Friedel-Crafts Alkylation of Arenes with 2-Halogeno-2-CF3-styrenes under Superacidic Conditions. Access to Trifluoromethylated Ethanes and Ethenes

Article abstract of DOI:10.1021/acs.joc.6b00419

The formation of the corresponding benzyl cations [ArHC⁺-CH(X)CF₃] takes place under protonation of E-/Z-2-halogeno-2-CF₃ styrenes [ArCH=C(X)CF₃, X = F, Cl, Br] in superacids. The structures of these new electrophiles were studied by means of NMR and theoretical DFT calculations. According to these data, in the case of bromo derivatives, the formed cations, most probably, exist as cyclic bromonium ions; however, in the cases of chloro and fluoro derivatives, open forms are more preferable. Subsequent reaction of these benzyl cations with arenes proceeds as Friedel-Crafts alkylation to afford 1,1-diaryl-2-halo-3,3,3-trifluoropropanes [Ar(Ar′)CH-CH(X)CF₃] in high yields (up to 96%) as a mixture of two diastereomers. The prepared halogenopropanes were easily converted into the corresponding mixtures of E-/Z-trifluoromethylated diarylethenes [Ar(Ar′)C=CCF₃] (in yields up to 96%) by dehydrohalogenation with base (KOH or t-BuOK). The mechanism of elimination (E₂ and Ecb) depends on the nature of the leaving group and reaction conditions.

Full text of DOI:10.1021/acs.joc.6b00419

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Article
Friedel-Crafts Alkylation of Arenes with 2-Halogeno-2-CF3-Styrenes under
Superacidic Conditions. Access to Trifluoromethylated Ethanes and Ethenes
Maria A. Sandzhieva, Anna N. Kazakova, Irina A. Boyarskaya, Alexander Yu.
Ivanov, Valentine Georgievich Nenajdenko, and Aleksander Viktorovich Vasilyev
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00419 • Publication Date (Web): 26 May 2016
Downloaded from http://pubs.acs.org on June 4, 2016
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FriedelꢀCrafts Alkylation of Arenes with 2ꢀHalogenoꢀ2ꢀCF3ꢀStyrenes under
Superacidic Conditions. Access to Trifluoromethylated Ethanes and Ethenes
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Maria A. Sandzhieva,a Anna N. Kazakova,b Irina A. Boyarskaya,b Alexandr Yu. Ivanov,c
Valentine G. Nenajdenko,d* Aleksander V. Vasilyeva*
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aDepartment of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per., 5, Saint
Petersburg , 194021, Russia
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bDepartment of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University,
Universitetskaya nab., 7/9, Saint Petersburg , 199034, Russia
cCenter for Magnetic Resonance, Research park, St. Petersburg State University, Universitetskiy pr. 26,
Saint Petersburg, Petrodvoretz, 198504 , Russia.
dDepartment of Chemistry, Lomonosov Moscow State University, Vorobievy Gory, 1, Moscow, 119899,
Russia
Corresponding Authors
* Eꢀmail: nen@acylium.chem.msu.ru (Valentine G. Nenajdenko);
* Eꢀmails: aleksvasil@mail.ru, a.vasilyev@spbu.ru (Aleksander V. Vasilyev)
Keywords: trifluoromethyl group, alkenes, superacid, carbocation, hydroarylation, dehydrohalogenation
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Graphical abstract
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CF3
Base (KOH
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CF3
Ar'
Ar
CF3
X
Ar'
Ar
CF3
Ar
Ar
X
Ar'H
-H+
or t-BuOK)
CF3SO3H
1
2
- HX
CF3
Ar
X
up to 96%
up to 96%
X
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diastereomers
D1: 1SR, 2SR
D2: 1SR, 2RS
X = F, Cl, Br
Z- from D1
E- from D2
DFT, NMR
Abstract
The formation of the corresponding benzyl cations [ArHC+–CH(X)CF3] takes palace under protonation of
Eꢀ/Zꢀ2ꢀhalogenoꢀ2ꢀCF3 styrenes [ArCH=C(X)CF3, X = F, Cl, Br] in superacids. The structure of these
new electrophiles were studied by means of NMR and theoretical DFT calculations. Accordingly to these
data, in the case of bromo derivatives the formed cations, most probably, exist as cyclic bromonium ions,
however in the cases of chloro and fluoro derivatives open forms are more preferable. Subsequent reaction
of these benzyl cations with arenes proceeds as FriedelꢀCrafts alkylation to afford 1,1ꢀdiarylꢀ2ꢀhaloꢀ3,3,3ꢀ
trifluoropropanes [Ar(Ar')CH–CH(X)CF3] in high yields (up to 96%) as a mixture of two diastereomers.
The prepared halogenopropanes were easily converted into the corresponding mixtures of Eꢀ/Zꢀ
trifluoromethylated diarylethenes [Ar(Ar')C=CCF3] (in yields up to 96 %) by dehydrohalogenation with
base (KOH or tꢀBuOK). The mechanism of elimination (E2 and Ecb) depends on nature of leaving group
and reaction conditions.
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INTRODUCTION
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Organofluorine compounds are widely used in chemistry, biology, medicine, nanotechnology, and
material science. Trifluoromethyl substituted alkenes are intensively explored as drugs, agrochemicals,
liquid crystals, etc. (Figure 1).1
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Ph
CF3
Ph
CF3
CF3
O
O
N
NC
N
Cl
Herbicide
F
O
HN
F
Ar
Liquid crystals
Panomifen
- anticancer agent
HO
Figure 1. Some examples of practically valuable CF3ꢀalkenes.
Synthesis of CF3ꢀalkenes is an important target in organic chemistry.2 These alkenes take part in
many various transformations with nucleophiles.3 They react with aryl halides,4 organosilanes,5
organoboron6 and organolithium compounds.7 CF3ꢀalkenes participate in reactions with enamines,8
enolates,9 terminal alkynes.10 They undergo oxidative cyclization with aldehydes,11 and may be involved
in many other reactions.12 CF3ꢀAlkenes are valuable monomers and they are used in chemistry of
polymers.13 But upꢀto date, there are only two examples of participation of CF3ꢀsubstituted alkenes in
FriedelꢀCrafts process under the superacidic activation.14 Analogous reactions with CF3ꢀalkenes having
additional halogens at the C=C bond are unknown up to the moment. The presence of a halogen atom (F,
Cl, Br) in the structure of cationic intermediates may stabilize these species via the formation of cyclic
halonium cations. These halonium ions are postulated as intermediates of electrophilic reactions of
alkenes.15 The stability of halonium ions is increased from light to heavy atoms. Iodonium and
bromonium salts were isolated, but generation of fluoronium ions was shown only recently.16
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Based on our preliminary communication17 and recent publications on reactions of CF3ꢀalkynes,18
CF3COꢀalkenes,19 and CF3ꢀallyl alcohols20 in acids, we undertook special study on reactions of CF3ꢀ
styrenes bearing at the double bond additional halogen atom under superelectrophilic activation.
The main goals of this work are: a) investigation of protonation of 1ꢀarylꢀ2ꢀhalogenoꢀ3,3,3ꢀ
trifluoropropenes (2ꢀhalogenoꢀ2ꢀCF3ꢀstyrenes) in superacids CF3SO3H (triflic acid) and FSO3H
(fluorosulfonic acid); b) theoretical (DFT) and experimental spectral (NMR) study of the formed
carbocations; c) FriedelꢀCrafts alkylation of arenes and study of synthetic potential of the method. Also,
one of the key point of this study is to check a stability of C2–X (X = F, Cl, Br) bond under superacidic
conditions. Usually this kind of carbonꢀhalogen bond is easily cleaved in superacids.21
Ar'H
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CF3
2
CF3
Ar'
1
CF3
2
H+
Ar'H
-H+
1
Ar
X
Ar
Ar'H
X
Ar
X
2
Z-/E-1
A
(D1/D2)
X = F, Cl, Br
CF3
Ar X
B
Scheme 1. Protonation of 1 leading to cations A, B followed by reaction with arenes
Protonation of styrenes 1 should proceed exclusively at C2 carbon giving rise to benzyl cations A,
due to the acceptor properties of CF3 group. Cations A may exist in form of halonium ions B (Scheme 1).
These species A and B may participate in FriedelꢀCrafts alkylation of arenes affording CF3ꢀdiarylethanes
2. The reaction of “closed” cations B with arenes may proceed stereoselectively (in SN2 manner),
opposite to the reactivity of “linear” cations A, for which a higher loss of stereoselectivity may be
observed due to attack of arene nucleophile from both sides of these species. In the latter case the reaction
should be less stereoselective and the formation of diastereomeric (D1/D2) mixtures of 2 should be
observed.
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RESULTS AND DISCUSSION
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Initial 1ꢀarylꢀ2ꢀhalogenoꢀ3,3,3ꢀtrifluoropropenes 1aꢀl were obtained by reaction of aryl aldehydes
with 1,1,1ꢀtrifluoroꢀ2,2,2ꢀtrihaloethanes.2aꢀc To estimate electronic properties of reaction intermediates, we
performed DFT calculations (B3LYP) of cations A, B, derived from styrenes 1 (Table 1). Charge
distribution, contribution of atomic orbital into molecular orbital, and global electrophilicity indices ω22
were calculated. In “open form” cations A1ꢀA12 atom C1 bears a positive charge (0.02ꢀ0.12 e) and has
large LUMO contribution (25.9ꢀ48.1%) (Table 1). These data indicate a coincidence of charge and orbital
control in reactivity of this carbon, as an electrophilic center. Calculations of “closed” halonium ions B1,
B6, B8, B9 (Table 1) showed that chloro (B1) and fluoro (B9) substituted cations were extremely unstable
they corresponded to transition states (one imaginary frequency), rather than local minimums. Bromo
substituted species B6, B8 are relatively stable. Comparison of the charge on C1 for pairs of cations A1ꢀ
B1, A6ꢀB6, A8ꢀB8, A9ꢀB9 reveals that species A have a greater positive charge on this carbon than
corresponding cations B, except for the fluoroꢀsubstituted pair A9ꢀB9. Also, in ions B1, B6, B8, B9 atom
C1 gives a large contribution to LUMO (up to 50 %). Halogen atoms X (F, Cl, Br) have a greater positive
charge and LUMO coefficients in cations B than in species A. However, for all bromo derivatives
participation of halogen in cation stabilization is much more considerable than for chloro and fluoro
species according to LUMO distribution. Comparison of electrophilicity indices reveals that cations A
have higher values of ω (5.4ꢀ6.7 eV) than the corresponding halonium ions B (3.9ꢀ4.5 eV). Thus, species
A should be more reactive than B.
