M. Husain, Q. Husain, Crit. Rev. Env. Sci. Tec.
2008, 38, 1.
[9] a) P. Baiocco, A. M. Barreca, M. Fabbrini, C.
Galli, P. Gentili, Org. Biomol. Chem. 2003, 1,
191; b) M. Fabbrini, C. Galli, P. Gentili, J. Mol.
Catal. B 2002, 16, 231.
[10] a) R. Bernini, F. Crisante, P. Gentili, F. Morana,
M. Pierini, M. Piras, J. Org. Chem. 2011, 76,
820; b) G. Cantarella, C. Galli, P. Gentili, New
J. Chem. 2004, 28, 366; c) P. Astolfi, P. Brandi,
C. Galli, P. Gentili, M. F. Gerini, L. Grecia, O.
Lanzalunga, New J. Chem. 2005, 29, 1308.
B. Ambhaikar, C. A. Guerrero, J. D. Gallagher, [19] EPT
potential redox was not found in the
J. Am. Chem. Soc. 2006, 128, 8678; d) U.
Jahn, D. Rudakov, Org. Lett. 2006, 8, 4481;
e) G. Sorin, R. Martnez Mallorquin, Y. Contie,
A. Baralle, M. Malacria, J-P. Goddard, L.
Fensterbank, Angew. Chem. Int. Ed. 2005, 44,
609.
literature, but E° for similar structures are
reported:E°=1.03VforN-methylphenothiazine
·+
(MPT)/MPT
versus NHE, D. Sun, S. V.
Rosokha, J. K. Kochi, J. Am. Chem. Soc. 2004,
126, 1388; E° = 0.925 V for promethazine
(PMZ)/PMZ·+ versus NHE, E. Madej, P.
[15] For selected examples, see: a) T. Cohen, K.
Wardman, Radiat. Phys. Chem. 2006, 75, 990.
McNamara, M. A. Kuzemko, K. Ramig, J.
[20] Close structures have recently been reported: X.
J. Landi, Jr., Tetrahedron 1993, 49, 7931; b)
Huang, R. Goddard, N. Maulide, Angew. Chem.
M. P. Sibi, M. Hasegawa, J. Am. Chem. Soc.
Int. Ed. 2010, 49, 8979.
2007, 129, 4124; c) U. Jahn, P. Hartmann, E.
[21] For examples of coupling of an alkyl radical
Kaasalainen, Org. Lett. 2004, 6, 257; d) U. Jahn,
with a sulfur-centered radical cation, see: J. A.
M. Müller, S. Aussieker, J. Am. Chem. Soc.
Murphy, in ‘Radical in Organic Synthesis’, Eds.
[11] For a review on SET
reactions, see: P. I. Dalko,
Tetrahedron 1995, 51, 7579.
[12] For reviews, see a) B. B. Snider, Chem. Rev.
2000, 122, 5212; e) J-P, Goddard, C. Gomez,
F. Brebion, S. Beauvière, L. Fensterbank, M.
Malacria, Chem. Commun. 2007, 2929.
P. Renaud, M. Sibi, Wiley-VCH: Weinheim,
2001, Vol. 1, pp 298-315 and references cited
therein.
1996, 96, 339; b) G. G. Melikyan, Org. React. [16] The E° redox potential of P.p. 504 has been
1997, 49, 427.
[22] M. Tosa, C. Paizs, C. Majdic, L. Poppe, P.
measured (0.79 V/NHE): D. S. Yaver, F. Xu, E.
J. Golightly, K. M. Brown, S. H. Brown, M. W.
Kolonits, I. A. Silberg, L. Novak, F.-D. Irimie,
[13] a) For a review, see: V. Nair, J. Mathew, J.
Prabhakaran, Chem. Soc. Rev. 1997, 26, 127;
b) A.-C. Durand, E. Dumez, J. Rodriguez, J.-P.
Dulcère, Chem. Commun. 1999, 2437.
[14] For selected examples, see: a) M. Schmittel, A.
Burghart, W. Malisch, J. Reising, R. Söliner, J.
Heterocycl. Commun. 2001, 7, 277.
Rey, P. Schneider, T. Halkier, K. Mondorf, H.
[23] G. Bélanger, F. Lévesque, J. Pâquet, G. Barbe,
Dalboge, Appl. And Environ. Microbiol. 1996,
62, 834.
J. Org. Chem. 2005, 70, 291.
[24] A. M. Farnet, A. C. Chevremont, G. Gil, S.
[17] E°= 0.69 V for ABTS·+
/ABTS versus NHE,
Gastaldi, E. Ferré, Chemosphere 2011, 82, 284.
see ref. [7b].
[25] J. M. Harkin, J. R. Obst, Experientia 1973, 29,
Org. Chem. 1998, 63, 396; b)Y. Ito, T. Konolke,
[18] S. Ebdrup, M. Schou Jensen, P. Vedsø, J. Chem.
381.
T. Harada, T. Saegusa, J. Am. Chem. Soc. 1977,
Soc., Perkin Trans. 1 1998, 351.
99, 1487; c) P. S. Baran, B. D. Hafensteiner, N.