New chiral 1,2-diamines and their use in zinc-catalyzed asymmetric hydrosilylation of acetophenone

Article abstract of DOI:10.1002/ejoc.200400129

The preparation of two new series of chiral 1,2-diamines and their use in the [ZnR₂-diamine]-catalyzed asymmetric hydrosilylation of acetophenone with poly(methylhydrosiloxane) (PMHS) in an aprotic medium is reported. The effect of structural m

Full text of DOI:10.1002/ejoc.200400129

FULL PAPER
New Chiral 1,2-Diamines and Their Use in Zinc-Catalyzed Asymmetric
Hydrosilylation of Acetophenone
[a]
[a]
[b]
[b]
´
Virginie Bette, Andre Mortreux,* Federico Ferioli, Gianluca Martelli, Diego Savoia,*
and Jean-Franc¸ois Carpentier*[c]
[b]
Keywords: Asymmetric catalysis / Diamine ligands / Hydrosilylation / PMHS / Zinc
The preparation of two new series of chiral 1,2-diamines and
of chiral centers, on the N-benzylic side-arms and on the
their use in the [ZnR2-diamine]-catalyzed asymmetric hy- ethylene bridge of the diamine skeleton, has been investig-
drosilylation of acetophenone with poly(methylhydrosilox-
ane) (PMHS) in an aprotic medium is reported. The effect of
structural modifications of the secondary diamine ligand, in
particular a possible cooperative effect of two different types
ated. A new diamine ligand giving up to 91% ee is described.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
uct of the silicon industry, that acts as an efficient alterna-
tive to noxious and expensive molecular hydrosilanes.[3,5]
Over the past two decades enantiomerically pure 1,2-di-
amines and some of their derivatives have attracted con-
siderable attention as chiral ligands in a variety of tran-
sition-metal-catalyzed asymmetric processes.[1] Noteworthy
is their application in the enantioselective reduction of Cϭ
O and CϭN bonds, mostly by hydrogenation and transfer
hydrogenation, in association with group 8 metals.[2] The
use of chiral diamines for the hydrosilylation/reduction of
carbonyl compounds is more restricted.[3] Recently, Mim-
oun et al. reported a chiral hydrosilylation system, based on
catalyst combinations of ZnEt2 and optically active second-
ary 1,2-diamines, that enables the reduction of simple aryl
alkyl ketones (Scheme 1).[4] High yields and enantioselectiv-
ities were obtained for the reduction of acetophenone using
C2-symmetric diamines as chiral ligands, for example, (S,S)-
N,NЈ-dibenzyl-1,2-diphenyl-1,2-ethanediamine (Bn-dpen, 1)
(up to 88% ee) or (S,S)-N,NЈ-ethylenebis(1-phenylethylam-
ine) (ebpe, 2) (up to 75% ee) (Scheme 2).[4a] The attractive-
ness of this system lies also in the use of poly(methylhydro-
siloxane) (PMHS), a safe and inexpensive polymer coprod-
Scheme 1
In this contribution, we report some results related to the
zinc-catalyzed asymmetric hydrosilylation of acetophenone
with PMHS using differently substituted chiral secondary
1,2-diamines;[4b,4c] some of these diamines are new and were
designed with the aim of improving the enantioselectivity
of the reaction. In particular, we investigated the catalytic
ability of two series of such ligands: the ligands of the first
series combine the structural features of Bn-dpen (1) and
ebpe (2) and were prepared in order to assess the possible
cooperative effect of chiral centers at the 1,2-positions of
the ethylene backbone and at the α-position of the N-benzyl
arms, that is, 3aϪd; the second series consists of ortho-phe-
nyl-substituted analogues of Bn-dpen, that is, 4b,c
(Scheme 2). The impact of the ligand structure and relative
stereochemistry on the catalyst activity and enantioselectiv-
ity has been investigated.
[a]
´
Chimie Organique Appliquee, UPRESA 8010 CNRS-
´
Universite de Lille 1, ENSCL
BP 108,
59652 Villeneuve d’Ascq Cedex, France
E-mail: andre.mortreux@ensc-lille.fr
Dipartimento di Chimica ЈG. CiamicianЈ, Universita di
[b]
[c]
`
Bologna,
Via Selmi 2, 40126 Bologna, Italy
E-mail: savoia@ciam.unibo.it
´
´
Organometalliques et Catalyse, UMR 6509 CNRS-Universite
de Rennes 1, Institut de Chimie,
Campus de Beaulieu, 35042 Rennes Cedex, France
Fax: (internat.) ϩ33-223-236-939
E-mail: jean-francois.carpentier@univ-rennes1.fr
3040
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400129
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Chiral 1,2-Diamines in Zinc-Catalyzed Asymmetric Hydrosilylation of Acetophenone
FULL PAPER
chromatography of the crude mixtures obtained by the
addition of 2-methoxyphenyl- and 2,5-(dimethoxyphenyl)-
magnesium chloride to the imine 5 at 0 °C led to the iso-
lation, in a pure state, of only the two prevalent dia-
stereomers of both compounds in moderate to low yields
[19Ϫ33% for (1R,2R)-3b,c and 13Ϫ17% for (1S,2S)-3b,c].