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Table 1. Selected characteristics of cations A1ꢀA12, B1, B6, B8, B9 (DFT calculations)
CF3
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X = Cl, R = H (a), 3-Me (b), 4-Me (c), 4-Cl (d), 4-MeO (e);
X = Br, R = H (f), 4-Cl (g), 4-MeO (h);
X = F, R = H (i), 4-Me (j), 4-Cl (k), 4-MeO (l)
X
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R
Z-/E-1a-l
CF3
CF3
X
H+
CF3
1
2
1 2
1
X = F, Cl, Br
Ar
2 X
Ar
Ar
X
A1-A12
Z-/E-1a-l
B
cation
X
R in Ar EHOMO
eV
,
ELUMO
eV
,
ω,a eV q(C1),b q(C2),b q(X)b
k(C1)
k(X)
LUMO,с %
LUMO,с %
Cl
Cl
Cl
Cl
Cl
Br
H
ꢀ8.67
ꢀ8.34
ꢀ8.63
ꢀ8.80
ꢀ5.12
ꢀ5.06
ꢀ4.91
ꢀ5.11
ꢀ4.54
ꢀ5.06
ꢀ5.07
ꢀ4.54
ꢀ5.18
ꢀ4.94
ꢀ5.16
ꢀ4.54
ꢀ4.00
ꢀ3.72
ꢀ3.56
ꢀ3.92
6.7
6.8
6.1
6.6
5.4
6.6
6.6
5.5
6.8
6.2
6.6
5.4
4.5
4.0
3.9
4.4
0.12
0.12
0.09
0.10
0.03
0.11
0.09
0.03
0.12
0.08
0.10
0.02
0.02
ꢀ0.10
ꢀ0.11
0.19
ꢀ0.32
ꢀ0.32
ꢀ0.32
ꢀ0.32
ꢀ0.31
ꢀ0.38
ꢀ0.38
ꢀ0.37
0.11
0.11
0.11
0.12
ꢀ0.24
ꢀ0.30
ꢀ0.30
0.19
0.06
0.05
0.04
0.05
0.02
0.11
0.15
0.11
ꢀ0.36
ꢀ0.36
ꢀ0.36
ꢀ0.36
0.32
0.55
0.53
ꢀ0.20
48.1
29.7
27.0
29.1
28.7
34.7
30.9
30.4
25.9
22.7
23.1
28.1
48.5
50.0
42.1
17.2
4.4
4.2
5.4
4.5
A1
A2
A3
A4
A5
A6
A7
A8
A9
A10
A11
A12
B1
3ꢀMe
4ꢀMe
4ꢀCl
4ꢀMeO ꢀ8.37
5.7
H
ꢀ8.60
ꢀ8.58
16.7
13.5
14.6
0.7
0.6
0.7
1.2
3.5
12.9
18.4
15.0
Br 4ꢀCl
Br 4ꢀMeO ꢀ8.21
F
F
F
F
Cl
Br
H
4ꢀMe
4ꢀCl
ꢀ8.73
8.68
ꢀ8.92
4ꢀMeO ꢀ8.48
H
H
ꢀ8.05
ꢀ7.94
B6
B8
B9
Br 4ꢀMeO ꢀ7.32
ꢀ7.96
F
H
aGlobal electrophilicity index ω = (EHOMO + ELUMO) 2/8(ELUMO ꢀ EHOMO); bNatural charges; cContribution of atomic
orbitals into the molecular orbital.
Calculated geometries of cations A1ꢀA12 (see SI) show that dihedral angles θ between planes
including atoms CipsoꢀAr–C1–C2–X(F, Cl, Br) are ~108ꢀ110° for chloroꢀsubstituted (X = Cl) species A1ꢀA5
and ~104ꢀ105° for bromoꢀsubstituted (X = Br) cations A6ꢀA8 (see selected examples in Figure 2). These
angles indicate that halogen atom is located above the plane including aryl ring and carbocationic center
C1, revealing that bond C2–X is almost perpendicular to this plane. This orientation of halogen X should
be the most favorable for partial positive charge delocalization from C1 to atom X. Contrary to that, in
fluoroꢀsubstituted (X = F) cations A9ꢀA12 the angle θ is ~147ꢀ153° (see SI and A9 in Figure 3). So, for
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these species fluorine X lies almost in the same plane containing aryl ring and C1 atom. That reveals the
minimal possibilities for charge delocalization from C1 to fluorine atom in A9ꢀA12. Thus, calculated
geometries of A1ꢀA12 show that halogen atom X in chloro and bromo substituted ions A1ꢀA8 may
participate in positive charge delocalization, leading to the formation of halonium cations B, that does not
take place for fluorinated species A9ꢀA12.
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103.9
107.9
A1
A6
153.7
A9
B8
Figure 2. Calculated geometries of the selected species A1, A6, A9, B8 (dihedral angle θ between planes
including atoms CipsoꢀAr–C1–C2–X(F, Cl, Br) is depicted for A1, A6, A9).
Then we undertook NMR study of protonation of styrenes 1aꢀl in the superacids CF3SO3H and
FSO3H. Accordingly to 1H NMR, no protonation occurs below ꢀ20 °C for 1aꢀl in these superacids. But at
higher temperatures between ꢀ20 and 20 °C protonation of the double bond takes place and formation of
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oligomers is observed (see below). Among all studied alkenes 1aꢀl, we succeeded to catch intermediate
cation only in the case of methoxyphenyl substituted alkene 1h, which gave protonated species in FSO3H
at 0 °C (see Figure 3, and other spectral data in Experimental section and SI). The assignment of signals in
proton and carbon spectra of this species was done based on 1H–13C HSQC spectrum (see SI).
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meta- H
Hortho-
3
CF3
2
FSO3H
CH2Cl2
ipso-
MeO
CH CH
1
C1H
para-
Br
meta-H
Hortho-
A8
OMe
C2H
2Hmeta-
Hortho- Hortho-
ppm
ppm
ppm
3 CF3
1 HC2
Br
C
3
CF3
CF3
2
2
1
MeO
CH CH
MeO
CH CH
MeO
1
Br
H
Br
A8'
A8
B8
Figure 3.1H NMR spectrum of A8 in FSO3H at 0°C (500 MHz, CH2Cl2 is added as internal standard).
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A new signal appeared in the H NMR spectrum of styrene 1h under protonation (doublet of
quartets at δ 5.81 ppm) (Figure 3). This signal corresponds to new proton attached to the carbon C2. The
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corresponding spinꢀspin interactions are detected in the signal of proton at C1 carbon in H NMR (Figure
3) and in the signal of CF3 group in 19F NMR (see Experimental section and SI). This protonated species,
most probably, may be described as cation A8 (see Scheme in Figure 3). Accordingly to 1H and 13C NMR
data, CipsoꢀAr–C1 bond has restricted rotation leading to broadening and nonequivalence of the signals of
aromatic orthoꢀ and metaꢀprotons and carbons (Figure 3, and SI), due to significant contribution of
mesomeric form A8′. One more evidence for this mesomeric form is a significant downꢀfield shift of
Cparaꢀ at 189.5 ppm in 13C NMR (Experimental section, SI), revealing a substantial positive charge
delocalization into pꢀmethoxyphenyl ring.
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But, more striking spectral behavior is shown by the position of the signal of carbocation center
13
+C1, which is very much upꢀfield shifted to 164.5 ppm in C NMR (see Experimental Section and SI).
Similar signal of other benzyl cations is usually registered in the region ~182ꢀ270 ppm (Figure 4). That
means that there is an additional structural possibility for charge delocalization in cation A8. Most
probably, this possibility may come from bromine atom resulting in the formation of halonium ion B8 (see
calculated structure in Figure 2).
OH
HO
HO
Ph
Ph
Me
OH
R
Ph
δC
SO2ClF, -60 oC) [23]
Ar
+
~196 ppm (HF-SbF5-
δC
+ ~201 ppm (FSO3H-SbF5-
SO2ClF, -80 oC) [25]
δC
+
~184-187 ppm
(TfOH, -30 oC) [24]
Ar
CF3
(or Et)
Me
Ar
Me
Ph
Et
H(or Me)
Ar'
Me
δC
+
~203-270 ppm (HF-
δC
+ ~182-207 ppm
δC
+ ~262 ppm (SbF5-
SbF5-SO2ClF, -78 oC) [27]
(TfOH, 20 oC) [18]
SO2ClF, -80 oC) [26]
Figure 4. 13C NMR chemical shifts of carbocation center of some benzyl cations ([18, 23ꢀ27]).
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Thus, NMR data on the protonation of alkene 1h in the superacid FSO3H clearly demonstrates that
the formed species A8 may exist at least in two additional mesomeric forms A8′ and B8. In other words,
the structure of protonated form of 1h may be described as a superposition of these mesomeric forms
having different contributions. And once again, nonequivalence and broadness of proton and carbon
signals in NMR spectra reflect the complex structure of this protonated species, which is hard to cauch.
