Enantioselectivity of chiral zirconocenes as catalysts in alkene hydro-, carbo- and cycloalumination reactions

Article abstract of DOI:10.1016/j.tetasy.2010.01.001

The enantioselectivity of chiral Zr catalysts L₁L₂ZrCl₂ [L₁ = L₂ = 1-neomenthylindenyl (Ind*), 1; L₁ = Cp, L₂ = Ind* 2; L₁ = Cp, L₂ = 1-neomenthylindenyl-4,5,6,7-tetrahydroindenyl (Cp*) 3] in the hydro-, carbo- and cycloalumination of alkenes by organoaluminium compounds (OAC) (AlMe₃, AlEt₃, HAlBu₂ⁱ) has been studied. It was found that OAC exhibit the most effect on the reaction chemo- and enantioselectivity. The reaction chemo- and enantioselectivity depend on the catalyst structure and reaction conditions (solvent type, catalyst concentration, temperature) as well. It is shown that the lack of asymmetric induction in the reaction of α-methylstyrene hydroalumination by HAlBu₂ⁱ, catalyzed with complexes 1 or 3, is the result of the formation of Zr hydride complexes of different structures as reaction intermediates. MTPA was used as a derivatization reagent for the enantiomeric excess estimation and absolute configuration assignment of β-chiral alcohols obtained after the oxidation and hydrolysis of the reaction products. The applicability of MTPA for the assignment of the absolute configuration of the stereogenic centre in β-ethyl substituted primary alcohols and β-alkyl-1,4-butanediols is shown.

Full text of DOI:10.1016/j.tetasy.2010.01.001

Tetrahedron: Asymmetry 21 (2010) 299–310
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselectivity of chiral zirconocenes as catalysts in alkene hydro-,
carbo- and cycloalumination reactions
a
a
a
Lyudmila V. Parfenova a, , Tatyana V. Berestova , Tatyana V. Tyumkina , Pavel V. Kovyazin ,
*
Leonard M. Khalilov a, Richard J. Whitby b, Usein M. Dzhemilev a
a Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 450075, Ufa, Prospect Oktyabrya, 141, Russian Federation
b School of Chemistry, University of Southampton, Highfield, Southampton, Hampshire SO17 1BJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
*
The enantioselectivity of chiral Zr catalysts L1L2ZrCl2 [L1 = L2 = 1-neomenthylindenyl (Ind ), 1; L1 = Cp,
Received 14 December 2009
Accepted 11 January 2010
Available online 1 March 2010
L2 = Ind* 2; L1 = Cp, L2 = 1-neomenthylindenyl-4,5,6,7-tetrahydroindenyl (Cp*) 3] in the hydro-, carbo-
and cycloalumination of alkenes by organoaluminium compounds (OAC) (AlMe3, AlEt3, HAlBui ) has been
2
studied. It was found that OAC exhibit the most effect on the reaction chemo- and enantioselectivity. The
reaction chemo- and enantioselectivity depend on the catalyst structure and reaction conditions (solvent
type, catalyst concentration, temperature) as well. It is shown that the lack of asymmetric induction in
the reaction of
a
-methylstyrene hydroalumination by HAlBui2, catalyzed with complexes 1 or 3, is the
result of the formation of Zr hydride complexes of different structures as reaction intermediates. MTPA
was used as a derivatization reagent for the enantiomeric excess estimation and absolute configuration
assignment of b-chiral alcohols obtained after the oxidation and hydrolysis of the reaction products. The
applicability of MTPA for the assignment of the absolute configuration of the stereogenic centre in b-ethyl
substituted primary alcohols and b-alkyl-1,4-butanediols is shown.
Ó 2010 Elsevier Ltd. All rights reserved.
A more promising approach is to modify the cyclopentadienyl
ligand in the zirconocene complexes via the introduction of chiral
substitutes. The best results are found when the cyclopentadienes
are non-symmetrically substituted so that the chiral substituent
may induce planar chirality on complexation to the zirconium. Thus,
1. Introduction
Catalytic systems using early transition metal complexes have
been developed for the hydro-, carbo- and cyclometallation reac-
tions of unsaturated hydrocarbons by organomagnesium and orga-
noaluminium compounds.1 These reactions have a high synthetic
potential, since they provide a wide variety of important mono-
mers for organic and organometallic chemistry, which may be
readily further elaborated upon. The application of chiral zircono-
cene catalysts in the reactions provides enantioselective methods
for alkene functionalization, but so far only a few complexes have
been investigated and enantioinductions are generally modest.2
The Brintzinger complexes 4a,b3 containing a chiral ethylene-
bis(tetrahydroindenyl)zirconocene moiety give good results for
the alkylmagnesiation of cis-alkenes with an allylic leaving group,
but the products lack the organometallic functionality needed for
further elaboration and the catalyst requires resolution.2,4
some C1- and C2-symmetric chiral Zr
p-complexes which exhibit
enantioselectivity in the carbo- or cycloalumination of alkenes are
known. Good results for the enantioselective carboalumination5
were obtained in the reaction of alkenes with AlMe3 in chlorine-con-
taining solvents, catalyzed with 8 mol % of bis-(1-neomenthylinde-
nyl) zirconium dichloride 1.6 The oxidation and hydrolysis of the
reaction media gave optically active 2-methyl-alkan-1-ols of 65–
85% ee enriched with (R)-enantiomers.
1. AlMe3, 8 mol% [1]
2. O2, H3O+
*
OH
R
R
65-85% ee
It was shown that reaction enantioselectivity significantly
depends on the catalyst structure. Thus, the reaction of 1-octene with
AlMe3 in the presence of 8 mol % of bis-(1-neoisomenthylindenyl)zir-
conium dichloride, bis(1-neoisomenthyl-4,5,6,7-tetrahydroindenyl)
zirconium dichloride, (R,R)-ethylenebis(4,5,6,7-tetrahydro-1-inde-
nyl)zirconium dichloride 4a, and (R,R)-ethylenebis(4,5,6,7-tetrahy-
dro-1-indenyl)zirconium-(R)-l0,l00-bi-2-naphtholate 4b provided
2-methyl-1-octanol of 50% ee (S), 6% ee (S), 8% ee (R), and 6% ee (R),
respectively.5
RMgCl, [(EBHTI)ZrX2]
R'
ZrX2
X = Cl, BINOL
O
HO
90-99%ee
(4a,b)
* Corresponding author.
E-mail address: luda_parfenova@mail.ru (L.V. Parfenova).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.001

300
L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
The addition of water or MAO to the reaction of AlMe3 with al-
kenes, catalyzed with complex 1, increases the rate of the process;
however, the reaction enantioselectivity remains at the same
level.7
1. 5% [Ti]
2. O2, H3O+
OH
OH
Si
[Ti] =
TiCl2
*
R
+ 2 Et-AlEt2
R
N
hexane
H3C
1. AlMe3 (4eq), 5 mol% [1]
H2O (1eq) or MAO
2. O2, H3O+
19-28%ee
H
*
OH
R
R
CH2Cl2, 12 h, -20-0 ºC
In addition to the C2-symmetrical catalysts, Zr complexes of C1-
symmetry were also synthesized, for example, cyclopentadienyl
(1-neomenthyl-4,5,6,7-tetrahydroindenyl) zirconium dichloride
3,14a,b where the planar chirality of a bound indenyl ligand is in-
duced from a neomenthyl substituent. An enantioinduction of
81–90% ee was obtained in the ethylalumination reaction of 2,5-
dihydrofurans. The cycloalumination of allylbenzene, catalyzed
with complex 3, as well as in the case of catalyst 1, proceeds with
an enantioselectivity of 30% ee.14c
55-90% ee
The asymmetric carboalumination of terminal alkenes in the
presence of bis(1-neomenthylindenyl)zirconium dimethyl acti-
vated by B(C6F5)3 in toluene at 0 °C gave the (R)-enantiomer of
the methylalumination product with 53–66% ee.8
The use of ethylenebisindenyl- or dimethylsilylbisindenyl-
substituted Zr catalysts for methylalumination of allylbenzene
gave products of 25–33% ee, although the [(S,S)-(EBI)Zr(l-
Me)2AlMe2][B(C6F6)4] catalyzed the reaction with styrene in
AlEt3, [3]
O2, H3O+
80% ee.9
OH
OH
AlEt
The methods described have been employed for the asym-
metric synthesis of various bioactive and natural product
compounds.10
Ph
H
30% ee
H
Ph
H
Ph
O2, H3O+
AlEt3, [3]
+
H
H
The carboalumination of terminal alkenes by AlEt3 in chlorine-
containing solvents in the presence of 8 mol % of 1, followed by
oxidative hydrolysis provides the corresponding (R)-alcohols with
enantiomeric excesses of 67–96%.11 The reaction enantioselectivity
depends on the type of solvent and reaction temperature. Thus, the
best result for terminal alkene ethylalumination of 94% ee was
achieved in the reaction of 1-hexene with AlEt3 in the presence
of 1 in CH2Cl2 at ꢀ25 °C.
