Pentafluorophenyl carbonyl compounds in the Reformatsky-type reactions promoted with Fe(CO)5-based metal complex systems

Article abstract of DOI:10.1016/j.jfluchem.2008.05.017

Iron pentacarbonyl is an effective promoter for additions of halogenated acid esters and nitriles to pentafluorophenyl carbonyl compounds 1, 4, and 5 by the Reformatsky-type reaction and reductive coupling of compound 1. The electron-withdrawing character

Full text of DOI:10.1016/j.jfluchem.2008.05.017

Journal of Fluorine Chemistry 129 (2008) 669–673
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Pentafluorophenyl carbonyl compounds in the Reformatsky-type reactions
promoted with Fe(CO)5-based metal complex systems
*
A.B. Terent’ev, T.T. Vasil’eva, O.V. Chahovskaya, N.E. Mysova, H.H. Hambardzumyan, K.A. Kochetkov
A.N. Nesmeyanov Institute of Organoelement Compounds, The Russian Academy of Sciences, Vavilov Str. 28, 119991 Moscow, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
Iron pentacarbonyl is an effective promoter for additions of halogenated acid esters and nitriles to
pentafluorophenyl carbonyl compounds 1, 4, and 5 by the Reformatsky-type reaction and reductive
coupling of compound 1. The electron-withdrawing character of the pentafluorophenyl group has a
significant effect on the reaction pathway and the type of the reaction products. The reactions involving
metal complex systems derived from Fe(CO)5 have a number of advantages such as a simple procedure
for carrying out, the lack of necessity to use anhydrous solvents and an inert atmosphere. The schemes of
the reactions have been proposed and the conditions for preparative syntheses of most products have
been optimized.
Received 7 December 2007
Received in revised form 30 May 2008
Accepted 30 May 2008
Available online 5 June 2008
Keywords:
Pentafluorophenyl-containing compounds
The Reformatsky-type reaction
Iron pentacarbonyl
ß 2008 Elsevier B.V. All rights reserved.
Reductive coupling
1. Introduction
been proposed as catalysts and promoters for organic synthesis
[15–19], at the same time the available metal carbonyls are used as
Today the expanding circle of reactions including metal insertion
into carbon–halogen bond followed by interaction with compounds
containing reactive groups such as carbonyl, nitrile, etc. are assigned
to Zaitsev–Barbier–Reformatsky reactions [1–5]. Various metals are
involved inthese reactionssuch aszinc[4], magnesium[6] and more
recently samarium [7], silicon [8], indium [5], etc. Although the
common conditions for above reactions are continuously being
improved, certain difficulties exist for carrying out them such as the
need to use anhydrous and volatile solvents and inert atmosphere,
low temperatures, heterogeneous medium, effective agitating and
activating a metal surface. A search for new approaches to
realization of additions of organohalogen compounds, specifically
organofluorine compounds, to the carbonyl group of aldehydes and
ketones is still being continued [9,10]. Taking into account the fact
that introduction of fluorine atoms into organic compounds often
leads to essential changes in their physical, chemical and biological
properties [2,3,11–14] it is of great interest to develop a new
methodology for the synthesis of multifunctional organofluorine
compounds that would be experimentally simple.
reagents much more rarely [20]. We reported the first examples
that Fe(CO)5 and homogenous Fe(CO)5-based metal complex
systems are effective promoters for the Reformatsky-type reac-
tions [21–23]. The above reactions are characterized by high yields,
high selectivity, and they can be carried out under simple
conditions such as either refluxing in benzene for several hours
or standing at room temperature, there is no need to use anhydrous
solvents and inert atmosphere. We studied these reactions by the
example of various types of carbonyl compounds and concluded
that the presence of Fe(CO)5 is most effective in the case of
pentafluorobenzaldehyde 1, this made it possible to perform
additions of various organohalogen compounds to 1 [24]. For
instance, a striking example of the Fe(CO)5-promoted reaction is
addition of allyl iodide to aldehyde 1 that occurs under mild
conditions to give secondary alcohol CH2 CHCH2-CH(OH)-C6F5 (2)
in almost quantitative yield [24]. We have also showed that
aldehyde 1 undergoes diastereoselective reductive coupling in the
presence of [Fe(CO)5 + HMPA] system to form the corresponding
decafluorodihydrobenzoine C6F5–CH(OH)–CH(OH)–C6F5 (3) [25].
