Electrosynthesis of benzolactones by nickel-catalyzed carboxylation of epoxide-functionalized aromatic halides

Article abstract of DOI:10.1055/s-2000-6486

The electrochemical, nickel-catalyzed carbon dioxide incorporation into 2-haloaryl epoxides led chemoselectively to different carboxylated products according to the nature of the substrate and to the catalytic system. Whereas terminal epoxide derivatives led to cyclic carbonates in good yields, disubstituted epoxides reacted through a first carbon-halogen bond carboxylation followed by epoxide ring opening. Five-membered ring benzolactones were selectively formed with cyclam as the ligand, whereas 6- membered ring isocoumarine derivatives were obtained using 2,2'-bipyridine.

Full text of DOI:10.1055/s-2000-6486

LETTER
245
Electrosynthesis of Benzolactones by Nickel-Catalyzed Carboxylation of
Epoxide-Functionalized Aromatic Halides
Patricia Tascedda, Elisabet Duñach*
Laboratoire de Chimie Bioorganique, Associé au CNRS, Université de Nice-Sophia Antipolis, 06108 Nice Cedex 2, France
Fax +33-492076151; E-mail: dunach@unice.fr
Received 8 November 1999
to the bromoalcoholate and ring closure to the cyclic car-
bonate with bromide elimination7.
Abstract: The electrochemical, nickel-catalyzed carbon dioxide in-
corporation into 2-haloaryl epoxides led chemoselectively to differ-
ent carboxylated products according to the nature of the substrate
and to the catalytic system. Whereas terminal epoxide derivatives
led to cyclic carbonates in good yields, disubstituted epoxides react-
ed through a first carbon-halogen bond carboxylation followed by
epoxide ring opening. Five-membered ring benzolactones were se-
lectively formed with cyclam as the ligand, whereas 6-membered
ring isocoumarine derivatives were obtained using 2,2'-bipyridine.
Key words: electrochemical, benzolactone, nickel, carbon dioxide,
epoxide
Scheme 1
The synthesis of benzolactone structures such as couma-
rines or isocoumarines has attracted much attention due to
their use as antitumoral, antifungal and antibacterial
agents.1
Two products were isolated; the 2-bromo (or 2-chlo-
ro)phenyl carbonate and the corresponding dehalogenated
styrene carbonate. The dehalogenation was more impor-
tant with X = Br. The carboxylation of 1 and 2 catalyzed
We describe here a new method of synthesis of isocouma-
rine and other benzolactone derivatives, based on the use
of an electrochemical carboxylation of epoxide-contain-
ing aromatic halides. The synthesis of isocoumarine struc-
tures generally involves the cyclization of functionalyzed
benzoic acid derivatives.2,3 Oxidation reactions of in-
danones have also been described.4,5
-
by Ni(bipy)32+2BF4 led to very similar results. The pres-
ence of KBr as supporting electrolyte (as compared to the
use of Bu4N+BF4 ), was an important factor to obtain good
-
conversions and yields of cyclic carbonate both with Ni-
cyclam and Ni-bipy catalytic systems. Thus, yields of cy-
clic carbonate went from 80 to 7% by changing from KBr
-
-
to Bu4N+BF4 in the Ni(bipy)32+2BF4 -catalyzed electro-
The electrochemical reactivity of terminal epoxides with
carbon dioxide for the synthesis of cyclic carbonates has
been examined.6 The reaction was catalyzed by Ni(cy-
carboxylation of styrene oxide.
Interestingly, CO2 was chemoselectively incorporated
into the oxirane ring and no carboxylation of the Ar-X
bond was observed, although the efficient electrocarbox-
ylation of aromatic halides has been reported in the pres-
ence of Ni-phosphine complexes10,11 as well as in the
presence of consumable anodes.12,13
clam)Br2 (cyclam = 1,4,8,11-tetraazacyclotetradecane),
2+
but could also be effected in good yields with Ni(bipy)3
,
-
2BF4 as the catalyst (bipy = 2,2’-bipyridine).7
We now describe that different chemoselectivities could
be observed in the related electrochemical carboxylation
of difunctional aromatic compounds 1-4, bearing epoxide
and halogen as the functional groups.8
In contrast with the results of the carboxylation of sub-
strates 1 and 2, when disubstituted epoxide derivatives 3
or 4 were electrolyzed with CO2 under the same electro-
chemical conditions, no cyclic carbonate was formed. The
reaction involved the activation and the carboxylation of
the Ar-X bond, and different reaction products were
formed depending on the nature of the catalytic system.
Thus, the electrocarboxylation of 3 in the presence of
The electrocarboxylation of substrates 1 and 2 in DMF
catalyzed by Ni(cyclam)Br2 in a single-compartment cell
led to the selective incorporation of CO2 into the oxirane
ring to form the corresponding cyclic carbonates in quan-
9
titative yields (Scheme 1). The best conditions for this
reaction were found to be the use of a magnesium anode,
with CO2 bubbling into the solution at atmospheric pres-
sure and KBr as the supporting electrolyte.
The reaction proceeds through the Mg2+ and Br- induced
oxirane ring opening and the parallel CO2 activation by
coordination to electrogenerated NiI(cyclam)Br complex.
The process is followed by the addition of activated CO2
-
Ni(bipy)32+ 2BF4 led to the formation of the isocoumarine
derivative, 5, in 73% selectivity, together with dehaloge-
nated compound 6 (27%), with an epoxide conversion of
77% (Scheme 2).
Synlett 2000, No. 2, 245–247 ISSN 0936-5214 © Thieme Stuttgart · New York