OH
90% ee
AlEt
O
HO
O
OAlEt2
However there has been little research on the stereoinduc-
tion mechanism for the enantioselective reactions of trialkylal-
anes (AlMe3, AlEt3) with olefins, in the presence of chiral
zirconocene catalysts. Therefore, the study on the influence of
various factors and reaction conditions on the enantioselectivity,
the structure of catalytically active centers and the mechanism
of their action is an important task whose solution will help
to predict the stereoselectivity of known and novel chiral cata-
lytic systems.
However, 1-decene cycloalumination by a Dzhemilev reac-
tion,12 catalyzed with 1, in hexane was less stereoselective and
gave 2-octyl-1,4-diol in only 33% ee.11
Herein we report the effect of the nature of the organoaluminium
compound, the catalyst structure and reaction conditions (solvent
type, temperature, reagent ratio) on the chemo- and enantioselec-
tivity of the hydro-, carbo- and cycloalumination of terminal alkenes
n-Oct
n-Oct
[1]
Et3Al,
OH
OH
[O]
hexane
AlEt
n-Oct
65%, 33% ee
catalyzed with chiral zirconium p-complexes. As an example of chi-
[1]
Et3Al,
[O]
n-Oct
n-Oct
ral Zr complexes we selected bis-(1-neomenthylindenyl)-zirconium
dichloride 1, which shows high enantioselectivity in alkene
carboalumination; cyclopentadienyl(1-neomenthylindenyl)zirco-
nium dichloride 2 and cyclopentadienyl (1-neomenthyl-4,5,6,7-tet-
rahydroindenyl) zirconium dichloride 3. The data obtained will be
used in experimental and theoretical investigations on the stereoin-
Al
OH
Et
CH3CHCl2
H
Et
H
63%, 92% ee
Moreover, low enantioselectivities of 19–28% ee were observed
in cycloalumination of allylbenzene and styrene with AlEt3 in the
presence of the titanium complex (+)-[g5 1-indenyldimethylsi-
:g
duction mechanism of chiral Zr
with alkenes.
p-complexes in reactions of OAC
lyl(a
-methylbenzyl)amido]titanium dichloride.13
H
H
H
H
H
H
H
H
H
Zr
Zr
Zr
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
1
2
3

L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
301
would render the metal center more electron poor and hence more
reactive towards alkene insertion.
2. Results and discussion
2.1. Enantioselective carboalumination of alkenes by AlMe3,
catalyzed with 1–3
2.2. Enantioselective carbo- and cycloalumination of 1-hexene
by AlEt3 in the presence of catalysts 1–3
The reaction of terminal alkenes (1-hexene, 1-octene) with
AlMe3, catalyzed by 2–8 mol % of complexes 1–3, gives predomi-
nantly carboalumination products 5a,b. Carboalumination/elimi-
nation 6a,b, hydroalumination 7a,b and dimeric products 8a,b
were identified as minor components (Scheme 1).
The results on the study of the effect of the catalyst structure
and concentration, solvent type and temperature on the chemo-
and stereoselectivity of the reaction are presented in Table 1.
It was found that the conversion of alkenes in the reaction with
AlMe3, catalyzed with complex 1 or 3, in CH2Cl2 significantly depends
on the amount of solvent. Thus, in the absence of solvent or in a small
amount of CH2Cl2 (mol ratio alkene/AlMe3/CH2Cl2 = 5:6:8), the reac-
tion runs with minimal conversion of ꢁ5%. The alkene conversion
rises to 51–94% when 10 times the quantity of CH2Cl2 was used. How-
ever, 54–95% alkene conversion is achieved in hydrocarbon solvents
such as benzene, toluene or hexane without dilution.
The reaction of alkenes with AlMe3, catalyzed with complex 1,
proceeds with the formation of carboalumination products pre-
dominantly with an (R)-configuration at the stereogenic center,
which is consistent with the literature data.5 The enantiomeric
excess of the methylalumination reaction is about 48–69% and
depends on the catalyst concentration, solvent type (in a number
of chosen solvents) and temperature in the range of 7–40 °C. When
the reaction proceeds without solvent, it gives an enantioselectiv-
ity of 63% ee, which belongs to the above interval. Increasing the
concentration of catalyst 1 from 2 to 8 mol % in toluene causes a
significant reduction of alkene conversion from 95% to 23%.
The reaction of AlMe3 with terminal alkenes in the presence of
2 mol % of complex 2 as a dilute solution in CH2Cl2 or 8% of com-
plex 3 as concentrated solutions in CH2Cl2 or benzene for 40 h runs
with low conversion of 8–10%, and yields only 6–8% of carboalumi-
nation product 5a,b. The yield of 5a,b was increased when the
reaction was carried out in the presence of 2 mol % of catalyst 3
in a diluted solution of CH2Cl2. As a result, we obtained the meth-
ylalumination product with a predominance of the (S)-enantiomer
(41% ee). Practically the same yield of 5 was observed in the reac-
tion of 1-octene with AlMe3, catalyzed with complex 2, in toluene.
However, the enantiomeric purity of the product was poor.
Low alkene conversion in the reaction with AlMe3, catalyzed
with complexes 2 or 3, could be explained by the well known
‘indenyl effect’,16 which would be expected to greatly increase
the rate of associative reactions such as the carbometallation in
1, and to a lesser extent in 2. If insertion occurs via a zirconoceni-
um intermediate [L1L2ZrMe+], the lower electron donation from the
two indenyl ligands in 1 compared to the one and zero in 2 and 3,
The interaction of AlEt3 with 1-hexene in the presence of 2–
8 mol % of1–3runswithhighconversion of65–99%providingcarbo-
11, 13, cyclo- 12 and hydroalumination 14 products (Scheme 2).
We have studied the influence of the structure and concentra-
tion of the catalyst, the nature of solvent and temperature on the
reaction chemo- and stereoselectivity (Table 2).
As can be seen from Table 2, the OAC type, catalyst structure
and the solvent nature are all major factors which determine the
chemo- and the enantioselectivity of the reaction. Complex 1
shows the higher chemo- and stereoselectivity in comparison with
catalysts 2 and 3 in the reaction of 1-hexene with AlEt3. Thus, the
maximum yield of ethylalumination product 11 of 74–86% with an
enantiomeric excess of 59–68% ee was achieved in CH2Cl2; and
high yield of aluminacyclopentane 12 of 56–81% with enantio-
meric purity of 21–36% ee was obtained in the presence of
2 mol % of 1 in hydrocarbon solvents both at room temperature.
It is noteworthy that in aromatic solvents (benzene, toluene),
enantiomeric excesses of 4–21% ee of cycloalumination product
12 were observed, which is considerably lower than that in hexane
(36% ee). Moreover, both products 11 and 12 are formed as (S)-
enantiomers. The assignment of the absolute configuration of b-
stereogenic center in 11 and 12 was made on the basis of the spe-
cific rotations of the corresponding alcohols 15 and 16 (Table 2).
Alcohol 15 derived after oxidation and hydrolysis of carboalumina-
tion product showed positive sign for its specific rotation in all
experiments with catalyst 1. Moreover, the reaction of the alcohol
with (S)-MTPACl predominantly gave the (R,S)-diastereomer of
MTPA ester 17 (see Section 2.4). Thus, the replacement of AlMe3
with AlEt3 causes the change of the absolute configuration of the
stereogenic center in carboalumination products from (R) to (S),
correspondingly. This result contradicts the data obtained in the
literature.11
Thus, the reaction of 1-hexene with AlEt3, catalyzed with com-
plex 1, in chlorinated solvent (CH2Cl2) predominantly gives the
ethylalumination product 11, while the use of hydrocarbon sol-
vents (benzene, toluene, hexene) increases the yield of cyclic
OAC 12. These facts are consistent with the results obtained in
the literature.11,12,17 The carboalumination pathway, as in the case
of CH2Cl2, remains the major route in the absence of solvent; how-
ever, low enantiomeric excesses for both 11 (9% ee) and 12 (8% ee)
were obtained.
Catalysts 2 and 3 showed less chemo- and enantioselectivity
than complex 1 in the reaction. Thus, the reaction of 1-hexene with
AlEt3 in CH2Cl2, catalyzed with 2–8 mol % of 2, provided products
Me
Me
[1-3]
R
AlMe2
+
+
AlMe2
*
+
AlMe3
+
R
R
R
R
R
7a,b
6a,b
5a,b
R = n-Bu (a), n-Hex (b)
8a,b
O2, H3O+
Ph
Me
Me
S-MTPA-Cl
3
CF3
3
O
*
2
1
*
OH
1
R
2
R
OMe
O
9a,b
10a,b
Scheme 1.

