Convenient, enantioselective hydrosilylation of imines in protic media catalyzed by a Zn-trianglamine complex

Article abstract of DOI:10.1039/c1ob05074e

Chiral hexamine macrocycle derived from trans-1,2-diaminocyclohexane (DACH) in a complex with diethylzinc efficiently catalyzes the asymmetric hydrosilylation of N-phosphorylated aryl-alkyl or aryl-aryl ketimines in protic media with enantiomeric excess o

Full text of DOI:10.1039/c1ob05074e

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PAPER
Convenient, enantioselective hydrosilylation of imines in protic media
catalyzed by a Zn-trianglamine complex†‡
Jadwiga Gajewy, Jacek Gawronski and Marcin Kwit*
Received 13th January 2011, Accepted 25th February 2011
DOI: 10.1039/c1ob05074e
Chiral hexamine macrocycle derived from trans-1,2-diaminocyclohexane (DACH) in a complex with
diethylzinc efficiently catalyzes the asymmetric hydrosilylation of N-phosphorylated aryl-alkyl or
aryl-aryl ketimines in protic media with enantiomeric excess of the product approaching 100%. The
cyclic structure of the trianglamine ligand increases the enantioselectivity and/or the yield of the
reaction, in comparison to the catalysis by acyclic N,N¢-dibenzyl-DACH ligands. Density functional
theory (DFT) computations on the structure of the model ligand-zinc complex and on the structures of
the pre-organized reactants together with the calculations of possible transition states allow
rationalization of the direction of the asymmetric induction of the hydrosilylation reaction. This is the
first example of asymmetric catalysis of the hydrosilylation reaction of ketimines with the use of a
readily available and inexpensive macrocyclic trianglamine ligand.
Introduction
Chiral amines are important synthetic targets due to their occur-
rence in many natural products and pharmaceuticals. In the last
few decades increased attention has been paid to the asymmetric
hydrogenation of imines as the source of chiral amines.1,2 However,
Scheme 1 [Zn-Diamine]-catalyzed hydrosilylation of imines.
this method requires the use of gaseous hydrogen and expensive
catalysts based mainly on the ruthenium or rhodium complexes.
Reductive abilities of PMHS [poly(methylhydrosiloxane)], which
alyst depend on the structures of the diamine and the substrate,11
is a safe and inexpensive alternative to monomeric silanes, allow
as well as on the presence of an additive, and reached 96% in
the synthesis of amines from activated imines without the use
the case of reduction of ortho-substituted benzophenones.12,13 It
of gaseous hydrogen. Effective catalysts derived from transition
should be noted that the recovered product was a silyl ether, which
metals such as Ti,3 Rh,4 Ru,5 Cu,6 and Re7 were employed for
had to be separated prior to proceeding with a somewhat sensitive
enantioselective hydrosilylation of ketones and imines, however
hydrolysis step. The [Zn-diamine] catalytic system operating in
the synthesis of complex catalysts or the use of specially mod-
protic conditions makes possible to avoid the hydrolysis step and
ified substrates was necessary.8 The use of [Zn-amine]-catalyzed
to significantly improve the conversion of the substrate, however
enantioselective hydrosilylation of aryl-alkyl ketones developed
at the expense of enantioselectivity, which dropped to 55% ee
by Mimoun et al.,9 further extended to imines (Scheme 1),10 made
in the case of acetophenone.14,15 Imines, having phenyl or benzyl
a breakthrough in practical synthesis of optically active alcohols
substituents at the nitrogen atom, which could not be reduced by
and amines via reduction of the carbon-heteroatom double bonds.
the [Zn-diamine] complex in toluene, were reduced in the mixture
According to this protocol a typical catalyst system is formed
of methanol and toluene (80/20, v/v). However, products of low
in situ from equimolar amounts of dialkyl zinc and a secondary
enentiomeric excess were obtained in these cases.15
diamine. Enantioselectivities obtained with the use of such a cat-
Park et al. reported recently on the use of [Zn-diamine]
catalysts for a highly enantioselective reduction of various acti-
vated imines in THF–methanol mixtures.10 The authors examined
Department of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-
780, Poznan´, Poland. E-mail: Marcin.Kwit@amu.edu.pl; Fax: (+48)-61-
N,N¢-ethylenebis(1-phenylethylamine) and (R,R)-dpen derivatives
829-1505
(dpen = 1,2-diphenyl-1,2-ethanediamine) as the chiral ligands
and diphenylsilane or PMHS as reducing agents. These authors
also rationalized the use of a protic solvent as a necessary
condition for easy cleavage of the strong zinc-nitrogen bond of
the amine product during the catalytic cycle. Alternatively, the
Zn–N(product) bond could be cleaved by the added silane.