In this work we have first performed the reaction of the
Reformatsky-type with perfluoro- and pentafluoroacetophenones
(4 and 5) in the presence of Fe(CO)5. Taking into account the new
examples of additions of organohalogen compounds to aldehyde 1,
we have compared the reactivity of pentafluorophenyl carbonyl
compounds 1, 4, and 5 in the reactions of the above type and
proposed the reaction mechanism.
Most metal complexes widely used in the organic synthesis are
either expensive or not easily available [5,7,10]. On the other hand,
iron oxides, salts and complexes are cheap and recently they have
* Corresponding author. Tel.: +7 499 1355033; fax: +7 499 1355085.
E-mail address: const@ineos.ac.ru (K.A. Kochetkov).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.05.017

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A.B. Terent’ev et al. / Journal of Fluorine Chemistry 129 (2008) 669–673
Scheme 1.
2. Results and discussion
Therefore, we have proposed a one-step process for preparation
of tertiary hydroxy esters and nitriles containing pentafluorophe-
nyl group in combination with methyl and trifluoromethyl groups.
In our opinion, the special properties of polyfluorinated carbonyl
compounds 1, 4, and 5 are associated with strong electron-
withdrawing character of the pentafluorophenyl group, this
indicates that the role of polar factors is significant in the reactions
under consideration. The results we have obtained supplement
well the existing opportunities for the synthesis of secondary
and tertiary fluorinated hydroxy compounds reported in literature
[9].
The use of pentafluorobenzaldehyde 1 in the Reformatsky-type
reactions allowed us to open the route to a wide circle of
functionally substituted secondary alcohols containing a penta-
fluorophenyl group [24]. A sharp increase in the yields of the
adducts was observed when going from perfluorobutyl iodide to
allyl iodide; this is associated with the fact that electrophilic
pentafluorobenzaldehyde 1 much more readily reacts with a
nucleophilic reagent than with an electrophilic one.
The reaction with iodoacetonitrile does make it possible to
obtain
one to prepare easily
Application of PASS Software [27] to fluorinated
alcohols predicted (with probability exceeding 95%) the
pronounced anti-ischemic activity for amine 7. Chiral amino
alcohols obtained from -hydroxy nitriles are of great importance
because of their biological activity and the possible applicability to
asymmetric synthesis as ligands [28,29].
The addition of methyl bromoacetate, the typical Reformatsky
reagent, to aldehyde 1 occurs at 110 8C to give 3-hydroxy-3-
pentafluorophenylpropionic acid methyl ester (8) in good yield; it
is accompanied by the formation of 3 as a by-product in the form of
b
-hydroxy nitrile 6 in high yield whose reduction allows
It is well known that organomagnesium compounds derived
from perfluoroalkyl halides can be obtained mainly as a result of
the exchange reaction of a perfluoroalkyl halide with an
g
-oxyamine 7 (Scheme 1).
g
-amino
a
alkylmagnesium halide; and it is difficult to use the Grignard
reactions for synthesizing pentafluorinated hydroxy compounds of
the considered series [30]. In this case reduction of substrate often
takes place and sometimes the reduction becomes the major
reaction, this results in low yields of the target products—
secondary and tertiary alcohols. At the same time, under the
conditions studied that result in products 8–16, there were not
found the substances corresponding to the reduction products of
the initial polyfluorinated compounds (according to GC–MS data)
such as diols or stilbenes.
b
a mixture of meso- and D,L-forms.
