CuII-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: Application in the enantioselective synthesis of orphenadrine and neobenodine

Article abstract of DOI:10.1002/chem.201200379

With certain amounts of sodium tert-butoxide and tert-butanol as additives, catalytic amounts of an inexpensive and easy-to-handle copper source Cu(OAc)₂·H₂O, a commercially available and air-stable non-racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96 %). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine. Copyright

Full text of DOI:10.1002/chem.201200379

FULL PAPER
DOI: 10.1002/chem.201200379
CuII-Catalyzed Asymmetric Hydrosil
ACTHUNTGRENNGyU lation of Diaryl- and Aryl Heteroaryl
Ketones: Application in the Enantioselective Synthesis of Orphenadrine and
Neobenodine
Yao-Zong Sui,[a] Xi-Chang Zhang,[a, b] Jun-Wen Wu,[a] Shijun Li,[a] Ji-Ning Zhou,[a]
Min Li,[a] Wenjun Fang,[b] Albert S. C. Chan,[c] and Jing Wu*[a]
Abstract: With certain amounts of
sodium tert-butoxide and tert-butanol
as additives, catalytic amounts of an in-
expensive and easy-to-handle copper
formed
a
versatile in situ catalyst
air, in high yields and with good to ex-
cellent enantioselectivities (up to
96%). In particular, the practical via-
bility of this process was evinced by its
successful applications in the asymmet-
ric synthesis of optically enriched
potent antihistaminic drugs orphena-
drine and neobenodine.
system for the enantioselective reduc-
tion of a broad spectrum of prochiral
diaryl and aryl heteroarylketones in
source CuACHTUNGTRENNUNG(OAc)2·H2O, a commercially
available and air-stable non-racemic di-
pyridylphosphine ligand, as well as the
stoichiometric desirable hydride donor
Keywords: alcohols
catalysis · copper · enantioselectivi-
ty · hydrosilylation
· asymmetric
polymethylhydrosiloxane
(PMHS),
Introduction
Optically active diaryl- and aryl heteroarylmethanols are
not only crucial structural elements in many physiologically
or/and biologically active molecules,[1] such as in antihista-
mines (R)-orphenadrine (1) and (S)-neobenodine (2)[1a,b]
and the medically useful histamine H1-antagonist (S)-carbi-
noxamine (3; Figure 1),[2] but they are also the precursors to
some potentially interesting ligand scaffolds (e.g., tetraaryl-
ethanes).[3] Thus, the development of efficient systems for
the catalytic enantioselective synthesis of diaryl- and aryl
heteroaryl alcohols is of substantial interest to both the aca-
demic community and the industrial sector.
Figure 1. Representative examples of biologically active compounds that
are derived from diaryl- or aryl heteroarylmethanols.
Typically, catalytic asymmetric approaches towards enan-
tiomerically enriched diarylmethanols can be divided into
three broad categories: 1) the enzyme-catalyzed enantiose-
lective reduction of diaryl ketones,[4] 2) the 1,2-addition of
aryl organometallic nucleophiles to aromatic aldehydes,[5]
and 3) the catalytic reduction of prochiral ketones.[5c,6] Inten-
sive study in this area has focused on the stereoselective ar-
[a] Y.-Z. Sui, X.-C. Zhang, J.-W. Wu, S. Li, J.-N. Zhou, M. Li,
Prof. Dr. J. Wu
College of Material
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
ACHTUNGTRENyNUGN lation of aromatic aldehydes and good-to-excellent enan-
tioselectivities have been realized by using a variety of aryl-
metallic reagents.[5,7–10] From both scientific and commercial
points of view, the asymmetric reduction of unsymmetrical
diaryl ketones as a direct route to single enantiomers of al-
cohols is potentially attractive. Accordingly, several strat-
egies, including reduction with lithium aluminum hydride
chiral amino alcohol complexes,[11] hydroboration catalyzed
by chiral oxazaborolidines,[5c,6a,12] and hydrogenation mediat-
ed by chiral diphosphine/diamine Ru complexes,[5c,6b,c,13]
have been developed. Nevertheless, reports on the asymmet-
ric hydrosilylation of diaryl ketones to benzhydrol deriva-
tives are relatively scarce. The first example was reported by
E-mail: jingwubc@hznu.edu.cn
[b] X.-C. Zhang, Prof. Dr. W. Fang
Department of Chemistry
Zhejiang University, Hangzhou 310027 (P.R. China)
[c] 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.201200379.
