Convenient enantioselective hydrosilylation of ketones catalyzed by zinc-macrocyclic oligoamine complexes

Article abstract of DOI:10.1002/adsc.200800801

Chiral macrocyclic tetra- and hexamine macrocycles derived from trans-1,2-diaminocyclohex-ane (DACH) in complexes with diethylzinc efficiently catalyze the asymmetric hydrosilylation of aryl alkyl ketones with enantiomeric excess of the product up to 89%. The cyclic structure of the triangla-mine ligand increases the enantioselectivity of the reaction, in comparison to the catalysis with the acyclic N,N′-dibenzyl-DACH ligand. Density functional theory (DFT) computations on the structures of ligand-zinc complexes and on the structures of these complexes with a coordinated acetophenone mole-cule allow us to rationalize the direction of the asymmetric induction of the hydrosilylation reaction as well as the superiority of the cyclic ligand compared to the acyclic one. This is the first example of asymmetric catalysis for the hydrosilylation reaction of ketones with the use of a readily available, inexpensive, and reusable macrocyclic trianglamine ligand.

Full text of DOI:10.1002/adsc.200800801

FULL PAPERS
DOI: 10.1002/adsc.200800801
Convenient Enantioselective Hydrosilylation of Ketones
Catalyzed by Zinc-Macrocyclic Oligoamine Complexes
a
a,
a,
´
Jadwiga Gajewy, Marcin Kwit, * and Jacek Gawronski *
a
´
Department of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
Fax : (+48)-61-829-1505; e-mail: Marcin.Kwit@amu.edu.pl or gawronsk@amu.edu.pl
Received: December 22, 2009; Published online: April 7, 2009
Dedicated to Professor Armin de Meijere on the occasion of his 70th birthday
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800801.
Abstract: Chiral macrocyclic tetra- and hexamine cule allow us to rationalize the direction of the asym-
macrocycles derived from trans-1,2-diaminocyclohex- metric induction of the hydrosilylation reaction as
ane (DACH) in complexes with diethylzinc efficient- well as the superiority of the cyclic ligand compared
ly catalyze the asymmetric hydrosilylation of aryl to the acyclic one. This is the first example of asym-
alkyl ketones with enantiomeric excess of the prod- metric catalysis for the hydrosilylation reaction of
uct up to 89%. The cyclic structure of the triangla- ketones with the use of a readily available, inexpen-
mine ligand increases the enantioselectivity of the re- sive, and reusable macrocyclic trianglamine ligand.
action, in comparison to the catalysis with the acyclic
N,N’-dibenzyl-DACH ligand. Density functional
theory (DFT) computations on the structures of Keywords: asymmetric catalysis; density functional
ligand-zinc complexes and on the structures of these theory; hydrosilylation; oligoamine macrocycles;
complexes with a coordinated acetophenone mole- zinc complexes
Introduction
air and moisture polymethylhydrosiloxane (PMHS)[9]
or monomeric silanes as the reducing agents, in com-
Asymmetric hydrosilylation (AHS) is one of the most bination with metal complexes of Ru, Rh, Cu, Ti, Fe
useful catalytic methods for the synthesis of enantio- and Zn, among other. PMHS is the best hydride
merically enriched secondary alcohols from prochiral donor among other silanes and it is more selective
ketones. Two other well-established methods rely toward functional groups compared to, for example,
either on asymmetric catalytic hydrogenation of ke- borane complexes. The chemoselectivity of reduction
tones with the use of chiral rhodium complexes as cat- can be tuned by the choice of the catalyst and, in this
alysts or on asymmetric reduction of ketones with di- context, Zn complexes appear to be highly promising
borane, catalyzed by chiral oxazaborolidines. Howev- in applications to cost-effective enantioselective hy-
er, the asymmetric hydrosilylation presents the advan- drosilylation of ketones, as can be seen in the follow-
tages of simplicity of the procedure combined with ing discussion.