As it was mentioned above, the formation of oligomers was detected on protonation of styrenes 1 in
the superacids CF3SO3H and FSO3H. We carried out preparative reactions and isolated these oligomers
obtained from compounds 1b,e,f in CF3SO3H at room temperature for 0.5 h. According to MALDIꢀMS
data (see SI) the oligomers are products of cationic polymerization, consisting of up to 14 subunits of
starting styrenes 1b,e,f.
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51
52
53
54
55
56
57
58
59
60
Then we studied FriedelꢀCrafts alkylation of arenes with styrenes 1 in CF3SO3H. Table 2 contains
data on these reactions of chloro 1aꢀe, bromo 1fꢀh, and fluoro 1iꢀl substituted styrenes. The reaction leads
to products of hydroarylation of double bond, 1,1ꢀdiarylꢀ2ꢀhalogenoꢀ3,3,3ꢀtrifluoropropanes Zꢀ/Eꢀ2. It
should be noted that no reaction is observed in trifluoroacetic acid CF3CO2H, which is too weak to
protonate such deactivated carbonꢀcarbon double bond in 1. Methoxyphenyl substituted compounds 1e,h,l
were protonated in sulfuric acid, they even interacted with benzene, but gave reaction products in much
lower yields, compared to CF3SO3H.
Various arenes may be involved in the reaction with alkenes 1 in CF3SO3H: benzene, toluene
(methylbenzene), isomeric xylenes (dimethylbenzenes), pseudocumene (1,2,4ꢀtrimethylbenzene), anisole
(methoxybenzene), veratrole (1,2ꢀdimethoxybenzene), and such deactivated arene as 1,2ꢀdichlorobenzene
(Table 2). This reaction affords the target CF3ꢀpropanes 2 in good yields. The reaction was very
regioselective relatively to aromatic substrates. Thus, the carbocation formed attacked only the paraꢀ
position of the substituted arenes (see reactions with toluene, oꢀxylene, anisole, and veratrol in Table 2).
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Table 2. Hydroarylation of Styrenes 1 in CF3SO3H, and Dehydrohalogenation of 2
CF3
X
Ar'
CF
X
Ar'
CF3
Ar'H, CF3SO3H
3 KOH or tBuOK
2
3
1
R
R
R
Ar′Ha
Ar′ for 2, 3
Entry
Z/Eꢀratio
for 1
X
R in Ar
D1/D2 for 2
and Z/E for 3
–
2
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(yield, %) (yield, %)
1
2
3
4
5
6
1a (83 : 17) Cl
1a (83 : 17) Cl
1a (83 : 17) Cl
1a (83 : 17) Cl
1a (83 : 17) Cl
1a (83 : 17) Cl
H
H
H
H
H
H
benzene b
toluene c
oꢀxylene c
mꢀxylene c
pꢀxylene c
Ph
2a (86)
2b (91)
2c (91)
2d (66)
2e (89)
3a (89)
3b (72)
3c (87)
3d (85)
3e (79)
4ꢀMeC6H4
37 : 63
53 : 47
29 : 71
67: 33
3,4ꢀMe2C6H3
2,4ꢀMe2C6H3
2,5ꢀMe2C6H3
pseudocumene c
2,4,5ꢀMe3C6H2
2,3,5ꢀ Me3C6H2
2f (73)
2g (14)
3f (74)
3g (15)
53: 47
50: 50
1,2−dichlorobenzene d
7
8
1a (83 : 17) Cl
1a (83 : 17) Cl
H
H
3,4ꢀCl2C6H3
4ꢀMeOC6H4
2h (22)
2i (70)
3h (89)
3i (87)
83 :17
42: 58
anisole c
9
10
1a (83 : 17) Cl
1b (83 : 17) Cl
H
3ꢀMe
veratrole d
3,4ꢀ(MeO)2C6H3
Ph
2j (43)
2k (78)
3j (86)
3k (85)
40: 60
77 : 23
benzene b
11
12
13
14
15
1c (86 : 14) Cl
1c (86 : 14) Cl
1d (75 : 25) Cl
1d (75 : 25) Cl
1d (75 : 25) Cl
4ꢀMe
4ꢀMe
4ꢀCl
4ꢀCl
4ꢀCl
benzene e
anisole e
benzene f
Ph
2b (96)
2l (66)
3b (87)
3l (81)
71 : 29
67 : 33
75 :25
63 :37
67 : 33
4ꢀMeOC6H4
Ph
2m (91)
2n (81)
2o (91)
3m (85)
3n (85)
3o (85)
anisole e
1,2−dichlorobenzene d
4ꢀMeOC6H4
3,4ꢀCl2C6H3
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
1e (91 : 9)
1e (91 : 9)
1e (91 : 9)
1f (89 : 11)
1f (89 : 11)
1f (89 : 11)
1f (89 : 11)
Cl 4ꢀMeO
Cl 4ꢀMeO
Cl 4ꢀMeO
benzene d
anisole d
veratrole d
benzene b
pꢀxylene c
anisole c
veratrole c
benzene b
anisole b
benzene d
anisolec
Ph
4ꢀMeOC6H4
3,4ꢀ(MeO)2C6H3
Ph
2i (89)
2p (89)
2q (27)
2r (88)
2s (67)
2t (95)
3i (94)
3p (91)
3q (96)
3a (89)
3e (68)
3i (87)
3a (90)
3m (95)
3n (95)
3i (87)
3p (81)
3q (96)
3a (90)
3b (88)
3m (92)
3n (82)
3i (93)
3p (89)
3q (92)
83 : 17
–
52 : 48
–
Br
Br
Br
Br
H
H
2,5ꢀMe2C6H3
4ꢀMeOC6H4
3,4ꢀ(MeO)2C6H3
Ph
35: 65
71 : 29
61 : 39
66 : 34
63 : 37
53 : 47
–
H
H
2u (80)
2v (76)
2w (52)
2t (54)
1g (75 : 25) Br
1g (75 : 25) Br
4ꢀCl
4ꢀCl
4ꢀMeOC6H4
Ph
1h (91 : 9)
1h (91 : 9)
1h (91 : 9)
1i (97 : 3)
1j (97 : 3)
1k (97 : 3)
1k (97 : 3)
1l (97 : 3)
1l (97 : 3)
1l (97 : 3)
Br 4ꢀMeO
Br 4ꢀMeO
Br 4ꢀMeO
4ꢀMeOC6H4
3,4ꢀ(MeO)2C6H3
Ph
2x (91)
2y (46)
2z (78)
2za (67)
2zb (92)
2zc (20)
2zd (90)
2ze (58)
2zf (28)
veratrole d
benzene b
benzene c
benzene f
anisole f
52 : 48
–
F
F
F
F
F
F
F
H
4ꢀMe
4ꢀCl
Ph
59: 41
56: 44
64 : 36
33 : 67
–
Ph
4ꢀCl
4ꢀMeOC6H4
Ph
4ꢀMeO
4ꢀMeO
4ꢀMeO
benzene d
anisole d
4ꢀMeOC6H4
veratrole e
3,4ꢀ(MeO)2C6H3
51 : 49
aMolar ratio 1 : arene 1 : 5, for benzene 1 : 17. Room temperature, 1 h. ꢀ10 °C, 3 h, with CH2Cl2 as coꢀsolvent. Room
b
c
d
temperature, 0.5 h. eꢀ10 °C, 0.5 h, with CH2Cl2 as coꢀsolvent. f60 °C, 1 h.
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The stereochemical result of the reaction is very important. This data gives us the information about
participation of a halogen X in stabilization of formed benzylic carbocations. In all cases the formation of
inseparable mixtures of two diastereomers of 2 (D1/D2) in a various ratio was observed. Moreover the
ratio of D1 and D2 differs from the Z/Eꢀratio of staring alkenes 1. These diastereomers 2 have different
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(R)ꢀ, (S)ꢀ configurations of atoms C1 and C2: D1 (1RS, 2RS) and D2 (1SR, 2RS). In all H, C, and F
NMR spectra, two sets of signals of each diastereomer 2 were detected (see SI). The exact structure of
these diastereomers can not be determined using NMR. However, we found simple way to resolve this
problem. We carried out dehydrohalogenation of compounds 2 to give alkenes 3, as inseparable mixture of
Z/Eꢀisomers, by treatment with a base (KOH or tꢀBuOK, Table 2). Alkenes 3 are structural analogs of
Panomifen, which is an antitumor drug (Figure 1). Therefore, synthesis of alkenes 3 is of significant
practical value.28
1
13
19
The Z/Eꢀratios for the alkenes 3 was the same as the D1/D2 ratios for their precursors 2 in cases of
chloro and bromo substituted derivatives. Based on these stereochemical data, one can conclude that
compounds 3 are formed from 2 in E2 elimination way. Diastereomers D1(1RS,2RS) gave Zꢀalkenes 3,
and diastereomers D2 (1SR,2RS) yielded Eꢀisomers 3, as it is presented in Scheme 2 with Newman
projections. The configuration of the Zꢀ and Eꢀisomers of 3 can be figured out by means of 1H NMR. The
signal of vinyl proton in Eꢀisomers 3 is low field shifted compared to the same signal in Zꢀisomer.18 Based
on these spectral regularity, we could elucidate the stereochemistry of Z/Eꢀalkenes 3 and, consequently,
resolve the structures of diastereomers 2, D1 and D2.