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Kagan and co-workers in 1980,[14] who employed a RhI-
DIOP[15] catalyst for the hydrosilylation of p-methylbenzo-
phenone in 26% ee. Brunner and Kuerzinger reported a re-
lated reaction in 1988[16] that used rhodium complexes to
afford the product in 37% ee.
Over the last decade, the application of copper hydride
complexes that were ligated by enantiomerically pure lig-
ACHTUNGTRENNUNGands in asymmetric hydrosilylation reactions has gained
a considerable amount of attention owing to the advantages
of using inexpensive metals and mild reaction conditions.[17]
Thus, a variety of copper-based catalytic hydrosilylation sys-
tems have been exploited for effecting the stereoselective
reduction of a wide range of simple ketones,[18–22] imines,[23]
as well as the 1,4-reduction of various a,b-unsaturated Mi-
chael acceptors,[24] with moderate to excellent enantioselec-
tivities. With respect to the prochiral diaryl ketonic sub-
strates, in 2005, we reported a CuF2/dipyridylphosphine
(Figure 2, P-Phos 4a or Xyl-P-Phos 4b)[25]/PhSiH3 system
was realized in air by using a copper(II)-dipyridylphosphine
(4a or 4b) catalyst. This catalyst system also exhibited high
efficiency and remarkable practical potential in the stereose-
lective hydrosilylation of a wide range of aryl alkyl and het-
eroaromatic ketones in good to excellent ee values (up to
97%) with a substrate-to-ligand (S/L) molar ratio of up to
50000.[30] Herein, we report the extension of this catalyst
system to the hydrosilylation of diaryl and aryl heteroaryl
ketones. Copper-catalyzed reactions proceeded smoothly in
air and gave access to structurally diverse alcohols in up to
96% ee. Furthermore, this process was applied to the asym-
metric synthesis of optically enriched orphenadrine (1) and
neobenodine (2), which possess potent anticholinergic and
antihistaminic activities.[1a,b]
Results and Discussion
Optimization of the copper-catalyzed reaction conditions: In
an initial study, 2-chlorobenzophenone (5a) was used as
a model substrate (Table 1). When compound 5a was mixed
with ligand (S)-4a (0.4 mol%), CuCl (5 mol%), and PMHS
(4 equiv) as the reductant in toluene at 08C in air, only 57%
conversion into (R)-6a (82% ee) was observed after 1.2 h.
Consistent with previous reports,[24d,e,k,31] the rate of reaction
was increased by adding certain amounts of sterically de-
manding alcohol tBuOH to the reaction mixture (Table 1, cf.
entries 2 and 1). Comparison studies showed that the further
introduction of tBuONa (5 mol%) into the catalyst system
allowed for the complete transformation of diarylketone 5a
into the desired alcohol with no diminution of the ee either
in air or under a N2 atmosphere (Table 1, entries 3 and 4
versus entry 2).[27,29,30] Moreover, less than 40% conversion
was obtained only if tBuONa was added in the absence of
alcohol, although the ee value remained unchanged
(Table 1, entries 5 and 3).
Figure 2. Dipyridylphosphine ligands.
which, to the best of our knowledge, allowed the first highly
asymmetric hydrosilylation of ortho-substituted benzophe-
nones with good to excellent enantioselectivity (up to
98%).[26] In 2008, Lee and Lipshutz[27] demonstrated that
CuH complexed with DTBM-SEGPHOS or DM-SEG-
PHOS[28] were efficient catalysts for the asymmetric hydrosi-
lylation of a broad range of ortho-substituted benzophenone
derivatives and selected aromatic-heteroaromatic ketones in
good to excellent yields and enantioselectivities. In a similar
manner to other reduction methods,[6a,b,13] meta- and para-
substituted benzophenones were converted into their corre-
sponding alcohols with low or moderate ee values[26,27] be-
cause of the lack of asymmetric bias in the transition state.
