Chiral ligands with pyridine donors in transition metal catalyzed enantioselective cyclopropanation and hydrosilylation reactions

Article abstract of DOI:10.1016/S0957-4166(00)00295-0

Copper(I) and rhodium(I) complexes prepared in situ from [Cu(OTf)(C₆H₆)_0.5] and [Rh(cod)Cl]₂ with a range of chiral 2,2'-bipyridines, 5,6-dihydro-1,10-phenanthrolines, 1,10-phenanthrolines and 2,2':6',2''-terpyridines were assessed as chiral catalysts for the enantioselective cyclopropanation of styrene with diazoacetates and for the hydrosilylation of acetophenone with diphenylsilane. Enantioselectivities up to 68% in the cyclopropanation and up to 32% in the hydrosilylation were obtained. Copyright (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00295-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 3419–3426
Chiral ligands with pyridine donors in transition metal
catalyzed enantioselective cyclopropanation and
hydrosilylation reactions
a,
a
a
b
Giorgio Chelucci, * Serafino Gladiali, Maria G. Sanna and Henri Brunner
a
Dipartimento di Chimica, Universit a` di Sassari, via Vienna 2, I-07100 Sassari, Italy
b
Institut f u¨ r Anorganische Chemie der Universit a¨ t Regensburg, D-93040 Regensburg, Germany
Received 12 July 2000; accepted 26 July 2000
Abstract
Copper(I) and rhodium(I) complexes prepared in situ from [Cu(OTf)(C H ) ] and [Rh(cod)Cl] with a
6
6 0.5
2
range of chiral 2,2%-bipyridines, 5,6-dihydro-1,10-phenanthrolines, 1,10-phenanthrolines and 2,2%:6%,2%%-ter-
pyridines were assessed as chiral catalysts for the enantioselective cyclopropanation of styrene with
diazoacetates and for the hydrosilylation of acetophenone with diphenylsilane. Enantioselectivities up to
68% in the cyclopropanation and up to 32% in the hydrosilylation were obtained. © 2000 Published by
Elsevier Science Ltd.
1
. Introduction
Recently, we have evaluated the utility of a number of chiral ligands with nitrogen donors
1
2
3
such as 2,2%-bipyridines 1, 5,6-dihydro-1,10-phenanthrolines 2 and 1,10-phenanthrolines 3
Scheme 1) as chiral controllers in the enantioselective Pd-catalyzed allylic alkylation of
(
1
,3-diphenylprop-2-enyl acetate. The differences in the catalytic activity and stereoselectivity
Scheme 1.
*
Corresponding author.
0
957-4166/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0957-4166(00)00295-0

