Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: Highly enantioselective synthesis of valuable alcohols

Article abstract of DOI:10.1002/chem.201102157

In the presence of PhSiH₃ as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)₂·H ₂O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9 % enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10 000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98 % ee) and exceedingly high turn-over rates (up to 50 000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.

Full text of DOI:10.1002/chem.201102157

DOI: 10.1002/chem.201102157
Copper(II)-Catalyzed Hydrosilylation of Ketones Using Chiral
Dipyridylphosphane Ligands: Highly Enantioselective Synthesis of Valuable
Alcohols
Feng Yu,[a] Ji-Ning Zhou,[a] Xi-Chang Zhang,[a] Yao-Zong Sui,[a] Fei-Fei Wu,[a]
Lin-Jie Xie,[a] Albert S. C. Chan,[b] and Jing Wu*[a]
Abstract: In the presence of PhSiH3 as
the reductant, the combination of
enantiomeric dipyridylphosphane li-
strate-to-ligand molar ratio (S/L) of up
to 10000. The present protocol also al-
lowed the hydrosilylation of a diverse
spectrum of alkyl aryl ketones with ex-
cellent enantioselectivities (up to
98% ee) and exceedingly high turn-
over rates (up to 50000 S/L molar ratio
in 50 min reaction time) in air, under
very mild conditions, which offers great
opportunities for the preparation of
various physiologically active targets.
The synthetic utility of the chiral prod-
ucts obtained was highlighted by the
efficient conversion of optically en-
riched b-halo alcohols into the corre-
sponding styrene oxide, b-amino alco-
hol, and b-azido alcohol, respectively.
gands and CuACHTUNGTRENNUNG(OAc)2·H2O, which is an
easy-to-handle and inexpensive copper
salt, led to a remarkably practical and
versatile chiral catalyst system. The ste-
reoselective formation of a selection of
synthetically interesting b-, g- or d-halo
alcohols bearing high degrees of enan-
tiopurity (up to 99.9% enantiomeric
excess (ee)) was realized with a sub-
Keywords: alcohol
·
asymmetric
catalysis · copper · enantioselectivi-
ty · hydrosilylation
Introduction
plied in the asymmetric hydrosilylation of prochiral ketones.
With respect to the stereoselective hydrosilylation mediated
by chiral copper catalysts,[2f–h,13] a landmark work was de-
scribed in 1984 by Brunner and Miehling[14] for which CuH-
DIOP[15] asymmetric catalysis was used for the reduction of
acetophenone with 38.8% ee. A significant breakthrough
was accomplished by Lipshutz et al. in 2001,[13b–d] whereby
an especially active CuICl/diphosphane (e.g., 3,5-xyl-MeO-
BIPHEP[16] or DTBM-SEGPHOS[17])/tBuONa catalyst
system was developed to effect highly enantioselective hy-
drosilylation of a broad assortment of prochiral ketones,[18]
with substrate-to-ligand molar ratios (S/L) of up to 100000.
Concomitant with Lipshutzꢀs work in 2001, Riant and co-
workers[19] disclosed an air-accelerated and base-free CuF2/
BINAP[20]/PhSiH3 system that catalyzed the reduction of
some alkyl aryl ketones with moderate to excellent enantio-
selectivities. Since then, a variety of effective copper cata-
lysts that derive from enantiomerically pure diphosphanes
(such as BINAP, DTBM-SEGPHOS or MeO-BIPHEP de-
Discovery of truly efficient methods leading to enantiomeri-
cally enriched secondary alcohols, which constitute valuable
intermediates for the preparation of structurally interesting
and biologically active compounds, is a significant objective
in organic synthesis.[1] The enantioselective hydrosilylation
of ketones, as a desirable transformation towards chiral al-
cohols, has gained considerable attention due to the mild re-
action conditions required and because of the operational
simplicity.[2] Since the early reports that appeared three de-
cades ago,[3] a variety of transition-metal catalysts, especially
those based on rhodium,[4] ruthenium,[5] and iridium,[6] as
well as some less expensive metals such as titanium,[7] zinc,[8]
tin,[9] iron,[10,11] and cobalt,[12] have been exploited and ap-
[a] F. Yu, J.-N. Zhou, X.-C. Zhang, Y.-Z. Sui, F.-F. Wu, L.-J. Xie,
Prof. Dr. J. Wu
College of Material,
rivatives) and CuACTHNUTRGENNGU ACHTUGNTRENNUGN
(OAc)2·H2O,[21] [CuF(PPh3)3·2MeOH],[22]
Chemistry and Chemical Engineering
and Key Laboratory of Organosilicon Chemistry
and Material Technology of Ministry of Education,
Hangzhou Normal University,
Hangzhou 310036 (P. R. China)
Fax : (+86)-571-2886-8023
CuCl[23] or some heterogeneous copper sources,[24] have been
applied in the relevant hydrosilylation reactions. Additional-
ly, some efficient copper catalysts bearing chiral monophos-
phane[25] or tetraoxazoline[26] ligands have also been devel-
oped for the hydrosilylation of simple ketones.