In addition, upon exposure to the copper-catalyzed hydrosi-
lylation conditions, diaryl ketone substrates often showed in-
ferior reactivity to aryl alkyl ketones under otherwise identi-
cal conditions.
Very recently, we established a new set of reaction condi-
tions to facilitate the copper-catalyzed enantioselective 1,4-
reduction of b-(acylamino)acrylates.[29] In the presence of
stoichiometric polymethylhydrosiloxane (PMHS), a low-cost
and air-stable hydride donor, with tBuONa and tBuOH as
additives, the formation of a range of b-alkyl-b-amino acid
derivatives with high levels of enantiopurity (up to 99%)
The roles of the alcohol and the base in the increased re-
action rate remain unclear at present. It appeared that, in
the initial step of the catalytic cycle, upon combining (S)-P-
Table 1. Effects of additives on the copper-catalyzed hydrosilylation of 2-
chlorobenzophenone (5a).[a]
Entry
Alcohol
Base
Conv. [%][b]
ee [%][c]
1
2
3
–
–
–
57
66
99
99
34
82
78
81
81
82
tBuOH
tBuOH
tBuOH
–
tBuONa
tBuONa
tBuONa
4[d]
5
[a] Reaction conditions: substrate (35 mg, 0.33m in toluene). [b] Conver-
sion was determined by NMR spectroscopy and GC. [c] The ee values
were determined by chiral HPLC analysis; the absolute configuration
was determined by comparison of the retention times with literature data
(see the Supporting Information). [d] Performed under a N2 atmosphere.
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CuII-Catalyzed Asymmetric Hydrosilylation of Ketones
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Phos with CuCl and tBuONa, chiral CuI complex [(tBuO)-
CuL*] (A, L*=(S)-P-Phos) was likely formed. Also, in the
final step, the copper alkoxide intermediate [{(1Ar)-
of mono-substituted benzophenones (5a–5h) in air. As
shown in Scheme 1, the complete reduction of most of the
substrates into their corresponding substituted benzhydrols
ACHTUNGTRENNUNG
(2Ar)HCO}CuL*] (B) may have been protonated by the al-
cohol additive tBuOH to give the desired chiral diaryl alco-
hol product and copper complex A. Complex A may have
been capable of undergoing s-bond metathesis with PMHS
more-rapidly than either CuCl or copper alkoxide inter-
mediate
B to generate active copper hydride species
[CuHL*] (C), which is conjectured to be the rate-limiting
step.[17f,24d,30,31a]
Next, we examined the effects of various CuI and CuII
precursors on the enantioselective reduction of compound
5a under a given set of conditions (Table 2, entries 1–6).
Table 2. Effects of the copper salt and the ligand on the copper-catalyzed
asymmetric hydrosilylation of compound 5a in air.[a]
Entry
Copper salt
Ligand
T
[8C]
Conv.
[%][b]
ee
[%][c]
1
2
3
4
5
6
CuF2
CuCl2
CuCl2·2H2O
CuBr2
(S)-4a
(S)-4a
(S)-4a
(S)-4a
(S)-4a
(S)-4a
(S)-4a
(S)-4b
(S)-4c
0
0
0
0
0
94
84
80
12
81
78
82
82
82
81
81
87
88
88
[Cu
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
A
Scheme 1. Effect of the substituent on the copper-catalyzed asymmetric
hydrosilylation of aryl phenyl ketones (5) in air.
N
0
93
7[d]
8[d]
9[d]
U
À30
À30
À30
>99
>99
>99
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
(6a–6h) within 12 h was observed in the presence of ligand
(S)-4d at À508C (86–95% yield). The position of the sub-
stituent on the phenyl ring of benzophenone had a significant
effect on the stereoselectivity. Substrates that contained
either electron-withdrawing or electron-donating ortho-sub-
stituents (5a–5d) afforded the desired alcohols (6a–6d, re-
spectively) with moderate to good ee values (70–90%).
However, the presence of a meta- or para-substituent (5e–
5h) resulted in a substantial drop in enantioselectivity (3–
38% ee). Moreover, the introduction of a more-electron-
withdrawing o-chloro or o-bromo unit was conductive to
higher ee values (compounds 6a and 6c versus compounds
6b and 6d),[8i,8 m,13a,13b,13e,27] which may have been because
the extent of the coplanarity of the benzene rings with C=O
in the transition state largely relied on the asymmetric bias
that was generated from the two aryl groups that were con-
nected to the C=O functional group.
