Catalytic enantioselective dehydrogenative Si-O coupling of oxime ether-functionalized alcohols

Article abstract of DOI:10.1016/j.tet.2011.06.102

Asymmetric silylation of alcohols is an unusual but effective approach to their kinetic resolution, and the Cu-H-catalyzed dehydrogenative Si-O coupling is particularly noteworthy as dihydrogen is formed as the sole by-product. Our laboratory had previously reported on diastereoselective (with silicon-stereogenic silanes) and enantioselective (with achiral silanes) Si-O couplings of azine donor-functionalized alcohols. The limitation, that is, the requirement of a nitrogen donor atom, prompted us to seek equally useful donor groups. Oxime ethers were identified as a suitable alternative, and we describe herein the preparation of a series of oxime ether-functionalized alcohols. To assess different substitution patterns in their kinetic resolution, these were tested in the reagent-controlled Si-O coupling using a silicon-stereogenic silane. The optimal substituents at the oxime carbon atom (dr=85:15 in the diastereoselective coupling) were then chosen for the related catalyst-controlled Si-O coupling but selectivity factors were only moderate.

Full text of DOI:10.1016/j.tet.2011.06.102

Tetrahedron 68 (2012) 3468e3479
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalytic enantioselective dehydrogenative SieO coupling of oxime
ether-functionalized alcohols
*
Andreas Weickgenannt, Jens Mohr, Martin Oestreich
€
€
€
€
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, Corrensstraße 40, D-48149 Munster, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2011
Received in revised form 14 June 2011
Accepted 23 June 2011
Available online 13 July 2011
Asymmetric silylation of alcohols is an unusual but effective approach to their kinetic resolution, and the
CueH-catalyzed dehydrogenative SieO coupling is particularly noteworthy as dihydrogen is formed as
the sole by-product. Our laboratory had previously reported on diastereoselective (with silicon-
stereogenic silanes) and enantioselective (with achiral silanes) SieO couplings of azine donor-
functionalized alcohols. The limitation, that is, the requirement of a nitrogen donor atom, prompted
us to seek equally useful donor groups. Oxime ethers were identified as a suitable alternative, and we
describe herein the preparation of a series of oxime ether-functionalized alcohols. To assess different
substitution patterns in their kinetic resolution, these were tested in the reagent-controlled SieO cou-
pling using a silicon-stereogenic silane. The optimal substituents at the oxime carbon atom (dr¼85:15 in
the diastereoselective coupling) were then chosen for the related catalyst-controlled SieO coupling but
selectivity factors were only moderate.
Keywords:
Copper
Enantioselective silylation
Kinetic resolution
Oxime ethers
Silicon
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
were superior to chelating ligands in both SieO couplings, and
that creates a rare stereochemical scenario in the enantioselective
Kinetic resolution is an established technique for the synthesis
of enantioenriched compounds.1 Chiral non-racemic alcohols are
a prominent class of substrates often accessed by kinetic resolu-
tion, through either acylation1,2 or oxidation.3 Conversely, stereo-
selective silylation of alcohols is still uncommon despite the
prevalence of silicon protecting groups in organic chemistry.4 Ki-
netic resolution of alcohols based on asymmetric silylation is,
therefore, synthetically attractive.5 For this, organo- and transition
metal-catalyzed approaches were developed in the last decade. On
the one hand, after a seminal contribution by Ishikawa et al.,6
Hoveyda et al. reported the enantioselective silylation of racemic
1,2-/1,3-diols7 (kinetic resolution) and meso-configured diols8a and
triols8b (desymmetrization), employing chlorosilanes and a small
peptide-like catalyst. On the other hand, our laboratory introduced
both diastereo-9ꢀ11 and enantioselective12 CueH-catalyzed SieO
couplings of a variety of azine donor-functionalized secondary9,12
and tertiary10 alcohols. Asymmetric induction in the former ca-
talysis originates from a silicon-stereogenic hydrosilane13 (reagent
control) whereas a chiral ligand is the source of chirality in the
latter (catalyst control). Monodentate ligands, achiral or chiral,
case where only a single chiral ligand is responsible for enantio-
mer discrimination.12
The proposed mechanism of the dehydrogenative SieO coupling
is supported by quantum-chemical calculations (Scheme 1).9b The
catalytic cycle begins with in situ-generated CueH complex A.
Coordination of alcohol B is accompanied by the release of
* Corresponding author. E-mail address: martin.oestreich@uni-muenster.de
(M. Oestreich).
Scheme 1. Proposed mechanism of dehydrogenative SieO coupling (Do¼donor group).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.102

A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
3469
dihydrogen, thereby yielding the coordinatively saturated complex
C. Dissociation of one monodentate ligand in the assumed rate-
determining step produces the coordinatively unsaturated com-
plex D, and the vacant coordination site (box) in D is now available
alcohol oxidation level. That aldehyde turned out to be rather un-
stable and was, therefore, directly converted into desired rac-3 by
the addition of PhMgBr (entry 1, Table 1). This procedure was then
extended to the preparation of several alcohols rac-4erac-9 by
variation of the Grignard reagent. Electron-donating (entry 2, Table
1), electron-withdrawing (entry 3, Table 1) and sterically de-
manding (entry 4, Table 1) substituents on the aromatic ring were
tolerated. A heterocyclic group (entry 5, Table 1) as well as alkyl
for the coordination of silane E. The subsequent irreversible s-bond
metathesis through transient F is likely to be the stereochemistry-
determining step of this catalysis. Catalytically active A is regen-
erated in this step.
Alcohol B must bind to Cu(I) in bidentate fashion to participate
in the catalysis. Without donor functionalization, no reaction was
observed under the standard reaction conditions of the enantio-
selective SieO coupling.12 The azine donors used so far are, how-
ever, of limited synthetic value (left, Fig. 1), and synthetically more
versatile donor groups would certainly extend the scope of our
catalyst-controlled kinetic resolution.12 We, therefore, set out to
identify equally effective donor groups, and found oxime ethers to
be promising (right, Fig. 1). We describe herein the preparation of
oxime ether-functionalized alcohols as well as their diastereo- and
enantioselective silylation.14
Table 1
Synthesis of N-Boc-protected b-hydroxyhydroxylamines: variation of the carbinol
substituent (cf. Scheme 2)
Entry
RMgX
Compound
Yield (%)
1
PhMgBr
79
2
4-MeOC6H4MgBr
41
Fig. 1. Azine- and oxime ether-functionalized alcohols.
2. Results and discussion
2.1. Preparation of oxime ether-functionalized alcohols
3
4-CF3C6H4MgBr
60
A new general route to the targeted oxime ether-functionalized
alcohols (right, Fig. 1) had to be developed as published procedures
rely on regioselective epoxide opening by nucleophiles.14,15 The
selectivities are moderate, particularly with aryl-substituted ep-
oxides. More importantly, the regioisomers formed are usually not
separable by conventional flash column chromatography. Kibayashi
et al. had reported the preparation of the phenyl-substituted b-
hydroxyhydroxylamine rac-10 (cf. Scheme 3), a viable precursor for
4
5
6
2-MeC6H4MgBr
2-ThiophenylMgBr
MeMgI
53
97
33
the corresponding oxime ether.16 However, this protocol had only
been applied to phenyl-substituted b-hydroxyhydroxylamines, and
that made it unsuitable for our purpose. Moreover, that reaction
sequence was not practical on a multigram scale in our hands.
Our approach was motivated by the need for a reliable access that
would allow for the gram-scale synthesis of differently substituted
oxime ether-functionalized alcohols. It commenced with N-Boc-
protected hydroxylamine 1, a commercially available and easily ac-
cessible compound.17 Its condensation with methyl
a-bromoacetate
afforded 2 in 61% yield on a reasonable scale (Scheme 2).
Building block 2 was reduced with DIBAL-H to the corre-
sponding aldehyde (not shown) without any overreduction to the
7
i-PrMgCl
37
Scheme 2. Gram-scale synthesis of 2 and subsequent reductioneaddition.

3470
A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
Table 3
groups were also installed successfully (entries 6 and 7, Table 1). All
of these reactions were performed on multigram scale.
Synthesis of acetone-derived oxime ethers: variation of the carbinol substituent (cf.
lower, Scheme 3)
With the alcohol rac-3 in hand, the corresponding
oxime ether was obtained using a straightforward procedure. The
Boc group was removed with aqueous hydrochloric acid and the
b-hydroxy-
Entry
Substrate
Product
Yield (%)
b
-
hydroxyhydroxylamine rac-10 was isolated in 98% yield after 1 h
(upper, Scheme 3). Condensation of rac-10 with different ketones
11e15 under the reaction conditions described by Reese et al.18
yielded oxime ethers rac-16erac-20 in good isolated yields (up-
per, Scheme 3 and entries 1e5, Table 2). Even the sterically crowded
bis-iso-propyl substituted oxime ether rac-18 was accessible albeit
in lower yield (entry 3, Table 2).
1
rac-3
69
2
rac-4
27
3
rac-5
88
Scheme 3. Alternative ways to access the oxime ether-functionalized alcohols rac-
16erac-26: two-step protocol versus one-pot procedure.
Table 2
Synthesis of
b
-hydroxyoxime ethers: variaton of oxime ethers (cf. upper, Scheme 3)
Ketone Compound Yield (%)
4
rac-6
66
Entry
1
48
5
rac-7
22
2
3
87
40
6
7
rac-8
rac-9
20
47
4
77 (E,Z>95:5)
The N-Boc-protected hydroxylamines rac-4erac-9 were con-
verted into acetone-derived oxime ethers (lower, Scheme 3 and
entries 2e7, Table 3). Preliminary experiments had shown before
that these oxime ethers were most reactive in the dehydrogenative
SieO coupling. In the course of these experiments, we established
a simplified procedure for the oxime ether synthesis. We found that
the deprotection and the subsequent condensation are possible in
one pot by treatment of rac-3erac-9 and acetone with TFA in
CH2Cl2eH2O¼2:1 (lower, Scheme 3). The oxime ethers were iso-
lated in moderate to good yields (entries 1e7, Table 3).
5
86 (E,Z¼89:11)

A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
3471
2.2. Diastereoselective SieO couplings
(S)-16 was reduced using NaBH3CN to afford hydroxylamine (S)-32.
Facile cleavage of the NeO bond16 in (S)-32 with Mo(CO)6 resulted in
quantitative formation of known (S)-33. The absolute configuration
of (S)-33 was determined by comparison of the sign of the optical
rotation.22 By this, the relative configuration of 28 was assigned as
(SiS,R), agreeingwith the stereochemical preferenceseenwith azine-
functionalized alcohols.9
Moreover, this racemization-free reaction sequence demon-
strates the ease of converting oxime ethers into synthetically more
useful chiral 1,2-diols in excellent overall yield.
