Universal method for the functionalization of β-bromovinyl trifluoromethyl ketones of cyclobutene series

Full text of DOI:10.1134/S0012500810050046

ISSN 0012ꢀ5008, Doklady Chemistry, 2010, Vol. 432, Part 1, pp. 133–135. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.B. Koldobskii, N.P. Tsvetkov, V.N. Kalinin, 2010, published in Doklady Akademii Nauk, 2010, Vol. 432, No. 2, pp. 188–190.
CHEMISTRY
Universal Method for the Functionalization of βꢀBromovinyl
Trifluoromethyl Ketones of Cyclobutene Series
A. B. Koldobskii, N. P. Tsvetkov, and V. N. Kalinin
Presented by Academician Yu.N. Bubnov October 14, 2009
Received November 10, 2009
DOI: 10.1134/S0012500810050046
Unsaturated trifluoromethyl ketones are a new tuted fluorineꢀcontaining enones [5], whereas similar
extremely promising class of compounds whose propꢀ enones with the C=C bond being incorporated into a
strained small ring have been unknown until recently.
Very recently, we found an unusual reaction of
[2+2] cycloaddition of 1ꢀtrifluoroacetylꢀ2ꢀhaloacetyꢀ
lenes to simple alkenes that proceeded in the absence
erties in recent two decades have been intensively
studied in medicine [1], biochemistry [2], and molecꢀ
ular biology [3]. Moreover, these compounds are
widely used in organic synthesis [4]. It is of special
synthetic interest to use unsaturated trifluoromethyl
of light and catalyst to give ꢀhalovinyl trifluoromethyl
β
ketones containing a leaving group in the
β
position,
ketones of cyclobutene series [6, 7]. With the use of
corresponding bromides 1a–1f, we attempted to
develop a general method for the displacement of broꢀ
mine atom by different aryl and hetaryl substituents to
whose structural features provide a possibility to carry
out functionalization reactions and to synthesize difꢀ
ferent fluorineꢀcontaining heterocyclic compounds
[4]. However, these transformations have hitherto form new
β
ꢀarylvinyl trifluoromethyl ketones of
been studied only for the simplest acyclic
β
ꢀsubstiꢀ cyclobutene series.
CH3
COCF3
CH3
COCF3
COCF3
COCF3
Br
Br
1b
Br
Br
1a
1c
1d
COCF3
COCF3
Br
Br
1e
1f
At the first stage of research, we established that Reactions with arylzinc chlorides (2ꢀthienylꢀ, 2ꢀ
furylꢀ, 4ꢀfluorophenylꢀ, and phenylzinc chlorides)
are very slow and lead to a complex mixture of prodꢀ
ucts in low yield. We have found, however, that the
addition of catalytic amounts of tetrakis(tripheꢀ
nylphosphine)palladium (the Negishi reaction)
considerably accelerates the process and allows
preparation in high yields of corresponding crossꢀ
coupling products 2–7 where bromine atom is disꢀ
placed by an aryl group.
organolithium compounds and Grignard reagents
bind mainly at the carbonyl group of unsaturated
ketones
1 to yield corresponding tertiary alcohols,
the C=C bond and the halogen atom being intact.
Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, ul. Vavilova 28, Moscow,
119991 Russi
133