The minor diastereomers (1S,2R)-3b,c could not be com-
pletely separated from the (1R,2R)-3b,c diastereomers.
Scheme 2
Results and Discussion
Preparation of the Chiral 1,2-Diamines
The 1,2-disubstituted-1,2-diamines were prepared by
double addition of the appropriate organometallic reagent
to the corresponding 1,2-bis(imine) 5, derived from the con-
densation of glyoxal with 2 equivalents of (S)-1-(phenyl)-
ethylamine (Scheme 3).[6] The 1,2-diphenyl- and 1,2-di-
butyl-substituted compounds 3a and 3d are known com-
pounds, and are available by the addition of PhMgCl and
nBuLi to 5 in THF at Ϫ78 °C, respectively.[7,8] In addition,
a new series of secondary diamines have been developed as
an ortho-substituents affect the orientation of the phenyl
rings at the 1,2-positions, and consequently the overall con-
formation of the diamine ligand in the intermediate zinc
complex involved in the enantio-determining step. To ex-
plore the effect of ortho-substituents on catalytic activity
and enantioselectivity, 2-methoxyphenyl and 2,5-dimeth-
oxyphenyl substituents were selected and the new diamines
3b,c were prepared according to the route described in
Scheme 3, starting from 5 and the relevant Grignard re-
agents. Although the efficiency and diastereoselectivity of
the first step can be in part controlled by the appropriate
choice of Grignard reagent and experimental conditions
(e.g. syringe-controlled addition of the organometallic re-
agent, temperature),[6,8] our choice was to achieve moderate
Scheme 3
The N,NЈ-dibenzyl derivatives (1S,2S)- and (1R,2R)-4b,c
stereocontrol as we wished to obtain all three possible were then prepared by a three-step sequence (Scheme 3).
stereoisomers [i.e. with the (1S,2S), (1R,2R) and (1S,2R) The first step was the reductive cleavage of the N,NЈ-sub-
configurations], and assess their behavior in the zinc-cata- stituents (chiral auxiliaries) of 3b,c using ammonium for-
lyzed hydrosilylation/reduction of a model ketone. Column mate and Pd/C in refluxing methanol,[9] which gave the cor-
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V. Bette, A. Mortreux, F. Ferioli, G. Martelli, D. Savoia, J.-F. Carpentier
FULL PAPER
responding primary 1,2-diamines (1S,2S)- and (1R,2R)-6b,c
in 75Ϫ81% yields. The crude primary diamines, being
rather sensitive to air, light and acidic media, were directly
used in the next step to avoid the loss of products during
purification. In our hands, the direct N,NЈ-dibenzylation of
6b,c under the conditions used by Alexakis et al. for the
N,NЈ-dibenzylation of 1,2-cyclohexanediamine (benzyl bro-
mide, KI, K2CO3, EtOH, room temp.)[10] was not success-
ful, providing yields of less than 10% of the desired com-
pounds 4b,c. Better results were achieved by conventional
N-benzoylation to give the amides 7b,c, followed by re-
duction with borane-dimethyl sulfide in THF at reflux. By
using this route, the enantiomers (1R,2R)-4b,c were ob-
tained in 37% overall yield (2 steps) as some loss of the
products occurred during crystallization and chromato-
graphic purification. The same two-step sequence was ap-
plied to the other diastereomers (1S,2S)-7b,c to obtain the
desired secondary 1,2-diamines (1S,2S)-4b,c.
Table 1. Reduction of acetophenone with the ZnEt2/diamine/
PMHS system
Entry[a] 1,2-Diamine
Time [h][b] Yield [%] ee [%] (Conf.)