To assess different substitution patterns of the oxime ether-
functionalized alcohols rac-16erac-19 in their kinetic resolution,
these were initially tested in the reagent-controlled SieO coupling
using asilicon-stereogenic silane. As mentionedearlier, our previous
work on stereoselective SieO couplings had clearly demonstrated
that a donor group tethered to the carbinol carbon atom is essential
for sufficient reactivity and high stereoselectivity (cf. Scheme 1).9ꢀ12
Azines, that is, nitrogen-containing aromatic heterocycles, had
proven to be optimal although oxazoles and thiazoles were also
effective.9b Conversely, unfunctionalized alcohols without that ni-
trogen donor atom were ineffective in the diastereoselective cou-
pling,9a,b and the same trend was also seen in the enantioselective
coupling.12 We believe that the level of diastereoselectivity is
a qualitative indicator as to whether the donor group actually co-
ordinates to the Cu(I) atom, thereby imparting increased rigidity in
the stereochemistry-determining step through two-point binding.
We therefore subjected rac-16erac-19 to the diastereoselective
SieO coupling with our cyclic silane rac-2719 using the standard
reaction setup (Table 4).9a,b To our delight, oxime ether rac-16
reacted with promising diastereoselectivity (entry 1, Table 4). The
diastereomeric ratio of 85:15 for the acetone-derived oxime donor
comes close to the diastereomeric ratio of 92:8 previously obtained
with the pyridine donor.9a,b That result clearly verifies the N(sp2)e
Cu(I) interaction. Its sterically more hindered congener rac-17
reacted with comparable selectivity but diminished conversion
(entry 2, Table 4). Any further increase of the steric bulk at the
oxime carbon atom thwarted turnover (entries 3 and 4, Table 4).
2.4. Synthesis of cyclic silanes
The above findings in the diastereoselective SieO coupling of
the oxime ether-functionalized alcohols were promising, and the
development of the related enantioselective variant was the next
logical step. Achiral silanes with the general formula MeAr2SiH had
been ideal in the CueH-catalyzed coupling of alcohols with an
azine donor.12 We decided to again screen all of these silanes in the
present study but, this time, we planned to also include achiral
cyclic silanes in our survey. These cyclic silanes (35 and 36, Scheme
5 as well as 38, Scheme 6) might be considered rigidified versions of
acyclic MeAr2SiH, and cyclic systems had always been superior to
acyclic counterparts in the diastereoselective SieO couplings.9
Cyclic 35 and 36 were prepared from 34 (Scheme 5). Regiose-
lective two-fold metalation with n-BuLi in THF was followed by
addition of the appropriate RSiCl3 and reduction with LiAlH4. Si-
lanes 35 and 36 were isolated in good yields.
Strained cyclic silanes are usually more reactive due to strain-
release Lewis acidity,23 and we had already utilized that effect in
reagent-controlled SieO coupling of unreactive tertiary alcohols.10
As a result, silanes with the silicon atom embedded into a five-
membered ring are expected to be more reactive than related six-
membered ring systems. Strained 38 was accessed from 3724 by
two-fold BreLi exchange with t-BuLi in Et2O followed by treatment
with MeSiCl2H (Scheme 6). Silane 38 was isolated in 58% yield.
Table 4
Diastereoselective SieO coupling: screening of oxime ethers
2.5. Enantioselective SieO couplings
The reaction setup CuCleCs2CO3eTHF (with chiral ligand L1)
developed for kinetic resolution of azine donor-substituted alco-
hols12 failed to catalyze the enantioselective SieO coupling of the
corresponding oxime ether-substituted alcohols. In turn, a cata-
lystebaseesolvent combination similar to that of the diastereo-
selective catalysis (CuCleNaOt-Buetoluene)9 was optimal, and no
b
Entry
Oxime ether
R0
R00
Silyl ether
Conversiona (%)
drrac
1
2
3
4
rac-16
rac-17
rac-18
rac-19
Me
Et
i-Pr
t-Bu
Me
Et
i-Pr
Me
rac-28
rac-29
rac-30
rac-31
66 (20)c
40 (27)c
<10
85:15
82:18
d
N.d.d
20
undesired base-catalyzed background reaction was observed.25
A
a
Determined by GLC analysis using n-hexadecane as an internal standard.
Determined by 1H NMR analysis using baseline-separated resonance signals.
Isolated yield of analytically pure product in parentheses.
Not determined.
b
c
screening of dozens of monodentate and bidentate ligands then
revealed that phosphonite ligand L126 was again the best ligand.12
Moreover, only oxime ethers derived from acetone (cf. Table 3)
were reactive enough, and we selected rac-16 as the model substrate.
Our next goal was to identify a suitable silane (Table 5). We
screenedseveralrepresentative triorganosilanes. Et3SiH(39) wasnot
sufficiently reactive (entry 1, Table 5). As expected, aryl substitution
brought about increased reactivity (entries 2 and 3, Table 5), and
MePh2SiH (41) produced reasonable conversion (entry 3). The slow-
reacting enantiomer (S)-16 was isolated in 23% ee at 36% conversion,
corresponding to s¼3.0. This value is significantly lower than that
obtained for the related azine donor-functionalized alcohol
(s¼13.9).12 AnextensivesurveyofMeAr2SiH42e49withvariedsteric
and electronic properties was conducted but, regrettably, none was
as effective as parent 41 (entries 4e11, Table 5). No improvement was
seen with cyclic 35, 36 and 38 (entries 12e14, Table 5).
d
2.3. Assignment of the relative and absolute configuration
The relative configuration of rac-28 was of particular interest as it
would further validate similarities between the oxime and azine
donor groups in the SieO coupling. If both favor the same relative
configuration, the same mechanistic model might apply (cf. Scheme
1).9b To determine the relative and absolute configurations of rac-28,
we performed the kinetic resolution of rac-16 now employing
enantiomerically enriched (SiR)-27 (Scheme 4). The oxime ether (S)-
16 was obtained in 27% ee at 33% conversion, corresponding to an
apparent selectivity factor20 of sapp¼4.4;21 (SiS,R)-28 was formed
with dr¼85:15. That selectivity factor is not exactly matching the
theoretical value of stheo¼11.7 (calculated from drrac¼85:15)21 pri-
marily due to the use of an enantioimpure resolving silane, (SiR)-27
with 90% ee. The configurations were then unambiguously estab-
lished by chemical correlation. For this, the slow-reacting alcohol
These poor selectivity factors were somewhat surprising as the
reagent-controlled SieO coupling had proceeded with promising
diastereomeric ratios (cf. Section 2.2), comparable to those
obtained for alcohols with a tethered azine donor.9 Our previous

3472
A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
Scheme 4. Determination of the relative and the absolute configuration of (S)-16 by chemical correlation.
based on a CO2Me-to-CHO reduction and subsequent addition of
Grignard reagent. The N-Boc-protected -hydroxyhydroxyl-
amines thus obtained are either deprotected to yield the corre-
sponding free -hydroxyhydroxylamines or converted in one-step
a
b
b
into a variety of oxime ethers with good to excellent yields on gram
scale. The diastereoselective SieO coupling verified that these ox-
ime ethers are indeed useful substrates for the reagent-controlled
kinetic resolution but selectivities have not been satisfying in
catalyst-controlled kinetic resolution by means of the enantiose-
lective SieO coupling so far.
Scheme 5. Synthesis of the six-membered ring silanes 35 and 36.
4. Experimental
4.1. General
Reagents obtained from commercial suppliers were used with-
out further purification unless otherwise noted. All reactions were
performed in flame-dried glassware under a static pressure of ar-
gon. Liquids and solutions were transferred with syringes. All sol-
vents were purified following standard procedures. Toluene was
degassed prior to use. Solvents used for extraction and chroma-
tography (cyclohexane, tert-butylmethyl ether, ethyl acetate,
CH2Cl2) were distilled prior to use. Analytical thin layer chroma-
tography was performed on silica gel 60 F254 glass plates by Merck,
and flash chromatography was performed on silica gel 60
Scheme 6. Synthesis of the five-membered ring silane 38.
work9,12 had suggested that donor-functionalized alcohols would
behave similarly in the diastereo- and enantioselective variants of
our kinetic resolution. It is now obvious that this assumption can-
not be generalized.
We, nevertheless, subjected acetone-derived oximes rac-
21erac-26 with different substituents at the carbinol carbon atom
to the optimized protocol using silane 41 (Table 6). Electron-rich,
electron-poor and sterically hindered aryl groups were tolerated
(entries 1e3, Table 6). The same was true for a heteroaromatic as
well as a small aliphatic substituent (entries 4 and 5, Table 6). A i-
Pr-substituted alcohol was too unreactive (entry 6, Table 6). All
selectivities obtained were low, clearly showing that oxime ether
donor group is not able to rival any of the azine donors in the
enantioselective CueH-catalyzed SieO coupling.
(40e63 m
m, 230e400 mesh, ASTM) by Merck. 1H, 13C, and 19F NMR
spectra were recorded in CDCl3 on Bruker AV 300, AV 400 and
Varian 500 Inova and 600 unity plus instruments. Infrared spectra
were recorded on a Digilab Excalibur Series FTS 4000 spectropho-
tometer. Enantiomeric excesses were determined by analytical
HPLC analysis on an Agilent 1200 Series with Daicel chiral sta-
tionary phases and by analytical GLC analysis on a GC-17A in-
strument by Shimadzu using an SE-54 quartz capillary column.
Optical rotations were measured on a PerkineElmer 341 polarim-
eter. Melting points (Mp) were measured at a Thompson Scientific
apparatus and are not corrected. High resolution mass spectrom-
etry (ESI-MS) as well as elemental analyses were performed by the
analytical facility at the Organisch-Chemisches Institut, University
3. Summary
In summary, we elaborated a new general access to oxime ether-
€
substituted alcohols (
b-hydroxyoxime ethers). Their preparation is
of Munster.