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G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
observed with these ligands have been ascribed to the different conformational mobility induced
in the catalyst by the heterocyclic template. The five-membered chelate ring resulting from the
coordination of these ligands to the metal is most probably locked in a single conformation in
the case of 1,10-phenanthroline derivatives, whereas a certain degree of conformational freedom
is allowed in the case of 2,2%-bipyridine ligands, due to the inherently higher flexibility of this
backbone. An intermediate situation is found in the 5,6-dihydrophenanthrolines 2 where the
coplanarity of the two pyridine rings is not mandatory.
Pursuing our interest in this field, we have extended the application of ligands 1–3 to other
metal-catalyzed asymmetric processes. In this paper we report the results obtained in the
enantioselective Cu(I)-catalyzed cyclopropanation of styrene with diazoacetates and in the
enantioselective Rh(I)-catalyzed hydrosilylation of acetophenone with diphenylsilane. For the
sake of comparison with 1–3 and for a better understanding of the scope of chiral ligands with
pyridine donors in the Rh(I)-catalyzed hydrosilylation, we have further pursued our study of
this reaction to also include the ligands 9–13, previously prepared in our laboratories. All these
derivatives present the 2,2-dimethylnorpinan-2-yl unit as the unique chiral pendant. Ligands 9,
1
2 and 13 have also previously been examined in the Cu(I)-catalyzed cyclopropanation of
4
styrene with modest results.
2
. Results and discussion
2
.1. Copper(I)-catalyzed asymmetric cyclopropanation
It has been repeatedly shown that C -symmetric 2,2%-bipyridines are capable of providing high
2
5
ees in the enantioselective cyclopropanation of olefins with diazoesters. While there are no data
on the use of C -symmetric 1,10-phenanthrolines in this reaction, a very low ee was obtained in
2
4
the single isolated experiment where a C -symmetric 1,10-phenanthroline was used.
1
The reaction of styrene with ethyl diazoacetate, to give the trans- and cis-cyclopropanes 4 and
5
, was chosen as the model for the evaluation of the efficiency of ligands 1–3 in the
6
copper(I)-catalyzed asymmetric cyclopropanation of olefins. The reaction was carried out at rt
by slow addition of ethyl diazoacetate to a solution of styrene in methylene chloride containing
the copper(I)–ligand adduct. This was prepared in situ by adding the appropriate amount of
ligand 1–3 to copper(I) trifluoromethanesulfonate–benzene complex [Cu(OTf)(C H ) ].
6
6 0.5
The results obtained in these runs are summarized in Table 1. Ligands 1a–3a (R=H) provide
effective Cu(I)-catalysts, but negligible enantioselectivities. An ee in double figures (10% for the
cis-cyclopropane) was obtained only in one case with 1a as the ligand.
As a general trend, the introduction of an alkyl group onto the carbon adjacent to the
heterocyclic ring of all the ligands 1–3 displays a positive effect on the enantioselectivity of the
reaction. The ees for both trans- and cis-isomers 4 and 5 increase substantially when the
hydrogen of 1a–3a was substituted by a methyl group leading to 1b–3b. Increasing the steric
bulk of the alkyl substituent from methyl to benzyl led to a sharp improvement in the ee in the
case of ligands 1 and 2, while in the case of ligand 3 it had no significant effect on the
trans-isomer and it was even detrimental for the cis-isomer.
A further increase of the stereoselectivity was obtained when t-butyl diazoacetate was used in
place of the ethyl ester. With this reagent, the ees were in the range of 60–70% with all the
ligands 1–3 and were basically identical for all the cyclopropanes, with the exception of the

G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
3421
Table 1
a
Enantioselective cyclopropanation of styrene with diazoacetates
b
c
c
d
Ligand
Diazoacetate
R
Yield (%)
Trans:cis ratio
4:5
% ee
Configuration
4+5
4
5
4
5
1a
1b
1c
1c
2a
2b
2c
2c
3a
3b
3c
3c
Et
Et
Et
74
66
61
55
65
63
67
61
64
57
51
58
70:30
58:42
63:37
77:23
64:36
68:32
60:40
70:30
68:32
64:36
60:40
78:22
10
11
45
68
3
19
37
64
2
1R, 2S
1S, 2R
1S, 2R
1S, 2R
1R, 2S
1S, 2R
1S, 2R
1S, 2R
1R, 2S
1S, 2R
1S, 2R
1S, 2R
20
61
64
1R, 2R
1R, 2R
1R, 2R
t
Bu
Et
Et
Et
24
47
65
3
30
32
66
1R, 2R
1R, 2R
1R, 2R
1S, 2S
1R, 2R
1R, 2R
1R, 2R
t
Bu
Et
Et
Et
22
12
38
t
Bu
a
The ligand (34 mmol) in CH Cl (2.5 ml) was added to a suspension of [Cu(OTf)(C H6)0.5] (8 mg, 32 mmol) in
2
2
6
CH Cl (2.5 ml). After 30 min, the mixture was filtered through packed adsorbent cotton under argon and, to the
2
2
filtrate, was added styrene (1.59 ml, 13.87 mmol). Diazoacetate (2.5 mmol) in CH Cl (2.5 ml) was added dropwise
2
2
over a period of 1 h and then stirred for 24 h.
b
Isolated yield, based on the diazoacetate, for the mixture of trans- and cis-cyclopropanes.
Determined by GC analysis on a chiral column.
Assignment according to Ref. 7.
c
d
cis-configured product arising from 3c (38%). This (and the previous) dichotomic behaviour of
the phenanthroline based ligands 3 is hard to rationalize.
The beneficial effect of the t-butyl substitution was modest in the case of ligand 1, but was
significant for ligand 3 where a doubling of the ee of the trans-cyclopropane occurred.
The presence of larger groups, both in the ligand and in the diazoester, also affects the
trans–cis diastereoselectivity which improves moderately with the steric bulk of the substituents,
approaching the limiting value of 60% de.
Notably, the presence of an alkyl substituent in the structures of 1–3 caused a chiral switch
of the configuration of both cyclopropanes to those obtained from the unsubstituted ligands
1
a–3a: this suggests that the stereochemistry of the reaction is basically dictated by the new
stereocentre originating from the introduction of the alkyl substituent onto the basic structure
a and that this stereocentre has a mismatching stereotopic relationship with those preexisting on
the bridge.
The dependence of the stereoselectivity on the rigidity of the ligand was not at all consistent.
In the case of the methyl substituted ligands b, an increase of the rigidity was met by a modest,
but definite increase in the ee for both the cyclopropane esters. The benzyl substituted
derivatives c performed exactly opposite. Due to these contrasting trends, no meaningful
conclusion could be drawn at this point for the structure–activity relationship.

