Catalytic olefination reaction of carbonyl compounds. A study on stereoselectivity of alkene formation

Article abstract of DOI:10.1023/A:1026077309403

The mechanism of formation of alkene stereoisomers in the catalytic olefination reaction of carbonyl compounds was studied. 4-Chlorobenzaldehyde hydrazone 1 stereoselectively reacts with a number of F-, Cl-, Br-, and I-containing polyhaloalkanes in the presence of catalytic amounts of CuCl to give ω-substituted styrenes 2 with the more thermodynamically stable alkene isomer being the major product. A model for the formation of the stereoisomers of alkenes 2 in the olefination reaction is proposed. Stereoselectivity of the reaction is determined by elimination of copper(II) halides from the lowest-lying conformers of organocopper intermediates II. According to quantum-chemical calculations, the elimination should involve the staggered conformations with antiperiplanar arrangement of C-Hal and C-Cu bonds and proceed by the E2 anti-elimination mechanism. The results of quantum-chemical calculations are in good agreement with the experimental E/Z alkene isomer ratios.

Full text of DOI:10.1023/A:1026077309403

Russian Chemical Bulletin, International Edition, Vol. 52, No. 8, pp. 1835—1840, August, 2003
1835
Catalytic olefination reaction of carbonyl compounds.
A study on stereoselectivity of alkene formation
V. G. Nenaidenko,aꢀ V. N. Korotchenko,a A. V. Shastin,b D. A. Tyurin,a and E. S. Balenkovaa
aDepartment of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 932 8846. Eꢀmail: nen@acylium.chem.msu.ru
bInstitute of Problems of Chemical Physics, Russian Academy of Sciences,
142432 Chernogolovka, Moscow Region, Russian Federation.
Eꢀmail: shastin@icp.ac.ru
The mechanism of formation of alkene stereoisomers in the catalytic olefination reaction
of carbonyl compounds was studied. 4ꢀChlorobenzaldehyde hydrazone 1 stereoselectively
reacts with a number of Fꢀ, Clꢀ, Brꢀ, and Iꢀcontaining polyhaloalkanes in the presence of
catalytic amounts of CuCl to give ωꢀsubstituted styrenes 2 with the more thermodynamically
stable alkene isomer being the major product. A model for the formation of the stereoisomers of
alkenes 2 in the olefination reaction is proposed. Stereoselectivity of the reaction is determined
by elimination of copper(II) halides from the lowestꢀlying conformers of organocopper interꢀ
mediates II. According to quantumꢀchemical calculations, the elimination should involve the
staggered conformations with antiperiplanar arrangement of C—Hal and C—Cu bonds and
proceed by the E2 antiꢀelimination mechanism. The results of quantumꢀchemical calculations
are in good agreement with the experimental E/Z alkene isomer ratios.
Key words: catalysis, copper salts, carbonyl compounds, hydrazones, carbenes, alkenes,
olefination, elimination, stereoselectivity.
Recently,1—4 we have reported on a new catalytic
olefination reaction (COR) of carbonyl compounds. It
was shown that Nꢀunsubstituted hydrazones of aromatic
aldehydes and ketones treated with polyhaloalkanes in
the presence of catalytic amounts of CuCl are transformed
into corresponding substituted alkenes. Stereoselective
formation of the double carbon—carbon bond, resulting
in the more thermodynamically stable alkene isomer as
the major product was also observed. In this work we
elucidate factors responsible for stereoselectivity of alkene
formation.
Polyhaloalkanes were taken in a fiveꢀfold excess with reꢀ
spect to hydrazone 1, which reacts with these compounds
to give a mixture of Eꢀ and Zꢀisomers of alkenes 2a—f
(Scheme 1).