1[c]
2[c]
3
4
5
(1S,2S)-1
α(S,S)-2
18
18
98
99
4
56
11
30
66
33
56
44
78
Ͼ 99
Ͼ 99
Ͼ 99
94
88 (S)
75 (S)
Ͻ 5 (nd)
84 (R)
37 (R)
25 (R)
91 (R)
78 (R)
78 (R)
33 (R)
67 (R)
83 (R)
83 (S)
83 (S)
87 (S)
84 (R)
(1R,2R)-α(S,S)-3a 72
(1S,2S)-α(S,S)-3a 170
(1S,2R)-α(S,S)-3a 48
(1R,2R)-α(S,S)-3b 216
(1S,2S)-α(S,S)-3b 288
6
7
8[d]
(1S,2S)-α(S,S)-3b
18
40
9
10
11
(1R,2R)-α(S,S)-3d 48
(1S,2S)-α(S,S)-3d
(S,S)-4b
44
72
72
18
96
72
12
(R,R)-4b
13[d]
14
(R,R)-4b
(R,R)-4c
15
(S,S)-4c
Ͼ 99
It should be underlined that attempted resolution of d,l-
3b, obtained by reductive dimerization of N-ortho-(meth-
oxybenzylidene)benzylamine[11] with zinc/methanesulfonic unless otherwise stated.
acid and chromatographic separation of the meso dia-
stereomer, failed using both 1 and 2 equivalents of tartaric
acid. Analogously, we did not find suitable conditions for
[a]
PMHS/acetophenone/ZnEt2/diamine,
60:50:1:1,
[aceto-
phenone] ϭ 0.89  in toluene. Reactions were carried out at 20 °C
[b]
[c]
Reaction time not optimized.
See
ref.[4a] [d] Reaction was carried out at 50 °C.
the separation of the enantiomers of 4b,c by HPLC analysis (the enantioselectivity of all the systems reported in this
on a chiral column. This would have been useful to assess paper is constant over the whole reaction time, as deter-
the ee of these compounds when obtained from the chiral mined by GLC monitoring). While nBu derivatives 3d af-
bis(imine) 5. However, their enantiomeric purity was in- forded poor ee’s (Entries 9 and 10), introduction of an or-
directly demonstrated using the results of the enantioselec- tho-methoxyphenyl substituent at the 1,2 positions (3b) al-
tive hydrosilylation reactions of acetophenone, as the en- lowed a promising 91% ee to be obtained (Entry 7); this is
antiomers of both diamines 4b,c afforded (almost) the same the highest enantioselectivity so far achieved in this new
degree of enantiocontrol (vide infra).
hydrosilylation/reduction of acetophenone. This good per-
formance may possibly be due to hindered (restricted) ro-
tation of the phenyl moiety. On the other hand, quite low
reaction rates were observed with all of these mixed ligands,
Zinc-Promoted Asymmetric Hydrosilylation of
Acetophenone
The secondary chiral diamines prepared in this work, in probably because of their increased bulkiness compared
combination with ZnEt2, were investigated in the hydrosilyl- with ligands 1 and 2. Presumably, the size of the aryl sub-
ation/reduction of acetophenone, chosen as a model sub- stituents on the ethylene chain affects the conformation/mo-
strate, using PMHS as the reducing agent (Scheme 1). Rep- bility of the N-(1-phenylethyl) substituents, whose steric ef-
resentative results are reported in Table 1 and are compared fects are thus more important in the reactive intermediate
to those obtained under the same conditions with chiral (Zn complex). In the case of 3b, reduction at a higher tem-
diamines 1 and 2 (Entries 1 and 2).[4a]
perature (50 °C) led to increased activity of the catalytic
The so-called mixed ‘‘ebpe-dpen’’ diamines 3, in which system, allowing a satisfactory conversion to be achieved
both types of chiral centers are present, led to classical after a reasonable reaction time, although with a reduction
‘‘matched’’ and ‘‘mismatched’’ effects (Entries 3Ϫ10). The in the enantioselectivity (Entry 8).