We have recently established a particularly efficacious
asymmetric hydrosilylation system involving CuF2, dipyridyl-
phosphane (Scheme 1, P-Phos 1a or Xyl-P-Phos 1b),[27] and
PhSiH3, that rendered competitive levels of enantioinduc-
tion (up to 98% ee) and activity for the reduction of aryl
E-mail: jingwubc@hznu.edu.cn
[b] Prof. Dr. A. S. C. Chan
State Key Laboratory of Chiroscience
and Institute of Creativity,
Hong Kong Baptist University (Hong Kong)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201102157.
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FULL PAPER
Scheme 1. Chiral dipyridylphosphane ligands.
Scheme 3. Examples of synthetic applications of chiral b-, g- or d-halo al-
cohols.
alkyl, diaryl, and hetero-aromatic ketones under ambient
conditions.[28] The excellent practical potential of this cata-
lyst system prompted us to further broaden its application
scope. Particularly, we were very interested in the reduction
of some ketonic substrates, the products of which could
serve as key synthetic intermediates of some structurally
versatile or physiologically active targets such as the wide-
spectrum agricultural fungicide (S)-MA20565 (2),[29a] the
NK-1 receptor antagonist aprepitant (3),[29b] and the b3-adre-
nergic receptor agonist 4[29c] (Scheme 2).
Optically active halo alcohols are especially significant
structural elements for the formation of biologically active
compounds, such as chiral epoxides, diols, and amino alco-
hols, due to the versatility conferred by the presence of the
halogen that can readily act as a good leaving group
presence of catalytic amounts of (S)-1 plus an easy-to-
handle and inexpensive copper salt, CuACHTUNRTGENUNG(OAc)2·H2O, a series
of a-, b- and g-halo substituted ketones were reduced quan-
titatively by employing PhSiH3 as the hydride source with
up to 99.9% ee (S/L up to 10000), which, to the best of our
knowledge, represented the highest enantioselectivities ach-
ieved to date through hydrosilylation of such educts. The
synthetic utility of the method was highlighted by the effi-
cient transformation of representative optically enriched b-
halo alcohols into the corresponding styrene oxide, b-amino
alcohol, and b-azido alcohol, respectively. Furthermore,
under ambient atmosphere and mild reaction conditions, the
present catalyst system displayed good to excellent stereose-
lectivities (up to 98% ee) and extraordinarily high reactivi-
ties (S/L up to 50000 in 50 min reaction time on a 25 g sub-
strate scale) for a diverse range of alkyl aryl ketones.
Results and Discussion
Optimization of the copper-catalyzed asymmetric hydrosily-
lation (Table 1): Previous studies on the copper-catalyzed
hydrosilylation reactions indicated that the counter-ion of
copper precursors often played a crucial role in the genera-
tion of an active catalyst.[19,22,28] This prompted us to further
broaden the scope of the application of copper salts to find
a more practical copper source with both higher efficacies
and wider applications. In the initial study, multifarious
copper precursors were tested in the reduction of the model
substrate acetophenone 5 in air by utilizing 0.1 mol% (S)-
1a ligand and 1.2 equivalents of PhSiH3 as the reductant
(Table 1). The results indicated that the extent of conver-
sions or the enantioselectivities achieved varied considerably
as a function of the counter-ion of copper salts. Similar to
the results obtained under an N2 atmosphere,[28a] both anhy-
drous and hydrated CuF2 furnished (S)-1-phenylethanol 6
quantitatively after 2 h with 79 and 76% ee (Table 1, en-
tries 1 and 2), respectively. Whereas all other copper(I)- or
copper(II)-halides showed poor activities (Table 1, entries 3–
7). Promising results were also obtained by applying
Scheme 2. Selected valuable bioactive targets derived from chiral alco-
hols.