† Electronic supplementary information (ESI) available: Data on the
HPLC separation of enantiomers, products literature references, spectral
characterization of new compounds, computational details, total and
relative energies and Cartesian coordinates for all calculated compounds.
See DOI: 10.1039/c1ob05074e
‡ Dedicated to Professor Derek R. Boyd on the occasion of his 70th
birthday.
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Detailed analysis of the available literature precedents led us
to a conclusion that in the case of [Zn-diamine]-catalyzed ketone
hydrosilylation improvements could be made by judicious choice
of a chiral ligand. Among many precursors of diamine ligands,
enantiopure trans-1,2-diaminocyclohexane (DACH) appears ex-
ceptional, as it can be the source of virtually unlimited number
of diamine structures. We have recently reported that chiral tetra-
and hexamine macrocycles derived from DACH in complexes with
diethylzinc efficiently catalyze asymmetric hydrosilylation of aryl
alkyl ketones with enantiomeric excess of the product up to 89%.11
It seemed obvious that the development of a practical and efficient
catalytic system for the reduction of imines could also be based on
cyclic or acyclic DACH derivatives. Herein we describe a highly
enantioselective hydrosilylation of imines, catalyzed by readily
available Zn-diamine catalysts. We also propose rationalization
of enantioselectivity of the process, on the basis of the results of
DFT calculations.
or macrocyclic structure of the ligand will stabilize the structure
of the zinc complex and will improve reaction selectivity.
N,N¢-Dibenzyl derivatives 1 and 2 were obtained through simple
condensation of the appropriate aldehyde with DACH, followed
by reduction of the imine bonds. Trianglamine 3 is readily obtained
in a one-pot procedure from DACH and terephthalaldehyde, with
the yield over 95%.17
Since the stereoselectivity of hydrosilylation reaction depends
not only on the catalyst structure but also on the structure
of the substrate, for the initial studies we have chosen several
model imines 4a–4d, derived from acetophenone, differing in the
substitution pattern of the nitrogen atom (Fig. 1). Additionally we
aimed at showing the effect of the solvent, silane and the catalyst
load on the efficiency of the reaction.
Standard conditions involved generation of the zinc complex
by the addition of equimolar amount of diethylzinc in hexane
to a solution of the ligand in toluene (or in other solvents like
dichloromethane, THF, methanol or a mixture of toluene and
methanol). After 0.5 h at room temperature the imine and the
silane were addedandthe reaction was runat room temperaturefor
24 h and then quenched with methanolic NaOH solution (Scheme
1). This last step could be omitted if the reaction was run under
protic conditions. It should be noted that the order of addition of
the reagents to the reaction vessel did affect neither the yield nor
enantioselectivity of the reaction.
Results and discussion
From the library of available ligands we selected the three,
known for their efficiency in other hydrosilylation reactions.11,16
These ligands, shown in Fig. 1, were readily available either
as acyclic DACH derivatives, such as the dibenzylDACH (1)
and its dimethoxy derivative (2) or as a chiral heteraphane,
trianglamine (3). We reasoned that the additional methoxy groups
We initially examined the effect of N-substitution of the imines
on the yield and enantioselectivity of the [Zn-1]-catalyzed hydrosi-
lylation (Table 1). The catalyst load in all cases was 5 mol% and
model imines 4a–4d used in this study had different N-substituents,
i.e. OH, OBn, p-methoxyphenyl (PMP) or diphenylphosphinyl
(POPh2) (oxime 4a was an intermediate in the synthesis of 4d).
Among the four imines tested two (4a and 4b) did not undergo
hydrosilylation under the above-mentioned conditions (Table 1,
entries 1–4), regardless the silane used. The use of oxime 4a
resulted in the recovery of almost all starting material. In the case
of N-benzyloxyderivative 4b we did not observe any progress of the
reaction, even if the reaction time was prolonged to 48 h. Although
in the case of 4c and 4d the reactions were not complete within
24 h, promising reaction enantioselectivities (53–99% ee) were
observed (Table 1, entries 5–9). Yields of isolated products were
not satisfactory and prolongation of the reaction time for another
24 h had only little effect on the conversion of the substrate. It
is pertinent to note that 4d is only partially soluble in non-polar
solvents and lowering the reaction temperature caused a further
drop of the yield without any profound effect on enantioselectivity
Fig. 1 Ligands 1–3 and imines 4–7 used in this study.