[a] Reaction conditions: substrate (65 mg, 0.33m in toluene). [b] Conver-
sions were determined by NMR spectroscopy and GC analysis. [c] The ee
values were determined by chiral HPLC analysis; the absolute configura-
tion was determined by comparison of the retention times with literature
data (see the Supporting Information). [d] Reaction time 3 h.
The counterion of the copper salts didn’t have any obvious
influence on the reaction. With the exception of CuBr2
(Table 2, entry 4), the product, (R)-6a, was afforded in
above 80% conversion and 78–82% ee after 1.2 h (Table 2,
entries 1–3, 5, and 6) in most cases. In terms of both activity
and enantioselectivity, CuACHTNUGTRNEUNG(OAc)2·H2O, an easy-to-handle
and inexpensive copper resource appeared to be the best
choice (Table 2, entry 6). Further investigation demonstrated
that lowering the reaction temperature was beneficial for
enhancing the enantioselectivity whilst a longer reaction
time was required for complete conversion (Table 2, cf. en-
tries 7 and 6). In addition, sterically more-demanding lig-
ACHTUNGTRENNUNGands (S)-4b and (S)-4c possessed similar efficacies com-
pared to parent ligand (S)-4a (Table 2, entries 8 and 9
versus entry 7).
Asymmetric hydrosilylation of ortho-substituted unsymmet-
rical diaryl ketones: Having envisaged that the presence of
an o-Br or o-Cl substituent on one of the aryl groups in un-
symmetrical diaryl ketones could be favorable for the hydro-
silylation reactions with higher degrees of enantioselection,
we designed a broad range of structurally diverse ortho-sub-
stituted unsymmetrical diaryl ketones (7a–7r; Table 3 and
Scheme 2) that could be conveniently prepared by the nu-
cleophilic addition of appropriate aryl magnesium bromides
Asymmetric hydrosilylation of aryl phenyl ketones: With
the aforementioned optimized conditions in hand, we
turned to establishing the general utility of this Cu-catalyzed
procedure for the asymmetric hydrosilylation of a selection
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to 2-bromobenzaldehyde or 2-chlorobenzaldehyde, followed
by oxidation of the resultant alcohol with pyridinium chloro-
chromate (PCC; see the Supporting Information).[32] We
chose these substrates based on two considerations: 1) the
ortho-substituted bromine- or chlorine atom could act as an
enantiodirecting functional group in the Cu-catalyzed hydro-
silylation step; 2) the halogen groups could be readily re-
moved from the alcohol products, if needed.
o-Cl- or o-Br-phenyl aryl ketones that contained para- or
meta-substituted electron-deficient (Table 3, entries 1, 2, 7,
and 8) and electron-rich aryl groups (Table 3, entries 3–6
and 9–12) all underwent facile hydrosilylation under the op-
timized conditions to afford the desired alcohols in good to
excellent enantiopurity (up to 95% ee) and high yield. With
the exception of substrates 7e (Table 3, entry 5) and 7i
(Table 3, entry 9), the reduction of o-Br-substituted diaryl
ketones afforded higher enantioselectivities than those of re-
lated o-Cl-substituted substrates under otherwise identical
conditions (Table 3, for example, cf. entries 1 and 2, and en-
tries 3 and 4). As expected, ortho-chlorophenyl ortho-meth-
ylphenyl ketone (7m) was reduced in quantitative yield in
only 69% ee (Table 3, entry 14), presumably owing to the
Scheme 2. CuII-catalyzed asymmetric hydrosilylation of ortho-substituted
unsymmetric diaryl ketones 7n–7r in air.