(Scheme 3). Thus, a number of strategies for the asymmetric
reduction of halo-substituted ketones to enantiomeric halo
alcohols, such as hydroboration catalyzed by chiral oxaza-
borolidines,[30] transfer hydrogenation mediated by chiral
Rh[31] or Ru catalysts,[32] and the Ru-catalyzed hydrogena-
tion,[33] have been accordingly developed with good to excel-
lent enantioselectivities. Nevertheless, non-precious-metal-
catalyzed stereoselective hydrosilylation methods that can
be used to generate these kinds of alcohols has received rel-
atively little attention[7f,18c,34] and remain a challenge. In this
contribution, it was of great interest to note that, in the
CuOAc, Cu
sor (Table 1, entries 8–10). With respect to the other copper
salts, including CuCN, Cu(acac)2 (acac: acetylacetonate),
ACHTUNGTERNNUG(OAc)2, or CuACHTUNTGREN(NGUN OAc)2·H2O as the copper precur-
AHCTUNGTRENNUNG
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J. Wu et al.
Table 1. Effects of counter-ions and solvents on the copper-catalyzed
asymmetric hydrosilylation of 5.[a]
Copper salt (mol%)
S/L
Solvent Conv [%][b] ee [%][c]
1
2
3
4
5
6
7
8
CuF2 (2)
CuF2·2H2O (2)
CuCl (2)
CuI (2)
CuCl2 (2)
CuCl2·H2O (2)
CuBr2 (2)
CuOAc (2)
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
1000 toluene
98
>99
<5
<5
<5
<5
<5
>99
>99
>99
<5
19
79
76
76
68
64
8
48
76
75
79
76
76
34
41
<5
77
13
51
70
47
91
9
Cu
Cu
ACHTUNGTRENNUNG
10
11
12
13
14
15
16
17
18
19
20
ACHTUNGTRENNUNG
CuCN (2)
Cu
Cu
ACHTUNGTRENNUNG
A
11
82
39
99
CuF
A
Cu
Cu
Cu
Cu
Cu
Cu
N
250 dioxane
250 THF
250 CH2Cl2
250 CHCl3
250 CH3CN
50 toluene
25
<5
<5
7
21[d] Cu
H
>99
[a] Reaction conditions: substrate (36–361 mg; substrate concentration=
0.3–0.5 molLÀ1). [b] The conversions were determined by NMR and GC
analyses. [c] The ee values were measured by chiral GC analysis. The ab-
solute configuration was determined by comparing the retention time
with known data. [d] Reaction time: 24 h, reaction temperature: À208C.
Scheme 4. Copper-catalyzed asymmetric hydrosilylation of halo-substitut-
ed ketones in air.
halo alcohols (8a–k) with good to excellent enantiopurities
(84–99.9% ee).
and CuF
(PPh3)3·2EtOH, among others, either poor activities
The coordinative a-bromo group of the substrates did not
interfere with catalyst performance. Thus, with (S)-1b as the
chiral ligand, a-bromoacetophenone (Scheme 4, 7a) was
quantitatively reduced to (S)-2-bromo-1-phenylethanol (8a)
in 94% ee within 24 h. The latter compound could be con-
verted into the antinociceptive opioid antagonist
(1S,5R,2’S)-9 (Scheme 5).[36a] Introduction of the electron-
withdrawing Cl group to the 4’-position of 7a diminished
the optical yield (8b vs. 8a). However, replacement of the
4’-Cl with electron-donating CH3 or CH3O groups was bene-
ficial and led to an enhancement in stereoselectivities (8c
and 8d vs. 8a).
Unlike a-halo ketones, b- or g-halo ketone substrates with
either an electron-withdrawing or an electron-donating sub-
stituent on the aromatic ring (Scheme 4, 7e–k) could be
converted into the corresponding halo alcohols in good
yields with over 95% ee (8e–k). (R)-Fluoxetine 10
(Scheme 5), which is prescribed for the treatment of psychi-
atric disorders or some metabolic problems,[36b] had been
synthesized by the group of Corey through the CBS reduc-
tion of b-chloropropiophenone 7e as a key step.[37a] Utilizing
or low selectivities were observed (Table 1, entries 11–15).
In consideration of the practical applications, Cu-
ACHTUNGTRENNUNG(OAc)2·H2O, which is inexpensive and stable towards both
air and moisture, appeared to be the most preferable choice.