the use of inexpensive silanes as reducing agents. One
Chiral rhodium catalysts often use bidendate P,P,
of the main targets of current studies on AHS is the P,N or N,N ligands, such as PYTHIA,[10] PYBOX[11] or
development of catalytic systems that would comply HETPHOX.[12] High enantioselectivities (over 90%
with the criteria of high efficiency (catalyst tunover, ee) for the standard AHS of acetophenone were
yield, enantioselectivity), low cost and feasibility of achieved with chiral diphosphine[13] or pyridine-phos-
recovery of the catalyst as well as with possible envi- phine[14] ligands having a ferrocene structural unit, as
ronmental regulations. A number of experimental cat- well as with a chiral P,S ligand reported by Evans.[15]
alytic procedures for asymmetric hydrosilylation of Recently chiral CACHTNUGRTNEUNG
(carbene),N ligands for rhodium[16]
ketones has been developed in recent years, see re- and N-heterocyclic carbene ligands for ruthenium[17]
views.[1–8] These procedures usually make the use of were introduced. However, the catalytic systems
inexpensive, easily handled, non-toxic and stable to
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Jadwiga Gajewy et al.
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based on rhodium or ruthenium generally suffer from Results and Discussion
their high cost and require elaborate preparation.
Copper(I) hydride complexes, despite their known Asymmetric Hydrosilylation
preference for conjugate addition to carbonyl com-
pounds, are useful also in highly enantioselective hy- We have previously shown that DACH can be used
drosilylation of (hetero)aryl alkyl ketones. However, for the ready, thermodynamically driven construction
these reductions require expensive chiral diphosphine of various imine and amine macrocycles, by its con-
ligands, such as 3,5-xyl-MeO-BIPHEP,[18] BINAP[19,20] densation with dialdehydes, followed by reduction of
or DTBM-SEG-PHOS,[21] although in several cases the imine bonds. For the present study we have select-
the catalyst could be used at a very low load (S/C> ed trianglimine 1[30] trianglamines 2, 3,[30,31] 4,[32,33] and
1000:1).
rhombamine 5,[34] as well as N,N’-dibenzyl-DACH (6)
Recently, an iron-catalyzed enantioselective hydro- as a reference ligand.
silylation of aryl alkyl ketones has been disclosed by
Trianglamine 2 can be obtained in a one-pot proce-
Beller et al.[22] The reaction in several cases was found dure from DACH and terephthaldehyde with a yield
highly enantioselective (up to 99% ee), with the use of over 95%.[31] Trianglamine 2 has already been used
of a diphosphine ligand Me-DUPHOS.
as a chiral shift reagent for NMR spectra,[35] as a
Titanium catalysts for hydrosilylation are usually chiral probe for anion recognition in ion-trap ESI-
based on the titanocene chiral framework, titani- MS[36] and as a chiral ligand for copper-catalyzed
ACHTUNGTRENNUNG
um(IV) derivatives with other chiral ligands being enantioselective Henry reaction.[37]
less effective.[5] Notably, Buchwald et al. reported the
use of ansa-titanocene EBTHI with tetrahydroindenyl
Ligands 2–6 feature the same secondary 1,2-di-
ACHTUNGTRENaNUNG mine structure embedded in the cyclohexane ring.
substituents as ligands for titanium, giving the prod- We anticipated that the macrocyclic structures of the
ucts of hydrosilylation of ketones with up to 99% ligands would result in a higher degree of asymmetric
ee.[23]
induction of the hydrosilylation reaction of aryl alkyl
Zinc complexes of chiral secondary amines were in- ketones.
