Russian Chemical Bulletin, International Edition, Vol. 53, No. 2, pp. 435—442, February, 2004 435
10665285/04/53020435 © 2004 Plenum Publishing Corporation
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 416—422, February, 2004.
unsaturated trifluoromethyl ketones with
V. G. Nenajdenko,
S. V. Druzhinin, and E. S. Balenkova
Department of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 932 8846. Email: email@example.com
The reactions of
unsaturated trifluoromethyl ketones containing aromatic and
heteroaromatic substituents with 1morpholinocyclopentene, 1morpholinocyclohexene, and
1methyl4morpholino1,2,5,6tetrahydropyridine were studied. The reactions proceeded ste
reospecifically to give the corresponding bicyclo[3.2.1]octane, bicyclo[3.3.1]nonane, and
Key words: unsaturated trifluoromethyl ketones, enamines, stereochemistry, cycloaddition.
In recent years, considerable attention has been given
to the development of new procedures for the synthesis of
fluorinecontaining compounds, which are often used in
both medicine and agricultural chemistry.
urated trifluoromethyl ketones serve as convenient build
ing blocks for the introduction of the trifluoromethyl group
into different classes of acyclic, carbocyclic, and hetero
cyclic compounds. However, their properties have not
been adequately investigated.
The reaction of the only unsaturated trifluoromethyl
ketone, viz., 4ethoxy1,1,1trifluorobut3en2one (1a),
with 1pyrrolidinocyclohexene in anhydrous Et
described in the literature.
The reaction gave rise to
nan9one as a single diastereomer (Scheme 1).
In all cases, the reactions of trifluoromethyl ketones 1a
and 1b with enamines 2a—c in aqueous EtOH (Scheme 2)
afforded a product (in a nearly quantitative yield), which
was identified as 1,1,1trifluoro4(morpholin4yl)but
3en2one (4), instead of the expected bicyclic hydroxy
ketone 3a. Apparently, this reaction pathway is associated
with the influence of the polar solvent, and the reaction
proceeds at the nitrogen atom of the amino fragment of
enamine rather than at the
It is known that
unsaturated trifluoromethyl ke
tones containing a substituent, which is capable of being
eliminated, at position 4 can differ radically in the reac
tivity and the reaction pathway from
trifluoromethyl ketones devoid of such substituents.
this connection, we studied the reactions of ketones con
taining aryl and hetaryl substituents
with various cy
We chose 1,1,1trifluoro4phenylbut3en2one
(1c) and 1morpholinocyclohexene (2b) as model sub
strates. The reactions were carried out in 96% EtOH
C followed by treatment of the reaction mixture
with an aqueous NH
Cl solution to hydrolyze iminium
intermediates. Bicyclic ketone 3c was isolated from the
reaction mixture. Therefore, the reaction is not finished
at the step of formation of the Michael adduct and results
in cyclization of the iminium intermediate to give a bi
cyclic derivative (Scheme 3).
Bicyclic hydroxy ketone 3c was isolated as a single
diastereomer. To confirm the structure and reveal the
orientations of the substituents, we carried out Xray dif
fraction analysis and established that the phenyl substitu
ent and the hydroxy group are in the axial positions,
whereas the trifluoromethyl group is in the equatorial po
sition (Fig. 1). It was found that there is no intramolecu
lar hydrogen bond between the proton of the hydroxy
group and the oxygen atom of the carbonyl group, whereas
the proton of the hydroxy group and the oxygen atom of