302
L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
Table 1
25
Reaction of terminal alkenes with AlMe3, catalyzed with 1–3 (mole ratio [Zr]: alkene/AlMe3/solvent = 1–4:50:60:60–80) and specific ½aꢂD of alcohols 9a,b
L2ZrCl2
1
[Zr] (mol %)
Alkene
Solvent
Time (h)
Temp (°C)
Alkene conversion (%)
Product ratio,a (ee%,b R/S)
½ ꢂ (9a,b) (CH2Cl2)
a 2D5
5a,b
6a,b
7a,b
8a,b
2
2
2
2
2
2
2
2
2
8
8
8
8
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Octene
1-Hexene
1-Hexene
—
20
20
20
24
20
20
24
20
20
20
20
20
20
19
40
17
7
40
19
7
17
19
20
20
22
22
5
60c
82c
76c
80
95
2
99 (63,R)
97 (69,R)
86 (53,R)
91 (54,R)
84 (59,R)
96 (65,R)
99
97 (52,R)
92 (48,R)
98 (69,R)
39 (73,R)
47
—
—
2
—
2
—
—
11
1
—
—
—
—
38
26
2
—
1
12
9
5
3
—
3
8
—
CH2Cl2
CH2Cl2
CH2Cl2
C6H5CH3
C6H5CH3
C6H5CH3
C6H6
+8.2 (c 1.6)d
+6.2 (c 3.3)
+7.1 (c 5.3)
—
—
—
—
—
—
—
—
—
7
+7.6 (c 1.1)
—
61
54
56c
23
5
+6.1 (c 1.3)
+5.4 (c 0.9)
+7.3 (c 1.4)
+8.9 (c 0.9)
—
C6H14
CH2Cl2
C6H5CH3
CH2Cl2
CH2Cl2
2
23
27
5
94c
86 (69,R)
+10.3 (c 1.9)e
2
3
2
2
1-Octene
1-Octene
CH2Cl2
C6H5CH3
40
40
22
22
8c
97
99 (3,R)
—
—
2
—
1
1
—
59c
+0.1 (c 2.0)
2
8
8
1-Hexene
1-Hexene
1-Hexene
CH2Cl2
CH2Cl2
C6H6
40
40
40
22
22
22
53c
9
7
97 (41,S)
88
64
—
—
—
—
12
18
3
—
18
a
b
c
GC yield of hydrolysis products.
Determined from the (R)- -methoxy-a-trifluoromethylphenylacetate derivatives of alcohols 9a,b.
a
Mole ratio alkene:AlMe3/solvent = 50:60:800.
Lit. data for (R)-2-methyl-1-octanol: ½a D25
ꢂ
¼ þ11:2 (c 4.7, CH2Cl2).15a,c
d
e
Lit. data for (R)-2-methyl-1-hexanol: ½a D25
ꢂ
¼ þ14:2 (c 6.96, ether),15a
½
a 2D5
ꢂ
¼ þ13:6 (c 21.5, ether).15b
Et
Et
[1-3]
AlEt2
+
+
+
n-Bu
AlEt3
+
AlEt2
*
n-Bu
AlEt
*
n-Bu
n-Bu
n-Bu
14
Ph
11
12
13
CF3
O2, H3O+
O2, H3O+
OH
O
OMe
4
1
Ph
3
4
3
O
4
CF3 S-MTPA-Cl
OMe
4
3
3
S-MTPA-Cl
*
O
*
n-Bu
18
1
2
2
n-Bu
*
1
OH
*
OH
Ph
1
O
2
2
n-Bu
n-Bu
CF3
OMe
O
15
16
O
17
Scheme 2.
11 and 12 with mole ratio 1:1, where the enantiomeric purity of 11
was 10–27% ee with a predominance of the (S)-enantiomer, and
the enantiomeric excess of 12 was 20–24% ee of (R)-isomer.
Replacing the chlorine-containing solvent with benzene increases
the yield of 12, but, simultaneously reduces its enantiomeric purity
[4% ee, (R)]. Catalyst 3 exhibited low enantioselectivity in reactions
run in CH2Cl2 both in the carboalumination pathway [ꢁ8–15% ee,
(R)] and in cycloalumination [ꢁ15% ee, (R)]. Furthermore, the use
of benzene as solvent in the reaction significantly increases the
enantiomeric excess of the aluminacyclopentane (R)-enantiomer
to 29% ee.
As follows from Table 2, the reaction pathway depends on the
catalyst concentration and temperature. Thus, it was shown that
increasing the concentration of 1 from 2 to 8 mol % raises the yield
of ethylalumination product 11 in CH2Cl2 and benzene. The same
behavior was found for catalyst 3 as well. The catalyst concentra-
tion and temperature had little effect on the reaction enantioselec-
tivity when it was carried out in CH2Cl2 but have a marked effect in
benzene.
As was shown previously,18 the zirconium catalysed carbo- and
cycloalumination of alkenes and alkynes using AlEt3 are complex
multistep process that proceed with the participation of a number
of Zr,Al-intermediates. The reaction stages include processes of int-
erligand exchange, b-C–H-activation and alkene coordination on
catalytically active centers. All of the reaction components (OAC,
catalyst, solvent) are important in determining the structure and
electronic nature of the catalytically active center in the Zr,Al-
intermediate, and hence the activity and enantioinductions. The
use of AlEt3 in the reactions provides the fast interligand exchange
in L2ZrCl2–AlEt3 system,19 and therefore, rapid formation of the ac-
tive Zr,Al-intermediates responsible for the carbometallation path-
way. In addition the processes of b-C–H-activation in Zr alkyl
species give the complexes which afford the cyclometallation path.
Therefore, the high conversion of alkene in the case of AlEt3 can be
achieved regardless of the catalyst type.
Earlier Erker et al.6 showed that the temperature and nature of
the solvent could effect the conformational mobility of
p-ligands in
1 and related complexes providing a mixture of rotamers with C2

L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
303
Table 2
Reaction of 1-hexene with AlEt3, catalyzed with 1–3 (mole ratio [Zr]/alkene/AlMe3 = 1–4:50:60)
a 2D5
ꢂ
15e (CH2Cl2)
½ ꢂ
a 2D5 16f (CH2Cl2)
L2ZrCl2
[Zr] (mol %)
Solvent
Time (h)
Temp (°C)
Alkene conversion (%)
Product ratio,a % (ee%, R/S)
½
11
12
13
14
1
2
2
2
2
2
2
2
2
2
8
8
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
C6H6
C6H6
C6H6
C6H5CH3
—
C6H6
3
3
12
12
3
30
22
10
0
30
22
0
10
22
22
22
22
88
99
99
90
67
99
98
88
80
99
65b
99
70 (53,S)
75 (68,S)
57 (52,S)
60 (53,S)
31 (33,S)
14 (32,S)
26 (14,S)
25
62 (9,S)
65 (55,S)
14 (8,S)
93 (59,S)
14 (5,S)
21 (5,S)
32 (7,S)
36 (5,S)
58 (4,S)
80 (21,S)
51 (11,S)
60 (10,S)
19 (8,S)
35 (7,S)
86 (36,S)
7 (3,S)
—
4
16
—
11
4
11
6
15
15
11
—
—
+0.4 (c 1.9)
+0.3 (c 0.8)
—
—
+0.3 (c 1.2)
—
—
—
+2.6 (c 0.3)
—
—
—
+1.4 (c 0.1)
—
—
—
—
—
—
—
7
—
1
—
—
—
3
12
12
5
3
20
3
+0.5 (c 0.6)
—
+3.3 (c 0.4)
+2.1 (c 0.4)
+0.9 (c 0.1)
+2.5 (c 0.2)
C6H14
CH2Cl2
—
2
2
2
8
8
CH2Cl2
CH2Cl2
C6H14
3
3
20
22
22
22
85c
99c
78
35 (27,S)
36 (10,S)
19
46 (20,R)
37 (24,R)
67 (26,R)
1
4
4
3
11
6
+1.3 (c 1.4)
—
—
ꢀ2.9 (c 2.6)
—
ꢀ3.5 (c 1.3)
3
2
2
4
8
8
2
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(CH2Cl)2
C6H6
3
3
3
3
3
3
3
22
22
22
22
22
22
22
80
41 (9,S)
36 (13,R)
68 (14,R)
72 (15,R)
73 (8,R)
30
27 (15,R)
38 (11,R)
13
—
14
6
3
2
20
8
7
14
13
—
—
—
—
—
99c,d
99c,d
99c,d
98c
83
ꢀ1.3 (c 0.9)
—
—
—
3
ꢀ1.1 (c 0.5)
—
10
11
—
—
—
60 (29,R)
27 (9,R)
ꢀ3.4 (c 0.9)
C6H6
90
42
20
ꢀ0.9 (c 1.2)
a
b
c
Determined by GC–MS of deuterolysis products.
Low conversion could be caused by the poor solubility of complex 1 in hexane.
The formation of byproducts (up to 15%) containing 7 and 9 carbon atoms was observed according to GC–MS data.