Scheme 1
4ꢀChlorobenzaldehyde hydrazone (1) was chosen as
the model compound for studying stereoselectivity of the
COR. The olefinating agents were polyhaloalkanes of difꢀ
ferent nature, namely, chloroform (CHCl3); bromoꢀ
dichloromethane (CHBrCl2); bromoform (CHBr3);
iodoform (CHI3); trichlorofluoromethane (CCl3F);
1,1,1ꢀtrichloroꢀ2,2,2ꢀtrifluoroethane (CCl3CF3); and
1,1,2ꢀtrichloroꢀ1,2,2ꢀtrifluoroethane (CCl2FCClF2). Reꢀ
actions of hydrazone 1 with polyhaloalkanes were studied
using two systems: (1) DMSO (solvent)—aqueous amꢀ
monia (base) and (2) ethanol—1,2ꢀethylenediamine. Earꢀ
lier,1,2 these reaction systems were shown to provide optiꢀ
mum conditions for olefination. The reactions were carꢀ
ried out in the presence of catalyst (CuCl, 10 mol.%).
a
b
c
d
e
f
X
Y
H
Cl
H
Br
H
I
F
Cl
Cl
CF3
F
CClF2
Hal = Br, Cl
No target βꢀchlorostyrene was obtained in the reacꢀ
tion of CHCl3 with hydrazone 1. This is apparently due to
very low reactivity of CHCl3 in the olefination reaction.
Treatment of hydrazone 1 with other haloforms results in
the corresponding βꢀhalostyrenes 2a—c. The reactions in
DMSO are characterized by higher yields. For instance.
the reaction of hydrazone 1 with CHBrCl2 results in
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1740—1745, August, 2003.
1066ꢀ5285/03/5208ꢀ1835 $25.00 © 2003 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Nenaidenko et al.
βꢀchlorostyrene 2a while the reactions with CHBr3 and
CHI3 result in βꢀbromostyrene 2b and βꢀiodostyrene 2c,
respectively. It is quite unexꢀ
pected that stereoselectivity of
the formation of haloalkenes
in system 1 reduces as follows:
2a > 2b > 2c (Table 1), whereas
the reverse order should be exꢀ
a very strong and ambiguous effect on stereoselectivity of
the Wittig reaction involving αꢀhaloylides, resulting in
vinyl halides.6—8
Earlier,2,4 we have proposed a catalytic cycle, which
describes the mechanism of alkene formation upon treatꢀ
ing hydrazones of carbonyl compounds with polyhaloꢀ
alkanes. The key reaction stage involves a copper—carbene
complex I generated in the oxidation of hydrazone
(Scheme 2). Similar copper—carbene complexes are conꢀ
ventional intermediates of carbene transfer reactions cataꢀ
lyzed by copper compounds.9 Subsequent reactions of
complex I with polyhaloalkanes results in the target
alkenes.
pected from consideration of
X = Cl (a), Br (b), I (c).
steric factors (volumes of haloꢀ
gen atoms at the double bond).5
System 2 was found to provide optimum conditions
for the reactions with freons, resulting in the correspondꢀ
ing fluorineꢀcontaining alkenes 2d—f.
Scheme 2
The nature of the solvent and the base has a strong
effect on both the yields of the target alkenes 2a—f and
the ratio of the isomeric products (see Table 1). However,
this influence is ambiguous. For instance, treatment of
hydrazone 1 with bromoform enhances the reaction
stereoselectivity on going from DMSO to ethanol, whereas
the formation of alkene 2e in the reaction of the model
compound with CCl3CF3, becomes a less stereoselective
process. The E/Z ratios obtained for the reactions with
CHBrCl2, CHI3, and freon CCl2FCClF2 are nearly indeꢀ
pendent of the reaction medium. Probably, this variety of
effects is due to different solvation of reaction intermediꢀ
ates and to the influence of the ligand environment of the
catalyst. In particular, the solvent nature is known to have
Ar = 4ꢀClC6H4; L = NH3, en, solv, Hal–.