Involving the less reactive pentafluorophenyl ketones 4 and 5 in
the Reformatsky reaction makes it possible to synthesize function-
ally substituted tertiary alcohols with a pentafluorophenyl group.
Perfluoroacetophenone 4 undergoes the reaction with halogenated
compounds on heating in chlorobenzene; the reaction is not
virtually accompanied by formation of by-products such as
unsaturated compounds and diols unlike reaction with aldehyde
1 (Table 1).
In the case of pentafluoroacetophenone 5 the yields of the
target products are somewhat lower than those in the case of
ketone 4 (Table 2) and a by-product, namely 1,2-bis(pentafluor-
ophenyl)propen-1-ol (12), is formed as a result of aldol condensa-
tion in about 10% yield. Unlike the reductive coupling of aldehyde
1, diastereoselectivity of the above reactions (Tables 1 and 2) is not
high, and the diastereoisomer ratio is about 2:1.
When we considered the possible reaction mechanism
(Scheme 2), we reasoned from the fact that the charge-transfer
complexes of the (A) type are formed in systems including Fe(CO)5
and organohalogen compounds as we showed earlier using UV
spectroscopy. Decomposition of the above complexes provides
initiation of the reactions [26].
The transition state of the reactions can be represented in the
form of organoiron complex (B), including either 1 (or 4 or 5) and
anion resulted from the electron transfer in the system Fe(CO)5–RX
(X = Hal) [24]. The strong electron-accepting effect of the penta-
fluorophenyl group facilitates the nucleophilic attack of the anion
at the electrophilic centre of the carbonyl compound.
Our studies of reaction mixtures resulted from Reformatsky-
type reactions involving aldehyde 1, showed the presence of traces
of decafluorodihydrobenzoine
3 [25]. The formation of the
corresponding dihydrobenzoines from ketones 4 and 5 was not
observed under the similar conditions unlike aldehyde 1.
Table 1
Reaction of brominated esters and nitriles with perfluoroacetophenone 4
Table 2
Reaction of halogenated esters and nitriles with pentafluoroacetophenone 5
Entry
R
Y
Product
Yield (%)
1a
2
H
COOCH3
COOCH3
CN
8
9
65
70
65
71
Entry
R
Y
Solvent
Product
Yield(%)
CH3
CH3
H
3
10
11
1a
2
H
COOCH3
CN
ClC6H5
C6H6
13
14
15
16
35
25
70
45
4
COOCH3
H
3
CH3
CH3
COOCH3
CN
C6H6
a
Addition of methyl bromoacetate to pentafluorobenzaldehyde 1 has been
performed that was accompanied by the formation of diol 3 (5%) and unsaturated
compound.
4
ClC6H5
a
The reaction with JCH2CN occurs similarly.

A.B. Terent’ev et al. / Journal of Fluorine Chemistry 129 (2008) 669–673
671
Scheme 2.
Scheme 3.
The formation of product 3 made it possible to study the
conditions for the reductive coupling of aldehyde 1 in detail. We
have shown that in the presence of [Fe(CO)5 + HMPA] system,
identified reaction product as well as 1,2-di(pentafluoropheny-
l)ethanone 18 decafluorostilbene 19, whereas diol 3 was absent
4
(Scheme 4). It should be noted that stilbene 17 was registered as
the only reaction product when a fivefold decrease of the initial
concentration of 1 in the solution was used. To clarify the role of
water in the above abnormalities we carried out the reaction with
aldehyde 1 in the presence of the water added in the equivalent
amount (1 mmol). In this case product 3 was obtained again, and
stilbene 17 was virtually absent. Therefore, in reductive coupling
pentafluorobenzaldehyde 1 exhibits the dual reactivity depending
on the presence of water in the system (even in trace amounts). The
synthesis of stilbenes from various aldehydes was earlier reported
in the presence of either AlCl3 + Zn [32] or InCl3 + Zn [33] systems,
where the reactions were carried out in anhydrous acetonitrile
under refluxing, and the mechanisms were not considered.