best results, in terms of enantioselectivity, were obtained
The introduction of an α-methyl substituent on the N-
with the diastereomers (1S,2S)-α(S,S), which is consistent benzyl arms lowers the activity and enantioselectivity of the
with the fact that both (1S,2S)-Bn-dpen (1) and α(S,S)-ebpe catalyst system, as compared with N-Bn-dpen (1). There-
(2) lead to the same major enantiomer of 2-phenylethanol. fore, the use of 1,2-diaryl-N,NЈ-dibenzyldiamines 4b,c, ana-
Quite low enantioselectivity was achieved with the ‘‘mis- logues of 1, was investigated (Entries 11Ϫ15). Significantly
matched’’ pairs (1R,2R)-α(S,S), whereas the pseudo-meso higher reaction rates were obtained with 4b,c, confirming
derivative (1S,2R)-α(S,S)-3a gives intermediate perform- the fact that steric bulkiness is the likely cause of the modest
ance (Entry 5). Disappointingly, the results for the 3a series catalytic activity of systems based on ligands 3.[12] Surpris-
indicate that no cooperation occurs within this system: in- ingly, the enantioselectivity of the system based on the 2-
deed, the enantioselective performance of the ‘‘matched’’ methoxyphenyl-substituted diamine 4b was found to be
(1S,2S)-α(S,S) ligand (84% ee, ∆∆G# ϭ 1.45 kcal·molϪ1
was in between that of N-Bn-dpen (88% ee, ∆∆G# ϭ 1.64 for the mixed ebpe-dpen ligands 3b, in which the ortho-
kcal·molϪ1) and ebpe (75% ee, ∆∆G# ϭ 1.16 kcal·molϪ1
methoxy substituent was observed to have a positive effect
)
lower than that of 1, in contrast with the trend observed
)
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Chiral 1,2-Diamines in Zinc-Catalyzed Asymmetric Hydrosilylation of Acetophenone
FULL PAPER
and concentrated to give an oil (6.28 g). The mixture could not
be analyzed by GC-MS analysis owing to decomposition of the
secondary diamines 3b,c. 1H NMR analysis showed the presence
of the (1R,2R) and (1S,2S) diastereomers in a 68:32 ratio, whereas
the (1R,2S) diastereomer was not discerned; moreover, anisole and
1-phenylethylamine, the latter deriving from hydrolysis of the start-
ing diimine or the intermediate α-aminoimine, were present. The
pure diastereomers were obtained by column chromatography
(SiO2, cyclohexane/EtOAc mixtures). The (1R,2R) isomer of 3b was
further purified by crystallization (MeOH) to give a white crystal-
on the enantioselectivity (Entry 7). The enantioselectivity
of 4b is, however, not affected by temperature, which allows
the reaction to be completed within much shorter time per-
iods than systems based on 3b, whilst still maintaining a
reasonably high level of enantioselectivity (Entry 13).
In conclusion, two new series of chiral diamines have
been developed and their behaviour in the asymmetric
hydrosilylation of acetophenone has been thoroughly inves-
tigated. Relatively high enantioselectivity could be reached,
although the introduction of substituents onto the ligand line solid.
backbone led to quite modest catalyst activity. No simple
(1R,2R)-α(S,S)-3b: Yield 1.17 g (19%); m.p. 104Ϫ106 °C. [α]2D0
ϭ
structure-selectivity relationship has been established so far
that would allow a rational design of the optimum ligand.
Ϫ184.4 (c ϭ 0.77, CHCl3). IR (neat): ν˜max. ϭ 3305, 3061, 3025,
1599, 1586, 1490, 1463, 1368, 1242, 753, 700 cmϪ1 1H NMR
.
(300 MHz, CDCl3): δ ϭ 1.24 (d, J ϭ 6.6 Hz, 6 H, CHCH3), 2.35
(br. s, 2 H, NH), 3.36 (s, 6 H, OCH3), 3.42 (q, J ϭ 6.6 Hz, 2 H,
CHCH3), 3.92 (s, 2 H, NCHCHN), 6.59 (d, J ϭ 8.4 Hz, 2 H, Ar),
6.78 (t, J ϭ 7.8 Hz, 2 H, Ar), 6.97Ϫ7.13 (m, 4 H, Ar), 7.13Ϫ7.34
(m, 10 H, Ph) ppm. C32H36N2O2 (480.65): calcd. C 79.96, H 7.55,
N 5.83; found C 79.90, H 7.57, N 5.82.
Experimental Section
General: Optical rotations were measured with a digital polarimeter
at 25 °C in a 1-dm cell and [α]D values are given in 10Ϫ1
deg·cm3·gϪ1. 1H NMR spectra were recorded with a Varian Gemini
instrument at 300 or 200 MHz for samples in CDCl3 which was
(1S,2S)-α(S,S)-3b: Yellow oil, yield 1.07 g (17%). [α]2D0 ϭ Ϫ29.4 (c ϭ
0.57, CHCl3). IR (neat): ν˜max. ϭ 3296, 3060, 3027, 1599, 1490,
1
stored over Mg: H chemical shifts are reported in ppm downfield
1463, 1243, 1029, 753, 700 cmϪ1 1H NMR (300 MHz, CDCl3):
.
from TMS and were determined by reference to the residual 1H
(δ ϭ 7.25 ppm) solvent peak; 1H chemical shifts are reported in
ppm relative to CHCl3 (δH ϭ 7.27 ppm). GLC analyses were per-
formed on Chrompack CP 9001 apparatuses equipped with a flame
ionization detector and, respectively, BPX5 (25 m ϫ 0.32 mm,
SGE) and chiral Chirasil-DEX CB (25 m ϫ 0.25 mm, Chrompack)
columns. MS spectra were recorded at an ionizing voltage of 70 eV
with a HewlettϪPackard 5970 or 5890 spectrometer with GLC in-
jection. Microanalyses were carried out at the chemistry depart-
δ ϭ 1.33 (d, J ϭ 6.6 Hz, 6 H, CHCH3), 2.30 (br. s, 2 H, NH), 3.51
(s, 6 H, OCH3), 3.64 (q, J ϭ 6.6 Hz, 2 H, CHCH3), 4.41 (s, 2 H,
NCHCHN), 6.54 (d, J ϭ 8.4 Hz, 2 H, Ar), 6.73 (t, J ϭ 7.2 Hz, 2
H, Ar), 7.0 (t, J ϭ 7.2 Hz, 2 H, Ar), 7.08Ϫ7.32 (m, 12 H, Ph and
Ar) ppm.