troduced by Mimoun as chiral catalysts for the enan-
Standard conditions involved generation of the zinc
tioselective hydrosilylation of ketones, with enantiose- complex by the addition of equimolar amount of di-
lectivities up to 88% ee.[24] Most frequently used ethylzinc in hexane to a solution the ligand in toluene
chiral secondary amines include derivatives of trans- (or any other solvent). After 0.5 h the ketone and the
1,2-diaminocyclohexane (DACH), trans-1,2-diamino- silane were added and the reaction was run at room
cyclopentane, 1,2-diphenyl-1,2-diaminoethane and 1- temperature for 24 h and then quenched with metha-
phenylethylamine. Introduction of two different chiral nolic NaOH solution (Scheme 1). The screening of li-
centers into the ligand gave rise to synergistic effects, gands was conducted along with a screening of the
leading to an increase of the enantioselectivity of hy- type of silane and reaction conditions used for the hy-
drosilylation reaction.[25,26] Chiral N,S chelating ligands drosilylation of acetophenone (Table 1). With a cata-
appear to be less effective in the zinc-catalyzed hydro- lyst loading of 3.5 mol% we observed moderate to
silylation of ketones;[27] however, recent results with good enantioselectivity of the hydrosilylation of ace-
the use of bis-tert-thiophenylmethyl derivative of tophenone in the case of ligands 2–6. No reaction was
DACH were promising (enantioselectivities up to observed with trianglimine ligand 1, regardless the
83% ee).[28] Finally, it has been found that ortho-multi- silane used (entries 1–4). This is in contrast to the re-
substituted benzophenones can be enantioselectivelly sults of Mimoun et al. who used successfully simple
reduced (up to 96% ee of the product) with chiral di- diimine derivatives of DACH for the hydrosilylation
ACHTUNGTRENNUNG
amine-Zn-diol complexes (chirality residing in the di- of acetophenone.[24]
A
A more detailed inspection of the data of Table 1
We reasoned that the ease of formation of chiral di- shows that the highest enantioselectivity (ee 88%) of
amine-zinc complexes and their relatively high effi- the hydrosilylation of acetophenone was achieved
ciency as chiral catalysts should lead to the develop- with trianglamine ligand 2 in toluene solution using
ment of more affordable and practical procedures for diphenylsilane as a reductor (entry 5). Lowering the
the enantioselective hydrosilylation of prochiral ke- temperature of reaction to À258C (entry 6) did not
tones. Improvements could be made by a judicious lead to any improvement of the enantioselectivity.
choice of chiral ligands. Among the synthetic chiral Changing the solvent to dichloromethane or THF
diamines, DACH appears to be the primary source of (entries 7 and 8) did improve the conversion of aceto-
virtually unlimited diamine structures. Simple N,N’-di- phenone from 85% to 95% at the expense of the
alkyl derivatives of DACH were earlier tested by enantioselectivity (drop to 77% or 81% ee of the
Mimoun et al. in the asymmetric hydrosilylation of product). Substituting diphenylsilane with PMHS (en-
acetophenone; however, they provided the product of tries 9–11) resulted in a 5% drop in conversion and
reduction with moderate 52–70% ee[24]
enantioselectivity of the hydrosilylation in toluene so-
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Table 1. Asymmetric hydrosilylation of acetophenone cata-
lyzed by zinc-L complexes.
Entry
L
Silane
Solvent Conv.[a] [%] ee[a] [%]
1
2
3
4
5
6
1
1
1
1
2
Ph2SiH2 toluene
0
0
0
0
–
–
–
–
PhSiH3
Et3SiH
PMHS
toluene
toluene
toluene
Scheme 1. Hydrosilylation conditions.
Ph2SiH2 toluene 85
88 (S)
84 (S)
77 (S)
81 (S)
83 (S)
65 (S)
65 (S)
58 (S)
60 (S)
82 (S)
77 (S)
77 (S)
–
lution and a further drop in enantioselectivity (to
65% ee) in dichloromethane and THF solutions. A
product of lower ee (58–60%) was obtained in the hy-
drosilylation of acetophenone with phenylsilane and
triethylsilane (entries 12 and 13).
2[b] Ph2SiH2 toluene 99
7
8
9
2
2
2
2
2
2
2
3
3
3
3
4
4
5
5
5
6
6
Ph2SiH2 DCM
Ph2SiH2 THF
95
95
PMHS
PMHS
PMHS
PhSiH3
Et3SiH
toluene 80
DCM
THF
toluene 99
THF trace
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
88
trace
Hexamine ligand 3 has a vase-like structure (ac-
cording to molecular modelling), quite different from
a planar triangular structure of 2. Nevertheless, it also
catalyzed the asymmetric hydrosilylation of acetophe-
none, although with slightly lower enantioselectivity
(82%) compared to 2 (entries 14 and 15). The use of
phenylsilane gave inferior results (entry 16) whereas
triethylsilane did not give any significant amount of
the reduction product (entry 17, see also entry 22).