We assume the following steps of the reaction when it is
carried out in an anhydrous solvent on heating (Scheme 4): the
formation of metallocarbene followed by intracomplex coupling
aldehyde
1 gives corresponding 3 as D,L-isomer in almost
quantitative yield.
The formation of product 3 can be explained by the scheme that
includes one-electron transfer from the iron atom to aldehyde 1 to
form an anion-radical in the iron ligand sphere, addition of the new
aldehyde molecule to the anion-radical particle (this step may be
sterically hindered in the case of ketones 4 and 5) to give alkoxide
(C), and its hydrolysis leading to diol (Scheme 3). The first step is
confirmed by the data concerning the charge-transfer complexes
[6], and formation of the similar anion-radical particles was
observed by ESR in particular in the Fe(CO)5 system with amines,
amides, phosphines, etc. [20,31].
We obtained unexpected results when the reductive coupling of
1 was carried out in anhydrous benzene at 80 8C. The reaction
mixture was found to contain decafluorostilbene 17 as the major
Scheme 4.

672
A.B. Terent’ev et al. / Journal of Fluorine Chemistry 129 (2008) 669–673
to give stilbene 17, reacting the carbene complex (D) with
aldehyde, i.e. insertion of the carbine into C–H and C O bonds to
yield ketone 18 and oxirane 19, respectively. The presence of
moisture hinders the carbine formation and as a result diol 3
became the major product.
4.2. Pentafluorophenyl hydroxy compounds derived from 1
4.2.1. 3-Hydroxy-3-pentafluorophenylpropionic acid methyl ester (8)
(110 8C, ClC6H5, 4 h). Yield 62%, mp 53–55 8C, diastereoisomer
ratio 1:1.5. 1H NMR (400 MHz, CDCl3):
d 2.76–3.14 (2H, AB part of
In our opinion, the fact that stilbene 17 is the only product when
the reaction is carried out at fivefold dilution, indicates that the
formation of stilbene is of intracomplex character and products 18
and 19 are formed in an intermolecular manner.
The substantial distinctions in the results of the reactions
with perfluorobenzaldehyde 1 (Scheme 4) and benzaldehyde
[23] reflects the effect of the polar substituents in the benzene
ring of aldehyde 1. Judging from the experimental data, the
electron-withdrawing pentafluorophenyl group facilitates sta-
bilization of the carbene complex D, unlike the phenyl group in
benzaldehyde; this can explain the dual character of the
ABX system, JAB = 22.32 Hz, JAX = 12.64 Hz, JBX = 12.64 Hz), 3.50 (1H,
s), 5.47–5.51 (1H, m, X part of ABX system). 19F NMR (282 MHz,
CDCl3):
d
À64.92 (m, 2F), À76.35 (t, 1F, J = 20.8 Hz), À83,75 (m, 2F).
GC–MS: m/z (Irel): 270 [M]+ (0.4), 252 [MÀH2O]+ (25.7), 197
[C6F5CH(OH)]+ (83.3), 195 [C6F5CO]+ (52.4), 167 [C6F5]+ (24), 74
[CH3COOCH3]+ (55.1), 43 [CH3CO]+ (100). Anal. Calcd for C10H7F5O3:
C, 44.44; H, 2.59; F, 35.18. Found: C, 44.17; H, 2.40; F, 35.67.
4.3. Pentafluorophenyl hydroxy compounds derived from 4
4.3.1. 4,4,4-Trifluoro-3-hydroxy-2-methyl-3-
reactivity of pentafluorobenzaldehyde
reaction conditions.