This was also noted recently by Buchwald,[35] Yun,[21a] Lip-
shutz,[21b–c] and Beller et al.[25] In addition, the reaction was
strongly solvent-dependent, and toluene was found to be the
best choice (Table 1, entries 16–20 vs. entry 10). Although
dioxane was also apparently much more conducive than
other solvents to both reactivity and enantioselectivity
(Table 1, entry 16), the high freezing-point limited its use at
a lower temperature. Further examination demonstrated
that lowering the reaction temperature facilitated a signifi-
cant enhancement in enantioselectivity at the expense of re-
action rate (Table 1, entry 21 vs. entry 10).
Asymmetric hydrosilylation of halo-substituted ketones
(Scheme 4): An important exploration of the widespread ap-
plication of the present catalyst system was in the synthesis
of high-valued optically enriched alcohol intermediates for
chiral pharmaceutical or agricultural targets. With the afore-
mentioned preferred conditions in hand, we first set out to
evaluate the efficiency of the present system for the catalytic
asymmetric reduction of various halo-substituted ketones in
air. Gratifyingly, as illustrated in Scheme 4, the present pro-
tocol allowed access to a variety of desirable b-, g-, and d-
CuACHTUNTRGNEUNG(OAc)2·H2O with (S)-1b as catalyst, the desired product
8e was obtained in 97% ee at À208C. Synthesis of the ezeti-
mibe analogue 11 (Scheme 5), which possesses the potential
of inhibiting cholesterol absorption,[36c] requires the synthe-
sis of a g-halo alcohol intermediate such as 8 f. To our de-
light, the enantioselective hydrosilylation of 7 f took place
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Enantioselective Hydrosilylation of Ketones
FULL PAPER
Table 2. Asymmetric hydrosilylation of aryl methyl ketones 13a–n in
air.[a]
Substrate
Ar
t [h]
Conv [%][b]
ee [%][c]
1
2
3
4
5
6
7
13a
13b
13c
13d
13e
13 f
13g
13h
13i
13j
13k
13l
13m
13n
4-NO2C6H4
4-ClC6H4
4-BrC6H4
4-CH3C6H4
3-ClC6H4
3-CH3OC6H4
2-ClC6H4
2-CH3C6H4
2’-naphthyl
3-CF3C6H4
3,5-(CF3)2C6H3
4-CF3C6H4
3-NO2C6H4
4-FC6H4
4
12
12
24
12
12
12
24
24
12
24
12
12
12
>99
98
98
98
>99
98
99
92
98
96
98
95
97
94
92
95
77
77
96
93
96
96
96
95
Scheme 5. Selected valuable bioactive targets derived from chiral halo al-
cohols.
8[d]
9
10
11
12
13
14
99
97
99
99
smoothly in up to 99.9% ee by using the present system
(Scheme 4). Furthermore, d-chloroalcohol 8i is the synthetic
precursor of the potent class III antiarrhythmic agent (R)-
ibutilide 12 (Scheme 5). The reduction of 7i by phosphina-
mide-mediated hydroboration and rhodium-catalyzed hydro-
silylation methods afforded 8i in 75[37b] and 88% ee,[34b] re-
spectively. In this study, 8i was provided neatly in 95% ee
through the copper-catalyzed hydrosilylation of 7i in the
presence of (S)-1a ligand.
[a] Substrate (27–100 mg; substrate concentration=0.3–0.8 molLÀ1
) in
toluene. [b] The conversions were determined by NMR and GC analyses.
[c] The ee values were determined by chiral GC analysis. The absolute
configuration was determined by comparing the retention time or optical
rotation with known data. [d] Compound (S)-1a was used as a ligand.
aration of Sch-350634 (15; Scheme 6), which can inhibit the
replication of HIV-1 through blockade of its entry into cells
and thus could serve as a potential new target for antiviral
therapy.[38] Optically active 14m could be transformed into
b3-adrenergic receptor agonist 4 (Scheme 2), which is used
for the treatment of obesity, noninsulin-dependent diabetes
mellitus, and frequent urination.[29c] Additionally, an efficient
route to AMG 628 (16; Scheme 6), which is a vanilloid re-
Asymmetric hydrosilylation of alkyl aryl ketones: Encour-
aged by the successful hydrosilylation of halo-substituted ke-
tones, we then applied the present catalyst system to the
enantioselective reduction of a wide range of aryl methyl
ketones 13a–n under a given set of conditions. As the find-
ings in Table 2 indicate, the outcomes of the reactions large-
ly depended on the position of the substituents on the aro-
matic ring of the ketone substrate, and use of the sterically
encumbered ligand 1b was beneficial to both higher optical
yields and faster reaction rates in most cases. Substituents
on either the para- (Table 2, entries 1–4) or meta- (Table 2,
entries 5 and 6) position of acetophenone resulted in higher
ee values (92–98%) than those obtained with ortho-substi-
tuted substrates (Table 2, entries 7 and 8). 2-Acetonaph-
thone (13i) was converted into the expected (S)-product
with 96% ee (Table 2, entry 9).