Hydrosilylation of acetophenone with the large tri-
anglamine ligand 4 gave inferior results (entries 18
and 19) in terms of enantioselectivity compared to
the results with the smaller trianglamine ligand 2 (en-
tries 5 and 9). The same applies to the comparison of
the efficiency of rhombamine ligand 5 (entries 20 and
21) against the efficiency of ligand 2 (entries 5 and 9).
Ph2SiH2 toluene 99
PMHS
PhSiH3
Et3SiH
toluene 99
toluene 79
toluene trace
Ph2SiH2 toluene 95
PMHS toluene 99
Ph2SiH2 toluene 96
78 (S)
71 (S)
61 (S)
–
PhSiH3
Et3SiH
PMHS
toluene trace
toluene
toluene 99
0
–
78 (S)
–
Ph2SiH2 toluene
0
[a]
Conversions and enantiomeric excesses were determined
by HPLC with a CHIRALPAK IA column.
Reaction was carried out at À258C.
[b]
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Table 2. Zinc-L catalyzed asymmetric hydrosilylation of var-
ious aryl alkyl ketones according to Scheme 1.
Entry Ar
R
System[a] Yield [%] ee[b] [%]
1
2
3
4
5
6
7
8
Ph
Ph
Et
Cy
B
C
A
B
C
A
C
A
C
A
B
B
B
C
A
A
70
60
63
47
59
60
98
82
78
63
50
34
52
65
97
62
86 (S)
89 (S)
82 (S)
81 (S)
78 (S)
43 (S)
54 (S)
72 (S)
64 (S)
81 (S)
11 (R)
9[c]
Scheme 2. Hydrosilylation conditions.
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-CN-C6H4
4-CN-C6H4
4-F-C6H4
Ph
Me
Me
Me
Me
Me
Me
Me
Me
CF3
CF3
Table 3. Effect of amount and stoichiometry of catalyst
2·ZnEt2 on enantioselectivity of hydrosilylation of acetophe-
none and 4-methylacetophenone with Ph2SiH2.
Entry
R
2·ZnEt2 [mol%]
Conv.[a] [%]
ee[a] [%]
9
10
11
12
13
14
15
16
1
2
3
4
5
6
7
8
H
H
H
H
3.5
85
93
98
85
88
73
12
82
63
82
74
74
74
75
27
26
3.5[b]
3.5[b]
3.5[b,d]
3.5[c,d]
3.5
4-F-C6H4
2,4,6-Me3C6H2 CF3
1-indanone
19 (R)
76 (S)
71 (S)
12 (S)
H
99
a-tetralone
b-tetralone
Me
Me
Me
Me
Me
Me
Me
>99
>99
>99
>99
>99
98
2.5
2.0
1.5
1.0
0.5
0.1
[a]
A=2, Ph2SiH2; B=2, PMHS; C=3, Ph2SiH2, catalyst 3.5
mol%, all reactions in toluene solution.
See Table 1.
9
[b]
[c]
10
11
12
Configuration not determined.
96
[a]
See Table 1.
[b]
[c]
[d]
2 equiv. of ZnEt2 were used for 1 equiv. of 2.
3 equiv. of ZnEt2 were used for 1 equiv. of 2.
Reaction was carried out at À258C.
Acyclic N,N’-dibenzyl-DACH 6 is used in this study
as a reference ligand. With the use of ligand 6 we ob-
tained the product of the hydrosilylation of acetophe-
none with 78% ee (entry 23), lower than with the use
of macrocyclic ligand 2 (88% ee). Surprisingly, no hy-
drosilylation product was obtained when diphenylsi- 6). Lower enantioselectivity was observed with a Zn/
lane was used in the reaction (entry 24). L ratio of 2:1 (entry 2) and even more pronouncedly
Efficiency of zinc catalysts with ligands 2 and 3 was with a Zn/L ratio of 3:1 (entry 3) which was expected
investigated with various aryl alkyl ketones (Table 2). to lead to a full saturation of ligand 2. However, low-
Products of reduction with ees over 75% were ob- ering the reaction temperature to À258C provided
tained with ketones bearing no other heteroatom (en- the hydrosilylation product in higher ee (entry 4, ee
tries 1–5, 14). 4-Methoxyacetophenone and 4-cyano- 82%, entry 5, ee 63%). Lowering the amount of the
ACHTUNGTRENNUNGacetophenone gave the products of hydrosilylation in catalyst (Zn/L ratio of 1:1) from 3.5 mol% (entry 6)
lower ee (43–72%, entries 3–9), although 4-fluoroace- to 1.0 mol% (entries 7–10) caused a small drop in
tophenone reacted normally (ee 81%, entry 10). Phar- enantioselectivity which remained constant in the
maceutically important aryl trifluoromethyl ketones range 2.5 to 1.0 mol%. A further decrease of catalyst
were hydrosilylated with low enantioselectivity (en- amount to 0.5 or 0.1 mol% led to a significant loss of
tries 11–13), a result not surprising in view of the pre- enantioselectivity (entries 11, 12, ee 26–27%).