Table 1 Effect of N-substitution on the yield and enantioselectivity of the [Zn-1]-catalyzed hydrosilylation of imines 4a–4da
Entry
Imine
Silane
Solvent
Conversion [%]
Yieldb [%]
Eec [%]
1
2
3
4
5
6
7
8
9
4a
4a
4b
4b
4c
4c
4d
4d
4d
Ph2SiH2
PMHS
Toluene
Toluene
Toluene
THF
Toluene
Toluene
Toluene
Toluene
Toluene
0
0
0
0
nd
nd
99
90
89
0
0
0
0
30
50
82
14
28
0
0
0
0
14
53
92
96
99
Ph2SiH2
Ph2SiH2
Ph2SiH2
(EtO)3SiH
Ph2SiH2
(EtO)3SiH
PMHS
a Reaction time 24 h, room temperature, ligand 5 mol%. b Isolated yields, average of two runs. c Determined by HPLC using a CHIRALPAK IA column.
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Table 2 Effect of ligand, silane and solvent on the yield and enantiose-
lectivity of the [Zn-diamine]-catalyzed hydrosilylation of imine 4da
Table 3 Enantioselective hydrosilylation of N-diphenylphosphinyl
ketiminesa
Entry Ligand Silane
Solvent
Yieldb [%] Eec [%]
Entry
Imine
Ligand
Yieldb [%]
Eec [%]
1
2
3
4
5
6
7
8
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
3
3
3
3
Ph2SiH2
Ph2SiH2
Ph2SiH2
(EtO)3SiH Toluene
PMHS
Ph2SiH2
Ph2SiH2
Ph2SiH2
(EtO)3SiH Toluene
PMHS
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Toluene
THF
82
71
92
84
92
96
99
90
86
87
98
94
>99
92
94
97
>99
97
96
96
96
1
2
3
4
5
6
7
8
9
5
5
5
6
6
6
7
7
7
1
2
3
1
2
3
1
2
3
91
80
62
93
94
35
80
88
91
94 (S)
92 (S)
Toluene/MeOHd 62
97 (S)
14
28
82
70
13 (nd)d
67 (nd)d
61 (nd)d
88 (R)
85 (R)
94 (R)
Toluene
Toluene
THF
Toluene/MeOHd 74
9
16
16
66
85
64
10
11
12
13
14
15
16
17
18
19
Toluene
Toluene
THF
a Reducing agent Ph2SiH2, all reactions in toluene–methanol (4 : 1, v/v)
solution, catalyst 2 mol%, room temperature, reaction time 24 h. b Isolated
yields, average of two runs. c Determined by HPLC with a CHIRALPAK
IA column. d Absolute configuration not determined.
CH2Cl2
Toluene/MeOHd 58
MeOH
54
6
(EtO)3SiH Toluene
(EtO)3SiH Toluene/MeOHd 52
PMHS
PMHS
Toluene
56
Toluene/MeOHd 72
enantioselectivity of the hydrosilylation in toluene and toluene–
methanol mixture of solvents, however the yield of the isolated
product was higher (entry 19, Table 2).
a Reaction conditions: ligand 5 mol%, silane 1.2 eq, room temperature,
reaction time 24 h. b Isolated yields, average of two runs. c Determined by
HPLC using a CHIRALPAK IA column. d Solvents ratio 4 : 1 (v/v).
The efficiency of the reaction could be further increased by
lowering the load of the [Zn-3] catalyst down to 1 mol% and this
surprisingly resulted in a slight increase of enantioselectivity (up
to 98%) at the expense of the yield (drop to 62%). On the other
hand, catalyst overload (up to 15 mol%) did not affect neither
the enantioselectivity nor the yield of the reaction. Changing
the ratio Zn to 3 from 1 : 1 through 2 : 1 to 3 : 1 reduced both
the enantioselectivity and conversion of the substrate, which is
in full agreement with our previous experimental findings for
hydrosilylation of ketones.11
Ligand 2, having additional methoxy groups, provided enan-
tioselectivity of hydrosilylation reaction comparable to ligand
1 (entries 6–10, Table 2). This is in contrast to the result of
asymetric hydrosilylation of various prochiral ketones, where
ligand 2 provided the highest enantioselectivities of the products.