A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
3473
Table 5
Enantioselective SieO coupling: screening of silanes
Entry
Silane
R1
R2
Silyl ether of
fast-reacting
enantiomer
Enantiomeric excess
(ee) of slow-reacting
enantiomer (S)-16a (%)
Conversionb (%)
Selectivity factor20,21
s
1
2
3
4
5
6
7
8
39
40
41
42
43
44
45
46
47
48
49
Et
Ph
Et
Me
Ph
(R)-50
(R)-51
(R)-52
(R)-53
(R)-54
(R)-55
(R)-56
(R)-57
(R)-58
(R)-59
(R)-60
d
14
23
d
6
<10
23
36
<10
20
18
11
27
17
d
3.2
3.0c
d
Me
Me
Me
Me
Me
Me
Me
Me
Me
2-Tolyl
3-Tolyl
2-Naphthyl
3,5-Xylyl
4-Tolyl
4-t-BuC6H4
4-MeOC6H4
4-CF3C6H4
1.7
2.6
d
9
d
10
7
1.9
2.2
d
9
10
11
d
<10
26
44d
2.5
12
13
35
Me
(R)-61
17
35
31d
60
2.6
2.2
36
i-Pr
(R)-62
14
38
Me
(R)-63
6
26d
1.5
a
Determined by chiral GLC analysis using a Supelco beta-DEX 225 column.
Determined by GLC analysis using n-hexadecane as an internal standard.
Average of five runs.
b
c
d
Disiloxane formed as by-product.
4.2. Methyl-2-(tert-butoxycarbonylaminooxy)acetate (2)
134 mmol, 1.00 equiv), and the mixture was maintained at 60 ꢁC for
30 min. Methyl -bromoacetate (20.5 g, 134 mmol, 1.00 equiv) was
a
To a solution of KOH (7.52 g, 134 mmol, 1.00 equiv) in MeOH
(200 mL) was added tert-butylhydroxycarbamate (1, 17.8 g,
subsequently added, immediately forming a white precipitate. The
mixture was maintained at 60 ꢁC for 18 h. After evaporation of the
Table 6
Enantioselective SieO coupling: substrate scopea,b
Entry
Oxime ether
R
Silyl ether of fast-reacting enantiomer
Yield (%)
Slow-reacting enantiomer
Conversiond (%)
Selectivity factor20,21
s
Yield (%)
eec (%)
1
2
3
4
5
6
rac-21
rac-22
rac-23
rac-24
rac-25
rac-26
4-MeOC6H4
4-CF3C6H4
2-Tolyl
2-Thienyl
Me
(R)-64
(R)-65
(R)-66
(R)-67
(R)-68
(R)-69
74
65
68
81
de
d
(S)-21
(S)-22
(S)-23
(S)-24
(S)-25
(S)-26
99
99
89
97
de
d
27
32
21
46
48
46
45
36
d
2.5
2.8
2.0
2.9
3.1
d
30
24f
<10
i-Pr
a
All reactions were conducted using CuCl (5.00 mol %), NaOt-Bu (5.00 mol %), silane 41 (0.650 mol %) and the indicated oxime ether-functionalized alcohol rac-21erac-26 in
toluene at rt for 40 h.
b
All values are avarages of two runs.
Determined by HPLC analysis using Chiralcel and Chiralpak columns (baseline separation of enantiomers).
Determined by GLC analysis using n-hexadecane as an internal standard.
Isolation failed.
c
d
e
f
Determined by chiral GLC analysis using a Supelco beta-DEX 225 column.

3474
A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
solvents, the residue was suspended in water (30 mL) and extracted
with CH2Cl2 (6ꢂ30 mL). The combined organic phases were dried
over MgSO4, the solvent was removed in vacuo, and the residue was
purified by distillation.
344.1080. Found: 344.1078. Anal. Calcd for C14H18F3NO4: C, 52.34;
H, 5.65; N, 4.36. Found: C, 52.63; H 5.53; N 4.13.
4.3.4. rac-tert-Butyl-2-hydroxy-2-(2-methylphenyl)ethoxy-
carbamate (rac-6). White solid; yield: 53% (entry 4, Table 1). Rf¼0.15
(cyclohexaneeethyl acetate 4:1). Mp 116 ꢁC. 1H NMR (300 MHz,
Colorless viscous oil; yield: 61%. Bp 98e110 ꢁC at 0.34 mbar. 1H
NMR (300 MHz, CDCl3):
d
1.41 (s, 9H), 3.72 (s, 3H), 4.39 (s, 2H), 7.97
28.1, 52.0, 72.5, 82.1, 156.4,
(s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d
CDCl3):
d
1.52 (s, 9H), 2.32 (s, 3H), 3.70 (dd, J¼11.7, 9.8 Hz, 1H), 3.89
170.1 ppm. IR (ATR): 3322, 1980, 1742, 1439, 1369, 1247, 1220, 1164,
1118, 631 cmꢀ1. HRMS (ESI) calcd for C8H15NO5Na [(MþNa)þ]:
228.0842. Found: 228.0840. Anal. Calcd for C8H15NO5: C, 46.82; H,
7.37; N, 6.83. Found: C, 46.82; H, 7.63; N, 6.98. Spectroscopic data
are identical with those previously reported.27
(dd, J¼11.7, 2.4 Hz, 1H), 4.00 (s, 1H), 4.20 (dd, J¼9.7, 2.3 Hz, 1H),
7.10e7.26 (m, 3H), 7.50 (br s,1H), 7.56 (dd, J¼7.5,1.4 Hz,1H) ppm. 13C
NMR (75 MHz, CDCl3): d 19.1, 25.3, 67.5, 81.4, 83.0,126.2,126.4,127.7,
130.3,134.7,137.3,158.7 ppm. IR (ATR): 3390, 3313, 3200, 2976, 2937,
1711, 1489, 1368, 1282, 1255, 1164, 1116, 1087, 760 cmꢀ1. HRMS (ESI)
calcd for C14H21NO4Na [(MþNa)þ]: 290.1363. Found: 290.1358.
4.3.5. rac-tert-Butyl-2-hydroxy-2-(thiophen-2-yl)ethoxycarbamate
(rac-7). White solid; yield: 97% (entry 5, Table 1). Rf¼0.14 (cyclo-
hexaneeethyl acetate 4:1). Mp 103 ꢁC. 1H NMR (300 MHz, CDCl3):
4.3. General procedure for the preparation of N-boc-
protected b-hydroxyhydroxylamines
d
1.51 (s, 9H), 3.88 (dd, J¼11.7, 9.5 Hz, 1H), 4.01 (dd, J¼11.6, 2.8 Hz,
1H), 4.24 (dd, J¼9.5, 2.8 Hz, 1H), 4.88 (br s, 1H), 6.97e7.01 (m, 2H),
7.27 (m, 1H), 7.56 (br s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
28.2,
To a solution of 2 (1.00 equiv) in THFetoluene¼1:1 (1 M) cooled
to ꢀ78 ꢁC is added a solution of DIBAL-H (1.00 M in n-hexane,
2.08 equiv) over a period of 20 min, and the mixture is stirred for
additional 30 min. A solution of the appropriate Grignard reagent
(1.0 M in THF, 5.00 equiv)dfreshly prepared by the addition of the
respective halide (5.00 equiv) to a suspension of Mg (5.00 equiv) in
THFdis added. The reaction mixture is warmed to rt and main-
tained at this temperature for 18 h. The reaction is quenched by
addition of saturated aqueous NaHCO3, the phases are separated,
the aqueous phase is extracted with CH2Cl2, and the combined
organic phases are dried over MgSO4. After evaporation of the
solvents, the residue is purified by flash column chromatography
on silica gel (cyclohexaneetert-butylmethyl ether).
d
67.1, 82.2, 83.1, 124.2, 124.9, 126.8, 142.6, 158.7 ppm. IR (ATR): 3325,
3166, 2971, 1697, 1504, 1288, 1165, 1116, 1093, 904, 711, 645,
623 cmꢀ1
.
HRMS (ESI) calcd for C11H17NO4SNa [(MþNa)þ]:
282.0770. Found: 282.0768. Anal. Calcd for C11H17NO4S: C, 50.95; H,
6.61; N, 5.40. Found: C, 50.90; H, 6.40; N, 5.26.
4.3.6. rac-tert-Butyl-2-hydroxypropoxycarbamate (rac-8). Colorless
oil; yield: 33% (entry 6, Table 1). Rf¼0.07 (cyclohexaneeethyl ace-
tate 4:1). 1H NMR (300 MHz, CDCl3):
d
1.12 (d, J¼6.5 Hz, 3H), 1.48 (s,
9H), 3.15 (s, 1H), 3.56 (dd, J¼11.4, 9.5 Hz, 1H), 3.77 (dd, J¼11.4,
2.4 Hz, 1H), 4.04 (m, 1H), 7.38 (br s, 1H) ppm. 13C NMR (75 MHz,
CDCl3): d 17.6, 28.3, 64.1, 82.0, 82.8, 158.6 ppm. IR (ATR): 3273, 2978,
4.3.1. rac-tert-Butyl-2-hydroxy-2-phenylethoxycarbamate
(rac-
2935, 1713, 1457, 1368, 1279, 1253, 1163, 1110, 624 cmꢀ1. HRMS (ESI)
3). White solid; yield: 79% (entry 1, Table 1). Rf¼0.20 (cyclo-
calcd for C8H17NO4Na [(MþNa)þ]: 214.1050. Found: 214.1041.
hexaneeethyl acetate 1:1). Mp 102 ꢁC. 1H NMR (300 MHz, CDCl3):
d
1.42 (s, 9H), 3.66 (dd, J¼11.6, 9.8 Hz, 1H), 3.84 (dd, J¼11.6, 2.6 Hz,
1H), 4.14 (br s, 1H), 4.88 (dd, J¼9.8, 2.5 Hz, 1H), 7.14e7.33 (m, 5H)
ppm. 13C NMR (75 MHz, CDCl3):
28.3, 70.7, 82.8, 83.1, 126.4, 127.9,
4.3.7. rac-tert-Butyl-2-hydroxy-3-methylbutoxycarbamate
(rac-
9). White solid; yield: 37% (entry 7, Table 1). Rf¼0.14 (cyclo-
d
hexaneeethyl acetate 4:1). Mp 60 ꢁC. 1H NMR (300 MHz, CDCl3):
128.5, 139.4, 158.6 ppm. IR (ATR): 3358, 3156, 2983, 1716, 1492,
1456, 1368, 1279, 1251, 1165, 1118, 1100, 1071, 917, 841, 763, 699,
629 cmꢀ1. HRMS (ESI) calcd for C13H19NO4Na [(MþNa)þ]: 276.1206.