viously reported lack of success in similar cases. b-Tet-
ralone having two methylene groups flanking the car-
bonyl group was hydrosilylated with low enantioselec- Stereochemical Considerations
tivity (entry 16, ee 12%), in contrast to the result with
a genuinely aryl alkyl ketone – a-tetralone (entry 15, In order to clarify the enantioselectivity of the hydro-
ee 71%). The yields of isolated products reported in silylation reaction using trianglamine ligands we per-
Table 2 vary significantly, depending on the substrate formed DFT studies,[38] starting from the structures of
and the reduction system used.
the trianglimine 2-dimethylzinc as well as N,N’-diben-
A survey of the effect of the amount and stoichiom- zyl-DACH (6)-dimethylzinc complexes (dimethylzinc
etry of the zinc-ligand system on enantioselectivity of was used instead of diethylzinc in order to simplify
hydrosilylation of acetophenone and 4-methylaceto- the calculations). These structures were optimized
phenone (Scheme 2) is summarized in Table 3.
with the use of the PM3 Hamiltonian and then single-
Our initial studies were carried out with 3.5 mol% point energies were calculated at the B3LYP/6-
of the catalyst having a Zn/L ratio of 1:1 (entries 1, 31G(D) level and fully optimized at this level for
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Figure 1. Calculated at the B3LYP/6-31G(D) level lowest energy structures of trianglamine 2·ZnMe2 complexes and the
lowest-energy conformer of 6·ZnMe2 complex. Hydrogen atoms are omitted for clarity.
2·ZnMe2 and 6·ZnMe2 complexes only (see Support- This number is increased to four for the lowest-
ing Information for computational details).
energy trianglamine conformer obtained by the
Both free trianglamine 2 and N,N’-dibenzyl-DACH MM3-AM1 protocol. Additionally, the macrocycle
(6) molecules show a remarkable ability to change structures in which both b and b’ correspond to GÀ
their conformation as a consequence of rotation are not available. As a result of these restrictions,
À
about the C N bonds or by configuration inversion at there are only a few sequences of torsion angles avail-
nitrogen atoms. Our previous study has shown that able for macrocyclic trianglamine 2. It should be
free ligand 2 possesses a large number of conformers noted that all-T conformations of a and b angles,
belonging to families of similar structures.[31] These giving the expanded ring structure of the highest D3
structures are defined by the signs and values of tor- symmetry, is not of the lowest energy structure of 2.
À
À À
À À
sion angles [a=C(N) C(N) N C(H2); b=C(N) N
Starting from the all-T conformation of 2 we calcu-
À
C(H2) C(Ar)] obtained from rotation of the carbon- lated the structures of trianglamine complexes with 1,
nitrogen bonds forming the macrocycle. These torsion 2 or 3 molecules of dimethylzinc (Figure 1). Following
angles are normally restricted to either gauche (GÀ) the X-ray data available, we assumed that amine hy-
or trans (T) combinations. Whereas the number of T drogen atoms are not displaced by dimethylzinc and
bond arrangements in the macrocycle is not limited, that the zinc atom is bonded to vicinal nitrogen atoms
the number of GÀ bond arrangements is, as each GÀ through the electron lone pairs, as earlier proposed
angle produces additional ring folding. In the X-ray by Mimoun.[24] The all-T low energy structure is pre-
determined structures there are no more than three served
in
trianglamine-dimethylzinc
complex
GÀ bond arrangements in the entire ring (out of 2·2ZnMe2 and 2·3ZnMe2, the latter having the high-
twelve a and b angles present in the macrocycle). est symmetry D3. In the most interesting case of
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Jadwiga Gajewy et al.