(1R,2R)-1,2-Bis(2,5-dimethoxyphenyl)-N,NЈ-bis[(S)-1-phenylethyl]-
1,2-ethanediamine [(1R,2R)-α(S,S)-3c]: Yellow oil, yield 1.76 g
(33%). [α]2D0 ϭ Ϫ120.1 (c ϭ 0.97, CHCl3). IR (neat): ν˜max. ϭ 3297,
3058, 3022, 3000, 1607, 1587, 1496, 1464, 1272, 1217, 1048, 759,
`
ment of the Universita di Bologna. IR spectra were recorded with
a Nicolet 510 FTIR spectrophotometer; absorption maxima are
expressed in wave numbers (cmϪ1). Chromatographic separations
were performed on columns of SiO2 (Merck, 230Ϫ400 mesh) at
medium pressure. Melting points are uncorrected.
1
701 cmϪ1. H NMR (200 MHz, CDCl3): δ ϭ 1.23 (d, J ϭ 6.6 Hz,
6 H, CHCH3), 2.07 (br. s, 2 H, NH), 3.32 (s, 6 H, OCH3), 3.42 (q,
J ϭ 6.6 Hz, 2 H, CHCH3), 3.70 (s, 6 H, OCH3), 3.88 (s, 2 H,
NCHCHN), 6.54 (d, J ϭ 8.8 Hz, 2 H, Ar), 6.64 (dd, J ϭ 8.8,
3.0 Hz, 2 H, Ar), 6.87 (m, 2 H, Ar), 7.0 (m, 4 H, Ph), 7.10Ϫ7.30
(m, 6 H, Ph) ppm. C34H40N2O4 (540.71): calcd. C 75.52, H 7.46,
N 5.18; found C 75.49, H 7.48, N 5.17.
Bn-Dpen (1),[13] ebpe (2),[4a] 1,2-diimine 5,[14]and diamines 3a[7,8]
and 3d[7] were prepared following reported procedures and rigor-
ously purified by distillation or column chromatography and sub-
sequent recrystallization. Benzoyl chloride was distilled before use
under N2. ZnEt2 (1.1  solution in toluene) was purchased from
Aldrich and used as received. Acetophenone (99%, Aldrich) was
distilled from over CaH2 and degassed before use. PMHS (Aldrich)
was degassed before use. All other chemicals were used as pur-
chased from Aldrich or Fluka. Toluene was freshly distilled from
a Na/K amalgam and degassed before use. Solvents for organic
synthesis were purified and dried following standard procedures.
(1S,2S)-1,2-Bis(2,5-dimethoxyphenyl)-N,NЈ-bis[(S)-1-phenylethyl]-
1,2-ethanediamine [(1S,2S)-α(S,S)-3c]: Yellow oil, yield 0.70 g
(13%). [α]2D0 ϭ Ϫ41.2 (c ϭ 0.38, CHCl3). IR (neat): ν˜max. ϭ 3283,
3051, 3022, 1601, 1587, 1497, 1464, 1273, 1218, 1048, 700 cmϪ1
.