Aryl methyl substrates 13j–n (Table 2, entries 10–14)
were also examined in the reaction, the reduction products
of which constitute key structural elements of some biologi-
cally active compounds. For example, (S)-MA20565 (2;
Scheme 2), which is a potent agricultural fungicide with a
new effective pharmacophore,[29a] could be synthesized from
14j, and was conveniently furnished in 93% ee at À208C in
air upon exposure of the corresponding ketone to (S)-1b li-
gated to copper hydride (Table 2, entry 10). With the hydro-
silylation system developed here, 14k, 14l, and 14m
(Table 2, entries 11–13) were efficiently produced in as high
as 96% ee. Compound 14k is the crucial chiral building
block for aprepitant 3 (Scheme 2), which is an NK-1 recep-
tor antagonist for the treatment of chemotherapy-induced
emesis.[29b] Product 14l is a useful intermediate for the prep-
Scheme 6. Selected valuable bioactive targets derived from chiral secon-
dary alcohols.
ceptor-1 antagonist, relies on access to a valuable nonrace-
mic precursor 14n,[39] which was furnished in 95% ee in this
study (Table 2, entry 14).
To further investigate the general applicability of the pres-
ent system, the hydrosilylation of a series of alkyl aryl ke-
tones possessing different lengths of alkyl chains was sys-
tematically studied (Scheme 7, 17a–c). When the methyl
group of acetophenone (Table 1, 5) was changed to an ethyl
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J. Wu et al.
group (17a), the enantiopurity of the corresponding alcohol
was found to increase from 91 (Table 1, entry 21) to 96%
(Scheme 7, 18a). Interestingly, further lengthening the alkyl
chain gradually diminished the optical yield to 91% (18b
and 18c vs. 18a).
Scheme 9. Functionalization of optically active b-halo alcohol 8a.
Scheme 7. Asymmetric hydrosilylation of alkyl aryl ketones 17a–c in air.
ucts (Scheme 9): Chiral halo alcohols are important building
blocks for the manufacture of a variety of structurally inter-
esting and biologically active compounds. With the availabil-
ity of a practical and economic catalytic method for the
highly enantioselective synthesis of halo alcohols, a range of
other optically enriched molecules becomes accessible. A
convenient protocol, outlined in Scheme 9, allowed the con-
version of b-halo alcohols into the corresponding styrene
oxides, which are useful synthetic intermediates of various
pharmaceuticals such as a1-, b2-, and b3-adrenergic receptor
agonists.[40] For instance, treatment of (R)-2-bromo-1-phe-
nylethanol (8a; Scheme 4, 93% ee) with 2m aqueous NaOH
in methanol at 08C gave chiral styrene oxide (R)-19[31a]
(93% ee) in 81% isolated yield after 1 h. Another syntheti-
cally useful functionalization involved the facile transforma-
tion of 8a into a valuable chiral b-amino alcohol (R)-20[41] in
75% yield by treating a methanol solution of 8a with a
large excess of 30% aqueous NH4OH at room temperature
for only 2 h. Moreover, 8a was readily converted into b-
azido alcohol (R)-21[33] in 71% isolated yield in the presence
of 5 equiv NaN3 in DMF at 808C for 8 h under an N2 atmos-
phere. Anthelmintic 22, which is used to treat infections of
parasitic worms, could be further prepared from b-azido al-
cohol.[42] Another reported noteworthy application of b-
azido alcohols is the construction of heterocyclic com-
pounds, such as triazolooxazine 23.[43]
Catalyst activities (Scheme 8): Although stereoselectivity is
a major concern in asymmetric synthesis, the ability to con-
duct the reaction at a high substrate-to-catalyst ratio without
loss of enantioselectivity is an important measure of the
commercial feasibility of a reaction. The activity and air-sta-
bility of the present catalyst was therefore evaluated by con-
ducting the reduction of 3-chloro-1-(4-fluorophenyl)propan-
1-one (7 f) at room temperature in air with an S/L ratio of
100 to 10000 (Scheme 8). The desired product 8 f was ob-
tained cleanly in 90% ee after 4 h with an S/L ratio of 100.