Found: 276.1211. Anal. Calcd for C13H19NO4: C, 61.64; H, 7.56; N,
5.53. Found: C, 62.00; H, 7.52; N, 5.28.
d
0.96 (d, J¼6.8 Hz, 3H), 0.96 (d, J¼6.8 Hz, 3H), 1.46 (s, 9H), 1.69 (m,
1H), 3.57 (ddd, J¼9.3, 6.1, 2.1 Hz, 1H), 3.68 (dd, J¼10.9, 9.3 Hz, 1H)
superimposed by 3.70 (br s, 1H), 3.89 (dd, J¼10.9, 2.1 Hz, 1H), 7.50
(br s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d 18.4, 18.9, 28.3, 30.6,
72.9, 80.4, 82.6, 158.4 ppm. IR (ATR): 3380, 3161, 2961, 2943, 2878,
1710, 1502, 1462, 1368, 1278, 1253, 1179, 1151, 1128, 1115, 1026, 1008,
817, 675 cmꢀ1. HRMS (ESI) calcd for C10H21NO4Na [(MþNa)þ]:
242.1363. Found: 242.1348. Anal. Calcd for C10H21NO4: C, 54.77; H,
9.65; N, 6.39. Found: C, 54.74; H, 9.86; N, 6.26.
4.3.2. rac-tert-Butyl-2-hydroxy-2-(4-methoxyphenyl)ethoxy-
carbamate (rac-4). White solid; yield: 41% (entry 2, Table 1). Rf¼0.04
(cyclohexaneeethyl acetate 10:1). Mp 103 ꢁC. 1H NMR (300 MHz,
CDCl3):
d
1.50 (s. 9H), 3.73 (dd, J¼11.6, 9.8 Hz, 1H), 3.79 (s, 3H), 3.88
(dd, J¼11.6, 2.7 Hz, 1H), 4.60 (s, 1H), 4.91 (dd, J¼9.8, 2.6 Hz, 1H), 6.87
4.4. 2-Aminooxy-1-phenylethanol (10)
(d, J¼8.8 Hz, 2H), 7.30 (d, J¼8.4 Hz, 2H), 7.53 (s, 1H) ppm. 13C NMR
(75 MHz, CDCl3):
d
28.3, 55.4, 70.2, 82.7, 82.9, 113.9, 127.6, 131.4,
To a solution of N-Boc-protected hydroxylamine rac-3 (762 mg,
3.01 mmol, 1.00 equiv) in toluene (15 mL) was added concd HCl
(3 mL) at 60 ꢁC, and the mixture was maintained at 60 ꢁC for 1 h.
The reaction mixture was quenched with saturated aqueous
Na2CO3 (20 mL) at rt, the phases were separated, the aqueous phase
was extracted with CH2Cl2 (4ꢂ10 mL), and the combined organic
phases were dried over MgSO4. After evaporation of the solvents,
the title compound 10 (450 mg, 98%) was obtained as a colorless oil
without further purification.
158.6, 159.3 ppm. IR (ATR): 3385, 3180, 2977, 2934, 1705, 1613, 1513,
1489, 1368, 1284, 1251, 1171, 1112, 1074, 1035, 831 cmꢀ1. HRMS (ESI)
calcd for C14H21NO5Na [(MþNa)þ]: 306.1312. Found: 306.1301.
4.3.3. rac-tert-Butyl-2-hydroxy-2-(4-trifluoromethylphenyl)ethoxy-
carbamate (rac-5). Pale yellow solid; yield: 60% (entry 3, Table 1).
Rf¼0.21 (cyclohexaneeethyl acetate 4:1). Mp 117 ꢁC. 1H NMR
(300 MHz, CDCl3):
d
1.51 (s, 9H), 3.72 (dd, J¼11.7, 9.7 Hz, 1H), 3.94
(dd, J¼11.7, 2.7 Hz, 1H), 4.34 (br s, 1H), 5.02 (dd, J¼9.6, 2.4 Hz, 1H),
1H NMR (400 MHz, CDCl3):
(dd, J¼11.9, 2.7 Hz, 1H), 4.18 (br s, 3H), 5.06 (dd, J¼8.3, 2.7 Hz, 1H),
7.24e7.45 (m, 5H) ppm. 13C NMR (100 MHz, CDCl3):
74.0, 80.1,
d
3.75 (dd, J¼11.9, 8.4 Hz, 1H), 3.82
7.43 (s, 1H), 7.52 (d, J¼8.7 Hz, 2H), 7.60 (d, J¼8.2 Hz, 2H) ppm. 13C
NMR (75 MHz, CDCl3):
d
28.3, 70.2, 82.5, 83.4, 124.3 (q,
d
JC,F¼271.9 Hz), 125.5 (q, JC,F¼3.8 Hz), 126.7, 130.0 (q, JC,F¼32.4 Hz),
126.3, 127.9, 128.6, 140.5 ppm. IR (ATR): 3310, 2920, 2871, 1589,
1494, 1453, 1199, 1064, 1025, 758, 701, 632 cmꢀ1. HRMS (ESI) calcd
for C8H11NO2Na [(MþNa)þ]: 176.0682. Found: 176.0683. Spectro-
scopic data are identical to those reported previously.16
143.5, 158.9 ppm. 19F NMR (282 MHz, CDCl3):
d
ꢀ62.5 ppm. IR
(ATR): 3420, 3243, 1715, 1321, 1280, 1257, 1163, 1127, 1093, 1063,
1017, 606 cmꢀ1. HRMS (ESI) calcd for C14H18F3NO4Na [(MþNa)þ]:

A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
3475
4.5. General procedure for the preparation of phenyl-
substituted -hydroxyoxime ethers
Found: 258.1449. Anal. Calcd for C14H21NO2: C, 71.46; H, 8.99; N,
5.95. Found: C, 71.32; H, 8.91; N, 5.82.
b
A solution of hydroxylamine 10 in EtOH (1.5 M) is added to
a solution of the appropriate ketone (1.00 equiv) in acetic acid
(1.05 equiv), pyridine (1.05 equiv), and EtOH (0.35 M) and heated at
reflux. After full conversion (monitored by TLC), the reaction mix-
ture is cooled to rt and quenched by addition of H2O. The phases are
separated, the aqueous phase is extracted with CH2Cl2, and the
combined organic phases are dried over MgSO4. After evaporation
of the solvents, the residue is purified by flash column chroma-
tography on silica gel (cyclohexaneetert-butylmethyl ether).
4.5.5. (E)-rac-Acetophenone-O-(2-hydroxy-2-phenylethyl)oxime
(rac-20). Colorless oil; yield: 86% (inseparable mixture of dia-
stereomers, E,Z¼89:11, entry 5, Table 2). Rf¼0.28 (cyclo-
hexaneeethyl acetate 4:1). GLC (SE-54): tR¼21.1 min (Z),
tR¼22.2 min (E). 1H NMR (300 MHz, CDCl3):
d 2.29 (s, 3H, E), 2.25 (s,
3H, Z), 3.52 (br s, 1H), 4.09 (dd, J¼12.2, 8.4 Hz, 1H, Z), 4.18 (dd,
J¼11.9, 2.7 Hz, 1H, Z), 4.25 (dd, J¼12.0, 8.3 Hz, 1H, E), 4.34 (dd,
J¼12.0, 2.9 Hz, 1H, E), 5.08 (dd, J¼8.5, 2.0 Hz, 1H, Z), 5.16 (dd, J¼8.3,
2.8 Hz, 1H, E), 7.28e7.69 (m, 9H), 7.94e7.99 (m, 1H) ppm. 13C NMR
(75 MHz, CDCl3):
d 13.0, 74.2, 79.1, 126.2, 126.4, 127.9, 128.5, 128.6,
4.5.1. rac-Propan-2-one-O-(2-hydroxy-2-phenylethyl)oxime
(rac-
129.6, 136.2, 140.4, 156.3 ppm. IR (ATR): 3416, 2925, 1495, 1452,
1369, 1309, 1061, 1026, 916, 698 cmꢀ1. HRMS (ESI) calcd for
C16H17NO2Na [(MþNa)þ]: 278.1151. Found: 278.1149.
16). Colorless oil; yield: 69% (entry 1, Table 2). Rf¼0.25 (cyclo-
hexaneetert-butylmethyl ether 10:1). GLC (SE-54): tR¼15.6 min. 1H
NMR (400 MHz, CDCl3):
8.4 Hz, 1H) superimposed by 4.10 (s, 1H) superimposed by 4.17 (dd,
d
1.90 (s, 3H), 1.92 (s, 3H), 4.09 (dd, J¼12.0,
J¼12.0, 3.0 Hz, 1H), 5.07 (dd, J¼8.4, 3.0 Hz, 1H), 7.27e7.44 (m, 5H)
4.6. General procedure for the preparation of different
hydroxyoxime ethers
b-
ppm. 13C NMR (100 MHz, CDCl3):
d 15.6, 21.9, 74.0, 78.2, 126.3, 127.7,
128.3,140.5,156.3 ppm. IR (ATR): 3417, 2920,1452,1368,1074,1026,
915, 700, 646, 621 cmꢀ1. HRMS (ESI) calcd for C11H15NO2Na
[(MþNa)þ]: 216.0995. Found: 216.0978. Anal. Calcd for C11H15NO2:
C, 68.37; H, 7.82; N, 7.25. Found: C, 68.73; H, 7.79; N, 6.91.
(S)-16 (32 mg, 89% yield, 23% ee, entry 3, Table 5): ee was de-
termined by GLC analysis on a chiral stationary phase (Supelco
To a solution of the appropriate N-Boc-proctected b-hydroxy-
hydroxylamine (1.0 equiv) in CH2Cl2eH2O¼2:1 (0.5 equiv) and
acetone (5.0 equiv) is added trifluoroacetic acid (26 equiv), and the
solution is stirred overnight. The reaction is quenched by addition
of saturated aqueous NaHCO3, and the phases are separated. The
aqueous phase is extracted with CH2Cl2, and the combined organic
phases are dried over MgSO4. After evaporation of the solvents, the
residue is purified by flash column chromatography on silica gel
(cyclohexaneetert-butylmethyl ether).
capillary column
b-DEX 225, length: 30 m, internal diameter:
0.25 mm, thickness of covalently bond stationary phase: 0.25 mm,
carrier gas: N2, injector temperature: 240 ꢁC, detector temperature:
250 ꢁC, flow rate 1 mL/min, temperature program: 120 ꢁC iso-
therm): tR¼89.34 [(S)-16], 94.04 [(R)-16]. ½a D20
ꢀ16.6 (c 1.06, CHCl3).