The order of reagents mixing was changed: (1) catalyst, (2) solvent and alkene, (3) AlEt3.
d
e
Lit. data for (S)-2-ethyl-1-hexanol: ½a D25
ꢂ
¼ þ3:3 (c 5.3, CHCl3),15d
½
a 2D5
ꢂ
¼ þ2:6,15g
½
a 2D5
ꢂ
¼ þ3:4 (CHCl3)15i (R)-2-Ethyl-1-hexanol: ½a 2D5
ꢂ
¼ ꢀ3:7 (neat),15a
½
a 2D5
ꢂ
¼ ꢀ3:4,15d
½
a 3D0
ꢂ
¼ ꢀ3:05,15e
½
a 2D5
ꢂ
¼ ꢀ3:4.15f
Lit. data for (S)-2-butyl-1,4-butanediol: ½a D25
ꢂ
¼ ꢀ1 (c 1.5, EtOH).15h
f
and C1-symmetry and, therefore, defining stereoselectivity of the
complexes. It seems that the reaction of Zr complex with OAC un-
der appropriate conditions (solvent and temperature) results in
one of stabilized rotamers of Zr,Al-complex, which causes high
enantioselectivity of the process, for example, carboalumination
(Scheme 3). The dependence of enantioselectivity on the OAC type,
catalyst structure and reaction conditions (solvent, temperature)
can be attributed to the various ratio of rotameric forms of a
Zr,Al-intermediates. Moreover, the dependence of the reaction ste-
reoselectivity on the temperature and catalyst concentration
proves the existence of kinetic control during the process, that is,
difference in the rate of formation, activity and lifetime of the ac-
tive intermediates responsible for the production of definite enan-
tiomers. Some results remain incomprehensible. One of them is the
comparatively equal enantioselectivities of complexes 1 and 3 in
the alkene cycloalumination, although the complexes belong to
different symmetry groups—C2 and C1, correspondingly. Another
question regards the incapability of simultaneous realization of
high enantiomeric yield in carbo- and cycloalumination reactions.
Therefore, the problem of the stereoinduction mechanism needs
the extra experimental and theoretical study.
induction. However, the enantiomeric excess obtained in both
cases was less than 1%.
In order to study the causes of low enantioselectivity in hydroa-
lumination reaction, we attempted to synthesize the hydride com-
plex CpCp*ZrH2 23 (Scheme 5). The most effective method among
the known ones3c,20 for the synthesis was found to be the hydroge-
nation of dimethyl complex CpCp*ZrMe2.20a Complex CpCp*ZrMe2
22 was synthesized in the reaction of 3 with LiMe according to the
method described in the literature.20a
The dimethyl complex obtained is stable under an argon atmo-
sphere and is readily soluble in ether, hydrocarbon and aromatic
solvents. The methyl groups bonded with Zr are inequivalent and
exhibit two different signals in the NMR spectra: at ꢀ0.10 and
ꢀ0.11 ppm in 1H, and at 34.6 and 31.6 ppm in 13C spectrum.
Hydrogenation of the dimethyl complex in hexane overnight
gave a white suspension which was poorly soluble in aromatic sol-
vents. We were expecting to form dihydride 22, but the 1H NMR
contained numerous Cp-signals in a low field together with multi-
ple signals around 4 ppm consistent with terminal hydrides. The
abundance of Cp-signals could be related with cis–trans isomerism
*
of dimer complexes [CpCp ZrH2]2, which are formed during the
reaction and exist in equilibrium with monomer.20a
2.3. Hydroalumination of
a
-methylstyrene by HAlBui2 in the
The lack of asymmetric induction in the hydroalumination reac-
tion may be due to the complex mixture of intermediate hydride
complexes, which are responsible for the olefin hydrometallation.
presence of catalysts 1 or 3
Complexes 1 and 3 were tested as catalysts in the hydroalumi-
nation reaction of prochiral alkene
-methylstyrene by HAlBu2i
a
2.4. Assignment of absolute configuration of b-chiral alcohols
(Scheme 4). We found that in the presence of 4 mol % of the cata-
lyst 3 even after a long reaction time (24 h) and elevated temper-
ature (40 °C), only 30% conversion of olefin could be achieved
9a, 15, 16 using MTPA
Many effective methods for determining the absolute configu-
ration of chiral alcohols use derivatization reagents, for example,
MPA (methoxyphenyl acetic acid), MTPA (methoxytrifluorometh-
ylphenylacetic acid) and AMA (anthrylmethoxyacetic acid), by
the means of NMR spectroscopy together with computational
(GC). Hydroalumination of a-methylstyrene in the presence of cat-
alyst 1 proceeded with a conversion of 5%. The hydroalumination
product 19 was converted into alcohol 2-phenyl-propanol-1 20
with the isolated yields of 5–15% in order to study the asymmetric

304
L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
R
R*
R*
R'
AlR3
AlR3
R*
R*
R*
AlR2
Cl
Cl
Cl
R
R*
Cl
AlR3
R
R'
(R)
A1
C2
C2
A
R'
R*
R'
R
AlR3
AlR3
Cl
Zr
R
R'
AlR2
Cl
Cl
R*
R*
R'
Cl
Cl
(S)
Cl
AlR3
R
R*
R*
R*
R*
C2
R*
B1
AlR3
C2
B
1
R'
R*
R'
AlR3
R
Cl
(R) + (S)
R*
R*
R
Cl
R3Al
R*
C1
R*
C1
R3Al
Cl
Cl
R*
R'
C
C1
R*
R
Cl
AlR3
R*
C1'
C1
Scheme 3.
1
3
2
OH
O2, H3O+
(ee<1%)
AlBu2i
(20)
4 mol% 1 or 3
HAlBui2
-15%)
(~5
+
toluene, 24 h, 40 ºC
H3O+
(19)
(~5-30%)
Scheme 4.
methods.21a Although the absolute configurations of the
compounds reported above seem secure from the reported specific
rotations, we wished to establish if theoretical calculations of
chemical shifts in MTPA esters could correctly predict the configu-
rations of alcohols 9a, 15 and 16, and thus be available for applica-
tion to systems for which there is no literature information.
Chiral alcohol 15, which was isolated in the experiments with
catalyst 1, always had a specific rotation (Table 2), whose compar-
ison with literature data15a,d,f,g,i provided the assignment of abso-
lute configuration of the b-stereogenic center as (S). The reaction
of 15 with (S)-MTPACl, gave (R)-MTPA ester 17, whose 1H NMR
spectrum exhibited diastereotopic splitting of the triplet signal of
the methyl group of the ethyl substituent. The most intensive trip-
let at 0.80 ppm was assigned to the (R,S)-diastereomer, and the
lowest intensity triplet at 0.81 ppm to the (R,R)-diastereomer.
We carried out the conformational analysis of MTPA ester 17 via
DFT (PBE/3z) calculations (Program Priroda 6.0).22a The main fac-
tors, which defined the selection of the quantum chemical method,
were the following: (i) the program reproduces well the structure,
NMR chemical shifts of organic and organometallic compounds,23
(ii) the computational speed; (iii) the program implies adequate
consideration of electronic correlation.
At first, we considered the conformers of the initial MTPA. As
follows from Figure 1, the most likely structure of MTPA is the con-
former, in which the OMe has a syn-periplanar (sp) configuration
with respect to the C@O group.
These data are consistent with the conformational composition
of MPA (methoxyphenylacetic acid) and 9-AMA (9-anthrylmeth-
oxyacetic acid),21c but are contrary to the data presented in the
literature.21b on MTPA conformers (calculated by MM and AM1).
On the basis of the conformational analysis of MTPA we consid-
ered the conformers of MTPA ester 17 [for both (R,R)- and (R,S)-dia-
stereomers]. Thus, the sp configuration of MTPA fragment was
chosen. Our calculations also show the predominance of anti-peri-
Thus,
D
dRS has positive value of +0.01 ppm. The 13C NMR spectra
of 1715i showed splitting of the C1, C3 and C5 carbon atom signals
(Table 3). Assignment of the NMR signals of diastereomers gave
D
dRS <0 for C1 and C5, and dRS >0 for C3.
D

L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
305
H
H
H
H
H
H
2 LiMe
Zr
Zr
Me
Me
Et2O, -78 ºC
-LiCl
Cl
Cl
(22)
(3)
H2 (70 bar)
Cp'
hexane
Cp'
Cp'
Cp
Zr
Cp'
H
H
H
H
H
H
Zr
Zr
Cp
2
Zr
Cp
Zr
Cp
H
H
H
Cp
H
Cp'
cis-
trans-
(23)
Scheme 5.
Table 3
Comparison of experimental and theoretical d(13C) of MTPA esters 10a and 17 (d(13C) calculated for sp/ap/ap conformers of 17, and for sp/ap/+sc conformer of 10a)
Compound
Diastereomer
d(13C), ppm
C1
C2
C3
C4
C5
Exp.