When the S/L ratio was increased to 10000, no substantial
decrease of ee values was observed under otherwise identi-
cal conditions. To our excitement, further investigations in-
dicated that the hydrosilylation of 4’-nitroacetophenone
(13a) was completed in less than 1 h even when the S/L
ratio was increased to 50000. As depicted in Scheme 9,
when 25 g of 13a was treated with only 2.4 mg of (S)-1b, 1
mol% CuACHTUNGTRENNUNG(OAc)2·H2O, and 1.2 equiv of PhSiH3 at room
temperature in air, the reaction took place smoothly to
afford product 14a neatly with 91% ee after only 50 min.
Functionalization of optically enriched hydrosilylation prod-
Conclusion
We have developed a remarkably effective and versatile
copper-catalyzed asymmetric hydrosilylation system, which
is generated in situ from the stable and inexpensive copper
salt CuACHTNUTGRENUNG(OAc)2·H2O, chiral P-Phos ligand (S)-1, and the hy-
dride donor PhSiH3. The present system furnished excellent
enantioselectivities (up to 98% ee) and exceedingly high
turnover rates (S/L up to 50000 molar ratio in 50 min reac-
tion time) in air, under very mild conditions, and could be
used for the formation of a diverse spectrum of chiral alco-
Scheme 8. Asymmetric hydrosilylation on large scales.
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Enantioselective Hydrosilylation of Ketones
FULL PAPER
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hols, offering great opportunities for the preparation of vari-
ous physiologically active compounds. In particular, the
asymmetric synthesis of a vast array of valuable b-, g- or d-
halo alcohols was realized with excellent stereocontrol (up
to 99.9% ee and 10000 S/L ratio), which, to the best of our
knowledge, represents the highest enantioselectivities ob-
served for these substrates based on nonprecious-metal or-
ganocopper chemistry. The optically enriched b-halo alcohol
products were efficiently transformed into the synthetically
versatile chiral molecules, including styrene oxides, b-amino
alcohols, and b-azido alcohols. Notably, the present protocol
allows both catalyst and reactants to be handled in air with-
out special precautions.
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Experimental Section
General procedure for the asymmetric hydrosilylation in air (Table 1,
entry 21): CuACHTUNGTRENNUNG
(OAc)2·H2O (8.0 mg, 4.0ꢂ10À2 mmol) and (S)-P-Phos (1a;
13.0 mg, 2.0ꢂ10À2 mmol) were weighed under air and placed in a 25 mL
round-bottomed flask equipped with a magnetic stirring bar. Toluene
(1.0 mL) was added and the mixture was stirred at RT for 20 min. Phe-
nylsilane (150 mL, 1.2 mmol) in toluene (0.5 mL) was added and the mix-
ture was cooled to À208C. A solution of acetophenone (5; 120 mg,
1.0 mmol) in toluene (0.5 mL) was added under vigorous stirring, and the
flask was stoppered. The reaction was monitored by TLC. Upon comple-
tion, the reaction mixture was treated with 10% HCl (2.0 mL) and the
organic product was extracted with diethyl ether (3ꢂ3 mL). The com-
bined extract was washed with water, dried with anhydrous sodium sul-
fate, filtered through a plug of silica gel, and concentrated in vacuo to
give the crude product. The conversion and the enantiomeric excess of
the product (S)-1-phenylethanol (6) were determined by 1H NMR and
chiral GC analyses to be more than 99 and 91%, respectively (Chirasil-
DEX CB 25 m ꢂ 0.25 mm, Varian, carrier gas, N2). The pure product was
isolated by column chromatography (ethyl acetate/petroleum ether=
1:4).
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We thank the National Natural Science Foundation of China (21172049,
21032003, 20672026), the New Century Excellent Talents in Chinese Uni-
versity Program awarded to Jing Wu (NCET-07–0250), the Natural Sci-
ence Foundation of Zhejiang Province (R406378), the Public Welfare
Technology and Application Program of Zhejiang Province
(2010C31042) and the Special Funds for key innovation team of Zhejiang
Province (2010R50017) for financial support.
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Received: July 13, 2011
thylphenyl)phosphino]-3,3’-bipyridine; a) J. Wu, A. S. C. Chan, Acc.
Published online: November 7, 2011
14240
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ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 14234 – 14240