Table 3. CuII-catalyzed asymmetric hydrosilylation of ortho-substituted unsymmetrical diaryl ketones 7a–7m in air.[a]
Entry
Substrate
X
T [8C]
t [h]
Yield [%]
ee [%][b]
1
2
X=Br, 7a
X=Cl, 7b
À50
À50
36
36
95
96
95 (+)
92 (+)
3
4
X=Br, 7c
X=Cl, 7d
À30
À30
15
15
94
95
92 (R)
91 (R)
5
6
X=Br, 7e
X=Cl, 7 f
À50
À50
36
36
92
96
77 (R)
91 (R)
7
8
X=Br, 7g
X=Cl, 7h
À50
À50
36
36
96
96
94 (+)
90 (+)
9
10
X=Br, 7i
X=Cl, 7j
À30
À30
15
15
96
95
81 (+)
87 (R)
11
12
X=Br, 7k
X=Cl, 7l
À50
À30
36
15
95
96
88 (R)
83 (R)
13
14
X=H, 5d
X=Cl, 7m
À50
À30
36
15
95
94
81 (S)
69 (R)
[a] Reaction conditions: substrate (0.5 mmol, 0.3m in toluene); full conversion was observed for all of the reactions. [b] The ee values were determined
by chiral HPLC analysis. The absolute configurations were determined by comparison of the retention times or optical rotations with literature data (see
the Supporting Information).
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CuII-Catalyzed Asymmetric Hydrosilylation of Ketones
FULL PAPER
lack of sufficient steric dissymmetry derived from the sub-
strates.
Furthermore, as shown in Scheme 2, several other ortho-
substituted unsymmetrical diaryl ketones (7n–7r) that con-
tained disubstituted aryl- or naphthyl groups also underwent
efficient and selective reaction to afford the desired alcohol
products in quantitative yield and with ee values of 82–96%.
In particular, the transformation of (2-chlorophenyl)(3,5-di-
methylphenyl)methanone (7p) neatly afforded the corre-
sponding alcohol (8p) in up to 96% ee, even at ambient
temperature.
Asymmetric hydrosilylation of aryl heteroaryl ketones: Al-
though enantioenriched aryl heteroaryl alcohols are regard-
ed as important intermediates and structural motifs in me-
dicinal chemistry, there are few reports of their catalytic
asymmetric synthesis.[4,8m–o,13c,e,27] Given the good perfor-
mance of our catalyst system in the hydrosilylation of diaryl
ketones, we were therefore interested in the extension of
our system to the stereoselective reduction of aryl heteroar-
yl ketones (Scheme 3). Similar to the results from the hydro-
silylation of diaryl ketones, the introduction of Cl- or Br
substituents at the ortho position of the phenyl ring in the
aromatic-heteroaromatic ketones was beneficial for the pro-
duction of their corresponding alcohols (10a–10d) with
modest to good ee values (74–83%). However, the absence
of an ortho-substituent on the phenyl ring resulted in a sub-
stantial erosion of the enantioselectivity (10e versus 10b
and 10c, and 10 f versus 10d).
Scheme 4. Asymmetric synthesis of (R)-orphenadrine 1 and (S)-neobeno-
dine 2.
Enantioselective synthesis of orphenadrine and neobeno-
dine: With an efficient catalyst system for the enantioselec-
tive hydrosilylation of diaryl ketones in hand, we sought to
apply this procedure to the asymmetric synthesis of antihis-
taminic agents (R)-orphenadrine (1) and (S)-neobenodine
(2).[33] Thus, the asymmetric hydrosilylation of ketones 5d
and 7c under similar conditions to those given in Table 3
proceeded smoothly in air to furnish non-racemic alcohols
6d and 8c in 81% and 92% ee, respectively (Scheme 4).
The ortho-substituted bromine group of compound 8c was
readily removed by lithiation with nC4H9Li (3 equiv) in
THF at À788C for 3 h, followed by hydrolysis, to give com-
pound 6h in quantitative yield and 91% ee. In contrast,
compound 6h was obtained in only 25% ee through the
direct reduction of its corresponding ketone (5h; Scheme 1).
Next, a mixture of the enantioenriched alcohol product and
2-chloro-N,N-dimethyl-acetamide in THF was treated with
sodium hydride at room temperature for 4 h to cleanly
afford amide intermediate 11 or 12. Finally, 1.2 equiv I2 was
added at 08C to the solution of NaBH4 (2.3 equiv) and
amide 11 or 12 in THF over 0.5 h and the mixture was
heated at reflux for 4 h followed by work-up with 10%
aqueous HCl to provide the target chiral product (R)-orphe-
nadrine (95% yield) or (S)-neobenodine (81% yield).