Calcd
Exp.
Calcd
Exp.
Calc.
Exp.
Calc.
Exp.
Calc.
10a
17
RR-
RS-
D
70.82
70.76
+0.06
80.80
81.61
ꢀ0.81
69.89
70.03
ꢀ0.14
32.31
32.36
ꢀ0.05
40.43
40.62
ꢀ0.19
32.71
32.67
+0.04
40.43
40.17
+0.26
dRS
RR-
RS-
68.09
68.12
ꢀ0.03
23.63
23.54
+0.09
31.15
30.91
+0.24
30.12
30.20
ꢀ0.08
39.25
39.69
ꢀ0.44
D
dRS
TS 1 ν= 44.1i cm-1
TS 2 ν= 17.9i cm-1
TS 1
TS 2
1.0 kcal/mol
1.2 kcal/mol
ap
sp
0.6 kcal/mol
0 kcal/mol
Figure 1. Energetic profile (D a–CO bond).
H0298) of conformational process in (R)-MTPA (rotation about C
planar (ap) conformation of MTPA-O and C1–C2 bonds. Therefore,
at a fixed fragment MTPA-O–C1 the rotation around C1–C2 bond
provides three rotamers: ap, ꢀsc (syn-clinal) and +sc, which are
the local minima on molecule PES (Fig. 2) (we consider the mole-
cules with the lowest energy among all possible rotamers of the
ap, ꢀsc and +sc conformers).
ap/ap conformer among the three mentioned is important, because
it provides the main contribution into the NMR chemical shifts.21c
According to Figure 2, the shielding effect which is caused by
the close position of the Ph and L1 groups should be significantly
exhibited only for sp/ap/ap conformers of ester 17. Therefore, the
1H NMR signal of methyl protons of ethyl group in (R,S)-diastereo-
mer of 17 should be shifted upfield relative to the signal of (R,R)-
diastereomer due to the anisotropy of the phenyl ring. This
As follows from Table 4, rotamer sp/ap/ap is the most populated
conformer for both diastereomers of 16. The domination of the sp/

306
L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
H
O
H
O
H
H
O
H
H
MeO
F3C
MeO
F3C
MeO
F3C
L2
L1
H
O
O
O
L1
H
L2
Ph
Ph
Ph
H
L2
L1
sp/ap/+sc
sp/ap/-sc
sp/ap/ap
L1
L1
H
H
H
H
H
H
H
H
H
L2
L2
L1
L2
OMTPA
OMTPA
OMTPA
Figure 2. Conformer composition of (R,S)- and (R,R)-diastereomers of MTPA esters 10a and 17 (10a: R,S- L1 = Me, L2 = Bu; R,R- L1 = Bu, L2 = Me; 17: R,S- L1 = Et, L2 = Bu, R,R-
1 = Bu, L2 = Et).
L
Table 4
Calculated thermodynamic parameters and populations of 10a and 17 conformers
H0298 (kcal/mol)
Compound
Diastereomer
Conformer
D
E (kcal/mol)
P (%)
D
10a
(R,R)
sp/ap/ap
sp/ap/ꢀsc
sp/ap/+sc
sp/ap/ap
sp/ap/ꢀsc
sp/ap/+sc
0.3
0.1
0
0.3
0.8
0
0.3
0.1
0
0.4
1.1
0
17.6
33.8
48.6
19.1
1.6
(R,S)
79.3
17
(R,R)
(R,S)
sp/ap/ap
sp/ap/ꢀsc
sp/ap/+sc
sp/ap/ap
sp/ap/ꢀsc
sp/ap/+sc
0
0
99.3
0.4
0.3
97.9
1.4
0.7
1.4
1.5
0
1.2
1.4
1.2
1.4
0
1.7
1.6
H
H
H
O
H
2
O
H
MeO
F3C
H
MeO
1
O
1
O
3
2
4
OMTPA2
F3C
Bu
Bu
4
3
OMTPA2
sp/ap/ap
sp/ap/ap
(R,R)-18
(R,S)-18
Scheme 6.
statement is confirmed by our DFT calculations of the 1H NMR
chemical shifts dMe = 0.56 ppm (R,S), 0.90 ppm (R,R),
RS >0, which
18 in the 1H NMR spectra. However, the 13C NMR spectra of 18
exhibited a double set of C2, C3 and C5 carbon atom signals and pre-
D
d
is consistent with the sign of experimental
D
dRS (+0.01 ppm).
liminary assignment of diastereomers gave
D
d
RS(C2) = ꢀ0.1 ppm,
Moreover, we calculated NMR 13C chemical shifts of C1, C3 and C5
D
d
RS(C3) = ꢀ0.17 ppm,
Dd
RS(C5) = +0.08 ppm. Furthermore, we ana-
carbon atoms (Table 3) of 17. As shown in Table 3, the calculated
lyzed the conformational composition of 18. The coordinates of the
atoms in the conformers of MTPA ester 17 were used as the origi-
nal approximation for the geometry parameters of rotamers of 18,
where the fragment MTPA-C1–C2 has the same sp/ap/ap conforma-
tion (Scheme 6) and the second MTPA fragment also has an ap con-
formation of MTPA-O and C3–C4 bonds.
d(13C) and sign of
D
dRS correspond to the experimental values for
the proposed structure of diastereomers. Thus, the theoretical cal-
culations confirmed the assignment of the absolute configuration
of the stereogenic centre of 2-ethyl-1-hexanol 15.
The literature data on the specific rotation,15h allowed us to
make a preliminary assignment of b-stereogenic center configura-
tion in (2R,S)-butyl-1,4-butandiol 16. We synthesized the (R)-
MTPA ester 18 in order to confirm this assignment. Unfortunately,
MTPA does not possess such a derivatization effect that would sat-
isfactorily split the signals of the (R,R)- and (R,S)-diastereomers of
As has been shown for 17, the predominance of the sp/ap/ap rot-
amer among the possible conformers is the criterion for configura-
tion assignment. Thus, we checked the domination of this rotamer
in 18. The search of the local minima among the rotamers derived
after the rotation of molecule fragments around the C1–C2 bond

L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
307
showed that the sp/ap/ap conformer does prevail. This means that
the anisotropic effect of the first MTPA group on chemical shifts of
C3 and C5 atoms should be the same as in 17. Assuming the fact of
the changing of substituent seniority order according to the (R,S)-
In summary, some remarks should be made. First, although the
energy barrier between the stable conformers of MTPA esters is
lower compared with the AMA esters,21c MTPA is still suitable for
the assignment of when the absolute configuration of the stereo-
genic centre in b-ethyl alcohols and 2-alkyl-1,4-butanediols. Sec-
ond, MTPA should not be used to determine the absolute
configuration in b-methyl primary alcohols. Moreover, the estab-
lishment of absolute configuration should be preceded by quan-
tum-chemical modeling of probable conformers in order to select
the appropriate shift-reagent.
nomenclature in 18, we should observe opposite signs for
D
dRS in
the 13C NMR spectra of 18 when compared with 17. Indeed signal
designation in 18 using 1D- and 2D-NMR spectra confirms this
statement. Thus, the presence of the second MTPA fragment in
18 does not have an affect on the predominance of sp/ap/ap rot-
amer; therefore, the criterion mentioned is saved. Moreover, anal-
ysis of conformer geometric parameters of (R,R)- and (R,S)-
diastereomers of 18 showed that second the MTPA fragment does
not influence on characteristic NMR shifts (C3 and C5).
3. Conclusion
Additionally, for the verification of selected criterium of abso-
lute configuration assignment of 18 we analysed temperature
dependence of NMR spectra in range 220–300 K. The monitoring
of changes in chemical shifts for carbon atoms was made from
the 13C spectra and for protons from the HSQC spectra. Thus,
decreasing the temperature to 220 K provided the shift of C2, C3
and C5 signals to the highfield and relative position of splitted sig-
nals of diastereomers practically does not change (R,R-18:
The effect of the organoaluminium compound nature, catalyst
structure, and reaction conditions (solvent type, temperature and
reagent ratio) on the chemo- and stereoselectivity of reactions of
trialkylalanes (AlMe3, AlEt3) with alkenes, catalyzed with chiral
Zr
p-complexes has been studied.
It was found that the OAC nature had the most effect on the
reactions chemo- and enantioselectivity. In the case of AlMe3, the
hydro- and carboalumination products, and alkene dimers are
formed. The catalytic reaction of AlEt3 with the olefins yields alu-
minacyclopentanes altogether with the hydro- and carboalumina-
tion products. The use of hydrocarbon solvents (benzene, toluene,
hexane) predominantly yields aluminacyclopentanes. Using chlori-
nated solvents (CH2Cl2, (CH2Cl)2) together with higher catalyst
concentration in the reaction with AlEt3 substantially increases
the yield of cyclic OAC.