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3
4
5
H
H
F3C
Ar'
1
Ar
6
(1R, 2R)
X
7
8
9
Ar'
Ar
CF3
(Z)-3
D1
or
H
-HX
10
11
12
13
14
15
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17
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31
32
33
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35
36
37
38
CF3
H
1
Ar
Ar'
(1S, 2S)
Ar'
1
CF3
2
X
Ar' is mor preferable than Ar
Ar
X
H
2
H
F3C
Ar
D1/ D2
1
Ar'
X
or
H
(1S, 2R)
Ar
CF3
(E)-3
-HX
D2
Ar'
CF3
H
1
Ar'
Ar
(1R, 2S)
X
Scheme 2. Newman Projections of 2 and Stereochemistry of Compounds 2 and 3.
Some moments should be pointed out concerning the elimination of HX from compounds 2.
Dehydrobromination proceeded smoothly with KOH in ethanol even at room temperature. In the case of
chloro derivatives 2aꢀq, it is necessary to use KOH under reflux in ethanol to get alkenes 3aꢀq (see
Experimental section). Dehydrofluorination needs harder conditions (KOH, reflux, ethanol, 20 h). The
elimination of HF in these conditions is not stereoselective and give alkene 3 with a Z/Eꢀratio of 1:1, in
spite of the ratio of diastereomers 2 being initially not 1 : 1 (Table 3). This reveals that, due to the strong
acceptor character of the CF3 and F groups, elimination of HF from compounds 2, most probably,
proceeds in E1cb way, rather than an E2 one (contrary to substances 2 with X = Cl, Br). It was found that
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dehydrofluorination of 2zꢀzf could be done stereoselectively with tꢀBuOK in THF, yielding the alkenes 3
with Z/Eꢀratios corresponding to that of D1/D2 for 2zꢀzf.
6
7
8
9
We observed also some additional processes during this type of FriedelꢀCrafts alkylation of arenes.
In some cases the reaction can be complicated by exchange of aryl groups. Thus, the reaction of 1a with
such strong πꢀnucleophile as pꢀxylene gave at room temperature, apart from target product 2e, the
compound 2zg (entries 2, 3, Table 3). The formation of 2zg can be explained by protonation of aryl group
or protonation of C1–CAr bond under superacidic conditions followed by elimination of arene molecule
and formation of the corresponding benzyl cation reacting with excess of pꢀxylene. There are two crucial
points for such aryl exchange. These are reaction temperature and ratio of starting styrene 1 and arene.
When ratio of 1 : arene is 1 : 1, the oligomers are formed only, due to concurrent reaction of cationic
polymerization of styrenes 1 (Table 3, entry 1, and see above MALDIꢀMS data on oligomerization). In
excess of pꢀxylene (ratios of 1 : arene 1 : 5) the oligomerization of 1 is completely suppressed (Table 3,
entry 2). So, to achieve hydroarylation of alkenes 1 we used excess of arenes as it is indicated in Table 2.
Lowering reaction temperature also allows to avoid aryl group exchange (Table 3, entries 4, 5). Reactions
of alkenes 1 with good πꢀnucleophiles (xylenes, anisol, veratrol) were mainly conducted at ꢀ10 °C to avoid
formation of byproducts (see Table 2). But, pꢀmethoxyphenyl substituted alkene 1h in reaction with pꢀ
xylene gave only exchange product 2zh even at ꢀ15 °C (Scheme 3), due to more efficient substitution of pꢀ
methoxyphenyl fragment. Recently we described similar aryl exchange group process and its suppression
for hydroarylation of cinnamides in superacids.29
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19
20
21
22
23
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25
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29
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45
46
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49
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51
52
53
54
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59
60
Table 3. Exchange of Aryl Group in Reaction of 1a with pꢀXylene
Me
Me
Me
Me
CF3
Me
Me
Me
CF3
CF3
CF3SO3H
+
+
Ph
Cl
Ph
Cl
Cl
Me
Z-/E- 1a
2e
2zg
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entry
reaction condition
ratio of 1a : pꢀxylene
reaction products
time, h ratio of 2e : 2zg whole yield of 2e : 2zg , %
temperature, °C
5
6
7
8
1
2
3
1 : 1
1 : 5
1 : 5
r.t.
r.t.
r.t.
0.5
0.5
5
quantitative formation of oligomers
9 : 1
90
37
1 : 1.4
9
4
5
1 : 5
1 : 5
ꢀ10
ꢀ10
0.25
3
1 : 0
1 : 0
60
89
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11
12
13
14
15
16
17
18
19
20
21
Me
Me
CF3
Br
Me
Me
Me
CF3
CF3SO3H
-15 oC, 15 min
+
Br
Me
2zh (44%)
Z-/E- 1h
MeO
22
23
24
25
26
27
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29
30
31
32
33
34
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40
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45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ratio of 1h : p-xylene 1 : 5
Scheme 3. Aryl exchange in the reaction of 1h with pꢀxylene. Molecular structures of 2zh (ellipsoid
contours of probability levels are 50 %).
Polymethyl substituted arenes, mesitylene and durene, did not participate in the reaction with
styrene 1 due to higher steric demand of carbocations formed by protonation of 1. At room temperature
styrenes 1 under the reaction conditions in the presence of mesitylene and durene formed only oligomers.
At lower temperature (ꢀ15 °C) the generated cation A8 from 1h did not react with mesitylene, but was
transformed into alcohol 4 (Scheme 4) after quench of the reaction mixture with water (see Experimental).
Me
HO
CF3
Br
CF3
Br
CF3SO3H
-15 oC, 15 min
Me
Me
MeO
MeO
Z-/E- 1h
4 (36%)
Scheme 4. Transformation of 1h into Alcohol 4
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Summarizing this part of the study (Tables 2, 3, Schemes 3, 4), some features of this reaction should
be pointed out. The reaction is very sensitive to the halogen atom X on the C=C bond and to substituents
on the arene ring in compounds 1. All bromo substituted (X = Br) compounds 1fꢀh are easily protonated
in CF3SO3H at ꢀ10 °C and smoothly react with arenes (entries 19ꢀ27, Table 2). Substrates 1iꢀl, having
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59
60
stronger electron acceptors X = Cl, F, need room temperature or 60 °C to react with arenes (entries 1ꢀ18,
28ꢀ34, Table 2). Apart from that, alkenes 1d and 1k, with X = Cl and F, respectively, bearing an acceptor
paraꢀchlorophenyl ring, are hardly protonated in CF3SO3H. Compounds 1d and 1k react with benzene at
higher temperature of 60 °C (entries 13, 30, 31, and Table 2). Other alkenes 1 containing electron
donating substituents (Me, OMe) on aryl ring react smoothly at ꢀ10 °C or room temperature (Tables 2).
Also, it should be mentioned that C2–X (X = F, Cl, Br) bond in compounds 2 is stable under superacidic
reaction conditions, due to the electron withdrawing influence of the neighboring CF3 group, despite of
many examples of cleavage of this kind of bond in superacids.21
In many cases the hydroarylation of double bond in 1 goes very stereoselectively leading mainly to
preferable formation of one of the diastereomers D1 or D2 (see D1/D2 ratios in Table 2). The ratio of
D1/D2, most probably, strongly depends on spatial factors. Despite the absence of high stereoselectivity in
this reaction, the data on the diastereomeric ratios for compounds 2 shed light on the reactivity of cations
A and B (Scheme 1). Thus, the stereoselectivity is reduced for fluoroalkenes 1iꢀl (X = F). Starting from
alkenes 1jꢀl having Z/Eꢀ ratio 97 : 3, the reaction led to compounds 2zꢀzf with D1/D2 ratios from 33 : 67
to 64 : 36 (Table 2). In this case a loss of stereoselectivity reveals that a cyclic fluoronium ion B cannot be
formed, and the stereocontrol could come only from a cation A. For bromoꢀ (X = Br) and chloroꢀ (X = Cl)
alkenes 1 the formation of cyclic ions B is more probable.
We also tested activation of styrenes 5a,b in CF3SO3H bearing at the double bond fluorine and
CF2Cl group and the subsequent reaction with arenes (Scheme 5). Activated by donating methoxyphenyl
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group, compound 5a is easily protonated at 0 °C and give the corresponding hydroarylation products 6a,b
in reaction with benzene and anisole respectively. The key point is a stability of C–Cl bond in compounds
5a,b under the superacidic conditions at 0 °C.
9
On the other hand, deactivated C=C bond in paraꢀchloro substituted styrene 5b is not protonated in
CF3SO3H even at elevated temperature 60 °C. This styrene reacts only in a way of FriedelꢀCrafts reaction
at C–Cl bond with arenes, followed by hydrolysis of two fluorine atoms under quench with water.
Fluorinated chalcones 7a,b are formed as a result of this reaction sequence. Reaction is highly
stereoselective, leading predominantly to Zꢀisomer of 7. E/ZꢀStereochemistry of compounds 7a,b was
determined by 1H–19F NOESY correlation between the vinyl proton and orthoꢀprotons on 3ꢀaryl ring (see
SI). Such 2ꢀfluorochalcones are hardly available compounds, they are in great interest due to biological
activity of chalcone derivatives, and there are just a few published methods for their synthesis.30
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60
Ar
CF2Cl
F
CF2Cl
CF3SO3H
0 oC, 1h
ArH
(benzene
or anisole)
+
F
6a (Ar = Ph, 58 %),
6b (Ar = 4-MeOC6H4, 96 %)
MeO
MeO
Z-/E- 5a
O
Ar
CF2Cl
CF3SO3H
60 oC, 2h
ArH
(benzene
or anisole)
F
+
F
Cl
Cl
Z-/E-7a (Ar = Ph, 63 %, Z- : E- 16 : 1),
Z-7b (Ar = 4-MeOC6H4, 65 %)
Z-/E- 5b
Scheme 5. Reactions of Styrenes E-/Z-5a,b with Arenes.