1
depending on the
pentafluorophenylbutyric acid methyl ester (9)
(110 8C, ClC6H5, 4 h). Yield 70%, mp 54–56 8C, diastereoisomer
ratio 1:1.5. 1H NMR (300 MHz, CDCl3):
d
1.58 (3H, d, J = 7 Hz), 3.71–
3.77 (1H, m), 4.87 (1H, s), 3.88 (3H, s). 19F NMR (282 MHz, CDCl3):
d
3. Conclusion
À1.43 (t, 3F, J = 8 Hz), À59.78 (m, 2F), À73.88 (t, 1F, J = 21 Hz),
À83.18 (m, 2F). GC–MS: m/z (Irel): 352 [M]ꢀ+ (2.40), 321
[MÀOCH3]+ (1.28), 283 [MÀOCH3]+ (7.70), 265 [C6F5(CF3)OH]+
(10.6), 195 [C6F5CO]+ (100.0), 88 [C2H5COOCH3]+ (65.7). Anal. Calcd
for C12H8F8O3: C, 40.90; H, 2.27; F, 43.18. Found: C, 40.62; H, 2.41;
F, 43.02.
Therefore, we have demonstrated the opportunity to use
Fe(CO)5-based systems for promoting the Reformatsky-type
reactions and diastereoselective reductive coupling for organo-
fluorine carbonyl compounds to give polyfunctional compounds
containing groups with potential biological activity. The reactions
involving metal complex systems derived from Fe(CO)5 have a
number of advantages such as a simple procedure for carrying out
(refluxing in either benzene or chlorobenzene for several hours),
the lack of necessity to use anhydrous solvents and an inert
atmosphere. The schemes of the reactions have been proposed and
the conditions for preparative syntheses of most products have
been optimized.
4.3.2. 4,4,4-Trifluoro-3-hydroxy-2-methyl-3-
pentafluorophenylbutyronitrile (10)
(110 8C, ClC6H5, 4 h). Yield 65%, mp 150 8C, diastereoisomer
ratio 1:3. 1H NMR (300 MHz, CDCl3):
d
1.52 (3H, d, J = 7 Hz), 3.90
(1H, q, J = 14 Hz), 4.21 (1H, s). 19F NMR (282 MHz, CDCl3):
d
À1,43
(t, 3F, J = 8 Hz), À61.35 (m, 2F), À70.53 (t, 1F, J = 21 Hz), À80.58 (m,
2F). GC–MS: m/z (Irel): 319 [M]ꢀ+ (1.5), 265 [C6F5(CF3)COH]+ (20.5),
250 [MÀCF3]+ (1.4), 195 [C6F5CO]+ (100.0), 167 [C6F5]+ (11.9), 69
[CF3]+ (5.1), 55 [CH3CH2CN]+ (48.1). Anal. Calcd for C11H5F8NO: C,
41.39; H, 1.58; F, 47.62; N, 4.38. Found: C, 41.51; H, 1.55; F, 47.70;
N, 4.36.
4. Experimental
GC–MS measurements were carried out on
a VG-7070E
instrument (EI, 70 eV). Because the mass spectra of the diaster-
eoisomers are almost identical, the spectrum of one of them is
given. GLC analysis was conducted on a LKhM-80 chromatograph,
a steel column (1300 Â 3 mm) with 15% SKTFT-50X on Chromaton-
N-AW, detector-catharometer, helium was used as a gas-carrier
(60 ml/min), temperature programming in the range of 50–250 8C
(68/min), the yields were determined by internal standard method.
The 1H and 19F NMR spectra were recorded on a Bruker WP-300
and 400 in CDCl3, the chemical shifts are given for either TMC or
CF3CO2H standards, respectively. All organic reagents were
purified by distillation. Compounds 1, 4 and 5 were delivered
from Scientific Industrial Association ‘‘P & M’’ (Russia). Fe(CO)5
from Fluka was used without additional purification.