D
D
d(C2) = 1.01 ppm,
d(C2) = 0.90 ppm,
D
d(C3) = 0.78 ppm, d(C5) = 0.68 ppm; R,S-18:
D
D
d(C3) = 0.72 ppm, Dd(C5) = 0.62 ppm). Chemi-
cal shifts of protons at C3 were more sensitive to temperature var-
iation. The upfield shift of the protons at C3 for the (R,R)-
diastereomer with temperature decrease in was greater than that
for the (R,S)-diastereomer [(R,R)-18:
Dd(H) = 0.31 ppm; (R,S)-18:
D
d(H) = 0.27 ppm]. This suggests that the protons at the C3 carbon
atom of (R,R)- diastereomer are arranged in the area of shielding
effect of Ph group of the first MTPA fragment.
The reaction of alkenes with AlMe3, catalyzed with complex
Indꢃ ZrCl2 1, proceeds with the formation of carboalumination
Thus, the 13C NMR signals of C3 and C5 carbon atoms of b-alkyl-
1,4-butanediol MTPA esters should be characteristic for the stere-
ogenic center assignment.
2
product predominantly with an (R)-configuration at the stereogen-
ic center. The use of AlEt3 in the reaction provides (S)-enantiomers
of carboalumination product and aluminacyclopentane.
The assignment of the stereogenic center in b-methyl alcohols
9a,b was made on the basis of the literature data on the specific
rotation angles.15a–c However, it was interesting to test whether
the same criteria, that were found for the MTPA esters 17 and
18, would be the same in the case of MTPA ester of 2-methyl-1-
hexanol 10a. We considered the conformational composition of
the (R,R)- and (R,S)-diastereomers of 10a, and the obtained infor-
mation was compared with the 1H and 13C NMR spectra. In the
experimental spectrum 1H NMR of 10a, the signal of the methyl
group at the b-stereogenic center did not undergo diastereotopic
It was shown that the catalyst structure and reaction conditions
influence the stereoinduction. Thus, complex Indꢃ ZrCl2 1 of the C2
2
symmetry group shows a higher chemo- and stereoselectivity
when compared with the C1 symmetry complexes 2 and 3, in the
reaction of 1-hexene with the AlEt3. In the case of the AlMe3 reac-
tion, the enantioselectivity does not depend on the solvent nature.
The effect of the solvent type on the enantiomeric excess of the
carbo- and cyclometallation products was observed in the reaction
with AlEt3. The highest stereoselectivity in ethylalumination prod-
ucts was achieved using chlorinated solvents, whereas the maxi-
mum enantiomeric excess of alumacyclopentanes is found in
hydrocarbon solvents.
splitting. Nevertheless, the protons at
double set of AB system signals, where for the (R,R)-diastereomer
the value of dAB(R,R) is 0.2 ppm, and for the (R,S)-diastereomer
dAB(R,S) is 0.06 ppm. the 13C NMR spectra of 10a showed a double
a-carbon atom exhibited a
D
It is shown that lack of asymmetric induction in the reaction of
D
a
-methylstyrene hydroalumination by HAlBui2, catalyzed with
set of C1, C2 and C4 carbon atom signals (Table 3). As shown in Ta-
ble 4, the calculated population of the sp/ap/ap conformer of MTPA
ester 10a is substantially lower than in the case of 17. Thus, the
predominance of sp/ap/+sc conformers for both diastereomers of
10a was observed. Figure 2 demonstrates that this conformer pos-
sesses the least shielding effect of the phenyl group on the substi-
tutes at the b-stereogenic center. Consequently, despite the close
structure of homologues of alcohols 9a and 15, it is incorrect to ap-
ply the same criteria in the assignment of the absolute configura-
tions of the stereogenic centres in the b-methyl substituted
primary alcohols using MTPA. Thus, theoretical chemical shifts
for 10a, which are presented in Table 3, are only consistent with
experimental for the C2 and C4 carbon atoms and are not in agree-
ment with the chemical shift of C1 (calculation was carried out for
the most likely conformer, sp/ap/+sc). Both the insufficient rigidity
of MTPA fragment and the conformational properties of the b-
methylalkoxy group define the specific redistribution of conform-
ers, which does not allow us to correlate the theoretical and exper-
imental NMR data.
complexes 1 or 3, is the result of the formation of Zr hydride com-
plexes of different structure (monomers and dimers with cis–trans
isomerism relative to the p-ligands) as reaction intermediates.
The use of MTPA for the assignment of absolute configuration in
b-chiral alcohols showed the applicability of the reagent for b-ethyl
substituted primary alcohols and b-alkyl-1,4-butanediols.
4. Experimental
4.1. General
All operations with organometallic compounds were carried out
under argon using Schlenk techniques. Solvents (benzene, toluene)
were dried by refluxing over i-Bu2AlH and freshly distilled prior to
use. Methylene chloride was dried over P2O5. Commercially avail-
able 98% AlEt3 and 97% AlMe3 (Aldrich) were involved in the reac-
tions. Catalysts 1–3 were prepared using the standard techniques
from ZrCl4 [(99.5%, Aldrich) 1,6a 2, 314a,c]. Complex 2 is unstable

308
L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
in air and light, especially in solution, therefore, it was synthesized
immediately prior to use.
was stirred for 3–24 h at 10–40 °C. Next, the reaction mixture was
decomposed with 10% HCl or DCl at 0 °C. The products were ex-
tracted with benzene; the organic layer was dried over Na2SO4 and
analyzed by GC or GC–MS. Another part of the reaction mixture
was cooled to 0 °C and dry oxygen passed through for 2 h. The resul-
tant mixture was further stirred under an oxygen atmosphere for
24 h, and then treated with 10% HCl and extracted with Et2O. The or-
ganic layer was dried over Na2SO4, filtered, and concentrated. Alco-
hol 9a was analyzed without isolation (distillation and column
chromatography are not suitable for 9a). Alcohol 9b was separated
by microscale distillation. Column chromatography of the mixture
15+16 on silica gel (hexane/Et2O 4:1) provided 15; then the column
was washed with acetone to give 16 as a colorless oil. The organic
fractions were concentrated and dried over Na2SO4. MTPA esters of
9a,b and 15 were prepared as described in the literature.5,11
The 1H and 13C NMR spectra were recorded on a Bruker
AVANCE-400 spectrometer (400.13 MHz (1H), 100.62 MHz (13C)).
Benzene-d6, toluene-d8 and CDCl3 were used as solvents. The sam-
ples were prepared in standard tubes of 5 mm diameter. Chemical
shifts are internally referenced to the TMS signal. Two-dimensional
NMR spectra (COSY HH, HSQC, HMBC) were measured using BBI
probe with standard pulse sequences.
The hydrolysis products of reaction mixture were analyzed on a
Carlo Erba gas chromatograph (He, column 50,000 ꢄ 0.32 mm,
fixed phase ‘Ultra-1’, flame-ionization detector). Mass spectra were
obtained on MD 800, TRIO 1000 VG Masslab (Great Britain)
spectrometer.
The enantioselectivity of the carbo- and cyclometallation reac-
tions was determined from the enantiomeric purity of correspond-
ing alcohols, which were derived after the oxidation of reaction
4.3.1. (2R,S)-Methyl-1-hexanol 9a
media. The alcohols were derivatised with (S)-(+)-
a
-methoxy-
a
-
1H NMR (CDCl3) d 0.88 (t, 3J = 6.8 Hz, 3H, CH2CH3), 0.89 (d,
3J = 6.8 Hz, 3H, CHCH3), 1.04–1.13 (m, 1H, CHCHHCH2), 1.31–1.42
(m, 1H, CHCHHCH2), 1.19–1.41 (m, 4H, CH2), 1.58 (oct, 3J = 6.4 Hz,
1H, CH), 3.38 (dd, 2J = 10.4 Hz, 3J = 6.4 Hz, 1H, CHHOH), 3.48 (dd,
2J = 10.4 Hz, 3J = 5.6 Hz, 1H, CHHOH). 13C NMR (CDCl3) d 14.2 (C7),
16.7 (C3), 23.1 (C6), 29.2 (C5), 33.0 (C4), 35.9 (C2), 68.5 (C1).
trifluoromethylphenylacetyl chloride [(S)-MTPA-Cl], and the so
formed diastereomeric esters analyzed by 1H5,11 and 13C NMR
spectroscopy. Analysis of the (R,R)- and (R,S)-diastereomers of
the MTPA esters of the substituted 1,4-butanediol 18 was carried
out using 13C NMR spectra obtained as a result of long-term accu-
mulation (ꢁ30,000 sc). Specific rotation angles [
a] were deter-
D
mined on a Perkin Elmer-341 polarimeter.