246
P. Tascedda, E. Duñach
LETTER
-
Bu4N+BF4 as the supporting electrolyte (entries 3, 4).
With a Mg anode (entries 1, 2) the isocoumarine 5 was
also formed but the reaction favored the formation of 6.
Very low conversions were attained when KBr was used
-
as supporting electrolyte instead of Bu4N+BF4 (entries 5,
6), in sharp contrast with the results obtained with the car-
boxylations of substrates 1 and 2. The use of Ni(bipy)Br2
as the catalyst (entry 7) replacing Ni(bipy)32+2BF4 afford-
ed low substrate conversion and high selectivity towards
-
Scheme 2
dehalogenated 6.
The chloroderivative 4 presented the same behaviour and
afforded the hydroxybenzolactone 5 in 69% selectivity
under the conditions of entry 4 (conversion of 62%,
Scheme 2).
The formation of 5 proceeded through the carboxylation
of the Ar-Br bond, followed by epoxide ring opening by
the carboxylate intermediate. The carboxylic acid-ep-
oxide derivative could be isolated when aliquots were di-
rectly hydrolyzed during electrolysis. By-product 6 was When substrate 3 was carboxylated in the presence of
-
formed by reductive cleavage and protonation by the elec- Ni(cyclam)2+2BF4 as the catalyst, a different 5-membered
trolytic medium14 of the aryl-halogen bond of 3.
ring lactone, 7, was obtained in 88% yield (Scheme 3 and
Table, entry 8). The alternative use of Ni(cyclam)Br2 as
the catalyst led also to 7 with a selectivity of 75% (entry
9).
Several experimental conditions were examined for this
novel tandem electrochemical carboxylation-cyclization
process with substrate 3 as the model compound, as
shown in the Table.
-
The Ni(cyclam)2+2BF4 -catalyzed electrocarboxylation of
chloro epoxide derivative 4 also afforded lactone 7 in 48%
yield (Scheme 3).
The best yields of 5 were obtained with the use of an Al/
stainless steel or with Al/C couple of electrodes and with
Table Electrocarboxylation reactions of substrate 3a).
Scheme 3
Our results indicate that the electrocarboxylation of di-
functional compounds 1-4 can be directed towards differ-
ent reaction products, depending on the nature of the
epoxide and of the catalytic system. Monosubstituted ep-
oxides 1 and 2 led selectively to the formation of cyclic
carbonates with partial dehalogenation. In contrast, disub-
stituted epoxides 3 and 4 reacted exclusively at the aryl-
halogen bond with carboxylate formation and further in-
tramolecular cyclization. The nature of the ligand associ-
ated to the nickel complex plays a determinant role in the
control of the reaction selectivity. Whereas the Ni-cyclam
system favors lactone 7 with epoxide ring opening on the
most substituted position, the Ni-bipy system directs the
reaction towards benzolactone 5, with carboxylate ring
opening on the less substituted epoxide position (Scheme
4).
In conclusion, this reaction presents a high substrate
chemoselectivity (cyclic carbonate or lactone according
to R = H or R = Me, respectively), as well as an interest-
ing regioselectivity, depending upon the ligands on the
nickel catalyst. The important role of the ligand determin-
ing the reaction selectivity has already been observed in
a) For general elecrocarboxylation procedure, see ref. 9. Catalyst A:
-
Ni(bipy)32+2BF4 ; catalyst B: Ni(bipy)Br2; catalyst C: Ni(cy-
-
clam)2+2BF4 ; catalyst D: Ni(cyclam)Br2.
Synlett 2000, No. 2, 245–247 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Electrosynthesis of Benzolactones by Nickel-Catalyzed Carboxylation
247
(5) J. N. Srivastava, D. N. Chaudhury J. Org. Chem. 1962, 27,
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Organomet. Chem., in press.
(8) Preparation of epoxides 3 and 4 was carried out following the
reference: E. J. Corey, M. Chaykovsky J. Am. Chem. Soc.
1965, 87, 1353.
(9) General electrochemical procedure: the electro-
carboxylations of 1-4 (3 mmol) were run in DMF (30-40 mL),
containing the supporting electrolyte (KBr or Bu4NBF4,
0.03M) and the corresponding Ni(II) complex (10 mol%) in a
single-compartment cell fitted with a Mg or Al/stainless steel
couple of electrodes, at room temperature and at atmospheric
CO2 pressure. Electrolyses were conducted at constant current
(60 mA) for 7 h, and then the solutions were heated at 50 °C
overnight, extracted with diethyl ether and aqueous HCl
(0.01M), washed with water, dried over MgSO4 and
evaporated. The crude products were purified by column
chromatography on silica-gel, with pentane-diethyl ether
mixtures as eluents. Products were analyzed by GC, 1H and
13C NMR and mass spectrometry, and the spectra compared
with those of authentic samples for the known compounds.
(10) M. Troupel, Y. Rollin, J. Périchon, J. F. Fauvarque New J.
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Scheme 4
other electrochemical Ni-catalyzed reactions involving al-
lyl aryl ethers.15 Work is in progress to determine the
mechanism and the particular role of the ligands in these
electrochemical carboxylation reactions.
References and Notes
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Article Identifier:
1437-2096,E;2000,0,02,0245,0247,ftx,en;G26699ST.pdf
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Synlett 2000, No. 2, 245–247 ISSN 0936-5214 © Thieme Stuttgart · New York