Conclusion
We have developed a versatile and practical copper-cata-
lyzed hydrosilylation method for the formation of a diverse
range of diaryl- and aryl heteroarylmethanols with good to
Scheme 3. CuII-catalyzed asymmetric hydrosilylation of aryl heteroaryl
ketones 9a–9 f in air.
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excellent ee values (up to 96%). Our catalyst system was
generated in situ by the combination of an inexpensive and
easy-to-handle copper source, CuACTHNUTRGNEU(NG OAc)2·H2O, a commercial-
ly available and air-stable chiral ligand, (S)-Xyl-P-Phos, and
a stoichiometric hydride donor, PMHS, in air with certain
amounts of tBuONa and tBuOH as additives. In particular,
the synthetic utility of the chiral products was highlighted by
the efficient transformation of enantiomerically enriched
diaryl alcohols into the anticholinergic and antihistaminic
agents (R)-orphenadrine and (S)-neobenodine.
Experimental Section
Typical procedure for the asymmetric hydrosilylation of diaryl ketones in
air: CuACHTUNGTRENNUNG(OAc)2·H2O (3.0 mg, 0.015 mmol), tBuONa (1.5 mg, 0.015 mmol),
and (S)-Xyl-P-Phos (1.0 mg, 0.0012 mmol) were weighted in air and
placed in a 25 mL round-bottomed flask that was equipped with a mag-
netic stirrer bar. Toluene (0.2 mL) was added and the mixture was stirred
at RT for 15 min. To the mixture was added a solution of PMHS (80 mL,
4 equiv) in toluene (0.1 mL) and the mixture was cooled to À508C. A so-
lution of 2-chlorobenzophenone 5a (65 mg, 0.3 mmol) in toluene
(0.3 mL) and tBuOH (60 mL, 4 equiv) was added under vigorous stirring
and the flask was stoppered. The reaction was monitored by TLC. Upon
completion, the reaction was quenched with 2.5m NaOH (2.0 mL) and
Et2O (2.0 mL) and the mixture was stirred vigorously for 1 h. The aque-
ous layer was extracted with Et2O (3ꢁ1 mL) and the combined organic
layer was washed with water, dried over anhydrous sodium sulfate, fil-
tered through a plug of silica gel, and concentrated under vacuum to pro-
vide the crude product. The conversion and enantiomeric excess of the
product (6a) were determined by NMR spectroscopy, GC (J & W Scien-
tific INNOWAX; 30 mꢁ0.25 mm, carrier gas: N2), and chiral HPLC
À
(Daicel Chiralcel OD H column, 25 cmꢁ4.6 mm) to be 97% and 90%,
respectively. The pure product was isolated by column chromatography
on silica gel (EtOAc/petroleum ether, 1:10; 65 mg, 94% yield).
Acknowledgements
We thank the National Natural Science Foundation of China (21172049,
21032003, 91127010, and 21072039), the Public Welfare Technology and
Application Program of Zhejiang Province (2010C31042), and the Special
Funds for the Key Innovation Team of Zhejiang Province (2010R50017)
for their generous financial support of this research.
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CuII-Catalyzed Asymmetric Hydrosilylation of Ketones
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Received: February 4, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
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J. Wu et al.
Could do with a copper: The Cu-cata-
lyzed conversion of diaryl- and aryl
heteroaryl ketones into their corre-
sponding alcohols proceeded in high
yields and with good to excellent ee
values. This process was used in the
asymmetric synthesis of two antihista-
mines.
Asymmetric Catalysis
Y.-Z. Sui, X.-C. Zhang, J.-W. Wu, S. Li,
J.-N. Zhou, M. Li, W. Fang,
A. S. C. Chan, J. Wu* ........ &&&& — &&&&
CuII-Catalyzed Asymmetric Hydrosil-
ACHTUNGTRENNUNGylation of Diaryl- and Aryl Heteroaryl
Ketones: Application in the Enantiose-
lective Synthesis of Orphenadrine and
Neobenodine
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These are not the final page numbers!