4.3.3. 4,4,4-Trifluoro-3-hydroxy-3-pentafluorophenylbutyric acid
methyl ester (11)
(110 8C, ClC6H5, 4 h). Yield 71%, mp 79 8C. 1H NMR (300 MHz,
CDCl3):
d
3.15 (1H, d, J = 17.4 Hz), 3.65 (1H, d, J = 17.4 Hz), 3.80 (3H,
À4.12 (t, 3F, J = 8 Hz),
s), 5.05 (1H, s). 19F NMR (282 MHz, CDCl3):
d
À60.34 (m, 2F), À73.88 (t, 1F, J = 20.71 Hz), À83.27 (m, 2F). GC–MS:
m/z (Irel): 338 [M]ꢀ+ (1.0), 269 [MÀCF3]+ (70.0), 265 [C6F5(CF3)OH]+
(23.7), 196 [C6F5C–OH]+ (16.7), 195 [C6F5CO]+ (100.0), 74
[CH3COOCH3]+ (4.6), 69 [CF3]+ (10.5), 43 [C2H3O]+ (32.1), 42
[C2H2O]+ (11.8). Anal. Calcd for C11H6F8O3: C, 39.07; H, 1.77; F,
44.95. Found: C, 39.23; H, 1.83; F, 45.05.
4.1. General procedures for the synthesis of hydroxy carbonyl
compounds. Reactions of pentafluorophenyl carbonyl compounds 1, 4,
and 5 with halogenated esters and nitriles
4.4. Pentafluorophenyl hydroxy compounds derived from 5
4.4.1. 1,3-Bis(pentafluoropheny)but-2-en-1-one (12)
19F NMR (282 MHz, CDCl3):
d
À63.23 (m, 2F), À71.61 (t, 1F,
A solution of a mixture of halogenated derivative (1 mmol),
carbonyl compound (1 mmol), Fe(CO)5 (2 mmol) in 1 ml of
benzene (or chlorobenzene) was heated with stirring for 4 h at
80 8C (or at 110 8C, respectively). Then the reaction mixture was
diluted with 2 ml of the solvent, treated with 1N hydrochloric acid,
twice washed with water, and dried over MgSO4. The reaction
products were isolated either by crystallization (solids) or
preparative GLC (liquids) using the phase that was used in GLC
analysis. The yields were determined by GLC using an internal
standard [24].
J = 20.5 Hz), À82.64 (m, 2F). GC–MS: m/z (Irel): 402 [M]ꢀ+ (49.0),
383 [MÀF]+ (63.2), 235 [MÀC6F5]+ (32.7), 207 [MÀC6F5C(O)]+
(26.7), 195 [C6F5CO]+ (100.0), 167 [C6F5]+ (45.4), 40
[MÀC6F5C(O)ÀC6F5]+ (59.0).
4.4.2. 3-Hydroxy-3-pentafluorphenylbutyric acid methyl ester (13)
(110 8C, ClC6H5, 4 h). Yield 35% (GLC). 1H NMR (300 MHz,
CDCl3):
3.73 (3H, s), 4.69 (1H, s). 19F NMR (282 MHz, CDCl3):
2F), À78.38 (t, 1F, J = 21 Hz), À84.45 (m, 2F). GC–MS: m/z (Irel): 269
d
1.73 (3H, s), 2.86 (1H, d, J = 17 Hz), 3.28 (1H, d, J = 17 Hz),
d
À63.23 (m,

A.B. Terent’ev et al. / Journal of Fluorine Chemistry 129 (2008) 669–673
673
[MÀCH3]+ (6.9), 266 [MÀH2O]+ (3.4), 237 [MÀCOF]+ (3.3), 211
[C6F5C(CH3)OH]+ (24.8), 195 [C6F5CO] (54.9), 181 [C6F5CH2]+ (7.5),
167 [C6F5]+ (19.4), 117 [C5F3]+ (13.4), 74 [CH3COOCH3]+ (21.8), 69
[CF3]+ (6.3), 59 [COOCH3]+ (10.1), 43 [C2H3O]+ (100), 42 [C2H2O]+
(27.1). Anal. Calcd for C11H9F5O: C, 46.48; H, 3.17; F, 33.45. Found:
C, 45.83; H, 3.02; F, 33.17.