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G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
2
.2. Rhodium(I)-catalyzed asymmetric hydrosilylation
8
Several years ago we reported the use of a range of 2,2%-bipyridines and 1,10-phenanthrolines,
9
including one 5,6-dihydro derivative, as ligands in the Rh(I)-catalyzed hydrosilylation of
acetophenone with diphenylsilane.
In the course of those investigations, it was pointed out that these chiral controllers could provide
catalysts of high efficiency in the hydrosilylation of acetophenone and that the best ees were
consistently obtained with the ligands bearing the chiral substituent as close as possible to the
reactive site of the catalyst. We concluded that the coordination of these ligands to the metal was
not inhibited by the presence of rather bulky substituents on the carbon adjacent to the nitrogen.
The best enantioselectivities were recorded with ligands 6 (72% ee), 7 (70% ee) and 8 (76% ee)
having the 2,2-dimethylnorpinan-2-yl group as the common chiral substituent (Scheme 2). As the
same chiral unit is present in ligands 1–3 in the form of a cycloalkeno-condensed substituent, we
became interested in checking the behaviour of these derivatives also in this Rh(I)-catalyzed
reaction.
Scheme 2.
10
In addition to the ligands 1–3, we have also assessed compounds 9–11 in the hydrosilylation
(
2
Scheme 3), which are the C -symmetric compounds corresponding to 6–8, and the two
2
1
1
,2%:6%,2%%-terpyridines 12 and 13, with C - and C -symmetrical structures, respectively. Terdentate
1
2
nitrogen ligands of similar design, but with two oxazolines in place of the two pyridines (Pybox),
have shown remarkable activity and enantioselectivity in the hydrosilylation of ketones with
1
2
Rh(I)-catalysts.
Scheme 3.

G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
3423
13
The results obtained in the Rh(I)-catalyzed hydrosilylation of acetophenone with diphenyl-
silane in the presence of ligands 1–3 and 9–11 are reported in Table 2. The degree of
hydrosilylation (conversion of acetophenone) and the relative amounts of the silyl enol ether 16
1
14
and of the silylalkyl ether 15 were determined by H NMR, while the ee was determined by
GC analysis on a chiral column of the carbinol 17 obtained after acid hydrolysis (Scheme 4).
Table 2
a
Enantioselective hydrosilylation of acetophenone with diphenylsilane
b
b
b
c
Ligand
Enolether (%)
Conversion (%)
Yield (%)
% ee
Configuration
1a
1b
1c
2
25
26
90
85
83
88
63
61
32
2
3
R
S
S
2a
2b
2c
36
27
32
82
85
72
56
61
49
21
1
0
R
S
S
3a
3b
3c
19
22
25
94
77
79
73
55
61
10
0
1
S
R
9
1
1
30
27
33
100
93
94
70
69
63
1
2
1
S
S
S
0
1
a
Ligand (0.2 mmol), [Rh(cod)Cl] (10 mg, 0.02 mol) and acetophenone (1 ml, 8.5 mmol) in CCl (2 ml) were stirred
2
4
at 25°C for 30 min. Diphenylsilane (1.6 ml, 8.6 mmol) was added at 0°C and then the mixture slowly warmed to 25°C
and stirred for 24 h.
b
c
1
Determined by H NMR spectroscopy according to Ref. 14.
Determined by chiral GC.
Scheme 4.
High levels of conversion and satisfactory yields were obtained with all the ligands after 24 h
at rt. Much to our surprise, however, in most cases the reaction was completely devoid of
enantioselectivity. Only with the unsubstituted cycloalkeno-condensed derivatives 1a–3a, a
modest but definite ee was obtained and this showed a decreasing trend in going from
bipyridines 1 to phenanthrolines 3. These last derivatives also induced a chiral switch in the
reaction product as compared to ligands 1 and 2.
We were particularly disappointed by the results obtained with the substituted ligands 1b–3b
and 1c–3c, where an enantioselectivity higher than the one observed with the unsubstituted
counterparts 1a–3a was confidently expected in view of the close proximity of one chirogenic
element of the ligand to the metal centre.