However, the scheme proposed gives no explanation
for the preferred formation of a particular alkene stereoiꢀ
somer in a given reaction. Therefore, we placed special
emphasis on the reaction of the copper—carbene comꢀ
plex I with polyhaloalkanes assuming that it involves copꢀ
per insertion into the carbon—halogen bond with the forꢀ
mation of an organocopper compound II (Scheme 3).
Analogous copper10,11 or nickel12 insertions into the carꢀ
bon—halogen bond are assumed to be the key stages of
Table 1. Parameters of reactions of hydrazone 1 with polyhaloalkanes
Reagent
DMSO—ammonia
Ethanol—ethylenediamine
∆E a
/kcal mol–1
E : Z a
Yield of 2 (%)
E : Z b
Yield of 2 (%)
E : Z b
CHCl3
CHBrCl2
CHBr3
CHI3
CFCl3
0
44
67
40
Traces
63
—
0
—
—
—
93 : 7
86 : 14
81 : 19
—
12 : 88
14 : 86
32
30
11
58
64
49
91 : 9
95 : 5
80 : 20
77 : 23
22 : 78
13 : 87
0.71
0.67
—
0.70
1.89
1.21
77 : 23
71 : 29
—
77 : 23
4 : 96
11 : 89
CCl3CF3
CCl2FCClF2
20
a Calculated.
b According to 1H NMR spectroscopy data.

Catalytic olefination of carbonyl compounds
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1837
transitionꢀmetal catalyzed addition of polyhaloalkanes to
olefins resulting in 1 : 1 adducts. Copper insertions into
the carbon—halogen bond of alkyl halides and allyl haꢀ
lides in the reactions with copper—isonitrile complexes
producing intermediates of the type II are also known.
Subsequent βꢀelimination of the CuII salt gives alkene 2.
It should be noted that elimination of halogen atoms from
the polyhalo compound occurs chemoselectively. Reꢀ
cently,13 we have shown that if the reactant molecule
contains several types of halogen atoms, the process alꢀ
most exclusively involves cleavage of the weakest carꢀ
bon—halogen bond with the heavier halogen atom.
It was reasonable to assume that stereochemistry of
alkene formation should be consistent with the laws of
bimolecular elimination reaction, E2. To confirm the apꢀ
plicability of our model to the observed stereoselectivity
of the reaction, we carried out quantumꢀchemical calcuꢀ
lations of the conformational energies17—22 of intermediꢀ
ates of the type II (Fig. 1 and 2).
The molecule of intermediate II can adopt several
conformations; in this case elimination of CuII salt from
different conformers can result in different isomers of
alkene 2. Our model assumes that intermediate organoꢀ
copper compounds II are rather stable and can reach a
thermodynamic conformational equilibrium and that
elimination itself occurs from the lowestꢀlying conformer.
In this case the alkene isomer ratio is determined by the
relative energies of conformers II. An analogous approach
was also applied to elimination from isomeric 2,3ꢀdiꢀ
bromobutanes.23 According to our calculations (see
Fig. 1), the energy difference between the eclipsed and
staggered conformations of intermediates II is rather large
(6—8 kcal mol–1). This allowed us to assume that elimiꢀ
nation of copper(II) halides should occur in the stagꢀ
gered conformers with antiperiplanar arrangement of
the carbon—halogen and carbon—copper bonds by the
antiꢀelimination mechanism E2. Conformational energy
minima (see Fig. 1 and 2) correspond to the staggered
conformations from which elimination of copper halides
does occur to give the olefination products. We believe
that the activation energy for elimination of copper(II)
halides should be the same for different conformers, since
the corresponding transition states of antiꢀelimination are
structurally similar.