In all cases the products of imines 4c and 4d reduction had (S)
configurations at the stereogenic center.
of the reaction. The use of 4c for hydrosilylation was further
hampered by the difficulties in removing the PMP group. On the
other hand, after reduction of imine 4d the diphenylphosphinyl
group could be readily hydrolyzed to give the desired amine.18
Therefore imines substituted at the nitrogen atom by the POPh2
group seemed to be the substrates of choice for hydrosilylation.
Further improvements of hydrosilylation procedure were therefore
limited to the model compound 4d and the screening of ligands
was conducted along with the screening of the type of silane and
reaction conditions used for hydrosilylation of 4d (Table 2, see
also the ESI for the full version of Table 2†). With the catalyst
load 5 mol% we observed good to excellent enantioselectivities of
the hydrosilylation of imine 4d with ligands 1–3. The conversion
values were usually high and ranged from 89% (entry 5, Table
2, ESI†) to nearly quantitative (entries 1, 3, 8, 14 and 19,
Table 2, ESI†). From practical point of view, more interesting
data for potential users are chemical yields of isolated products.
These values ranged from low 6% (entry 16, Table 2) to high
(85%, entry 12, Table 2) and better yields were obtained when
a mixture of toluene and methanol was used as the reaction
medium.
The data of Table 2 show that the highest enantioselectivity was
achieved with the use of trianglamine 3 as a ligand in either toluene
or methanol solution, and diphenylsilane as a reductor (entries 11
and 15, Table 2). The use of toluene–methanol solution (ratio
4 : 1, v/v) resulted in a small (ca. 3%) drop of enantioselectivity,
while yield of the product increased (entry 14, Table 2). Changing
the solvent from toluene to THF (entries 2, 7 and 12, Table 2)
did not affect the conversion of 4d (yields of isolated products
ranged from 70% to 85%), however we observed a decrease of
enantioselectivity of the reaction (drop to 84%, 86% or 92%).
Dichloromethane was found a good alternative as a solvent for
hydrosilylation of imines due to the high enantioselectivity of the
reaction (ee 94%, entry 13, Table 2). Substituting diphenylsilane
with PMHS (entries 18–19, Table 2) resulted in a 4% drop of
Having established 3 as the best performing chiral ligand,
various N-phosphinylimines were reduced by using 2 mol%
of the catalyst, 1.2 equivs. of diphenylsilane and toluene–
methanol [4 : 1 (v/v)] as a solvent. The results are summarized in
Table 3.
Reduction of ketimine 5 afforded the corresponding amine of
good ee (92–94%, entries 1 and 2, Table 3), trianglamine 3 gave the
best result in terms of enantioselectivity (ee 97%) at the expense of
the yield of the reaction (entry 3, Table 3). The same situation was
also observed for cyclic substrates such as 7: the product obtained
using ligand 3 had the highest enantiomeric purity (94% ee, entry
9, Table 3). It is worth adding that the product obtained from 7
had R absolute configuration of the stereogenic center, probably
due to a different binding pattern between the substrate and the
active catalyst. Contrary to these results, ligand 2 gave the best
results in terms of both enantioselectivity and chemical yield in
the case of highly demanding ketimine 6 (entry 5, Table 3). In
this case the only factor differentiating the faces of the substrate
molecule, and by this way affecting the enantiomers ratio, was a
methyl group in position 4 of one of the phenyl rings of ketimine
6. Due to the lack of crystals suitable for X-ray crystallography
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the absolute configuration of the amine obtained from ketimine 6
could not be determined.
tained with the use of COSMO/PBE0/def2-TZVPP//PBE0/6-
311G(d,p) method (the remaining computation results were
deposited as ESI†). The relative energies (in kcal mol-1) reported
here refer to the computed energy differences (DE) and unless
stated otherwise are given relative to the substrate molecule(s). In
the case of molecules having multiple conformational minima,
the energetic relationships were calculated and discussed by
taking into account the lowest-energy conformers. All calcula-
tions were carried out with the use of either Gaussian 0320 or
Turbomole 6.0 packages.21 In order to simplify the structures
for calculations, we have chosen N,N¢-dimethyldiaminoethane
as a diamine and ketimine 4d as the substrate. Since in this
work dimethyldiaminoethane represents the rigid structure of
DACH derivative, in all calculations we assumed a negative (H)N–
C–C–N(H) torsion angle (-60◦), that corresponds directly to
the experimentally determined (H)N–C–C–N(H) torsion angle
of (R,R)-DACH derivatives.17 Taking into account the recent
results10,11,15 and the results of our calculations, we propose the
following mechanism of the reaction (Scheme 2).