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Table 4. Symmetries and sequences of torsion angles calcu-
lated for the structures of trianglamine 2-dimethylzinc com-
plexes and for 6-dimethylzinc complex.
Complex
Sequence of torsion angles[c]
Symmetry
b
a
a’
b’
[a]
2·ZnMe2
161.7
166.2 166.2 161.7
C2
À74.1
157.3 169.1 À177.2
À177.2 169.1 157.3 À74.1
[b]
[b]
2·2ZnMe2
À176.0 171.0 171.0 À176.0 C2
162.0
162.4 172.1 À165.5
À165.5 172.1 162.4 162.0
À177.8 168.4 168.4 À177.8 D3
À177.8 168.4 168.4 À177.8
À177.8 168.4 168.4 À177.8
2·3ZnMe2
[a]
6·ZnMe2
157.5
164.3 164.3 157.5
C2
[a]
Fully optimized structure at B3LYP/6-31G(D) level.
Single-point energy at B3LYP/6-31G(D) level for PM3
optimized structures.
[b]
[c]
Torsion angles assignment:
.
2·ZnMe2 only one low energy conformer was found,
characterized by two b angles in a GÀ conformation.
Note, however, that the conformation of the ligand
around the Zn atom is all-T for the four consecutive
b,a,a’,b’ angles. The structure of this conformer is
close to the lowest-energy conformer of the free tri-
anglamine ligand 2. For structural details see Table 4.
A general feature of complexation of ZnMe2 with
trianglamine 2 is the formation of a fully expanded
(all-T) structure of the ligand with the addition of two
or three equivalents of ZnMe2. Similarly, the all-T
conformer of 2 is preferentially formed upon protona-
tion or upon formation of methylene bridges between
the vicinal NH groups in a reaction with formaldehy-
de.[34a]
Figure 2. Calculated at the B3LYP/6-31G(D) level structures
of trianglamine 2-ZnMe2-acetophenone complexes (only a
fragment of the trianglamine ring is shown for clarity).
Our data on the effect of the stoichiometry of Zn-
trianglamine 2 complexes on the efficiency of hydrosi- tures A1/A4, A2/A3 and A5/A6 represent pairwise
lylation (Table 3) suggest that the 1:1 complex repre- diastereomeric orientations of the acetophenone mol-
sents the structure of the most important species in- ecule, eventually leading to hydrosilylation products
volved initially in the hydrosilylation reaction. Coor- of opposite absolute configuration. Due to the energy
dination of the ketone substrate to the Zn-triangla- differences of diastereoisomeric structures, the A1/A4
mine 2·ZnMe2 complex results in the release of a pair favors the S configuration of the product whereas
À
methane molecule with the formation of Zn O coor- the R configuration is preferred in the case of the
dinated species A (Figure 2), in which one of the ni- much less populated structures A5/A6.
trogen atoms forms a bond to the carbon atom of the
Out of six structures calculated, the lowest energy
carbonyl group.[39] Complexation of acetophenone one (A1) appears to represent the transition structure
À
molecule with C N bond formation (structures A1, leading to the product of preferred configuration.
A4–A6) results in significant changes of the confor- Since the absolute configuration of the newly formed
mation of ligand 2 around the coordination site (e.g., chiral carbon atom in A1 is S and since the substitu-
G+GÀTG+ in A1, Figure 2, see also Figure A and tion of the C N bond by the C H bond in the subse-
À
À
Table A in Supporting Information). In the absence quent reaction with silane is believed to proceed with
of the C N bond (structures A2, A3) the conforma- retention of configuration,[24] the preferred enantio-
À
tion of the ring around the coordination site remains mer of the aryl methyl carbinol product should have
TTTT, as in the complex 2·ZnMe2. Note that struc- the S configuration. This is exactly as found experi-
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Convenient Enantioselective Hydrosilylation of Ketones
FULL PAPERS
mentally in all cases reported in Table 1 and Table 2 G+TTG+, different from the sequence of torsion
(note that there is a formal reversal of the absolute angles (TTTT) in the parent 6·ZnMe2 complex. There
À
configuration of trifluoromethyl carbinols, entries 13– is no evidence of C
(C=O) N bond formation in these
15 in Table 2).
two structures.