1H NMR (200 MHz, CDCl3): δ ϭ 1.33 (d, J ϭ 6.6 Hz, 6 H,
CHCH3), 2.28 (br. s, 2 H, NH), 3.51 (s, 6 H, OCH3), 3.60 (q, J ϭ
6.6 Hz, 2 H, CHCH3), 3.67 (s, 6 H, OCH3), 4.37 (s, 2 H,
NCHCHN), 6.50 (d, J ϭ 8.8 Hz, 2 H, Ar), 6.58 (dd, J ϭ 8.8,
2.8 Hz, 2 H, Ar), 6.82 (m, 2 H, Ar), 7.15Ϫ7.30 (m, 10 H, Ph) ppm.
Preparation of the Secondary 1,2-Diamines 3b,c. General Procedure
(1R,2R)- and (1S,2S)-1,2-Bis(2-methoxyphenyl)-N,NЈ-bis[(S)-1-
phenylethyl]-1,2-ethanediamine [(1R,2R)- and (1S,2S)-α(S,S)-3b]: A
catalytic amount of iodine and 2-bromoanisole (1.60 mL,
12.9 mmol) were added to a suspension of magnesium turnings
(1.22 g, 50.2 mmol) in THF (10 mL) under Ar. After the Grignard
reaction was started, a solution of 2-bromoanisole (4.00 mL,
Preparation of the Primary 1,2-Diamines 6b,c. General Procedure
(1R,2R)-1,2-Bis(2-methoxyphenyl)-1,2-ethanediamine [(R,R)-6b]: A
mixture of the secondary diamine (1R,2R)-3b (1.41 g, 2.90 mmol),
HCO2NH4 (3.70 g, 58.7 mmol) and Pd/C 10% (1.00 g) in MeOH
(40 mL) was refluxed for 10 h under Ar. After cooling to room
32.3 mmol) in THF (10 mL) was added dropwise over 10 min. temp., the mixture was filtered through a pad of Celite which was
After stirring for 20 min, the mixture was heated to 60 °C for 1 h.
The Grignard reagent obtained was added over 15 min to a solu-
washed with EtOH. The ethanolic solution was concentrated to
leave a yellowish oil, which was then dissolved in CH2Cl2 (20 mL).
tion of 1,2-diimine 5 (3.96 g, 15.0 mmol) in THF (30 mL) at 0 °C. An aqueous solution of NaOH (pH 11, 10 mL) was added, the
The mixture was stirred at 0 °C for 1 h, then at room temp. for 1 h mixture was stirred for 5 min and the organic phase was extracted
and quenched with water (20 mL). The organic phase was extracted with CH2Cl2 (3 ϫ 15 mL). The organic phase was washed with
with Et2O (3 ϫ 20 mL) and the ethereal layers were dried (Na2SO4) brine (20 mL), dried (Na2SO4) and concentrated to give the pri-
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V. Bette, A. Mortreux, F. Ferioli, G. Martelli, D. Savoia, J.-F. Carpentier
FULL PAPER
mary 1,2-diamine (R,R)-6b as a yellow oil (0.64 g, 81%); the com-
(1S,2S)-N,NЈ-Dibenzoyl-1,2-bis(2,5-dimethoxyphenyl)-1,2-ethanedi-
amine [(S,S)-7c]: (S,S)-7c was isolated by chromatography as a yel-
pound was about 95% pure by 1H NMR analysis and was not
further purified. [α]2D0 ϭ ϩ55.7 (c ϭ 0.89, CHCl3). IR (neat): lowish solid. Yield 0.22 g (31%); m.p. 78Ϫ80 °C. [α]2D0 ϭ Ϫ9.9 (c ϭ
ν˜max. ϭ 3364, 3297, 3072, 3029, 3000, 1600, 1487, 1368, 1235, 1109,
0.71, CHCl3).
1036, 746 cmϪ1 1H NMR (200 MHz, CDCl3): δ ϭ 1.83 (br. s, 4
.
Preparation of the N,NЈ-Dibenzyl-1,2-Diamines 4b,c. General Pro-
cedure
H, NH2), 3.79 (s, 6 H, OCH3), 4.46 (s, 2 H, NCHCHN), 6.73Ϫ6.88
(m, 4 H, Ar), 7.07Ϫ7.28 (m, 4 H, Ar) ppm. Partial decomposition
occurred during the GC-MS analysis. C16H20N2O2 (272.35): calcd.
C 70.56, H 7.40, N 10.29; found C 70.52, H 7.43, N 10.27.
(1R,2R)-N,NЈ-Dibenzyl-1,2-bis(2-methoxyphenyl)-1,2-ethanedi-
amine [(R,R)-4b]: A solution of the (R,R)-dibenzoyldiamine 7
(0.26 g, 0.50 mmol) in THF (4 mL) was slowly added to a solution
of BH3ϪSMe2 (170 µL, 1.70 mmol) in THF (4 mL) cooled to 0 °C
under Ar. The mixture was refluxed while stirring for 6 h, then
quenched at 0 °C with aq. NaOH. The organic phase was extracted
with Et2O (3 ϫ 7 mL), dried over Na2SO4 and concentrated to give
a yellowish oil. The pure N,NЈ-dibenzyldiamine was obtained as a
yellowish oil by chromatography on an Al2O3 column eluting with
cyclohexane/EtOAc mixtures (0.145 g, 58%). [α]2D0 ϭ Ϫ38.3 (c ϭ
0.85, CHCl3). IR (neat): ν˜max. ϭ 3306, 3061, 3026, 2999, 1599,
(1S,2S)-1,2-Bis(2-methoxyphenyl)-1,2-ethanediamine [(S,S)-6b]: Yel-
low oil, yield 0.59 g (75%). [α]2D0 ϭ Ϫ56.4 (c ϭ 1.21, CHCl3).