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CONCLUSIONS
4
5
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9
We have shown that 2ꢀhalogenoꢀ2ꢀCF3 styrenes in FriedelꢀCrafts reaction with arenes in CF3SO3H gave
rise to 1,1ꢀdiarylꢀ2ꢀhalogenoꢀ3,3,3ꢀtrifluoro propanes. This is a simple and efficient synthetic metod for
hydroarylation of double bond of such CF3ꢀstyrenes. The intermediate cationic species of this reaction
were studied by means of NMR and DFT calculations. Dehydrohalogenation of 1,1ꢀdiarylꢀ2ꢀhalogenoꢀ
3,3,3ꢀtrifluoro propanes under mild conditions resulted in the formation of 1,1ꢀdiarylꢀ3,3,3ꢀtrifluoro
propenes.
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EXPERIMENTAL SECTION
General information
1
NMR spectra were recorded on spectrometer (at 500 MHz, at 125 MHz, and at 470 MHz for H, 13C and
1
13
19F NMR spectra respectively) and on spectrometer (at 400, 100, and 376 MHz for H, 19F and C NMR
spectra respectively) using CDCl3 as a solvent or FSO3H and CF3SO3H to generate protonated forms of
1
styrenes 1 with CH2Cl2 as internal standard. The H and 13C spectra were calibrated using the residual
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signals of nondeuterated solvent as internal reference. The F spectra are referenced through the solvent
lock (2H) signal according to IUPAC recommended secondary referencing method and the manufacturer's
protocols. 19F NMR shifts are given relatively to the signal of CFCl3 (δ 0.0 ppm). 2D NOESY and HSQC
spectra were taken. High resolution mass spectra (HRMS) were carried out at MALDIꢀMS spectrometer
with 9.4 Tesla superconducting magnet equipped with a UV laser (Nd) in the positive ion mode or at
instrument for HRMSꢀESIꢀQTOF. Chromatoꢀmassꢀspectrometry data were obtained at system with HPꢀ
5MS capillary column (30 m × 0.25 mm), thickness of the stationary phase 0.25 ꢁm. Column
chromatography was performed on silica gel 40ꢀ63 ꢁm. Purity of compounds was monitored by TLC.
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Xꢀray analysis. A suitable crystals were selected and studied on the diffractometer for Xꢀray analysis. The
crystals were kept at 100(2) K during data collection. Using Olex231 the structure was solved with the
ShelXS32 structure solution program using Direct Methods and refined with the ShelXL refinement
package using Least Squares minimization. CCDC 1452574 – (2zh) contains the supplementary
crystallographic data, which can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.htmL
or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax:
(internat.)+44ꢀ1223ꢀ336ꢀ033; Eꢀmail: deposit@ccdc.cam.ac.uk.
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DFT calculations. All computations were carried out at the DFT/HF hybrid level of theory using Becke’s
threeꢀparameter hybrid exchange functional in combination with the gradientꢀcorrected correlation
functional of Lee, Yang, and Parr (B3LYP) by using GAUSSIAN 2009 program packages.33 The
geometries optimization were performed using the 6ꢀ311+G(2d,2p) basis set (standard 6ꢀ311 basis set
added with polarization (d, p) and diffuse functions). Optimizations were performed on all degrees of
freedom and solventꢀphase optimized structures were verified as true minima with no imaginary
frequencies. The Hessian matrix was calculated analytically for the optimized structures in order to prove
the location of correct minima and to estimate the thermodynamic parameters. Solventꢀphase calculations
used the Polarizable Continuum Model (PCM).
Starting 1ꢀarylꢀ2ꢀhalogenoꢀ3,3,3ꢀtrifluoropropenes 1aꢀl and 5a,b were synthesized and characterized
previously.2aꢀc
General Procedure for Reaction of Styrenes 1aꢀl, 5a,b with Arenes in the Superacid CF3SO3H.
Synthesis of Compounds 2aꢀzf, 4, 6a,b and 7a,b.
Stryrene 1 or 5 (0.3 mmol) was added dropwise to the stirred solution of arene (17 equiv. of benzene, or 5
equiv. of other arenes) in 1 mL of CF3SO3H. The mixture was stirred at temperature and time as indicated
in Tables 3ꢀ5 (in case of reaction temperature ꢀ10 °C 0.5 mL of CH2Cl2 was added as coꢀsolvent to
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increase the solubility of arene). Then reaction mixture was quenched with 100 mL of water. The aqueous
layer was extracted with CHCl3 (3×50 ml). The combined organic phases were washed with water (1×50
mL), saturated aqueous solution of NaHCO3 (1×50 mL), and with water again (2×50 mL). The extract was
dried over Na2SO4, and concentrated under reduced pressure. The crude mixture was purified by column
chromatography with gradient elution with petroleum ether (40ꢀ70) to EtOAc. The yields and
diastereomeric ratios for of compounds 2 are given in Table 2.
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Synthesis of alkenes 3aꢀq.
General Procedure for Dehydrohalogenation of Compounds 2aꢀy in KOHꢀEtOH.
Compound 2 (0.1 mmol) was added to solution of KOH (1 mmol) in EtOH (2 mL). The reaction mixture
was stirred at r. t. or with reflux for 15 or 20 h as indicated in Tables 3ꢀ5. Then it was diluted with 100 mL
of Et2O, washed with water (3×50 mL), dried over Na2SO4, and concentrated under reduced pressure. The
crude mixture was purified by column chromatography with gradient elution with petroleum ether (40ꢀ70)
to EtOAc. The yields and Zꢀ/Eꢀratios for compounds 3 are given in Table 2.
General procedure for dehydrohalogenation of compounds 2zꢀzf in tꢀBuOKꢀTHF.
TertꢀBuOK (1.1 mmol) was added to solution of compound 2 (0.1 mmol) in THF (1mL). The reaction
mixture was stirred at r. t. (2zb) or with reflux (2z, 2za, 2zcꢀ2zf) for 2 d. Then it was diluted with 100 mL
of CH2Cl2, washed with water (3×50 mL), dried over Na2SO4 and concentrated under reduced pressure.
The crude mixture was purified by column chromatography with gradient elution with petroleum ether
(40ꢀ70) to EtOAc. The yields and Zꢀ/Eꢀratios for of compounds 3 are given in Table 2.
Compounds 3aꢀp were obtained and characterized by ourselves previously,18 except for 3c, 3f, 3q (see
their properties below).
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3,3ꢀdiphenylpropane (2a). Yield 73 mg, 86 %. Colorless oil. 1Н NMR (500 MHz,
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СDCl3) δ 7.24 − 7.34 (m, 10Н), 4.95 (dq, J = 8.2, 6.7 Hz, 1Н), 4.52 (d, J 8.2 Hz, 1Н). C NMR (125
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MHz, CDCl3) δ 53.09, 59.70 (q, J = 29.9 Hz, СHCF3), 123.99 (q, J = 278.9 Hz, CF3), 127.38, 127.42,
127.88, 128.57, 128.67, 128.77, 139.46, 139.84. 19F NMR (470 MHz, CDCl3) δ ꢀ70.48 (d, J = 6.7 Hz);
MS (GCꢀMS, EI), m/z, (Irel., %): 284 [M]+ (7), 167 (100), 152 (25); HRMS (MALDI) m/z calcd for
C15H13ClF3 [M+H]+ 285.0652, found 285.0654.