At equal rates of elimination of copper(II) chloride
from the intermediate organocopper compound, the ratio
of alkene isomers and the reaction stereoselectivity should
be determined by the energy difference between two
antiperiplanar conformers of intermediates of the type II,
which correspond to minima on the conformational curves
and give two alkene isomers. Using the energy difference
between the minima on conformational curves, we calcuꢀ
lated the theoretical ratios of alkene isomers 2 (see Table 1)
assuming that conformers of the type II are in thermodyꢀ
namic equilibrium. The formula for calculations was as
follows: K = exp[–∆E/(RT )], where ∆E is the energy
difference between the corresponding minima on the conꢀ
formational curves and K is the ratio of conformers. Comꢀ
parison shows that the calculated and experimental isoꢀ
mer ratios are in good agreement. For instance, calculaꢀ
tions predict a lower stereoselectivity of the formation of
βꢀbromostyrene (2b) in the reaction with bromoform comꢀ
pared to the formation of βꢀchlorostyrene (2a), as is obꢀ
served experimentally.
Scheme 3
Ar = 4ꢀClC6H4
EC—Hal1 < EC—Hal
2
A large number of reductive coupling reactions of
polyhaloalkanes with carbonyl compounds in the presꢀ
ence of equimolar amounts of reducing agents (comꢀ
pounds of chromium14,15 and titanium16 in the lowest
oxidation states) have been reported. Here, the formation
of the double bond involves βꢀelimination of metal salts
from organometallic intermediates (Scheme 4).
Scheme 4
Calculations for the reactions involving CFCl3 and
CCl2FCClF2 give excellent agreement with the experiꢀ
mental data. Two diastereomeric intermediates of the

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Nenaidenko et al.
E/kcal mol–1
a
6
5
4
3
2
1
–140
–100
–60
–20
20
60
100
140
ϕ
E/kcal mol–1
b
7
6
5
4
3
2
1
–140
–100
–60
–20
20
60
100
140
ϕ
E/kcal mol–1
c
5
4
3
2
1
–140
–100
–60
–20
20
60
100
140
ϕ
Fig. 1. Conformational energies (E) of intermediates of the type II plotted vs. dihedral angle ϕ for the reactions with
bromodichloromethane (a), bromoform (b), and trichlorofluoromethane (c); ϕ is the angle Ar—C—C—Cl (a, c) or Ar—C—C—Br (b).

Catalytic olefination of carbonyl compounds
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
1839
E/kcal mol–1
a
7
6
5
4
3
2
1
–140
–100
–60
–20
20
60
100
140
ϕ
E/kcal mol–1
b
9
8
7
6
5
4
3
2
1
–140
–100
–60
–20
20
60
100
140
ϕ
Fig. 2. Conformational energies (E) of intermediates of the type II plotted vs. dihedral angle ϕ for the reactions with 1,1,1ꢀtrichloroꢀ
2,2,2ꢀtrifluoroethane (a) and 1,1,2ꢀtrichloroꢀ1,2,2ꢀtrifluoroethane (two diastereomers) (b); ϕ is the angle Ar—C—C—Cl.
type II can be formed in the latter case and each of them
is characterized by one conformational energy miniꢀ
mum corresponding to elimination of CuCl2. Therefore,
the ratio of alkene isomers 2f is determined solely by
the energy difference between the diastereomers. The
largest difference between the predicted isomer ratio and
the experimental data was found for the reaction with
CCl3CF3. Here, calculations predict a higher stereoꢀ
selectivity of the formation of alkene 2e compared
to that observed experimentally. This is likely due to
some limitations of our computational model, which igꢀ
nores the effect of different solvation of the initial comꢀ
pounds, intermediates, and the ligand environment of the
catalyst. In particular, freon CCl3CF3 contains a hydroꢀ
phobic trifluoromethyl group, which should have a draꢀ
matic effect on the behavior of this compound in the
reaction.
Thus, we analyzed the factors responsible for stereoꢀ
selectivity of alkene formation in the catalytic olefination
reaction. Our quantumꢀchemical calculations confirmed
the assumption of the formation of intermediates II folꢀ
lowed by transꢀelimination of CuII compounds. By and
large, conformational energy calculations allow a reasonꢀ
ably correct prediction of the ratio of alkene isomers 2a—f.