(1R,2R)-1,2-Bis(2,5-dimethoxyphenyl)-1,2-ethanediamine [(1R,2R)-
6c]: Yellow oil, yield 0.74 g (77%). [α]2D0 ϭ ϩ34.7 (c ϭ 1.16, CHCl3).
IR (neat): ν˜max. ϭ 3374, 3321, 3072, 1595, 1589, 1498, 1221, 1179,
1158, 1047, 871, 804, 753 cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ
1.65 (br. s, 4 H, NH2), 3.73 (s, 6 H, OCH3), 3.77 (s, 6 H, OCH3),
4.45 (s, 2 H, NCHCHN), 6.71 (m, 4 H, Ar), 6.88 (d, J ϭ 2.6 Hz,
2 H, Ar) ppm. C18H24N2O4 (332.40): calcd. C 65.04, H 7.28, N
8.43; found C 65.00, H 7.29, N 8.42.
1586, 1280, 1111, 1029, 751, 698 cmϪ1 1H NMR (200 MHz,
.
CDCl3): δ ϭ 2.51 (br. s, 2 H, NH), 3.53 (s, 6 H, OCH3), 3.57 (qAB,
J ϭ 13.2 Hz, 4 H, NCH2), 4.24 (s, 2 H, NCHCHN), 6.63 (d, J ϭ
8.4 Hz, 2 H, Ar), 6.79 (t, J ϭ 7.8 Hz, 2 H, Ar), 7.08 (t, J ϭ 7.8 Hz,
2 H, Ar), 7.16Ϫ7.34 (m, 12 H, Ar and Ph) ppm. C30H32N2O2
(452.60): calcd. C 79.61, H 7.13, N 6.19; found C 79.60, H 7.14,
N 6.18.
(1S,2S)-1,2-Bis(2,5-dimethoxyphenyl)-1,2-ethanediamine [(1S,2S)-
6c]: Yellow oil, yield 0.74 g (77%). [α]2D0 ϭ Ϫ27.8 (c ϭ 0.64, CHCl3).
Preparation of the Diamides 7b,c. General Procedure
(1S,2S)-N,NЈ-Dibenzyl-1,2-bis(2-methoxyphenyl)-1,2-ethanediamine
[(S,S)-4b]: Yield 0.12 g (49%). [α]2D0 ϭ ϩ33.3 (c ϭ 0.67, CHCl3).
(1R,2R)-N,NЈ-Dibenzoyl-1,2-bis(2-methoxyphenyl)-1,2-ethanedi-
amine [(R,R)-7b]: Triethylamine (0.45 mL, 3.30 mmol), benzoyl
chloride (0.38 mL, 3.30 mmol) and a catalytic amount of 4-(di-
methylamino)pyridine were added to a solution of the primary di-
amine (R,R)-6b (0.35 g, 1.30 mmol) in anhydrous CH2Cl2 (10 mL)
cooled to 0 °C under Ar. After 5 min the mixture was allowed to
reach room temp. and stirred for 5 h. Further triethylamine (90 µL,
0.70 mmol) and benzoyl chloride (75 µL, 0.7 mmol) were then ad-
ded and the mixture was stirred overnight. HCl (2 ) was added
until pH 4 was reached, followed by H2O (5 mL). The organic
phase was extracted with Et2O (3 ϫ 5 mL), washed with brine
(10 mL), dried (Na2SO4) and concentrated to give a yellowish solid
that was crystallized from cyclohexane/EtOAc (0.39 g, 63%). M.p.
78Ϫ80 °C. [α]2D0 ϭ Ϫ7.3 (c ϭ 0.98, CHCl3). IR (KBr): ν˜max. ϭ 3433,
3300 (br), 3062, 3029, 3007, 1638, 1524, 1488, 1291, 1247, 1021,
692 cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ 3.96 (s, 6 H, OCH3),
5.94 (dd, J ϭ 2.6, 6.2 Hz, NCHCHN), 6.67 (t, J ϭ 7.2 Hz, 2 H,
Ar), 6.85 (t, J ϭ 8.0 Hz, 4 H, Ar), 7.14 (t, J ϭ 8.0 Hz, 2 H, Ar),
7.33Ϫ7.52 (m, 6 H, Ph), 7.76 (m, 4 H, Ph), 7.98 (m, 2 H, NH)
ppm. C30H28N2O4 (480.56): calcd. C 74.98, H 5.87, N 5.83; found
C 74.96, H 5.88, N 5.82.