ꢃ
4.6.1. rac-Propan-2-one-O-[2-hydroxy-2-(4-methoxyphenyl)ethyl]
oxime (rac-21). White solid; yield: 27% (entry 2, Table 3). Rf¼0.19
(cyclohexaneeethyl acetate 4:1). Mp 77 ꢁC. GLC (SE-54):
4.5.2. rac-Pentane-3-one-O-(2-hydroxy-2-phenylethyl)oxime (rac-
17). Colorless oil; yield: 87% (entry 2, Table 2). Rf¼0.34 (cyclo-
hexaneeethyl acetate 4:1). GLC (SE-54): tR¼17.1 min. 1H NMR
tR¼18.4 min. 1H NMR (300 MHz, CDCl3):
d 1.91 (s, 3H), 1.91 (s, 3H),
(300 MHz, CDCl3):
d
1.06 (t, J¼7.7 Hz, 3H), 1.12 (t, J¼7.5 Hz, 3H), 2.24
3.20 (br s, 1H), 3.80 (s, 3H), 4.03 (dd, J¼12.0, 8.3 Hz, 1H), 4.10 (dd,
J¼12.0, 3.2 Hz,1H), 5.00 (dd, J¼8.3, 3.2 Hz,1H), 6.89 (d, J¼8.8 Hz, 2H),
(q, J¼7.4 Hz, 2H), 2.33 (q, J¼7.7 Hz, 2H), 4.04 (br s, 1H) super-
imposed by 4.07 (dd, J¼12.1, 8.2 Hz, 1H), 4.15 (dd, J¼12.2, 2.8 Hz,
1H), 5.06 (dd, J¼8.2 Hz, 2.7 Hz, 1H), 7.25e7.43 (m, 5H) ppm. 13C
7.32 (d, J¼8.4 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d 15.8, 22.1,
55.4, 73.9, 78.3, 113.9, 127.6, 132.6, 156.4, 159.3 ppm. IR (ATR): 3342,
2929,1612,1514,1463,1439,1366,1324,1303,1251,1172,1095,1077,
1034, 1018, 903, 879, 850, 824, 810 cmꢀ1. HRMS (ESI) calcd for
C12H17NO3Na [(MþNa)þ]: 246.1101. Found: 246.1096. Anal. Calcd for
C12H17NO3: C, 64.55; H, 7.67; N, 6.27. Found: C, 64.31; H, 7.71; N, 5.98.
(S)-21 (36 mg, 99% yield, 27% ee, entry 1, Table 6): ee was de-
termined by HPLC analysis on a chiral stationary phase (Daicel
Chiralcel OJ-H column, column temperature 20 ꢁC, solvent n-
NMR (75 MHz, CDCl3): d 10.3, 10.8, 21.5, 27.2, 74.6, 78.1, 126.3, 127.6,
128.3, 140.6, 164.7 ppm. IR (ATR): 3421, 2973, 2938, 2878, 1454,
1071, 1028, 908, 702 cmꢀ1. HRMS (ESI) calcd for C13H19NO2Na
[(MþNa)þ]: 244.1308. Found: 244.1311. Anal. Calcd for C13H19NO2:
C, 70.56; H, 8.65; N, 6.33. Found: C, 70.25; H, 8.47; N, 6.07.
4.5.3. rac-2,4-Dimethyl-3-pentanone-O-(2-hydroxy-2-phenylethyl)
oxime (rac-18). Pale yellow oil; yield: 40% (entry 3, Table 2). Rf¼0.22
heptaneei-propanol¼95:5, flow rate 0.80 mL/min,
l
¼254 nm):
(cyclohexaneetert-butylmethyl
ether
10:1).
GLC (SE-54):
tR¼18.87 [(S)-21], tR¼19.80 [(R)-21]. ½a D20
ꢃ
ꢀ1.5 (c 0.60, CHCl3).
tR¼18.5 min. 1H NMR (300 MHz, CDCl3):
d 1.10e1.17 (m, 12H), 2.57
(sept, J¼6.8 Hz, 1H), 3.08 (sept, J¼7.1 Hz,1H), 3.53 (br s,1H), 4.07 (dd,
J¼12.3, 7.8 Hz,1H), 4.16 (dd, J¼12.3, 2.6 Hz,1H), 5.06 (dd, J¼7.8, 2.6 Hz,
4.6.2. rac-Propan-2-one-O-[2-hydroxy-2-(4-trifluoromethylphenyl)
ethyl]oxime (rac-22). Yellow solid; yield: 88% (entry 3, Table 3).
Rf¼0.19 (cyclohexaneeethyl acetate 4:1). Mp 91 ꢁC. GLC (SE-54):
1H), 7.24e7.43 (m, 5H) ppm. 13C NMR (75 MHz, CDCl3):
d 19.0, 21.3,
28.3, 31.1, 75.1, 78.0, 126.4, 127.7, 128.4, 140.7, 170.2 ppm. IR (ATR):
3424, 2966, 2930, 2873,1454, 1365, 1071, 1012, 701, 632 cmꢀ1. HRMS
(ESI) calcd for C15H23NO2Na [(MþNa)þ]: 272.1621. Found: 272.1609.
tR¼15.1 min. 1H NMR (300 MHz, CDCl3):
d 1.87 (s, 3H), 1.91 (s, 3H),
3.96 (br s, 1H) superimposed by 4.03 (dd, J¼12.2, 8.1 Hz, 1H), 4.15
(dd, J¼12.2, 2.8 Hz, 1H), 5.10 (dd, J¼8.1, 2.6 Hz, 1H), 7.51 (d, J¼8.1 Hz,
2H), 7.60 (d, J¼8.2 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d 15.7,
4.5.4. (E)-rac-3,3-Dimethyl-2-butanone-O-(2-hydroxy-2-
phenylethyl)oxime (rac-19). Colorless oil; yield: 77% (E,Z>95:5,
entry 4, Table 2). Rf¼0.71 (cyclohexaneeethyl acetate 4:1). GLC (SE-
22.0, 74.0, 77.8, 124.3 (q, JC,F¼271.9 Hz), 125.4 (q, JC,F¼3.8 Hz), 126.6,
129.9 (q, JC,F¼32.3 Hz), 144.6 (q, JC,F¼1.2 Hz), 156.9 ppm. 19F NMR
(282 MHz, CDCl3):
d
ꢀ62.5 ppm. IR (ATR): 3308, 2922, 1716, 1620,
54): tR¼17.4 min. 1H NMR (600 MHz, CDCl3):
d
1.16 (s, 9H), 1.85 (s,
1418, 1322, 1156, 1114, 1066, 1016, 915, 880, 843, 612 cmꢀ1. HRMS
(ESI) calcd for C12H14F3NO2Na [(MþNa)þ]: 284.0869. Found:
284.0854. Anal. Calcd for C12H14F3NO2: C, 55.17; H, 5.40; N, 5.36.
Found: C, 55.06; H, 5.46; N, 4.92.
3H), 4.11 (dd, J¼12.3, 8.2 Hz, 1H), 4.17 (dd, J¼12.3, 2.4 Hz, 1H)
superimposed by 4.22 (br s,1H), 5.07 (dd, J¼7.8, 2.0 Hz,1H), 7.29 (m,
1H), 7.36 (dd, J¼7.4, 7.4 Hz, 2H), 7.41 (d, J¼7.6 Hz, 2H) ppm. 13C NMR
(100 MHz, CDCl3):
d
10.7, 27.6, 37.3, 75.1, 78.1, 126.3, 127.6, 128.4,
(S)-22 (41 mg, 99% yield, 32% ee, entry 2, Table 6): ee was de-
termined by HPLC analysis on a chiral stationary phase (Daicel
Chiralcel OJ-H column, column temperature 20 ꢁC, solvent n-
140.6, 165.2 ppm. IR (ATR): 3432, 2967, 2929, 2367, 1163, 1025, 910,
757 cmꢀ1. HRMS (ESI) calcd for C14H21NO2Na [(MþNa)þ]: 258.1465.

3476
A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
heptaneei-propanol¼95:5, flow rate 0.70 mL/min,
l
¼254 nm):
added and the mixture is maintained for 40 h. The reaction mixture
is directly subjected to flash column chromatography.
tR¼10.33 [(R)-22], tR¼11.15 [(S)-22]. ½a D20
ꢃ
ꢀ8.5 (c 0.78, CHCl3).
4.6.3. rac-Propan-2-one-O-[2-hydroxy-2-(2-methylphenyl)ethyl]ox-
ime (rac-23). White solid; yield: 66% (entry 4, Table 3). Rf¼ 0.29
(cyclohexaneeethyl acetate 4:1). Mp 60e61 ꢁC. GLC (SE-54):
4.7.1. (SiS*,R*)-2-Propanone-O-[2-(1-tert-butyl-1-silatetralinyl-1-
oxy)-2-phenylethyl]oxime (rac-28). Colorless oil; yield: 20% (in-
separable mixture of diastereomers, dr¼85:15, entry 1, Table 4).
Rf¼0.50 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-54):
tR¼16.5 min. 1H NMR (300 MHz, CDCl3):
d 1.91 (s, 3H), 1.93 (s, 3H),
2.37 (s, 3H), 3.02 (dd, J¼12.2, 8.4 Hz, 1H), 3.35 (br s, 1H), 4.11 (dd,
tR¼24.9 min. 1H NMR (300 MHz, CDCl3):
d
0.56 (dddd, J¼15.1, 5.7,
J¼12.2, 2.6 Hz, 1H), 5.28 (dd, J¼8.4, 2.6 Hz, 1H), 7.11e7.27 (m), 7.56
4.2, 1.4 Hz, 1H), 0.70 (ddd, J¼15.1, 12.2, 5.3 Hz, 1H), 0.97 (s, 9H)
superimposed by 0.83e1.02 (m, 1H), 1.38e1.45 (m, 1H), 1.79 (s, 3H),
1.83 (s, 3H), 2.42e2.55 (m, 1H), 2.59e2.77 (m, 1H), 3.96 (dd, J¼11.1,
4.2 Hz, 1H, SiS,R), 3.99 (dd, J¼11.2, 4.0 Hz, 1H, SiR,R), 4.14 (dd, J¼11.2,
7.8 Hz, 1H, SiR,R) superimposed by 4.14 (dd, J¼11.1, 7.8 Hz, 1H, SiS,R),
4.87 (dd, J¼7.8, 4.2 Hz, 1H, SiS,R), 4.92 (dd, J¼7.9, 4.0 Hz, 1H, SiR,R),
6.92 (d, J¼7.6 Hz, 1H, SiR,R), 6.98 (d, J¼8.0 Hz, 1H, SiS,R), 7.06 (d,
J¼8.1 Hz,1H, SiR,R), 7.09 (d, J¼7.6 Hz,1H, SiS,R), 7.18 (dd, J¼6.9, 6.9 Hz,
1H), 7.24e7.32 (m, 5H), 7.70 (dd, J¼7.2, 1.4 Hz, 1H) ppm. 13C NMR
(dd, J¼7.4, 1.1 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d 15.8, 19.2,
22.1, 71.2, 77.2, 126.2, 126.3, 127.6, 130.4, 134.9, 138.4, 156.3 ppm. IR
(ATR): 3350, 2969, 2934,1460, 1368,1084,1060, 1026, 907, 875, 827,
750, 725, 654 cmꢀ1. HRMS (ESI) calcd for C12H17NO2Na [(MþNa)þ]:
230.1151. Found: 230.1144. Anal. Calcd for C12H17NO2: C, 69.54; H,
8.27; N, 6.76. Found: C, 69.54; H, 8.20; N, 6.69.