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2ꢀСhloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(4ꢀmethylphenyl)ꢀ3ꢀphenylpropane (2b). Obtained as
a
mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 81 mg, 91 %. Colorless oil. 2bꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.31 − 7.35 (m, 4H), 7.20 − 7.25 (m, 3H), 7.11 − 7.16 (m, 2H), 4.95 (dq, J =
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8.7, 6.4 Hz, 1H, CHCl), 4.49 (d, J = 8.7 Hz, 1H, CHPh), 2.31 (s, 3H). С NMR (125 MHz, CDCl3) δ
20.97 (CH3), 52.76 (CHPh), 59.77 (q, J = 29.9 Hz, CCl), 124.01 (q, J = 278.4 Hz, CF3), D1+D2: 127.28,
127.33, 127.72, 127.82, 128.52, 128.54, 128.59, 128.75, 129.28, 129.45, 136.50, 136.86, 137.08, 137.12,
139.72, 140.09. 19F NMR (470 MHz, CDCl3) δ ꢀ70.42 (d, J = 6.4 Hz, СF3). 2bꢀD2(1SR/2RS):1Н NMR
(500 MHz, СDCl3) δ 7.31 − 7.35 (m, 4H), 7.20 − 7.25 (m, 3H), 7.11 − 7.16 (m, 2H), 4.94 (dq, J = 8.7, 6.4
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Hz, 1H, CHCl), 4.50 (d, J = 8.7 Hz, 1H, CHPh), 2.33 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected
signals) 21.0 (CH3), 52.7 (CHPh), 59.8 (q, CCl, J = 29.9 Hz), 124.0 (q, J = 278.4 Hz, CF3). 19F NMR (470
MHz, CDCl3) δ ꢀ70.47 (d, J = 6.4 Hz, СF3). MS (GCꢀMS, EI), m/z, (Irel., %) D1+D2: 298 [M]+ (10), 181
(100), 165 (29), 89 (6). HRMS (MALDI) (D1+D2) m/z calcd for C16H15ClF3 [M+H]+ 299.0809, found
299.0811.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(2,4ꢀdimethylphenyl)ꢀ3ꢀphenylpropane (2c). Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 85 mg, 91 %. Colorless oil. 2cꢀD1 (1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.23 − 7.35 (m, 5Н), 7.08 − 7.11 (m, 3H), 4.92 − 4.98 (m, 1Н, СНСF3), 4.46
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(d, J = 8.8 Hz, 1Н, СНPh), 2.24 (s, 3H), 2.22 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals)
19.30, 19.85, 52.82 (CHPh), 59.83 (q, J = 29.7 Hz, CHCF3), 124.04 (q, J = 278.8Hz, СF3); D1+D2: 125.1,
125.6, 127.2, 127.3, 127.8, 128.5, 128.6, 128.7, 129.1, 129.8, 129.9, 129.9, 135.7, 135.8, 136.8, 136.9,
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137.0, 137.3, 139.8, 140.2. 19F NMR (470 MHz, CDCl3) δ ꢀ70.41 (d, J = 6.4 Hz). 2cꢀD2(1SR/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.23 − 7.35 (m, 5Н), 7.08 − 7.11 (m, 3H), 4.92 − 4.98 (m, 1Н, СНСF3), 4.44
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(d, 1Н, J = 8.8 Hz, СНPh), 2.26 (s, 3H), 2.24 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals)
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19.3 (CH3), 19.9 (CH3), 53.0 (CHPh), 59.7 (q, J = 29.7 Hz, CHCF3), 124.0 (q, J = 278.8Hz, СF3). F
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NMR (470 MHz, CDCl3) δ ꢀ70.39 (d, J = 6.4 Hz). HRMS (MALDI) (D1+D2) m/z calcd for C17H17ClF3
[M+H]+ 313.0966, found 313.0968.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(2,4ꢀdimethylphenyl)ꢀ3ꢀphenylpropane (2d).Obtained as
a
mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 62 mg, 66 %. Colorless oil. 2dꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.31 − 7.35 (m, 4Н), 6.88 − 6.96 (m, 4H), 4.92 − 4.98 (m, 1Н, СНСF3), 4.45
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(d, J = 9.5 Hz, 1Н, СНPh), 2.32 (s, 3H), 2.29 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals)
21.33, 52.94 (СHAr2), 59.83 (q, J = 29.9 Hz, СHCF3,), 124.05 (q, J = 278.8 Hz, СF3), D1+D2: 125.61,
126.2, 127.3, 127.3, 127.9, 128.5, 128.6, 128.7, 129.0, 129.1, 138.0, 138.1, 138.2, 139.5, 139.7, 139.7,
140.0. 19F NMR (470 MHz, CDCl3) δ ꢀ70.58 (d, J = 6.9 Hz). 2dꢀD2(1SR/2RS):1Н NMR (500 MHz,
СDCl3) δ 7.31 − 7.35 (m, 4Н), 6.88 − 6.96 (m, 4H), 4.92 − 4.98 (m, 1Н, СНСF3), 4.42 (d, J = 9.5 Hz, 1Н,
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СНPh), 2.32 s (3H, CH3). С NMR (125 MHz, CDCl3) δ (selected signals) 21.4 (CH3), 53.4 (СHAr2),
59.7 (q, J = 29.9 Hz, СHCF3), 124.0 (q, J = 278.8 Hz, СF3). 19F NMR (470 MHz, CDCl3) δ ꢀ70.34 (d, J =
6.9 Hz). HRMS (MALDI) (D1+D2) m/z calcd for C17H17ClF3 [M+H]+ 313.0966, found 313.0960.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(2,5ꢀdimethylphenyl)ꢀ3ꢀphenylpropane (2e). Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 83 mg, 89 %. Colorless oil. 2eꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.22 − 7.33 (m, 5Н), 6.96 − 7.05 (m, 2H), 4.96 (dq, J =9.6, 5.8 Hz, 1Н), 4.69
(d, J = 9.6 Hz, 1Н), 2.40 (s, 3H), 2.32 (s, 3H). 13С NMR (125 MHz, CDCl3) δ (selected signals) 19.4
(CH3), 21.3 (CH3), 49.01 (СHAr2), 59.9 (q, J = 29.9 Hz, СHCF3), 124.1 (q, J = 278.8 Hz, СF3), D1+D2:
126.7, 127.2, 127.2, 127.4, 127.8, 127.9, 128.4, 128.6, 128.1, 130.8, 130.9, 132.4, 133.29, 135.6, 135.7,
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137.9, 138.3, 138.5, 139.1. 19F NMR (470 MHz, CDCl3) δ ꢀ69.92 (d, J = 5.8 Hz). 2eꢀD2(1SR/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.22 − 7.33 (m, 5Н), 6.96 − 7.05 (m, 2H), 4.97 (dq, J = 9.6, 5.8 Hz, 1Н,
СНСF3), 4.78 (d, J = 9.6 Hz, 1Н, СНPh), 2.40 (s, 3H), 2.34 (s, 3H). 13С NMR (125 MHz, CDCl3) δ
(selected signals) 19.4 (CH3), 21.2 (CH3), 47.7 (СHAr2), 60.1 (q, J = 29.9 Hz, СHCF3), 124.2 (q, J =
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278.8 Hz, СF3). F NMR (470 MHz, CDCl3) δ ꢀ70.95 (d, J = 5.8 Hz). HRMS (MALDI) (D1+D2) m/z
calcd for C17H17ClF3 [M+H]+ 313.0966, found 313.0965.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(2,4,5ꢀtrimethylphenyl)ꢀ3ꢀphenylpropane (2f). Obtained in mixture with
compounds 2g in ratio 2f : 2g 5.2 : 1 in a whole yield 85 mg, 87 %. Mixture of diastereomers
D1(1RS/2RS) and D2(1SR/2RS). Colorless oil. 2fꢀD1(1RS/2RS):1Н NMR (500 MHz, СDCl3) δ 7.22 − 7.31
(m, 6Н), 6.93 (m, 1H), 4.96 (m, 1Н, СНСF3), 4.74 (d, J = 9.6 Hz, 1Н, СНPh), 2.31 (s, 3H), 2.29 (s, 3H),
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2.21 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals) 19.17 (CH3), 19.21 (CH3), 19.70 (CH3),
48.78 (СHAr2), 60.10 (q, J = 29.7 Hz, СHCF3,), 124.20 (q, J = 278.8 Hz, СF3,), D1+D2: 127.1, 127.3,
127.8, 128.4, 128.5, 128.6, 129.0, 129.9, 132.3, 132.4, 132.7, 133.6, 134.2, 134.3, 135.3, 135.4, 135.5,
135.8, 138.9, 139.4. 19F NMR (470 MHz, CDCl3) δ ꢀ69.93 (d, J = 6.4 Hz). 2fꢀD2(1SR/2RS):1Н NMR (500
MHz, СDCl3) δ 7.22 − 7.31 (m, 6Н), 6.92 (m, 1H), 4.97 (m, 1Н, СНСF3), 4.65 (d, J = 9.6 Hz, 1Н, СНPh),
2.30 (s, 3H), 2.25 (s, 3H), 2.19 (s, 3H). 13С NMR (125 MHz, CDCl3) δ (selected signals) 19.1 (CH3), 19.2
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(CH3), 19.6 (CH3), 47.5 (СHAr2), 60.0 (q, J = 29.7 Hz, СHCF3), 124.2 (q, J = 278.8 Hz, СF3). F NMR
(470 MHz, CDCl3) δ ꢀ70.90 (d, J = 6.4 Hz). MS (GCꢀMS, EI), m/z, (Irel., %) D1+D2: 326 [M]+ (21), 209
(100), 194 (20), 179 (22), 165 (7). HRMS (MALDI) (D1+D2) m/z calcd for C18H19ClF3 [M+H]+
327.1122, found 327.1119.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(2,3,5ꢀtrimethylphenyl)ꢀ3ꢀphenylpropane (2g). Obtained in mixture with
compounds 2f in ratio 2f : 2g 5.2 : 1 in a whole yield 85 mg, 87 %. Mixture of diastereomers D1(1RS/2RS)
and D2(1SR/2RS). Colorless oil. 2gꢀD1(1RS/2RS):1Н NMR (500 MHz, СDCl3) δ 6.93 − 7.31 (m, 7Н),
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4.96 (m, 1Н, СНСF3), 4.87 (d, J = 9.8 Hz, 1Н, СНPh), 2.37 (s, 3H), 2.24 (s, 3H), 2.21 (s, 3H). F NMR
(470 MHz, CDCl3) δ ꢀ69.75 (d, J = 6.4 Hz). 2fꢀD2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 6.93 − 7.31
(m, 7Н), 4.97 (m, 1Н, СНСF3), 4.76 (d, J = 9.8 Hz, 1Н, СНPh), 2.37 (s, 3H), 2.24 (s, 3H), 2.21 (s, 3H).
19F NMR (470 MHz, CDCl3) δ ꢀ70.94 (d, J = 6.4 Hz). HRMS (MALDI) (D1+D2) m/z calcd for
C18H19ClF3 [M+H]+ 327.1122, found 327.1119
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2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(3,4ꢀdichlorophenyl)ꢀ3ꢀphenylpropane (2h). Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 23 mg, 22 %. Colorless oil. 2hꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.28 − 7.42 (m, 7Н), 7.15 − 7.20 (m, 1H), 4.90 (dq, J = 8.4, 6.4 Hz, 1Н,
СНСF3), 4.50 d (1Н, J = 8.4 Hz, СНPh). 19F NMR (470 MHz, CDCl3) δ ꢀ70.67 (d, J = 6.4 Hz). GСꢀMS:
m/z (Irel., %) D1+D2: 352 [M]+ (14), 235 (100), 200 (20), 179 (21), 165 (70). 2hꢀD2(1SR/2RS):1Н NMR
(500 MHz, СDCl3) δ 7.28 − 7.42 (m, 7Н), 7.15 − 7.20 (m, 1H), 4.89 (dq, J = 8.4, 6.4 Hz, 1Н), 4.46 (d, J =
8.4 Hz, 1Н), 19F NMR (470 MHz, CDCl3) δ ꢀ70.40 (d, J = 8.4 Hz). MS (GCꢀMS, EI), m/z, (Irel., %)
D1+D2: 352 [M]+ (14), 235 (100), 200 (20), 179 (21), 165 (70). HRMS (MALDI) (D1+D2) m/z calcd for
C15H11Cl3F3 [M+H]+ 352.9873, found 352.9872.
2ꢀСhloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀphenylpropane (2i). Obtained as
a
mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 66 mg, 70 %. Colorless oil. 2iꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.22 − 7.34 (m, 7Н), 6.84 (d, J = 8.7 Hz, 2H), 4.90 (dq, J =8.6, 6.0 Hz, 1Н,
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СНСF3), 4.47 (d, J = 8.6 Hz, 1Н, СНPh), 3.77 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals)
52.4 (СHPh), 55.2 (OCH3), 59.8 (q, J = 29.6 Hz, CClCF3), 114.1, 124.0 (q, J = 278.6 Hz, СF3);
D1+D2:127.2, 127.3, 127.8, 128.5, 128.6, 128.7, 128.9, 129.8, 131,4, 131.9, 139.8, 140.2, 158.8. 19F
NMR (470 MHz, CDCl3) δ ꢀ70.35 (d, J = 6.0 Hz). 2iꢀD2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.22 −
7.34 (m, 7Н), 6.87 (d, J = 8.7 Hz, 2H), 4.90 (dq, J =8.6, 6.0 Hz, 1Н, СНСF3), 4.49 (d, J = 8.6 Hz, 1Н,
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СНPh), 3.79 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals) 51.9 (СHPh), 55.2 (OCH3), 59.8
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(q, J = 29.6 Hz, CClCF3), 113.9, 124.0 (q, J = 278.6 Hz, СF3). 19F NMR (470 MHz, CDCl3) δ ꢀ70.58 (d, J
= 6.0 Hz). MS (GCꢀMS, EI), m/z, (Irel., %) D1+D2: 314 [M]+ (11), 197 (100), 165 (14), 153(13). HRMS
(MALDI) (D1+D2) m/z calcd for C16H15ClF3O [M+H]+ 315.0758, found 315.0756.
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2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(3,4ꢀdimethoxyphenyl)ꢀ3ꢀphenylpropane (2j). Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 44 mg, 43 %. Colorless oil. 2jꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.31 − 7.34 (m, 4Н), 6.78 − 6.89 (m, 3H), 4.91 (m, 1Н, СНСF3), 4.47 (d, J =
8.4 Hz, 1Н, СНPh), 3.86 (s, 3H), 3.84 (s, 3H). 13С NMR (125 MHz, CDCl3) δ (selected signals) 52.6
(СHAr2), 55.8 (OCH3), 55.9 (OCH3), 59.8 (q, CHCl, J = 29.9 Hz), 123.9 (q, СF3, J = 278.8 Hz), D1+D2:
111.1, 111.2, 111.4, 112.5, 120.1, 120.9, 127.3, 127.4, 127.8, 128.5, 129.7, 131.7, 132.3, 139.6, 140.0,
148.4, 148.8, 149.0. 19F NMR (470 MHz, CDCl3) δ ꢀ70.44 (d, J = 6.8 Hz). 2jꢀD2(1SR/2RS):1Н NMR (500
MHz, СDCl3) δ δ 7.31 − 7.34 (m, 4Н), 6.78 − 6.89 (m, 3H), 4.92 (m, 1Н, СНСF3), 4.48 (d, J = 8.4 Hz,
1Н, СНPh), 3.86 (s, 3H), 3.84 (s, 3H). 13С NMR (125 MHz, CDCl3) δ (selected signals) 52.3 (СHAr2),
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55.8 (OCH3), 55.9 (OCH3), 60.0 (q, J = 29.9 Hz, CHCl), 123.9 (q, СF3, J = 278.8 Hz). F NMR (470
MHz, CDCl3) δ ꢀ70.49 (d, J = 6.8Hz). HRMS (MALDI) (D1+D2) m/z calcd for C17H17ClF3O2 [M+H]+
345.0864, found 345.0867.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(3ꢀmethylphenyl)ꢀ3ꢀphenylpropane (2k). Obtained as
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mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 70 mg, 78 %. Colorless oil. 2kꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.06 − 7.37 (m, 9Н), 4.98 (dq, J = 8.7, 6.5 Hz, 1Н СНСF3), 4.53 (d, J = 8.7
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Hz, 1Н, СНPh), 2.36 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals) 21.0 (CH3), 52.3 (СHPh),
59.7 (q, J = 29.9 Hz, CCl), 124.0 (q, J = 278.8 Hz, CF3); (D1+D2): 124.8, 125.4, 127.3, 127.4, 127.9,
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128.1, 128.2, 128.4, 128.5, 129.6, 128.7, 129.4, 138.2, 138.4, 139.5, 139.6, 139.8, 139.9. F NMR (470
MHz, CDCl3) δ ꢀ69.95 (d, J = 6.5 Hz). MS: m/z (Irel., %): 300 [M+2]+ (4), 298 [M]+ (12), 181 (100), 165
(31), 89(7). 2kꢀD2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.06 − 7.37 (m, 9Н), 4.97 (dq, J = 8.7, 6.5
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Hz, 1Н СНСF3), 4.49 (d, J = 8.7 Hz, 1Н, СНPh), 2.34 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected
signals) 20.9 (CH3), 52.8 (СHPh), 59.7 (q, J = 29.9 Hz, CCl), 124.0 (q, J = 278.8 Hz, CF3). 19F NMR (470
MHz, CDCl3) δ ꢀ70.07 (d, J = 6.5 Hz). MS (GCꢀMS, EI), m/z, (Irel., %) D1+D2: 298 [M]+ (12), 181 (100),
165 (31), 89(7). HRMS (MALDI) (D1+D2) m/z calcd for C16H15ClF3 [M+H]+ 299.0809, found 299.0810.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀ(4ꢀmethylphenyl)propane (2l). Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 65 mg, 66 %. Colorless oil. 2lꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.11 − 7.24 (m, 6Н), 6.86 (d, J = 8.7 Hz, 2H), 4.91 (m, 1Н, СНСF3), 4.46 (d, J
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= 8.3 Hz, 1Н, СНAr), 3.79 (s, 3H), 2.31 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals) 20.1
(CH3), 51.6, 55.2, 60.1 (q, J = 29.7 Hz, СCl), D1+D2: 113.9, 114.1, 124.0 (q, J = 278.8 Hz, СF3), 127.6,
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128.3, 128.9, 129.3, 129.4, 128.8, 131.7, 132.2, 136.8, 136.9, 137.0, 137.2, 158.7. F NMR (470 MHz,
CDCl3) δ ꢀ70.52 (d, J = 6.3 Hz). GSꢀMS: m/z (Irel., %): 328.2 [M]+ (11), 211.3 (100), 165.2 (9). 2lꢀ
D2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.11 − 7.24 (m, 6Н), 6.83 (d, J = 8.7 Hz, 2H), 4.89 (m, 1Н,
СНСF3), 4.44 (d, J = 8.3 Hz, 1Н, СНAr), 3.77 (s, 3H), 2.33 (s, 3H). 13С NMR (125 MHz, CDCl3) δ
(selected signals) 21.0 (CH3), 51.9, 55.2 (OCH3), 59.9 (q, J = 29.7 Hz, СCl). 19F NMR (470 MHz, CDCl3)
δ ꢀ70.34 (d, J = 6.3 Hz). HRMS (MALDI) (D1+D2) m/z calcd for C17H17ClF3О [M+H]+ 329.0915, found
329.0912.
2ꢀChloroꢀ1ꢀ(4ꢀchlorophenyl)ꢀ3,3,3ꢀtrifluoroꢀ1ꢀphenylpropane (2m). Obtained as
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mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 87 mg, 91 %. Colorless oil. 2mꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.24 − 7.35 (m, 9Н), 4.91 (dq, J = 8.4, 6.8 Hz, 1Н, СНСF3), 4.52 (d, J = 8.4
Hz, 1Н, СНPh). 13С NMR (125 MHz, CDCl3) δ (selected signals) 52.1 (СHPh), 59.4 (q, J = 30.2 Hz,
СCl), 123.9 (q, J = 278.7 Hz, СF3). D1+D2: 127.6, 127.7, 128.5, 128.7, 128.9, 129.0, 129.2, 130.1, 133.4,
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137.8, 138.3, 138.9, 139.3. F NMR (470 MHz, CDCl3) δ ꢀ70.61 (d, J = 6.8 Hz). GSꢀMS: m/z (Irel., %):
318 [M]+ (11), 201 (100), 165 (45), 83 (5). 2mꢀD2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.24 − 7.35
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(m, 9Н), 4.91 (dq, J = 8.4, 6.8 Hz, 1Н, СНСF3), 4.50 (d, J = 8.4 Hz, 1Н, СНPh,). С NMR (125 MHz,
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CDCl3) δ (selected signals) 52.5 (СHPh), 59.4 (q, J = 30.2 Hz, СCl), 123.9 (q, J = 278.7 Hz, СF3). F
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[M+H]+ 319.0263, found 319.0260.