(1R,2R)-N,NЈ-Dibenzyl-1,2-bis(2,5-dimethoxyphenyl)-1,2-ethanedi-
amine [(R,R)-4c]: Yield 0.16 g (64%). [α]2D0 ϭ Ϫ9.7 (c ϭ 0.98,
CHCl3). IR (neat): ν˜max. ϭ 3305, 3060, 3026, 2994, 1604, 1588,
1
1221, 1048, 804, 734 699 cmϪ1. H NMR (200 MHz, CDCl3): δ ϭ
2.48 (br. s, 2 H, NH), 3.52 (s, 6 H, OCH3), 3.58 (qAB, J ϭ 13.2 Hz,
4 H, NCH2), 3.70 (s, 3 H, OCH3), 4.22 (s, 2 H, NCHCHN), 6.58
(d, J ϭ 8.7 Hz, 2 H, Ar), 6.64 (dd, J ϭ 8.7, 3.0 Hz, 2 H, Ar), 6.88
(m, 2 H, Ar), 7.18Ϫ7.40 (m, 10 H, Ph) ppm. C32H36N2O4 (512.65):
calcd. C 74.97, H 7.08, N 5.46; found C 74.94, H 7.09, N 5.45.
(1S,2S)-N,NЈ-Dibenzyl-1,2-bis(2,5-dimethoxyphenyl)-1,2-ethanedi-
amine [(S,S)-4c]: Yield 0.10 g (40%). [α]2D0 ϭ ϩ7.3 (c ϭ 0.67,
CHCl3).
Zn-Diamine-Catalyzed Asymmetric Hydrosilylation of Aceto-
phenone by PMHS. General Procedure: Catalytic reactions were
performed under nitrogen using standard Schlenk techniques. In a
typical experiment (Table 1, Entry 15), ZnEt2 (50 µL of a 1.1 
solution in toluene, 0.055 mmol), acetophenone (0.32 mL,
2.75 mmol) and finally PMHS (0.21 mL, 3.30 mmol) were success-
ively added to a solution of (S,S)-4c (28.2 mg, 0.055 mmol) in
freshly distilled toluene (2.5 mL). The resulting solution was stirred
with a magnetic stir bar at room temperature and the reaction was
monitored by GLC as follows: aliquot samples (ca. 0.1 mL) from
the reaction mixture were hydrolyzed by aqueous KOH (45% wt.);
the organic products (acetophenone and 1-phenylethanol) were ex-
tracted in diethyl ether, and this organic phase was analysed by
quantitative GLC. The enantiomeric purity of 1-phenylethanol was
assessed by GLC on a Chirasil-DEX CB column (110 °C, 0.70 bar).
When the same reaction was carried out on a preparative scale, no
aliquots were sampled and the final mixture was hydrolysed after
3 days and extracted as described above, to yield spectroscopically
pure 1-phenylethanol in more than 95% isolated yield.
(1S,2S)-N,NЈ-Dibenzoyl-1,2-bis(2-methoxyphenyl)-1,2-ethanedi-
amine [(S,S)-7b]: Pure (S,S)-7b was obtained by crystallization in a
yield of 0.36 g (58%). M.p. 79Ϫ81 °C. [α]2D0 ϭ ϩ8.1 (c ϭ 0.25,
CHCl3).
(1R,2R)-N,NЈ-Dibenzoyl-1,2-bis(2,5-dimethoxyphenyl)-1,2-ethanedi-
amine [(R,R)-7c]: (R,R)-7c was obtained by chromatography of the
crude reaction mixture on a column of SiO2 (cyclohexane/EtOAc).
Yellowish solid, yield 0.41 g (58%); m.p. 82Ϫ84 °C. [α]2D0 ϭ ϩ5.4
(c ϭ 0.95, CHCl3). IR (KBr): ν˜max. ؍ 3426, 3345 (br.), 3061, 2997,
1646, 1224, 1045, 804, 714 cmϪ1 1H NMR (300 MHz, CDCl3):
.
δ ϭ 3.72 (s, 6 H, OCH3), 3.93 (s, 6 H, OCH3), 5.83 (dd, J ϭ 2.7,
6.0 Hz, NCHCHN), 6.44 (d, J ϭ 3.0 Hz, 2 H, Ar), 6.67 (dd, J ϭ
3.0, 9.0 Hz, 2 H, Ar), 6.77 (d, J ϭ 9.0 Hz, 2 H, Ar), 7.40 (m, 6 H,
Ph), 7.76 (m, 4 H, Ph), 8.02 (m, 2 H, NH) ppm. C32H32N2O6
(540.62): calcd. C 71.09, H 5.97, N 5.18; found C 71.07, H 5.98,
N 5.16.
Acknowledgments
We thank the CNRS and PPG-SIPSY (PhD grant to V. B.) and
the Consorzio Interuniversitario Nazionale Metodologie e Processi
3044
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3040Ϫ3045

Chiral 1,2-Diamines in Zinc-Catalyzed Asymmetric Hydrosilylation of Acetophenone
FULL PAPER
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Received February 24, 2004
Eur. J. Org. Chem. 2004, 3040Ϫ3045
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3045