(S)-23 (30 mg, 89% yield, 21% ee, entry 3, Table 6): ee was de-
termined by HPLC analysis on a chiral stationary phase (Daicel
Chiralpak IC column, column temperature 20 ꢁC, solvent n-
(75 MHz, CDCl3): d
9.8 (SiS,R),10.2 (SiR,R),15.8 (SiS,R),15.9 (SiR,R),18.7,
heptaneei-propanol¼95:5, flow rate 0.80 mL/min,
l
¼254 nm):
21.9, 22.8 (SiS,R), 23.1 (SiR,R), 26.1, 35.7 (SiS,R), 35.8 (SiR,R), 73.8 (SiS,R),
74.0 (SiR,R), 79.5 (SiS,R), 79.6 (SiR,R), 125.0, 126.6 (SiR,R), 126.7 (SiS,R),
127.5, 128.0 (SiR,R), 128.2, 128.5, 129.5 ppm. IR (ATR): 2927, 2856,
1591, 1366, 1109, 1069, 976, 825, 739, 699, 615 cmꢀ1. HRMS (ESI)
calcd for C24H33NO2SiNa [(MþNa)þ]: 418.2173. Found: 418.2167.
tR¼11.74 [(R)-23], tR¼13.82 [(S)-23]. ½a D20
ꢃ
ꢀ4.0 (c 0.70, CHCl3).
4.6.4. rac-Propan-2-one-O-[2-hydroxy-2-(thiophen-2-yl)ethyl]oxime
(rac-24). Yellow oil; yield: 22% (entry 5, Table 3). Rf¼0.30 (cyclo-
hexaneeethyl acetate 4:1). GLC (SE-54): tR¼15.4 min. 1H NMR
(SiS,R)-28 (24 mg, 61% yield, dr¼85:15, Scheme 4): ½a 2D0
þ18.4 (c
ꢃ
(300 MHz, CDCl3):
d
1.90 (s, 3H),1.91 (s, 3H), 3.88 (br s,1H), 4.16 (dd,
0.76, CHCl3).
J¼12.1, 7.8 Hz, 1H), 4.24 (dd, J¼12.1, 3.1 Hz, 1H), 5.30 (dd, J¼7.8,
2.7 Hz, 1H), 6.97e7.03 (m, 2H), 7.26 (dd, J¼4.8, 1.4 Hz, 1H) ppm. 13C
4.7.2. rac-(SiS*,R*)-3-Pentanone-O-[2-(1-tert-butyl-1-silatetralinyl-
1-oxy)-2-phenylethyl]oxime (rac-29). Colorless oil; yield: 27% (in-
separable mixture of diastereomers, dr¼82:18, entry 2, Table 4).
Rf¼0.68 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-54):
NMR (75 MHz, CDCl3):
d 15.8, 22.0, 70.7, 77.8, 124.2, 124.9, 126.8,
144.1, 156.8 ppm. IR (ATR): 3396, 2920, 1437, 1368, 1077, 1033, 901,
702 cmꢀ1
222.0559. Found: 222.0560.
.
HRMS (ESI) calcd for C9H13NO2SNa [(MþNa)þ]:
tR¼26.2 min. 1H NMR (300 MHz, CDCl3):
d
0.55 (dddd, J¼15.1, 5.7,
(S)-24 (32 mg, 97% yield, 30% ee, entry 4, Table 6): ee was de-
termined by HPLC analysis on a chiral stationary phase (Daicel
Chiralpak IC column, column temperature 20 ꢁC, solvent n-
4.2, 1.4 Hz, 1H), 0.70 (ddd, J¼15.1, 12.2, 5.3 Hz, 1H), 0.96 (s, 9H), 0.99
(t, J¼7.6 Hz, 3H), 1.03 (t, J¼7.4 Hz, 3H), 1.35 (m, 1H), 1.77e1.89 (m,
1H), 2.10e2.34 (m, 4H), 2.42e2.57 (m, 1H), 2.58e2.77 (m, 1H), 3.94
(dd, J¼10.9, 4.7 Hz, 1H, SiS,R), 3.96 (dd, J¼11.1, 4.4 Hz, 1H, SiR,R), 4.14
(dd, J¼11.0, 7.8 Hz, 1H, SiR,R), 4.16 (dd, J¼10.9, 7.8 Hz, 1H, SiS,R), 4.86
(dd, J¼7.3, 4.7 Hz,1H, SiS,R), 4.91 (dd, J¼7.5, 4.4 Hz,1H, SiR,R), 6.92 (d,
J¼7.6 Hz, 1H, SiR,R), 6.98 (d, J¼8.9 Hz, 1H, SiS,R), 7.06 (d, J¼8.1 Hz, 1H,
SiR,R), 7.09 (d, J¼7.5 Hz, 1H, SiS,R), 7.14e7.32 (m, 6H), 7.71 (dd, J¼7.2,
heptaneei-propanol¼95:5, flow rate 0.80 mL/min,
l
¼254 nm):
tR¼15.06 [(R)-24], tR¼18.50 [(S)-24]. ½a D20
ꢃ
ꢀ8.6 (c 1.08, CHCl3).
4.6.5. rac-Propan-2-one-O-(2-hydroxypropyl)oxime
(rac-
25). Colorless oil; yield: 20% (entry 6, Table 3). Rf¼0.13 (cyclo-
hexaneeethyl acetate 4:1). GLC (SE-54): tR¼7.1 min. 1H NMR
1.4 Hz,1H) ppm. 13C NMR (75 MHz, CDCl3):
d 9.8,10.4,11.1,18.7, 21.4,
(300 MHz, CDCl3):
d
1.13 (d, J¼6.4 Hz, 3H), 1.84 (s, 3H), 1.91 (s, 3H),
21.5, 22.8, 26.1 (SiS,R), 26.2 (SiR,R), 35.7 (SiS,R), 35.8 (SiR,R), 73.7, 79.3,
125.1, 126.6 (SiR,R), 126.8 (SiS,R), 127.5, 127.9 (SiR,R), 128.1, 129.5,
131.1, 135.5, 142.5, 150.8, 163.0 ppm. IR (ATR): 2927, 2856, 1462,
1434, 1093, 1066, 975, 824, 738, 698, 616 cmꢀ1. HRMS (ESI) calcd for
C26H37NO2SiNa [(MþNa)þ]: 446.2486. Found: 446.2491.
2.95 (br s, 1H), 3.82 (dd, J¼11.6, 7.7 Hz, 1H), 3.96 (dd, J¼11.6, 2.6 Hz,
1H), 4.05 (dqd, J¼7.5, 6.5, 2.7 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3): d 15.6, 18.8, 21.9, 67.6, 78.3, 155.7 ppm. IR (ATR): 3410, 2971,
2921, 1437, 1370, 1260, 1071, 1045, 931 cmꢀ1. HRMS (ESI) calcd for
C6H13NO2Na [(MþNa)þ]: 154.0838. Found: 154.0835.
4.8. Configurational assignment of 16
4.6.6. rac-Propan-2-one-O-(2-hydroxy-3-methylbutyl)oxime
(rac-
26). Colorless oil; yield: 47% (entry 7, Table 3). Rf¼0.31 (cyclo-
4.8.1. (S)-2-Isopropylaminooxy-1-phenylethanol [(S)-32]. To a solu-
tion of the oxime ether (S)-16 (38.0 mg, 0.197 mmol, 1.00 equiv) in
MeOH (1 mL) was added a small portion of methyl orange and
NaBH3CN (156 mg, 2.48 mmol, 12.6 equiv) followed by the addition
of a methanolic solution of HCl (1 M, 2.5 mL) over a period of 1 h,
always maintaining the solution’s purple color. The reaction mix-
ture was quenched with saturated aqueous NaHCO3, the phases
were separated, the aqueous phase was extracted with CH2Cl2, and
the combined organic phases were dried over MgSO4. The hy-
droxylamine (S)-32 (32.0 mg, 83%) was obtained as a colorless oil
without further purification.
hexaneeethyl acetate 4:1). GLC (SE-54): tR¼15.1 min. 1H NMR
(300 MHz, CDCl3):
3H), 1.71 (m, 1H), 1.84 (s, 3H), 1.84 (s, 3H), 2.88 (br s, 1H), 3.60 (ddd,
d
0.91 (d, J¼6.8 Hz, 3H, H-4), 0.95 (d, J¼6.8 Hz,
J¼8.0, 6.3, 2.1 Hz, 1H), 3.93 (dd, J¼11.6, 7.8 Hz, 1H), 4.08 (dd, J¼11.6,
2.4 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d 18.1, 18.8, 22.0, 31.1,
75.5, 76.2, 155.8 ppm. IR (ATR): cmꢀ1. HRMS (ESI) calcd for
C8H17NO2Na [(MþNa)þ]: 182.1151. Found: 182.1150.
4.7. General procedure for the diastereoselective CueH-
catalyzed dehydrogenative SieO coupling using the silane
rac-27
Colorless oil; yield: 83%. Rf¼0.12 (cyclohexaneeethyl acetate
4:1). GLC (SE-54): tR¼15.5 min. 1H NMR (300 MHz, CDCl3):
d 1.10 (d,
J¼6.4 Hz, 3H),1.13 (d, J¼6.3 Hz, 3H), 3.25 (qq, J¼6.3, 6.3 Hz,1H), 3.77
(dd, J¼12.2, 8.1 Hz, 1H), 3.82 (dd, J¼12.2, 2.8 Hz, 1H), 4.82 (br s, 2H),
5.06 (dd, J¼8.1, 2.7 Hz, 1H), 7.25e7.30 (m, 1H), 7.32e7.41 (m, 4H)
Toluene (2 M) is added to CuCl (10 mol %), NaOt-Bu (10 mol %),
and tris(3,5-dimethylphenyl)phosphine (20 mol %). After 2 min,
a solution of the appropriate alcohol (1.00 equiv), the silane rac-27
(1.00 equiv) and n-hexadecane (few drops) in toluene (0.8 M) is
ppm. 13C NMR (75 MHz, CDCl3):
d 20.1, 20.2, 51.8, 75.2, 78.6, 126.3,
127.7, 128.5, 140.7 ppm. IR (ATR): 3374, 3249, 2966, 2917, 2871,

A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
3477
1453, 1381, 1346, 1064, 757, 702, 632 cmꢀ1. HRMS (ESI) calcd for
was extracted with tert-butylmethyl ether (4ꢂ20 mL), and the
combined organic phases were dried over MgSO4. After evapora-
tion of the solvents, the mixture was purified by flash column
chromatography (cyclohexane), yielding 38 (1.05 g, 58%) as a white
solid along with 4,4-di-tert-butylbiphenyl (3%).