134
KOLDOBSKII et al.
COCF3
Br
COCF3
Ar
Pd(PPh3)4
75–85%
+ Ar–Zn–Cl
20°C, THF
1
2–7
Ar is (a) 2ꢀTh (
), (b) 2ꢀFu (
), (c) 4ꢀF–Ph (
), (d) Ph (
)
F
S
O
It is worth noting that, in spite of the very high carꢀ
bonyl activity of the trifluoroacetyl group in ketones
the careful analysis of reaction products showed the arylzinc compounds under mild conditions to give
complete absence of tertiary alcohols that could result corresponding ꢀarylvinyl trifluoromethyl ketones 2–
retaining the cyclobutene fragment.
The revealed transformation seems to have a genꢀ
1,
eral character: all vinyl bromides react with different
1
β
from the addition of organozinc compounds to the
C=O bond.
7
CH3
CH3
COCF3
COCF3
Ar
COCF3
Ar
COCF3
Ar
Ar
2a–2d
3a–3d
COCF3
4a–4d
5a–5d
COCF3
[Ar is (a) 2ꢀTh, (b) 2ꢀFu, (c) 4ꢀF–Ph, (d) Ph]
Ar
Ar
7a–7d
6a–6d
It should be noted that substituted cyclobutenes are
of great interest as biologically active compounds [8];
in addition, they are universal reagents in organic synꢀ
thesis due to high reactivity [9]. However, until now,
neither the general method for the preparation of
cyclobutenes containing trifluoroacetyl group nor the
General Procedure for the Synthesis of Adducts 2–7
(a) Synthesis of 2ꢀthienylꢀ, 2ꢀfurylꢀ, and 4ꢀfluoꢀ
rophenylzinc chlorides. A solution of butyllithium in
hexane (6.2 mL of 1.6 M solution, 0.01 mol) was
added dropwise to a solution of 0.012 mol of
thiophene or 0.012 mol of furan in 10 mL of anhyꢀ
drous THF with stirring under an argon atmosphere
methods for the introduction of substituents in the
β
position of the strained endocyclic C=C bond have
been available and the conjugated trifluoroacetylcyꢀ
clobutenes have been unknown. The present work
offers broad access to this new class of compounds and
comprehensive study of its properties.
and cooling to 0
°
С. The reaction mixture was stirred
for 0.5 h at 0 . (Under these conditions, 2ꢀthienylꢀ
°
С
lithium and 2ꢀfuryllithium form in quantitative yield
[10].) 4ꢀFluorophenyllithium and phenyllithium were
obtained by the addition of 6.2 mL of a 1.6 M solution
of butyllithium in hexane (0.01 mol) to a stirred soluꢀ
tion of
(0.011 mol) in 10 mL of THF at –70
stirring of the reaction mixture for 1 h at –70
solution of 1.57 g (0.012 mol) of anhydrous ZnCl2 in
15 mL of THF was added dropwise to the prepared
solution or suspension of organolithium compound
p
ꢀfluorobromobenzene or bromobenzene
followed by
. A
°
С
EXPERIMENTAL
°
С
The synthesis of all organozinc compounds and
crossꢀcoupling reactions were carried out in an argon
atmosphere with the use of anhydrous solvents. Initial
bromocyclobutenes 1a–1f were obtained by the [2 +
2] cycloaddition of 1ꢀtrifluoroacetylꢀ2ꢀbromoacetyꢀ
lene to appropriate alkenes [6, 7]. In all experiments,
the structure of crossꢀcoupling products 2–7 was conꢀ
firmed by elemental analysis data, 1H and 13C NMR,
and IR spectra.
with stirring and cooling to –70
ture was allowed to warm to 20
°
С
, the reaction mixꢀ
°
С, and the resultant
organozinc compounds were further used in the crossꢀ
coupling reactions.
(b) Crossꢀcoupling reactions of cycloadducts 1a–1f
with organozinc compounds. One of compounds 1a–1f
DOKLADY CHEMISTRY Vol. 432
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UNIVERSAL METHOD FOR THE FUNCTIONALIZATION
135
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Halarnkar, S.J., Pestic. Biochem. Physiol., 1989, vol. 33,
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(0.01 mol) and 0.01 g (0.002 mol) of Pd(PPh3)4 were
added to a stirred solution of organozinc compound at
20
°
С in one portion. After an exothermic reaction
3. Allen, K.N. and Abeles, R.N., Biochemistry, 1989,
completed, the mixture was stirred for 18 h at 20
°
С,
vol. 28, pp. 135–148.
and 30 mL of a saturated solution of ammonium chloꢀ
ride was added. The organic layer was separated, and
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denko, V.G., Tetrahedron, 2007, vol. 63, pp. 7753–
7808.
5. Nenajdenko, V.G., Druzhinin, S.V., and Balenꢀ
kova, E.S., Chemistry of α,βꢀUnsaturated Trifluoromeꢀ
thyl Ketones, New York: Nova Sci. Publ., 2007.
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Dokl. Chem., 2005, vol. 404, part 1, pp. 174–177 [Dokl.
Akad. Nauk, 2005, vol. 404, no. 2, pp. 201–204].
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et al., Izv. Akad. Nauk, Ser. Khim., 2009, no. 7,
pp. 1390–1396.
the aqueous layer was extracted with ether (4 20 mL).
×
The combined organic extracts were washed with
20 mL of a saturated solution of ammonium chloride,
dried with sodium sulfate, and concentrated in a vacꢀ
uum. The residue was diluted with 30 mL of hexane,
catalyst decomposition products were separated by filꢀ
tration, and the filtrate was concentrated in a vacuum.
The residue was passed through a thin layer of silica gel
in a hexane–ethyl acetate (2 : 1) solution, and the
solution was concentrated. Adducts 2–7 were isolated
by column chromatography on silica gel with hexane–
ethyl acetate (2 : 1) as an eluent.
8. LeeꢀRuff, E., Adv. Strain Org. Chem., 1991, vol. 1,
pp. 167–213.
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vol. 103, pp. 1449–1483.
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DOKLADY CHEMISTRY Vol. 432
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2010