3424
G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
Contrary to our expectations, the introduction of an alkyl substituent onto the carbon
adjacent to the heterocyclic ring resulted in the reduction both of the chemical yield and of the
stereoselectivity of the reaction. During the preparation of the Rh(I)–ligand adducts in situ, we
observed that the colour of the solution changed from yellow to orange with ligands 1a–3a,
while with the substituted ligands, the solution remained yellow with no variation noticed. This
observation seems to indicate that the substituted ligands do not bind readily to rhodium.
The catalysts originating from ligands 9–11 were reasonably active, but also provided a
racemic product. It could not be ascertained if this should be ascribed to the C -symmetry or to
2
a failure in the binding determined by the presence of two encumbering substituents in the close
proximity of the donor centres.
Table 3 summarizes the results obtained in the Rh(I)-catalyzed hydrosilylation of aceto-
phenone with diphenylsilane in the presence of the 2,2%:6%,2%%-terpyridine ligands 12 and 13. These
tridentate ligands led to lower conversions and lower rates. This drawback was not counterbal-
anced by an increase in the ee which remained very poor and exceeded 10% in only one case.
A change in the solvent from methylene chloride to tetrachloromethane led to an increase in the
amount of the enol ether 16 and addition of silver fluoroborate had the same effect.
Table 3
a
Enantioselective hydrosilylation of acetophenone with diphenylsilane
Run
Ligand
Solvent
Reaction time
h)
Enolether
(%)
Conversion
(%)
Yield
(%)
ee
(%)
Conf.
b
b
b
c
(
1
2
3
4
5
6
7
12
12
12
12
13
13
13
CH Cl2
20
40
44
67
20
20
20
31
26
81
100
36
35
49
78
82
41
36
94
88
74
51
54
8
6
6
n.d.
S
S
2
d
CH Cl2
2
CCl4
CCl4
e
0
CH Cl2
53
55
37
1
2
14
S
S
S
2
CCl4
CCl4
e
a
Ligand (0.2 mmol), [Rh(cod)Cl] (10 mg, 0.02 mol) and acetophenone (1 ml, 8.5 mmol) in the appropriate solvent
2
(
2 ml) were stirred at 25°C for 30 min (if AgBF4 was added, stirring was continued for another 30 min).
Diphenylsilane (1.6 ml, 8.6 mmol) was added at 0°C and then the mixture slowly warmed to 25°C and stirred for the
appropriate time.
b
c
1
Determined by H NMR spectroscopy according to Ref. 14.
Determined by chiral GC.
In this case 12 and [Rh(cod)Cl] were stirred at 25°C for 72 h.
d
e
2
Eccess of AgBF was added.
4
Taken overall, the results assembled in Tables 1–3 show that the ligands with pyridine donors
used throughout this work are poorly suited chiral controllers in the Rh(I)-catalyzed hydrosilyl-
ation of acetophenone, while they seem to warrant attention for their possible applications in
the field of Cu(I)-catalyzed cyclopropanation. Further studies on this subject are currently in
progress in our laboratory.