C11H17NO2H [(MþH)þ] ([MþH]þ): 196.1332. Found: 196.1336.
4.8.2. (S)-1,2-Phenylethanediol [(S)-33]. According to a procedure
reported by Kibayashi et al.,16 Mo(CO)6 was added to a solution of
hydroxylamine (S)-32 (32.0 mg, 0.164 mmol, 1.00 equiv) in
MeCNeH2O¼15:1 (1.6 mL), and the reaction mixture was heated at
85 ꢁC for 1.5 h. The reaction was quenched with saturated aqueous
NaHCO3 after cooling to rt, the phases were separated, the aqueous
phase was extracted with CH2Cl2, and the combined organic phases
were dried over MgSO4. After evaporation of the solvents (S)-33
(22.0 mg, 97%, 25% ee) was obtained as a white solid without further
purification.
White solid; yield: 58%. Rf¼0.51 (cyclohexane). Mp 110 ꢁC. GLC
(SE-54): tR¼23.4 min. 1H NMR (300 MHz, CDCl3):
d 0.59 (d,
J¼3.9 Hz, 3H), 1.38 (s, 18H), 4.86 (q, J¼3.9 Hz, 1H), 7.48 (dd, J¼8.2,
2.1 Hz, 2H), 7.72 (d, J¼1.9 Hz, 2H), 7.74 (d, J¼8.2 Hz, 2H) ppm. 13C
NMR (75 MHz, CDCl3):
d
ꢀ5.6, 31.6, 34.8, 120.5, 127.7, 130.3, 135.6,
146.2, 149.9 ppm. IR (ATR): 2961, 2901, 2866, 2115, 1457, 1395, 1360,
1249, 1158, 1112,1059, 888, 821, 803, 748 cmꢀ1. HRMS (ESI) calcd for
C21H28Si [Mþ]: 308.1960. Found: 308.1938.
White solid; yield: 97%. Rf¼0.52 (cyclohexaneetert-butylmethyl
ether). Mp 59 ꢁC. 1H NMR (300 MHz, CDCl3):
d
2.43 (br s, 1H)
4.10. General procedure for the enantioselective CueH-
catalyzed dehydrogenative SieO coupling
superimposed by 2.81 (br s, 1H), 3.65 (dd, J¼11.3, 8.2 Hz, 1H), 3.76
(dd, J¼11.3, 3.6 Hz, 1H), 4.82 (dd, J¼8.1, 3.6 Hz, 1H), 7.28e7.38 (m,
5H) ppm. 13C NMR (100 MHz, CDCl3):
d
68.2, 74.8, 126.2, 128.2,
Toluene (2 M) is added to CuCl (5.00 mol %), NaOt-Bu (5.00 mol %),
and phosphonite L1 (12.5 mol %). 2 min later, a solution of the ap-
propriate alcohol (1.00 equiv), the silane (0.650 equiv) and n-hexa-
decane (few drops) in toluene (0.8 M) are added, and the mixture is
maintained at rt for 40 h. The reaction mixture is directly subjected to
flash column chromatography (cyclohexaneetert-butylmethyl ether).
128.7, 140.6 ppm. HRMS (ESI) calcd for C8H10O2Na [(MþNa)þ]:
161.0573. Found: 161.0578. Enantiomeric excess was determined by
HPLC analysis on a chiral stationary phase (Daicel Chiralcel OD-H
column, column temperature 20 ꢁC, solvent n-heptaneei-prop-
anol¼95:5, flow rate 0.70 mL/min, ¼254 nm): tR¼25.19 [(R)-33],
l
tR¼26.66 [(S)-33]. ½a D20
þ17.5 (c 0.08, CHCl3). Analytical data are
ꢃ
identical to those reported previously.22
4.10.1. (R)-Propan-2-one-O-(2-dimethylphenylsilyloxy-2-
phenylethyl)oxime [(R)-51]. Colorless oil; yield: 66% (entry 2, Table
5). Rf¼0.47 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-
4.9. General procedure for the synthesis of silaxanthenes and
silafluorenes
54): tR¼21.1 min. 1H NMR (300 MHz, CDCl3):
d 0.28 (s, 3H), 0.32 (s,
3H), 1.80 (s, 3H), 1.85 (s, 3H), 4.04 (dd, J¼11.4, 4.1 Hz, 1H), 4.11 (dd,
To a solution of diphenylether (34, 1.00 equiv) in THF (1 M) is
added n-BuLi (1.65 M in hexanes, 2.23 equiv), and the mixture is
heated at reflux for 8 h. At 0 ꢁC, the appropriate chlorosilane
(1.00 equiv) is added, and the mixture is stirred at rt for 13 h. LiAlH4
(1.50 equiv) is then added, and the mixture is heated at reflux for
7 h. The reaction is quenched with aqueous HCl (2 M). The phases
are separated, the aqueous phase is extracted with tert-butylmethyl
ether, and the combined organic phases are dried over MgSO4. After
solvent evaporation, the residue is purified by flash column chro-
matography on silica gel (cyclohexane).
J¼11.4, 8.0 Hz, 1H), 5.02 (dd, J¼8.0, 4.1 Hz, 1H), 7.24e7.37 (m, 8H),
7.54 (dd, J¼7.7, 1.8 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
ꢀ1.1,
ꢀ0.8, 16.0, 21.9, 73.8, 79.3, 126.5, 127.5, 127.8, 128.2, 129.5, 133.7,
138.3, 141.9, 154.9 ppm. IR (ATR): 2957, 2922, 1428, 1368, 1251, 1117,
1069, 1028, 887, 861, 828, 785, 743, 698, 648 cmꢀ1. HRMS (ESI) calcd
for C19H25NO2SiNa [(MþNa)þ]: 350.1547. Found: 350.1540. Anal.
Calcd for C19H25NO2Si: C, 69.68; H, 7.69; N, 4.28. Found: C, 69.94; H,
8.05; N, 4.35. ½a D20
ꢀ10.8 (c 1.13, CHCl3).
ꢃ
4.10.2. (R)-Propan-2-one-O-(2-methyldiphenylsilyloxy-2-
phenylethyl)oxime [(R)-52]. Colorless oil; yield: 67% (entry 3, Table
5). Rf¼0.41 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-
4.9.1. 9-Methyl-9H-9-silaxanthene (35). Colorless oil; yield: 61%.
Rf¼0.50 (cyclohexane). GLC (SE-54): tR¼17.2 min.1H NMR (300 MHz,
54): tR¼27.9 min. 1H NMR (300 MHz, CDCl3):
d 0.53 (s, 3H), 1.77 (s,
3H),1.83 (s, 3H), 4.06 (dd, J¼11.4, 3.8 Hz,1H), 4.22 (dd, J¼11.4, 8.2 Hz,
CDCl3):
d
0.59 (d, J¼3.6 Hz, 3H), 5.05 (q, J¼3.5 Hz,1H), 7.15 (ddd, J¼7.2,
7.2, 0.9 Hz, 2H), 7.20 (m, 2H), 7.45 (ddd, J¼8.7, 7.3, 1.8 Hz, 2H), 7.55 (dd,
1H), 5.10 (dd, J¼8.1, 3.8 Hz, 1H), 7.24e7.42 (m, 11H), 7.54e7.58 (m,
J¼7.3, 1.7 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
ꢀ3.2,115.5,118.3,
4H) ppm. 13C NMR (75 MHz, CDCl3):
d
ꢀ2.3, 15.9, 21.9, 74.3, 79.3,
122.8,131.7,134.9,160.0 ppm. IR (ATR): 3604, 3005, 2971, 2123,1592,
1424,1302,1267, 1220, 890, 809, 752, 633 cmꢀ1. HRMS (ESI) calcd for
C13H12SiOH [(MþH)þ]: 213.0736. Found: 213.0718.
126.7,127.6,127.8,128.2,129.7,129.8,134.5,134.6,136.5,136.6,141.7,
154.8 ppm. IR (ATR): 3069, 2957, 2920, 1428, 1368, 1254, 1113, 1068,
1028, 790, 736, 697, 643 cmꢀ1. HRMS (ESI) calcd for C24H27NO2SiNa
[(MþNa)þ]: 412.1703. Found: 412.1706. ½a 2D0
ꢀ15.5 (c 2.01, CHCl3).
ꢃ
4.9.2. 9-iso-Propyl-9H-9-silaxanthene (36). Colorless oil; yield: 45%.
Rf¼0.61 (cyclohexane). GLC (SE-54): tR¼18.9 min.1H NMR (500 MHz,
4.10.3. (R)-2-Propanone-O-[2-methyldi(3-methylphenyl)silyloxy-2-
phenylethyl]oxime [(R)-54]. Pale yellow oil; yield: 52% (entry 5,
Table 5). Rf¼0.36 (cyclohexaneetert-butylmethyl ether 10:1). GLC
CDCl3):
d
1.18 (m,1H),1.35 (m, 6H), 5.05 (m,1H), 7.24 (ddd, J¼7.3, 7.3,
1.0 Hz, 2H), 7.33 (m, 2H), 7.54 (ddd, J¼8.5, 7.2, 1.8 Hz, 2H), 7.67 (dd,
J¼7.3,1.8 Hz, 2H) ppm. 13C NMR (500 MHz, CDCl3):
d
13.8,17.7,114.3,
(SE-54): tR¼26.5 min. 1H NMR (300 MHz, CDCl3):
d 0.51 (s, 3H), 1.76
118.3,122.6,131.6,135.4,160.4 ppm. IR (ATR): 3067, 2942, 2863, 2118,
1592, 1422, 1301, 1267, 1217, 755 cmꢀ1. HRMS (ESI) calcd for
C15H16SiO2Na [(MþONa)þ]: 279.0812. Found: 279.0807.