Mechanistic and stereochemical considerations
In order to determine the factors that control the enantioselectivity
of the hydrosilylation reaction using DACH-based ligands we
performed DFT studies, including calculations of the structures
in the possible key steps of the reaction. Preliminary calculations
carried out at the PBE0/6-31G(d) level19,20 allowed to identity the
key intermediates and the transition states. For higher accuracy
calculations we employed the above-mentioned PBE0 hybrid
functional in conjunction with the enhanced 6-311G(d,p) basis set
(see ESI for details†). Additionally, single-point calculations with
the use of the same PBE0 hybrid density functional and enhanced
def2-TZVPP basis set21 were performed to get more accurate
energies. The effect of the solvent was approached by single-point
energy calculations at the PBE0/def2-TZVPP level with the use
of the Conductor-like Screening Model (COSMO)22 simulating
methanol solution, using the optimized structures according to
the generally accepted protocol.23
Zinc complex C1, formed in toluene–methanol solution from
appropriate diamine and diethylzinc in the first step of the assumed
catalytic cycle, undergoes the reaction with silane to provide the
Zn-hydrido complex C2 which is the effective reducing agent.
The results obtained with the use of each method showed the
same trend, so we could restrict our discussion to the results ob-
Scheme 2 Proposed reaction pathway for [Zn-diamine]-catalyzed reduction of activated imines.
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The second step of the catalytic cycle controls stereoselectivity
of the whole process and assumes binding the substrate to the
hydrido complex C2 with the formation of NH ◊ ◊ ◊ O P hydrogen
bonded structure C3 that is predisposed for hydrogen transfer
from Zn to the imine group. In the last stage (step 3) of the
catalytic cycle methanolysis of the intermediate product leads to
recovery of the tetradentate [Zn-(diamino)(OMe)2] species C1 and
N-diphenylphosphinyl amine. The formation of Zn–H species C2
from C1 as well as methanolysis of the intermediate product are
well known,15,16 thus we focus here mainly on the enantiodiscrim-
inating step 2 and on the reduction stage (Scheme 2).
Whereas calculations at the PBE0/6-311G(d,p) level did not
identify any stable structure characterized by a direct coordination
of the substrate to the zinc atom they have demonstrated that
complex C3 can exist in two (N)H ◊ ◊ ◊ O( P) bonded structures
a and b, which differ in the orientation of the ketimine moiety in
relation to the catalyst (Fig. 2a).
form a stronger hydrogen bond with the appropriate proton donor.
Calculated lengths of the NH ◊ ◊ ◊ O( P) hydrogen bonds are 1.96
˚
and 1.94 A, respectively, for C3a and C3b. The second factor that
excludes formation of the NH ◊ ◊ ◊ N(imine) hydrogen bond is steric
repulsion between the ketimine phenyl group and the diamine
ligand. Confirmation of the preference of the NH ◊ ◊ ◊ O( P)
hydrogen bond over that formed by ketimine nitrogen atom was
obtained by attempted calculation of the possible structure of
C2+4d complex stabilized by the NH ◊ ◊ ◊ N(imine) hydrogen bond.
Regardless the initial mutual orientation of the Zn-hydrido species
and the substrate, the resulting calculated structures were either
C3a or C3b.
The zinc center carries a more positive charge (1.43) than any
of the (N)H hydrogen atoms (0.42) and this may suggest that the
zinc is the preferred coordination center. However, at the PBE0/6-
311G(d,p) level of theory, we have not found any stable structure
which would contain the Zn–X (O,N) bond, in agreement with
previous findings.16
There are two possible acceptor centers for a hydrogen bond
in ketimine 4d: either the imine nitrogen atom or the oxygen
atom. Calculations of the atomic charges with the use of the
NBO method24 clearly show that the oxygen atom (-1.10) carries
a more negative charge than the imine nitrogen atom (-0.84).