4.3.2. (2R,S)-Methylhexyl (R)-
a-methoxy-a-
Geometric parameters optimization for the MTPA esters was car-
ried out by DFT calculations using program Priroda-08 developed by
D.N. Laikov.22a The generalized gradient approximation (GGA) for
theexchange-correlationfunctionalbyPerdew, BurkeandErnzerhof
was employed (PBE/3z).22b NMR shifts were calculated using the
method GIAO, which is implemented in the program.22c
trifluoromethylphenylacetate 10a
1H NMR (C6D6) d 0.81 (d, 3J = 6.4 Hz, 3H, CHCH3); 0.91 (t,
3J = 7.2 Hz, 3H, CH2CH3); 0.96–1.03 (m, 1H, CHCHHCH2); 1.18–
1.24 (m, 1H, CHCHHCH2); 1.17–1.27 (m, 4H, CH2CH3); 1.64 (oct,
3J = 6.0 Hz, 1H, CH); 3.53 (s, 3H, OCH3); 3.93 (dd, 2J = 10.6 Hz,
3J = 6.7 Hz, 1H, CHHOH), 4.13 (dd, 2J = 10.6 Hz, 3J = 5.6 Hz, 1H,
CHHOH) (RR); 4.00 (dd, 2J = 10.6 Hz, 3J = 5.8 Hz, 1H, CHHOH), 4.06
(dd, 2J = 10.6 Hz, 3J = 6.7 Hz, 1H, CHHOH) (SR); 6.98–7.21 (m, 2H,
Ph), 7.61–7.67 (m, 1H, Ph), 7.91–7.95 (m, 2H, Ph). 13C NMR
(C6D6) d 13.9 (C7), 16.5 (C3), 22.8 (C6), 28.8 (C5); 32.31 (R), 32.36
(S) (C2); 32.71 (RR), 32.67 (SR) (C4); 55.1 (OCH3); 70.82 (RR),
70.76 (SR) (C1); 124.4 (q, JC–F = 287 Hz, CF3), 127.4, 128.0, 129.2,
133.3 (Ph), 168.8 (C@O).
4.2. Synthesis and isolation of complex CpInd*ZrCl2
2
The synthesis of complex 2 was carried out using the method
described in the literature.14a,c The obtained yellow solid was
washed twice with dry hexane (2 ꢄ 15 ml) and treated with
50 ml of CH2Cl2, and the solution was filtered through the Celite.
The clear filtrate was concentrated in vacuo. The complex is unsta-
ble in solutions; therefore, it was quickly crystallized from methy-
lene chloride to give a bright yellow complex.
4.3.3. (2R,S)-Methyl-1-octanol 9b
1H NMR (CDCl3) d 0.89 (t, 3J = 6.8 Hz, 3H, CH2CH3), 0.92 (d,
3J = 6.8 Hz, 3H, CHCH3), 1.03–1.16 (m, 1H, CHCHHCH2), 1.36–1.44
(m, 1H, CHCHHCH2), 1.22–1.36 (m, 8H, CH2), 1.61 (oct,
3J = 6.8 Hz, 1H, CH), 3.51 (dd, 2J = 10.4 Hz, 3J = 5.6 Hz, 1H, CHHOH),
3.41 (dd, 2J = 10.4 Hz, 3J = 6.4 Hz, 1H, CHHOH). 13C NMR (CDCl3) d
14.1 (C9), 16.7 (C3), 22.8 (C8), 27.2 (C5), 29.8 (C6), 32.0 (C7), 33.4
(C4), 36.0 (C2), 67.8 (C1).
4.2.1. (g g
5-Cyclopentadienyl) ( 5-{1-[(1S,2S,5R)-2-isopropyl-5-
methylcyclohexyl]indenyl}) zirconium dichloride 2
½
a 2D5
ꢂ
¼ ꢀ75:0 (c 0.6, C6H5CH3). 1H NMR (CDCl3) d 0.04 (d,
3J = 6.7 Hz, 3H, CH3); 0.71 (d, 3J = 6.7 Hz, 3H, CH3); 0.96 (d,
3J = 6.4 Hz, 3H, CH3); 1.00–1.13 (m, 1H, CH2CHHCHCH3), 1.86–
1.98 (m, 1H, CH2CHHCHCH3); 1.45–1.57 (m, 2H, CH2CH2CHCH);
1.45–1.57 (m, 1H, CHCHHCH), 2.21 (dt, 2J = 12.0 Hz, 1H,
CHCHHCH); 1.24–1.36 (m, 1H, CH3CHCH3); 1.57–1.65 (m, 1H,
CHCHCH); 2.06–2.16 (m, 1H, CH2CHCH2), 3.77 (m, 1H,
CHCHCHCH2); 6.04 (s, 5H, Cp); 6.49 (d, AX, 3J = 3.2 Hz, 1H, CH);
7.11 (d, AX, 3J = 3.2 Hz, 1H, CH); 7.24–7.30 (m, 2H, CHCHCHCH);
7.63 (d, 3J = 7.6 Hz, 1H, CHCHCHCH); 7.84 (d, 3J = 8.0 Hz, 1H,
CHCHCHCH). 13C NMR (CDCl3) d 18.2 (C17), 22.3 (C19), 22.4 (C12),
23.6 (C18), 28.5 (C14), 29.2 (C16), 34.4 (C13), 36.2 (C10), 40.0 (C15),
48.3 (C11), 99.3 (C3), 116.7 (Cp), 124.0, 125.0, 126.1 (C1, C4, C9),
124.9 (C8), 124.8 (C7), 125.6 (C6), 125.8 (C5), 126.7 (C2).
4.3.4. (2R,S)-Methyloctyl (R)-a-methoxy-a-trifluoromethyl
phenylacetate 10b
1H NMR (C6D6) d 0.82 (d, 3J = 6.4 Hz, 3H, CHCH3); 0.99 (t,
3J = 7.2 Hz, 3H, CH2CH3); 0.98–1.08 (m, 1H, CHCHHCH2); 1.19–1.30
(m, 1H, CHCHHCH2); 1.13–1.37 (m, 6H, CH2); 1.31–1.41 (m, 2H,
CH2CH3); 1.66 (oct, 3J = 6.4 Hz, 1H, CH); 3.53 (s, 3H, OCH3); 3.94
(dd, 2J = 10.6 Hz, 3J = 6.7 Hz, 1H, CHHOH), 4.14 (dd, 2J = 10.6 Hz,
3J = 5.6 Hz, 1H, CHHOH) (RR); 4.02 (dd, 2J = 10.8 Hz, 3J = 5.8 Hz, 1H,
CHHOH), 4.07 (dd, 2J = 10.8 Hz, 3J = 6.4 Hz, 1H, CHHOH) (SR); 6.95–
7.18 (m, 2H, Ph), 7.60–7.66 (m, 1H, Ph), 7.92–7.96 (m, 2H, Ph). 13C
NMR (C6D6) d 14.1 (C9), 16.5 (C3), 22.7 (C8), 26.7 (C5), 29.5 (C6),
31.8 (C7); 32.35 (RR), 32.39 (SR) (C2); 33.04 (RR), 33.00 (SR) (C4);
55.1 (OCH3); 70.86 (RR), 70.81 (SR) (C1); 124.5 (q, JC–F = 287 Hz,
CF3), 127.6, 128.1, 129.4, 133.2 (Ph), 168.7 (C@O).
4.3. Reaction of terminal alkenes with AlR3 (R = Me, Et) in the
presence of L1L2ZrCl2 1–3
A 10 ml flask equipped with a magnetic stirrer and filled with ar-
gon was loaded with 2–8 mmol of L1L2ZrCl2 1–3, 0.3–3 ml of meth-
ylene chloride or 0.3 ml toluene (benzene), 100 mmol of alkenes
(1-hexene or 1-octene) and 120 mmol of AlR3. The reaction mixture
4.3.5. (2R,S)-Ethyl-1-hexanol 15
1H NMR (CDCl3) d 0.89 (t, 3J = 6.4 Hz, 6H, CH3), 1.20–1.45 (m, 4
H, CH2CH3), 1.20–1.34 (m, 4H, CH2), 1.34–1.45 (m, 1H, CH), 3.54 (d,

L. V. Parfenova et al. / Tetrahedron: Asymmetry 21 (2010) 299–310
309
3J = 4.8 Hz, 2H, CH2OH). 13C NMR (CDCl3) d 11.3 (C4), 14.3 (C8), 23.3
(C7), 23.6 (C3), 29.3 (C6), 30.3 (C5), 42.2 (C2), 65.5 (C1).