When the reaction was carried out in anhydrous benzene,
compound 17 (yield 25%) and small amounts of 18 and 19 were
isolated.
Decafluorostilbene (17). GC–MS: m/z (Irel): (cis-) 360 [M]+ (100),
341 [MÀF]+ (5), 192 [MÀC6F5H]ꢀ+ (12), 180 [C6F5CH]ꢀ+ (10); (trans-
) 360 [M]+ (100), 341[MÀF]+ (25), 192 [MÀC6F5H]+ (25), 180
[C6F5CH]+ (35).
4.4.3. 3-Hydroxy-3-pentafluorphenylbutyronitrile (14)
1,2-di(pentafluorophenyl)ethanone (18). 13C NMR (CDC13):
d
(80 8C, C6H6, 4 h). Yield 25%. 1H NMR (300 MHz, CDCl3):
d
1.90
(3H, s), 3.03 (1H, d, J = 16.7 Hz), 3.16 (1H, d, J = 16.7 Hz), 3.42 (1H,
s). 19F NMR (282 MHz, CDCl3):
211.9 (C O), 29.7 (CH2). GC–MS: m/z (Irel): 376 [M]+ (5), 358
[MÀF+H]+ (100), 195 [C6F5C(O)]+ (7).
d
À62.36 (m, 2F), À75.86 (t, 1F,
1,2-di(pentafluorophenyl)ethylene oxide (19). 13C NMR
J = 20.5 Hz), À82.76 (m, 2F). GC–MS: m/z (Irel): 233 [MÀH2O]+
(35.0), 211 [C6F5C(CH3)OH]+ (71.0), 195 [C6F5CO]+ (67.2), 167
[C6F5]+ (25.0), 117 (17.0), 41 (40.0), 43 [CH3CO]+ (100). Anal. Calcd
for C10H6F5NO: C, 47.81; H, 2.35; F, 37.85; N, 5.57. Found: C, 47.46;
H, 2.49; F, 38.10; N, 5.70.
(CDC13): d
62.4 (CHO). GC–MS: m/z (Irel): 376 [M]+ (1), 358
[MÀF+H]+ (100), 195 [C6F5C(O)]+ (15).
Acknowledgements
This work was supported by Russian Foundation for Basic
Research (Project 06-03-32820) and Russian Academy of Sciences
(Grant P-8).
4.4.4. 3-Hydroxy-2-methyl-3-pentafluorphenylbutyric acid methyl
ester (15)
(80 8C, C6H6, 4 h). Yield 70%. Product 15 exists in the form of two
diastereoisomers (ratio 1:1.5), which were isolated by preparative
GLC.
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(300 MHz, CDCl3):
d 1.34 (3H, d, J = 6 Hz), 1.62 (3H, s), 3.13 (1H,
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d
À63.13 (m, 2F), À78.18 (t, 1F, J = 20.8 Hz), À84.18 (m, 2F). GC–
MS: m/z (Irel): 211 [C6F5C(CH3)OH]+ (68.0), 195 [C6F5CO]+ (65.0),
167 [C6F5]+ (19.8), 88 [CH3CH2COOCH3]+ (100), 43 [CH3CO]+ (68.0).
Anal. Calcd for C12H11F5O3: C, 48.33; H, 3.72; F, 31.86. Found: C,
47.80; H, 3.65; F, 32.80.
Diastereoisomer II: 1H NMR (300 MHz, CDCl3):
d 1.25 (3H, d,
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1513–1522.