Therefore, the oxygen atom in the phosphinyl group is able to
Coordination mode of the substrate determines the absolute
configuration of the final product since the hydride attack may
occur from either re or si face of the ketimine moiety. In the case
of C3, formation of a conformer of a type leads to formation of
(S)-amine, whereas from conformer b (R) enantiomer is obtained.
Fig.
2 Lowest-energy structures of complexes C3 (a) and transitions states TSa and TSb (b) calculated at the COSMO/PBE0/
˚
def2-TZVPP//PBE0/6-311G(d,p) level (some interatomic distances are given in A).
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Scheme 3 Energy profile for the reduction of ketimine 4d calculated at the COSMO/PBE0/def2-TZVPP//PBE0/6-311G(d,p) level.
Energetically more favorable is conformer C3a, however the
calculated energy difference is only 0.21 kcal mol-1 and this
corresponds to a 59 to 41 ratio of conformers C3a to C3b. Binding
energies,25 defined as the energy difference between C3 complex
and the sum of the reactants C2 and 4d are 1.17 and 0.96 kcal
mol-1 for C3a and C3b, respectively.
Calculated transition structures TSa and TSb for reduction of
the imine bond in complexes C3a and C3b are shown in Fig.
2b. The main difference is the presence of the NH ◊ ◊ ◊ O( P)
hydrogen bond in TSa and its absence in TSb. This is reflected
in the calculated energy difference, TSa is over 2 kcal mol-1 more
stable than TSb. In TSa and TSb calculated interatom distances
and bond lengths are different. For example, the lengths of the
as the energy difference between the transition state and the
precursor complex). The values of Ea calculated for TSa and
TSb are 10.88 and 13.11 kcal mol-1 and this allows to estimate
enantioselectivity of the process as close to a 100%. This value
remains in excellent agreement with the best experimentally
obtained enantioselectivity (ee >99%) for hydrosilylation of 4d,
carried out in methanol solution. The values of Ea calculated at the
PBE0/def2-TZVPP//PBE0/6-311G(d,p) level for the structures
in the gas phase are 10.25 and 13.24 kcal mol-1 (for TSa and TSb,
respectively) and again point to reaction enantioselectivity close
to a 100%.
Conclusions
˚
N–Zn bonds are 2.13 and 2.08 A in the case of TSa and 2.12 and
˚
2.10 A in the case of TSb; the distance between the hydride and
We reported here a convenient method for enantioselective
hydrosilylation of aryl-alkyl or aryl-aryl ketimines, based on the
catalysis with zinc-hexamine macrocycle, readily available from
DACH. The use of inexpensive reducing agent (PMHS), generally
available activated imines and protic solvent (methanol–toluene)
which makes the hydrolysis of the silyl group unnecessary, are
further favorable features of the procedure. Trianglamine 3-ZnEt2
(1 : 1) complex catalyzes hydrosilylation of N-diphenylphosphinyl
ketimine 4d in toluene solution, using diphenylsilane, with over
99% ee and moderate yield (66%) of the product. The enantiose-
lectivity is similar to that obtained with the use of acyclic ligands
1 or 2 (ees 99 and 98%), however acyclic ligands provided the
product in a lower chemical yield. Yield of the product can be sig-
nificantly increased by the use toluene–methanol solution instead
toluene only, with only a little drop of enantioselectivity of the
reaction.
the acceptor carbon atom is much shorter in the case of TSa (1.69
˚
˚
A vs. 1.73 A). Opposite situation is observed for the P O bonds,
˚
a longer bond (1.51 A) is calculated for TSa, whereas for TSb
its length is 1.50 A. Characteristic NH ◊ ◊ ◊ O( P) hydrogen bond
calculated for TSa is shorter by 0.15 A than that calculated for
˚
˚
C3a whereas such a bond does not exist in TSb.
In the case of TSb a long distance (3.655 A) between the
˚
(N)H and the phosphinyl oxygen atoms excludes any attractive
interactions between both fragments. These data indicate strongly
that effective hydrogen transfer from zinc to the C N bond is
possible only in the transition state TSa.
Total reaction energy, defined as the energy difference between
the free energies of the products and the reactants, was calculated
taking as the substrates ketimine 4d, the Zn-hydrido complex C2
and a methanol molecule and as the products the amine and the
tetradentate complex C1. Total reaction energy amounted to DE =
-31.43 kcal mol-1. Calculated energy profile for the reduction of
imine 4d (involving steps 2 and 3) is shown in Scheme 3.