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2ꢀChloroꢀ 1ꢀ(4ꢀchlorophenyl)ꢀ3,3,3ꢀtrifluoroꢀ1ꢀ(4ꢀmethoxyphenyl)propane (2n). Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 85 mg, 81 %. Colorless oil. 2nꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.18 − 7.31 (m, 6Н),6,84 (d, J = 8.7 Hz, 2H), 4.85 (m, 1Н, СНСF3), 4.48 (d, J
= 8.1 Hz, 1Н), 3.78 (s, 3H). 13С NMR (125 MHz, CDCl3) δ (selected signals) 51.4 (СHAr), 55.2 (OCH3),
59.6 (q, J = 30.1 Hz, СCl), D1+D2: 114.0, 114.2, 123.7 (q, J = 278.4 Hz, СF3), 128.7, 128.8, 128.9, 129.1,
129.8, 130.0, 130.8, 131.4, 133.2, 138.1, 138.7, 158.8, 158.9 (Сarom). 19F NMR (470 MHz, CDCl3) δ ꢀ
70.48 (d, J = 7.6 Hz). GSꢀMS: m/z (Irel., %): 348 [M]+ (9.5), 231 (100), 196 (8), 153(14). 2nꢀ
D2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.18 − 7.31 (m, 6Н),6,87 (d, J = 8.7 Hz, 2H), 4.86 (m, 1Н,
СНСF3), 4.47 (d, J = 8.1 Hz, 1Н), 3.79 (s, 3H). 13С NMR (125 MHz, CDCl3) (selected signals) δ 51.35
(СHAr), 55.20 (OCH3), 59.75 (q, J = 30.1 Hz, СCl). 19F NMR (470 MHz, CDCl3) δꢀ70.47 (d, J = 7.6 Hz).
HRMS (MALDI) (D1+D2) m/z calcd for C16H14Cl2F3O [M+H]+ 349.0368, found 349.0371.
2ꢀChloroꢀ1ꢀ(4ꢀchlorophenyl)ꢀ1ꢀ(3,4ꢀdichlorophenyl)ꢀ3,3,3ꢀtrifluoropropane (2o).Obtained as a mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 106 mg, 91 %. Colorless oil. 2oꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.14 − 7.43 (m, 7Н), 4.83 (m, 1Н, СНСF3), 4.47 (d, J = 7.5 Hz, 1Н, СНAr).
13С NMR (125 MHz, CDCl3) δ (selected signals) 51.3 (СHAr), 59.0 (q, J = 31.0 Hz, СCl), 123.6 (q, J =
279.0 Hz, СF3). D1+D2: 127.1, 127.7, 128.0, 128.6, 129.0, 129.1, 129.2, 130.1, 130.5, 130.6, 130.8,
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130.8, 131.2, 132.0, 132.8, 133.9, 136.5, 137.2, 138.9, 139.4 (Сarom). F NMR (470 MHz, CDCl3) δ ꢀ
66.20 (d, J = 7.5 Hz). GSꢀMS: m/z (Irel., %):386 [M]+ (13), 269 (100), 233 (15), 199 (59), 163 (10). 2oꢀ
D2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.14 − 7.43 (m, 7Н), 4.83 (m, 1Н, СНСF3), 4.47 (d, J = 7.5
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Hz, 1Н, СНAr). 13С NMR (125 MHz, CDCl3) δ (selected signals) 51.1 (СHAr), 59.0 (q, J = 31.0 Hz,
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NMR (500 MHz, СDCl3) δ 7.24 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 6.86 (d, J = 8.6 Hz), 6.83 (f,
J = 8.3 Hz), 4.86 (dq, J = 8.4, 5.9 Hz, 1Н, СНСF3), 4.45 (d, J = 8.4 Hz, 1Н, СНPh), 3.79 (s, 3H), 3.77 (s,
3H). 13С NMR (125 MHz, CDCl3) δ 51.2 (СHAr2), 55.1 (OCH3), 55.2 (OCH3), 60.2 (q, J = 29.7 Hz,
СHCF3), 113.9, 114.1, 124.9 (q, J = 278.8 Hz, СF3), 128.8, 129.7, 131.8, 132.3, 158.7. 19F NMR (470
MHz, CDCl3) δ ꢀ70.44 (d, J = 5.9 Hz). GSꢀMS: m/z (Irel., %): 344 [M]+ (7), 227 (100), 212(6), 169(6),
113(10). HRMS (MALDI) m/z calcd for C17H17ClF3O2 [M+H]+ 345.0864, found 345.0865.
2ꢀChloroꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀ(3,4ꢀdimethoxyphenyl)propane (2q).Obtained as a
mixture of diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 30 mg, 27 %. Colorless oil. 2qꢀ
D1(1RS/2RS):1Н NMR (500 MHz, СDCl3) δ 7.21 − 7.25 (m, 2Н), 6.77 − 6.90 (m, 5H), 4.85 (m, 1Н,
СНСF3), 4.45 (d, J = 8.4 Hz, 1Н, СНAr2), 3.86 (s, 3H), 3.84 (s, 3H), 3.79 (s, 3H). 13С NMR (125 MHz,
CDCl3) δ (selected signals) 51.6 (СHAr2), 55.2, 55.8, 55.9, 60.1 (q, J = 29.7 Hz, СCl), D1+D2: 111.0,
111.2, 111.3, 112.3, 113.9, 114.1, 119.9, 120.6, 124.0 (q, J = 278.8 Hz, СF3), 125.7, 128.8, 129.7, 131.5,
132.0, 132.1, 132.7, 148.2, 148.8, 149.0, 158.7. 19F NMR (470 MHz, CDCl3) δ ꢀ70.55 (d, J = 6.4 Hz). 2qꢀ
D2(1SR/2RS):1Н NMR (500 MHz, СDCl3) δ 7.21 − 7.25 (m, 2Н), 6.77 − 6.90 (m, 5H), 4.85 (m, 1Н,
СНСF3), 4.43 (d, J = 8.4 Hz, 1Н, СНAr2), 3.86 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H). 13С NMR (125 MHz,
CDCl3) δ (selected signals) 51.4 (СHAr2), 55.2, 55.8, 55.9, 60.1 (q, J = 29.7 Hz, СCl). 19F NMR (470
MHz, CDCl3) δ ꢀ70.38 (d, J = 6.4 Hz). HRMS (MALDI) m/z calcd for C18H19ClF3O3 [M+H]+ 375.0969
found 375.0973.
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2ꢀBromoꢀ1,1,1ꢀtrifluoroꢀ3,3ꢀdiphenylpropane (2r). Yield 87 mg, 88 %. Colorless oil. 1Н NMR (500 MHz,
СDCl3) δ 7.22 − 7.35 (m, 10Н), 4.98 (dq, J = 9.0, 6.6 Hz, 1Н, СНСF3), 4.54 (d, J = 9.0 Hz, 1Н, СНPh).
13С NMR (125 MHz, CDCl3) δ 50.0 (q, J = 29.0 Hz, СHCF3), 53.6 (СHPh2), 123.9 (q, J = 277.0 Hz, СF3),
127.3, 127.4, 127.8, 128.3, 128.6, 128.7, 128.8, 140.1, 140.6. 19F NMR (470 MHz, CDCl3) δ ꢀ63.27 (d, J
= 6.6 Hz). MS (GCꢀMS, EI), m/z, (Irel., %) D1+D2: 330 [M+2]+ (10), 328 [M]+ (10), 167 (100), 152 (15).
HRMS (MALDI) m/z calcd for C15H13BrF3 [M+H]+ 329.0147, found 329.0149.
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2ꢀBromoꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(2,5ꢀdimethylphenyl)ꢀ3ꢀphenylpropane (2s). Yield 72 mg, 67 %. Obtained as a
mixture of diastereomers D1(1RS/2RS) and D2(1SR/2RS). Colorless oil. 2sꢀD1(1RS/2RS):1Н NMR (400
MHz, СDCl3) δ 7.24 − 7.31 (m, 6Н), 6.92 −7.02 (m, 2H), 4.98 (m, 1Н, СНСF3), 4.71 (d, J = 9.2 Hz, 1Н,
СНPh), 2.38 (s, 3H), 2.30 (s, 3H). 13С NMR (125 MHz, CDCl3) δ (selected signals) 19.3, 21.3, 49.5
(СHPh), 50.3 (q, J = 29.2 Hz, СBr), 124.1 (q, J = 277.5 Hz, СF3). D1+D2: 126.4, 127.1, 127.2, 127.4,
127.8, 127.9, 128.4, 128.5, 128.6, 128.7, 130.8, 130.9, 132.3, 133.0, 135.6, 138.5, 138.9, 139.0, 140.1. 19F
NMR (470 MHz, CDCl3) δ ꢀ67.03 (d, J = 7.0 Hz). 2sꢀD2(1SR/2RS):1Н NMR (400 MHz, СDCl3) δ 7.24 −
7.31 (m, 6Н), 6.92 −7.02 (m, 2H), 4.97 (m, 1Н, СНСF3), 4.77 (d, J = 9.2 Hz, 1Н, СНPh), 2.33 (s, 3H),
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Hz, СBr), 124.1 (q, J = 277.5 Hz, СF3). F NMR (470 MHz, CDCl3) δ ꢀ68.08 (d, J = 7.0 Hz). HRMS
(MALDI) (D1+D2) m/z calcd for C17H17BrF3 [M+H]+ 357.0460, found 357.0462.
2ꢀBromoꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀphenylpropane (2t). Obtained as
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mixture of
diastereomers D1(1RS/2RS) and D2(1SR/2RS). Yield 102 mg, 95 %. Colorless oil. 2tꢀD1(1RS/2RS):1Н
NMR (500 MHz, СDCl3) δ 7.22 − 7.34 (m, 7Н), 6.82 (d, J = 8.7 Hz, 2H), 4.91 (dq, J = 8.9, 7.0 Hz, 1Н,
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СНСF3), 4.48 (d, J = 8.9 Hz, 1Н, СНPh), 3.76 (s, 3H). С NMR (125 MHz, CDCl3) δ (selected signals)
50.3 (q, J = 29.0 Hz, СHCF3), 52.9 (СHAr2), 55.2 (OCH3), 123.9 (q, J = 277.0 Hz, СF3) D1+D2: 113.9,
114.1, 127.2, 127.3, 127.7, 128.2, 128.5, 128.6, 128.7, 128.9, 129.6, 132.2, 132.6, 140.5, 140.9, 158.7,
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