This enables us to conclude that the model proposed in
this work can be used to describe the reactions of carbene
complex I with polyhaloalkanes and subsequent alkene
formation. The results obtained give a better insight into
the mechanism of the COR and the nature of the accomꢀ
panying processes.

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Nenaidenko et al.
Experimental
This work was carried out with the financial support of
the Russian Foundation for Basic Research (Project Nos.
03ꢀ03ꢀ32052a and 03ꢀ03ꢀ32024a).
In this work we employed the nonempirical generalized
gradient approximation of the exchangeꢀcorrelation funcꢀ
tional PBE 96.17,18 Calculations were carried out using the
"PRIRODA" code written by D. N. Laikov19 and extended orꢀ
bital basis sets of contracted Gaussian functions. The contraction
patterns were as follows: (5s1p):[3s1p] for H, (11s6p2d):[4s3p2d]
for C, (11s6p2d):[4s3p2d] for F, (16s12p2d):[5s4p2d] for Cl,
(17s13p8d):[6s5p3d] for Cu, and (19s16p9d):[6s5p3d] for Br.
Earlier,20—22 this computational method proved itself in calcuꢀ
lations of complex organometallic systems containing various
metal and nonmetal atoms (Cr, Ti, Zr, Si, Sb, Bi) including
systems with nonꢀclassical interactions as highly efficient techꢀ
nique. The conformational energies were calculated by scanning
the dihedral angle formed by the leaving halogen atom, the
carbon atoms of the double bond, and the carbon atom of the
aromatic ring. At each value of the dihedral angle, calculations
were carried out with full optimization of the remaining geoꢀ
metric parameters of the molecule. The vibrational frequencies
at the minima of the potential curves were calculated using
analytical expressions for the first and second derivatives.
1H NMR spectra were recorded on a Varian VXRꢀ400 specꢀ
trometer in CDCl3 with SiMe4 as internal reference. TLC was
performed on Merck 60 F254 plates while column chromatograꢀ
phy was carried out on Merck silica gel (63—200 mesh).
4ꢀChlorobenzaldehyde hydrazone 1 was synthesized following
the known procedure.1 The commercially available polyhaloꢀ
alkanes were used as received.
Reaction of hydrazone 1 with polyhaloalkanes in DMSO (genꢀ
eral procedure). To a solution of freshly prepared hydrazone 1
(309 mg, 2 mmol) in DMSO (2 mL), concentrated aqueous
ammonia (0.68 mL) and freshly purified CuCl (20 mg, 0.2 mmol,
10 mol.%) were added, followed by the addition of the correꢀ
sponding polyhaloalkane (10 mmol) in one portion. The temꢀ
perature was maintained at 20 °C. The reaction mixture was
stirred for 24 h and poured into water (200 mL). The reaction
products were extracted with methylene chloride (3×20 mL),
the combined extracts were dried over sodium sulfate, methylꢀ
ene chloride was evaporated, and the reaction products were
isolated using column chromatography (SiO2). The Eꢀ and
Zꢀalkene isomers cannot be separated by column chromatoꢀ
graphy.
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Reaction of hydrazone 1 with polyhaloalkanes in ethanol (genꢀ
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(309 mg, 2 mmol) in ethanol (20 mL), ethylenediamine
(0.67 mL, 10 mmol) and freshly purified CuCl (20 mg, 0.2 mmol,
10 mol.%) were added, followed by the addition of the correꢀ
sponding polyhaloalkane (10 mmol) in one portion. The temꢀ
perature was maintained at 20 °C. The reaction mixture was
stirred for 24 h and poured in water (500 mL). The reaction
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ene chloride was evaporated, and the reaction products were
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The spectral and physical characteristics of compounds 2a—f
are in agreement with the published data.
Received January 24, 2003;
in revised form April 8, 2003