4.5.2. (2R,S)-Phenylpropyl (R)-a-methoxy-a-trifluoromethyl
phenylacetate 21
1H NMR (CDCl3) d 1.08 (d, 3J = 7.2 Hz), 1.11 (d, 3J = 7.2 Hz) (RR,
SR, 3H, CH3); 2.91 (sextet, 3J = 6.9 Hz), 2.95 (sextet, 3J = 6.9 Hz)
(RR, SR, 1H, CH); 3.37 (s), 3.39 (s) (RR, SR, 3H, OCH3); 4.15 (dd,
2J = 10.0 Hz, 3J = 6.6 Hz), 4.34, 4.36 (dt, 2J = 10.6 Hz, 3J = 6.7 Hz)
(RR, SR, 2H, CH2O); 6.90–8.15 (m, 10H, Ph). 13C NMR (CDCl3) d
17.70, 17.60 (RR, SR, C3); 38.70, 38.58 (RR, SR, C2); 55.13, 55.01
(RR, SR, OCH3); 70.9 (C1); 124.0 (q, JC–F = 287 Hz, CF3); 126.8–
129.36, 142.8, 145.5 (Ph); 168.3 (C@O).
4.3.6. (2R,S)-Ethylhexyl (R)-a-methoxy-a-trifluoromethyl
phenylacetate 17
1H NMR (C6D6) d 0.80 (t, 3J = 7.6 Hz, SR), 0.81 (t, 3J = 7.2 Hz, RR)
(3H, CHCH2CH3); 0.92 (t, 3J = 7.2 Hz, 3H, CH2CH2CH3), 1.21–1.28
(m, 4H, CH2CH3), 1.13–1.22 (m, 4H, CH2); 1.43–1.50 (m, 1H, CH);
3.51 (s, 3H, OCH3), 4.22 (dd, 2J = 10.6 Hz, 3J = 5.2 Hz, 1H, CHHOH),
4.10 (dd, 2J = 10.6 Hz, 3J = 5.6 Hz, 1H, CHHOH), 7.15–7.21 (m, 2H,
Ph), 7.60–7.65 (m, 1H, Ph), 7.69–7.74 (m, 2H, Ph). 13C NMR
(C6D6) d 10.7 (C4), 13.9 (C8), 22.9 (C7); 23.54 (SR), 23.63 (RR) (C3);
28.7 (C6); 30.20 (SR), 30.12 (RR) (C5); 38.6 (C2); 55.1 (OCH3);
68.12 (SR), 68.09 (RR) (C1); 124.5 (q, JC–F = 289 Hz, CF3), 127.5,
128.7, 129.0, 130.4 (Ph); 168.9 (C@O).
4.6. Synthesis of complex CpCp*ZrMe2 22
A 50 ml flask equipped with a magnetic stirrer and filled with
argon was loaded with 2 mmol of complex 3 (0.97 g). Et2O
(10 ml) was added at ꢀ78 °C forming a slurry, and 4 mmol of MeLi
solution (2.6 ml, 1.6 M in Et2O) was added via syringe. The reaction
mixture was warmed to room temperature and stirred for 12 h. A
clear solution with a white precipitate was formed. The solvent
was removed in vacuo and replaced with 20 ml of hexane, then
the mixture was filtered and the remaining white precipitate was
washed with hexane. The clear filtrate was concentrated, and
cooled to ꢀ51 °C. The formation of white microcrystalline precipi-
tate of 21 was observed with the yield of 61% (0.54 g).
4.3.7. (2R,S)-Butyl-1,4-butanediol 16
1H NMR (CDCl3) d 0.87 (t, 3J = 6.4 Hz, 3H, CH3), 1.16–1.37 (m, 6H,
CH2), 1.50–1.69 (m, 3H, CHCH2CH2OH), 3.40 (dd, 2J = 10.8 Hz,
3J = 6.8 Hz, 1H, CHCHHOH), 3.59–3.65 (m, 1H, CHCHHOH) 3.56–
3.59 (m, 1H, CH2CHHOH), 3.69–3.75 (m, 1H, CH2CHHOH). 13C
NMR (CDCl3) d 14.1 (C8), 23.1 (C7), 29.4 (C6), 31.6 (C5), 35.8 (C3),
39.3 (C2), 60.9 (C4), 67.4 (C1).
4.4. Synthesis of MTPA ester of (2R,S)-Butyl-1,4-butanediol 18
4.6.1. (g g
5-Cyclopentadienyl) ( 5-{1-[(1S,2S,5R)-2-isopropyl-5-
methylcyclohexyl]-4,5,6,7-tetrahydroindenyl}) zirconium
dimethyl 22
A 5 ml flask equipped with a magnetic stirrer and filled with ar-
gon was loaded with 2
ll of (2R,S)-butyl-1,4-butanediol 16, 20
ll
1H NMR (C6D6) d ꢀ0.10 (s, 3H, ZrCH3), ꢀ0.11 (s, 3H, ZrCH3); 0.62
(d, 3J = 6.6 Hz, 3H, CH3); 0.94 (d, 3J = 6.6 Hz, 3H, CH3); 0.97 (d,
3J = 6.6 Hz, 3H, CH3); 1.05–1.17 (m, 1H, CHCHHCH), 1.42–1.49 (m,
1H, CHCHHCH); 1.42–1.49 (m, 1H, CHCHCH); 1.58–1.89 (m, 4H,
CH2CH2); 1.70–1.89 (m, 2H, CH3CHCH3, CH2CHCH2); 1.57–1.89,
2.45–2.78 (m, 8H, CH2CH2CH2CH2), 2.89–2.98 (m, 1H,
CHCHCHCH2); 5.20 (d, AX, 3J = 3.0 Hz, 1H, CH); 5.57 (d, AX,
3J = 3.0 Hz, 1H, CH); 5.96 (s, 5H, Cp). 13C NMR (C6D6) d 18.4 (C17),
22.2 (C19), 22.1 (C12), 24.2 (C18), 24.6, 24.3, 23.6, 23.4 (C5–C8),
28.7 (C14), 29.5 (C16), 34.3 (C13), 34.6, 31.6 (ZrCH3), 36.2 (C10),
40.2 (C15), 48.0 (C11), 103.3 (C3), 106.9 (C2), 110.5 (Cp), 123.66,
124.54, 129.22 (C1, C4, C9).
of pyridine-d5, 0.2 ml of CDCl3 and 8
l
l S-MTPA-Cl. The mixture
was stirred for 24 h and benzene-d6 or toluene-d8 was added.
4.4.1. (R)-MTPA ester of (2R,S)-Butyl-1,4-butanediol 18
1H NMR (C6D6) d 0.86 (t, 3J = 6.8 Hz, 3H, CH3); 0.97–1.12 (m, 4H,
CH2CH2CH2CH3, CH2CH2CH3); 1.12–1.21 (m, 2H, CH2CH3); 1.41–
1.50 (m, 2H, CH2CH2OH); 1.50–1.59 (m, 1H, CH); 3.85 (dd,
2J = 11.2 Hz, 3J = 6.4 Hz, 1H, CHCHHOH), 3.94–4.18 (m, 3H,
CHCHHOH, CH2CH2OH); 3.48 (s, 6H, OCH3); 7.05–7.14 (m, 4H,
Ph), 7.51–7.89 (m, 6H, Ph). 13C NMR (C7D8) d 13.7 (C8), 22.6 (C7),
28.5 (C6); 29.95 (SR), 29.78 (RR) (C3); 30.19 (SR), 30.27 (RR) (C5);
34.11 (SR), 34.01 (RR) (C2); 54.9 (OCH3), 67.6 (C1), 63.6 (C4);
123.7 (q, JC–F = 287 Hz, CF3), 124.4 (q, JC–F = 287 Hz, CF3); 127.3–
130.2 (Ph); 168.9 (C@O), 166.2 (C@O).
Acknowledgements
4.5. Hydroalumination of
presence of catalysts 1 or 3
a
-methylstyrene by HAlBui2 in the
The authors thank the Foundation of the President of Russian
Federation (Program for Support of Leading Scientific Schools,
Grant NSh-2349.2008.3; Program for Support of Young Ph.D. Scien-
tists, Grant MK-4526.2007.3; Grant MK-4977.2007.3), the Russian
Foundation of Basic Research (Grant No. 08-03-97010), and the
Royal Society (International Incoming Short Visit, Southampton
University, 2006) for financial support.
A 10 ml flask equipped with a magnetic stirrer and filled with ar-
gon was loaded with 0.1 mmolof 1 or 3, 3 mlof toluene, 5 mmolof
a-
methylstyrene (0.65 ml), and 6 mmol of HAlBui2 (0.92 ml, 73%). The
reaction mixture was stirred for 40 h at 40 °C. Then part of the reac-
tion mixture was decomposed with 10% HCl or DCl at 0 °C. The prod-
ucts were extracted with benzene; further, the organic layer was
dried over Na2SO4 and analyzed by GC or GC–MS. Another part of
the reaction mixture was cooled to 0 °C and dry oxygen passed
through for 2 h. The resultant mixture was further stirred under an
oxygen atmosphere for 24 h, and then treated with 10% HCl and ex-
tracted with Et2O. The organic layer was dried over Na2SO4, filtered,
and concentrated. Column chromatography on silica gel (hexane/
ethyl acetate 1:1) provided 2-phenyl-1-propanol 19. The MTPAester
of 19 was prepared as described in the literature.5
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