J = 6 Hz), 1.80 (3H, s), 3.15 (1H, q, J = 14.3 Hz), 3.65 (3H, s), 3.98 (1H,
s). Anal. Calcd for C12H11F5O3: C, 48.33; H, 3.72; F, 31.86. Found: C,
48.21; H, 3.80; F, 32.59.
[9] Ch. Pooput, W.R. Dolbier, M. Medebielle, J. Org. Chem. 71 (2006) 3564–3568.
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Properties, Wiley, New York, 1995.
[13] H. Yamamoto (Ed.), Organofluorine Compounds, Chemistry and Applications,
Springer-Verlag, Berlin and Heidelberg, Germany, 2000.
[14] B.E. Smart, J. Fluor. Chem. 109 (2001) 3–11.
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A.D. Ryabov, C.P. Horwitz, T.J. Collins, J. Am. Chem. Soc. 127 (2005) 2505–2513.
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4.4.5. 3-Hydroxy-2-methyl-3-pentafluorphenylbutyronitrile (16)
(110 8C, ClC6H5, 4 h). Yield 45%, mp 54–56 8C, diastereoisomer
ratio 1.5:1. GC–MS: m/z (Irel): 211 [C6F5C(CH3)OH]+ (97.0), 195
[C6F5CO]+ (42.30), 167 [C6F5]+ (16.20), 55 [CH3CH2CN]+ (17.30), 43
[CH3CO]+ (100). Anal. Calcd for C11H8F5NO: C, 49.81; H, 3.01; F,
35.85; N, 5.28. Found: C, 50.24; H, 3.00; F, 35.47; N, 5.16.
Diastereoisomer I: 1H NMR (300 MHz, CDCl3):
d 1.40 (3H, d,
J = 7.08 Hz), 1.87 (d, 3H, J = 4.92 Hz), 3.10 (1H, s), 3.34–3.38 (1H,
m). 19F NMR (282 MHz, CDCl3):
J = 21 Hz), À82.62 (m, 2F).
d
À62.30 (m, 2F), À75.48 (t, 1F,
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Diastereoisomer II: 1H NMR (300 MHz, CDCl3):
d
1.44 (3H, d,
J = 7.05 Hz), 1.96 (d, 3H, J = 5 Hz), 3.25 (1H, s), 3.37–3.41 (1H, m);
A.B. Terent’ev, T.T. Vasil’eva, N.A. Kuzmina, E.I. Mysov, N.Yu. Kuznetsov, Yu.N.
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Russ. J. Org. Chem. 41 (2005) 1615–1617.
19F NMR (282 MHz, CDCl3):
d
À62.79 (m, 2F), À75.71 (t, 1F,
J = 21 Hz), À82.72 (m, 2F).
4.5. Reductive coupling of aldehyde 1
A solution of aldehyde 1 (1 mmol), Fe(CO)5 (2 mmol), and
HMPA (4 mmol) in benzene (1 ml) was heated at 80 8C for 4 h or
kept at room temperature for 3 days. Then the reaction mixture
was diluted with benzene, treated with diluted hydrochloric acid,
washed with water, and dried. After the solvent was evaporated,
the resulting mixture was analyzed and crystallized from benzene
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J. Gen. Chem. 63 (1993) 2267–2269.
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(Ed.), Predictive Toxicology, Marcel Dekker, New York, 2005, pp. 459–478.
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199–204.
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Chem. 65 (2000) 8123–8126.
to give D,L-1,2-di(pentafluorophenyl)-1,2-dihydroxyethane (3) in
ꢁ90% yield, mp 185 8C (185 8C lit. [25]). 1H NMR (CDC13):
d 5.38,
5.40 (2H, d, J = 6 Hz, CH), 2.50, 2.52 (2H, d, J = 6Hz, OH). GC–MS: m/
z (Irel): 197 [1/2M]+ (100). Anal. Calcd for C14H4F10O2: C, 42.6, H,
1.0, F, 48.2. Found: C, 42.94, H, 1.20, F, 46.81.
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