Other calculated structures (A2/A6) are of higher
Addition of the hydride to the prochiral carbon
energy and should participate in the reaction to a atom of the carbonyl group in structure B1 is pre-
much lower extent. In the two diastereoisomeric ferred from the re face, leading to the product of S
structures A2 and A3 the addition of the hydride is configuration. In the case of structure B2 which is sta-
more probable from the sterically less encumbered bilized by interaction of one of the hydrogen atoms of
face (broken arrow), re in A2 (leading to the product the methyl group with a tertiary nitrogen atom, no
of S configuration) and si in A3 (leading to R configu- preference for hydride attack towards re or si face is
ration of carbinol). Overall, the diversity of the calcu- evident. Other calculated structures (B3–B6) are of
lated transition structures shows that full success in much higher energy (>5 kcalmolÀ1) and do not
achieving control of enantioselectivity of hydrosilyla- appear to play a significant role in determining the
tion reaction with the present catalytic system has yet absolute configuration of the product. These struc-
À
to be achieved.
tures are characterized by the presence of the C(C
O)
=
According to calculations, there are two equal N bond but, unlike the cases A1/A6 discussed earlier,
energy structures B1 and B2 of the Zn-diamine 6 they are not pairwise similar, with the respect to the
complex with a coordinated acetophenone molecule conformation of ligand 6. This is evidently due to the
(Figure 3). These two structures are diastereoisomeric flexible nature of acyclic ligand in complexes B1–B6.
with the respect to the orientation of acetophenone Only one of the structures (B3) retains the all-T con-
molecule, with the sequence of torsion angles formation.
In summary, the contribution of two low energy
structures B1 and B2 to the formation of the product
provides a reasonable rationalization of the experi-
mentally observed lower enantioselectivity of hydrosi-
lylation with the use of flexible acyclic ligand 6, com-
pared to the more rigid macrocycle 2.
Conclusions
We report here a convenient method for the enantio-
selective hydrosilylation of aryl alkyl ketones, based
on the catalysis with zinc-polyamine macrocycles,
readily available from DACH. The trianglamine 2-
ZnEt2 (1:1) complex catalyzes the hydrosilylation of
acetophenone in toluene solution, using diphenylsi-
lane, with 88% ee of the product. This enantioselectiv-
ity is higher than that with the use of acyclic ligand 6
(ee 78%). Since trianglamine 2 can be conveniently
prepared by a one-pot procedure from inexpensive
tartrate salt of DACH and terephthalaldehyde,[31] the
Zn complex of 2 is a good alternative to previously
reported chiral catalysts.
In this paper we present, related to the previous
mechanistic study of Mimoun,[24] a plausible rationali-
zation of the observed enantioselectivity of hydrosily-
lation, by ligands derived from (R,R)-DACH which
provide preferentially carbinols of S configuration. It
is based on the DFT calculated low-energy structures
of the ligand-ZnMe2 (1:1) complexes, as well as the
structures of the complexes with coordinated aceto-
phenone molecules. The most stable structures found
for cyclic (2) and acyclic (6) ligands, although struc-
turally different, lead to the hydrosilylation products
of the same absolute configuration.
Figure 3. Calculated at the B3LYP/6-31G(D) level structures
of diamine 6-ZnMe2-acetophenone complexes.
Adv. Synth. Catal. 2009, 351, 1055 – 1063
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1061

Jadwiga Gajewy et al.
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In a 5-mL round-bottom flask ZnEt2 (12.5 mL, 1M in
hexane; 0.0125 mmol) and the appropriate chiral ligand
(0.0125 mmol) were dissolved in 1.5 mL of freshly distilled
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Adv. Synth. Catal. 2009, 351, 1055 – 1063
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1063