G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
3425
3
. Experimental
3
.1. General
Gas chromatographic analyses were performed with a HP 5900 chromatograph using He
60 kPa) as the carrier gas. Copper(I) trifluoromethanesulfonate benzene complex
Cu(OTf)(C H ) ], [Rh(cod)Cl] , ethyl and t-butyl diazoacetate were purchased from Aldrich.
(
[
6
6 0.5
2
The ligands were prepared according to reported procedures: 5,7-methano-6,6-dimethyl-2-(2-
1
1
pyridinyl)-5,6,7,8-tetrahydroquinoline 1a and the corresponding 8-methyl 1b and 8-benzyl
1
2
derivatives 1c, 8,10-methano-9,9-dimethyl-8,9,10,11-tetrahydrobenzo[b][1,10]phenanthroline 2a
and the corresponding 11-methyl 2b and 11-benzyl derivatives 2c, 8,10-methano-9,9-dimethyl-
,6,8,9,10,11-hexahydrobenzo[b][1,10]phenanthroline 3a and the corresponding 11-methyl 3b
and 11-benzyl derivatives 3c, 6,6%-bis[6,6-dimethylnorpinan-2-yl]-2,2%-bipyridine 9, 2,9-bis[6,6-
2
2
3
3
5
3
10
10
dimethylnorpinan-2-yl]-5,6-dihydro-1,10-phenanthroline 10,
2,9-bis[6,6-dimethylnorpinan-2-
1
0
11
yl]-1,10-phenanthroline 11,
6
6-[6,6-dimethylnorpinan-2-yl]-2,2%:6%,2%%-terpyridine 12
and
11
,6%%-bis[6,6-dimethylnorpinan-2-yl]-2,2%:6%,2’’-terpyridine 13.
.2. Asymmetric cyclopropanation of styrene: typical procedure
A solution of the ligand (34 mmol) in CH Cl (2.5 ml) was added to a suspension of
3
2
2
[
Cu(OTf)(C H ) ] (8 mg, 32 mmol) in CH Cl (2.5 ml). After 30 min, the mixture was filtered
through packed adsorbent cotton under argon and, to the filtrate, styrene (1.59 ml, 13.87 mmol)
6
6 0.5
2
2
was added. Then a solution of the diazoacetate ester (2.5 mmol) in CH Cl (2.5 ml) was added
2
2
dropwise over a period of 1 h. The mixture was stirred for 24 h at rt and then concentrated in
vacuo. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=
1
5/1) to afford a mixture of ethyl trans- and cis-2-phenyl-cyclopropane-1-carboxylates as a
colurless oil. The trans/cis ratio and the ee were determined by GC analysis on a diethyl-t-
butylsilyl b-cyclodextrin capillary column 25×0.25 mm operated at 60°C for 5 min, then
−
1
programmed at 3°C min to 160°C. [Retention times: 33.2 (1S,2S) and 33.5 (1R,2R) min for
trans 4; retention times: 31.4 (1R,2S) and 31.8 (1S,2R) min for cis-5].
3
.3. Asymmetric hydrosilylation of acetophenone: typical procedure
The catalyst was prepared by dissolving the precursor [Rh(cod)Cl] (10 mg, 0.02 mol) and the
2
ligand (0.2 mmol) in acetophenone (1 ml, 8.5 mmol) under argon. Then the proper solvent (2
ml) was added and stirring was continued for 30 min (if AgBF was added, the stirring time was
4
6
0 min). The mixture was cooled at 0°C and after 30 min diphenylsilane (1.6 ml, 8.6 mmol) was
added. The solution was slowly warmed up to rt and then stirred for 24 h (Table 2) or for an
appropriate length of time (Table 3). A sample was then taken (0.2 ml), diluted with CDCl (0.4
3
1
ml) and a H NMR (300 MHz) was recorded to determine the amount of silylenol ether
(
16/15+16), the degree of hydrosilylation (conversion of acetophenone, 15+16/14+15+16) and
14
the chemical yield of silylalkyl ether (15/14+15+16). The following integrals were used for the
analysis: l=5.70 ppm (s, Si-H, silylenol ether 16), l=5.40 ppm (s, Si-H, silylalkyl ether 15) and
l=2.50 ppm (s, CH , acetophenone 14).
3
The mixture was diluted with methanol (10 ml) and treated with a few crystals of p-TsOH.
After stirring at rt for 30 min the solvent was evaporated and the residue was distilled in a

3426
G. Chelucci et al. / Tetrahedron: Asymmetry 11 (2000) 3419–3426
Kugelrohr apparatus at 130°C/2 Torr. The enantiomeric excess (ee) was determined by GC
analysis on a diethyl-t-butylsilyl b-cyclodextrin column operated at 60°C for 5 min, then
−
1
programmed at 3°C min to 150°C. Retention times: 23.75 min [(R)-1-phenylethanol] and 24.20
min [(S)-1-phenylethanol].
Acknowledgements
This work was financially supported by Universit a` di Sassari and Ministero dell’Universita’ e
della Ricerca Scientifica e Tecnologica, Roma.
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2
3
4
5
6
7
8
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