Protic conditions (addition of methanol to toluene solution)
allowed the use of inexpensive poly(methylhydrosiloxane) as a
reducing agent. From the economical point of view this mod-
ification is a method of choice for hydrosilylation of imines.
Since trianglamine 3 can be conveniently prepared by a one-
pot procedure from inexpensive tartrate salt of DACH and
Path “a” leading to the product of (S) absolute configuration
is favored not only by the formation of a more stable initial
complex C3a, but also by a lower activation energy Ea (defined
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terephthalaldehyde,17 the Zn complex of 3 is a good alternative
to the previously reported chiral catalysts.
(0.5 mL, 4 : 1, v/v) and stirred under an argon atmosphere for
30 min. Then the solution (1.5 mL, toluene–methanol, 4 : 1,
v/v) of the corresponding imine (0.29 mmol) and diphenylsilane
(0.066 mL, 0.36 mmol) were added to the flask. The resulting
solution was stirred at room temperature for 24 h. Then NaOH
(1 mL, 1 M in MeOH) was added with vigorous stirring. The
reaction mixture was stirred for an additional hour at room
temperature and extracted with dichloromethane (3 ¥ 3 mL). The
combined organic extracts were washed with water and brine,
dried over anhydrous Na2SO4 and concentrated under vacuum.
The crude product was purified by column chromatography on
silica gel with hexane–EtOAc (10 : 1) as an eluent.
In this paper we present a plausible rationalization of the
observed enantioselectivity of the imine hydrosilylation, using
ligands derived from (R,R)-DACH which provide preferentially
amines of S configuration. It is related to the previous mechanistic
study of Bette15 and others16 and is based on the DFT calculated
low-energy structures of the [Zn(ligand)(OMe)(H)]-4d precursors,
as well as on the structures of the transition states leading
to the formation of the chiral product. Postulated formation
of a strong NH ◊ ◊ ◊ O( P) hydrogen bond appears crucial for
pre-organization of the reactants and determines the spatial
arrangements of both the catalyst and the ketimine. In this way
the enantioselectivity of the whole hydrosilylation process can be
rationally accounted for.
Acknowledgements
This work was supported by the Ministry of Science and Higher
Education, grant no. PBZ-KBN-NN204 312537. All calculations
were performed at Poznan´ Supercomputing and Networking
Center.
Experimental section
NMR spectra were recorded on a Bruker BioSpin 400 (400 MHz)
or Varian MR 300 (300 MHz) instruments at 25 ◦C using
CDCl3, DMSO or D2O as solvents, purchased from Sigma–
Aldrich. Chemical shifts are reported in ppm relative to the TMS
(1H and 13C NMR spectra) or D2O (31P NMR spectra) peaks.
Spectral assignments were obtained by the analysis of chemical
shifts and by comparison with literature data (see Table A in
the ESI for details†). Mass spectra were recorded on a AMD-
402 spectrometer. HPLC analyses were performed with the use of
a Hitachi LaChrom Elite system equiped with CHIRALPAK IA
column at room temperature. For the data on the HPLC separation
of enantiomers see Table B in the ESI.†
Notes and references
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Imine 6: m.p. 142–145 C; H NMR (300 MHz, CDCl3, d):
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J = 7.9 Hz, 3H), 2.41 (s, 3H); (400 MHz, DMSO, d): 7.83–7.79 (m,
4H), 7.54–7.39 (m, 13H), 7.26 (d, J = 8.1 Hz, 2H), 2.37 (s, 3H);
13C NMR (75.44 MHz, DMSO, d): 180.7, 141.5, 137.9, 137.7,
135.5, 135.3, 135.1, 133.8, 130.8, 130.7, 130.6, 130.5, 129.0, 128.5,
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◦
Product of imine 6 reduction: 177–179 C; [a]D = -2.8 (c 0.5,
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8.2 Hz, 4H), 5.45 (t, J = 10.7 Hz, 1H), 3.63 (s, 1H), 2.35 (s,
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131.74, 131.68, 131.58, 129.10, 128.60, 128.47, 128.37, 128.26,
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C26H24NOP, 397.15955; found 397.15824.
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In a 5-mL round-bottom flask ZnEt2 (5.93 mL, 1 M in hexane;
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a mixture of freshly distilled toluene and anhydrous methanol
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