(s, 3H), 1.83 (s, 3H), 2.27 (s, 3H), 2.31 (s, 3H), 4.05 (dd, J¼11.3, 4.0 Hz,
1H), 4.22 (dd, J¼11.3, 8.1 Hz, 1H), 5.06 (dd, J¼8.0, 3.9 Hz, 1H),
7.17e7.38 (m, 13H) ppm. 13C NMR (75 MHz, CDCl3):
d
ꢀ2.2, 15.9,
21.6, 21.7, 21.9, 74.2, 79.3, 126.8, 127.5, 127.7, 127.7, 128.2, 130.5,
131.6, 131.7, 135.2, 136.5, 136.5, 137.0, 141.8, 154.8 ppm. IR (ATR):
2920, 2869, 1453, 1368, 1252, 1118, 1068, 1036, 965, 862, 771, 758,
4.9.3. 2,7-Di-tert-butyl-9H-9-methylsilafluorene (38). To a solution
of dibromide 37 (2.48 g, 5.85 mmol, 1.00 equiv) in Et2O (50 mL)
cooled to ꢀ78 ꢁC was added t-BuLi (1.70 M in n-pentane, 13.8 mL,
23.4 mmol, 4.00 equiv), and the mixture was maintained for ad-
ditional 5 h at rt. Dichloromethyl silane (0.621 mL, 690 mg,
6.00 mmol, 1.02 equiv) was added at 0 ꢁC, and the reaction mixture
was allowed to warm to rt overnight. The mixture was quenched
with H2O (20 mL), the phases were separated, the aqueous phase
699, 645, 617 cmꢀ1
. HRMS (ESI) calcd for C26H31NO2SiNa
[(MþNa)þ]: 440.2016. Found: 440.2008. ½a 2D0
þ27.2 (c 0.83, CHCl3).
ꢃ
4.10.4. (R)-2-Propanone-O-[2-methyldi(2-naphthyl)silyloxy-2-
phenylethyl]oxime [(R)-55]. Colorless oil; yield: 98% (entry 6, Table
5). Rf¼0.33 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-

3478
A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
54): tR¼27.6 min. 1H NMR (300 MHz, CDCl3):
d
0.71 (s, 3H), 1.71 (s,
2866,1740,1594,1420,1304,1268,1219,1128,1109,1089,1076,1046,
3H), 1.71 (s, 3H), 4.10 (dd, J¼11.4, 3.8 Hz, 1H), 4.28 (dd, J¼11.4,
8.2 Hz, 1H,), 5.19 (dd, J¼8.2, 3.7 Hz, 1H), 7.27e7.34 (m, 3H),
7.38e7.42 (m, 2H), 7.44e7.53 (m, 4H), 7.64 (ddd, J¼8.1, 3.5, 1.1 Hz,
2H), 7.75e7.84 (m, 6H), 8.08 (d, J¼8.5 Hz, 2H) ppm. 13C NMR
885, 757, 700, 632, 606 cmꢀ1. HRMS (ESI) calcd for C26H29NO3SiNa
[(MþNa)þ]: 454.1809. Found: 454.1800. ½a 2D0
ꢀ10.4 (c 4.11, CHCl3).
ꢃ
4.10.9. (R)-2-Propanone-O-2-(2,7-di-tert-butyl-9-methyl-9-
silafluorenyloxy-2-phenylethyl)oxime [(R)-63]. Colorless oil; yield:
90% (entry 14, Table 5). Rf¼0.39 (cyclohexaneetert-butylmethyl
ether 10:1). GLC (SE-54): tR¼30.9 min. 1H NMR (300 MHz, CDCl3):
(75 MHz, CDCl3):
d
ꢀ2.1, 15.9, 21.8, 74.5, 79.3, 126.0, 126.7, 126.8,
127.1, 127.7, 127.8, 128.3, 128.5, 130.6, 130.6, 132.9, 134.0, 134.2,
135.8, 135.8, 141.7, 154.8 ppm. IR (ATR): 3053, 2957, 2922, 1499,
1454, 1368, 1327, 1256, 1087, 1032, 856, 818, 744, 701, 642 cmꢀ1
.
d 0.56 (s, 3H), 1.20 (s, 9H), 1.34 (s, 9H), 1.69 (s, 3H), 1.75 (s, 3H), 4.00
HRMS (ESI) calcd for C32H31NO2SiNa [(MþNa)þ]: 512.2016. Found:
(dd, J¼11.2, 4.3 Hz, 1H), 4.12 (dd, J¼11.1, 7.9 Hz, 1H), 4.88 (dd, J¼7.8,
4.3 Hz, 1H), 7.17 (d, J¼1.7 Hz, 1H), 7.20e7.28 (m, 5H), 7.35 (dd, J¼8.1,
2.1 Hz,1H), 7.43 (dd, J¼8.2, 2.1 Hz,1H), 7.57 (d, J¼1.8 Hz,1H), 7.60 (d,
J¼8.1 Hz, 1H), 7.63 (d, J¼8.1 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
512.2013. ½a 2D0
ꢀ19.7 (c 2.60, CHCl3).
ꢃ
4.10.5. (R)-2-Propanone-O-[2-methyldi(4-methylphenyl)silyloxy-2-
phenylethyl]oxime [(R)-57]. Colorless oil; yield: 59% (entry 8, Table
5). Rf¼0.44 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-
d
ꢀ3.2, 15.9, 21.8, 31.4, 31.6, 34.6, 34.8, 74.3, 79.3, 119.9, 120.0, 126.6,
127.6, 128.1, 128.2, 128.2, 129.7, 129.9, 134.1, 135.0, 141.7, 144.9, 145.1,
149.7, 150.0, 155.0 ppm. IR (ATR): 2961, 2869, 1740, 1454, 1362, 1251,
1113, 1063, 827, 790, 744, 700, 632 cmꢀ1. HRMS (ESI) calcd for
54): tR¼27.3 min. 1H NMR (300 MHz, CDCl3):
d 0.48 (s, 3H), 1.77 (s,
3H), 1.82 (s, 3H), 2.34 (s, 3H), 2.35 (s, 3H), 4.04 (dd, J¼11.3, 3.9 Hz,
1H), 4.19 (dd, J¼11.3, 8.1 Hz, 1H), 5.06 (dd, J¼8.0, 3.9 Hz, 1H),
7.10e7.15 (m, 3H), 7.18e7.36 (m, 6H), 7.44 (d, J¼7.8 Hz, 4H) ppm. 13C
C32H41NO2SiNa [(MþNa)þ]: 522.2799. Found: 522.2792. ½a 2D0
þ2.63
ꢃ
(c 2.40, CHCl3).
NMR (75 MHz, CDCl3):
d
ꢀ2.1, 15.9, 21.7, 21.9, 74.1, 79.3, 126.7, 127.5,
128.2, 128.6, 133.1, 133.2, 134.7, 134.7, 139.6, 141.9, 154.7 ppm. IR
(ATR): 3066, 3033, 3012, 2958, 2921, 2868, 1602, 1453, 1367, 1253,
1108, 1068, 1037, 964, 790, 775, 754, 699, 629 cmꢀ1. HRMS (ESI)
calcd for C26H31NO2SiNa [(MþNa)þ]: 440.2016. Found: 440.2025.
4.10.10. (R)-2-Propanon-O-[2-(4-methoxyphenyl)-2-methyl-
diphenylsilyloxyethyl]oxime [(R)-64]. Colorless oil; yield: 74% (entry
1, Table 6). Rf¼0.50 (cyclohexaneeethyl acetate 4:1). GLC (SE-54):
tR¼27.9 min. 1H NMR (300 MHz, CDCl3):
d 0.51 (s, 3H), 1.76 (s, 3H),
½
a 2D0
ꢃ
ꢀ22.4 (c 1.35, CHCl3).
1.82 (s, 3H), 3.80 (s, 3H), 4.02 (dd, J¼11.3, 3.8 Hz,1H), 4.19 (dd, J¼11.3,
8.2 Hz,1H), 5.03 (dd, J¼8.2, 3.8 Hz,1H), 6.83 (d, J¼8.7 Hz, 2H), 7.24 (d,
J¼8.5 Hz, 2H), 7.26e7.41 (m, 6H), 7.51e7.57 (m, 4H) ppm. 13C NMR
4.10.6. (R)-2-Propanon-O-[2-methylbis(4-trifluormethylphenyl)sily-
loxy-2-phenylethyl]oxime [(R)-60]. Colorless oil; yield: 83% (entry
11, Table 5). Rf¼0.33 (cyclohexaneetert-butylmethyl ether 10:1). 1H
(75 MHz, CDCl3):
d
ꢀ2.3,15.9, 21.9, 55.4, 73.8, 79.3,113.6,127.8,127.8,
129.7, 129.7, 133.9, 134.1, 134.5, 134.6, 136.5, 136.7, 154.7, 159.1 ppm.
IR (ATR): 3001, 2957, 2918, 1612, 1512, 1429, 1247, 1117, 1078, 1035,
792, 738, 700 cmꢀ1. HRMS (ESI) calcd for C25H29NO3SiNa [(MþNa)þ]:
NMR (300 MHz, CDCl3): d 0.59 (s, 3H), 1.73 (s, 3H), 1.81 (s, 3H), 4.06
(dd, J¼11.6, 3.4 Hz, 1H), 4.20 (dd, J¼11.6, 8.4 Hz, 1H), 5.11 (dd, J¼8.4,
3.4 Hz, 1H), 7.26e7.33 (m, 5H), 7.61 (m, 8H) ppm. 13C NMR (75 MHz,
442.1809. Found: 442.1816. ½a D20
ꢀ10.0 (c 0.33, CHCl3).
ꢃ
CDCl3):
d
ꢀ2.7, 15.8, 21.8, 74.8, 79.3, 124.2 (q, JC,F¼272.3 Hz), 124.5
(q, JC,F¼3.7 Hz), 126.5, 128.0, 128.5, 131.9 (q, JC,F¼32.3 Hz), 131.9 (q,
4.10.11. (R)-2-Propanone-O-[2-(4-trifluormethylphenyl)-2-methyl-
diphenylsilyloxyethyl]oxime [(R)-65]. Yellow oil; yield: 65% (entry 2,
Table 6). Rf¼0.47 (cyclohexaneetert-butylmethyl ether 10:1). GLC
JC,F¼32.3 Hz), 134.7, 134.8, 140.6, 140.7, 140.9, 155.0 ppm 19F NMR
(282 MHz, CDCl3):
d
ꢀ63.1. IR (ATR): 2924, 1740, 1392, 1322, 1164,
1122, 1059, 1019, 969, 829, 797, 757, 700, 629 cmꢀ1. HRMS (ESI)
calcd for C26H25F6NO2SiNa [(MþNa)þ]: 548.1451. Found: 548.1449.
Anal. Calcd for C26H25F6NO2Si: C, 59.42; H, 4.79; N, 2.67. Found: C,
(SE-54): tR¼24.7 min. 1H NMR (300 MHz, CDCl3):
d 0.56 (s, 3H), 1.75
(s, 3H), 1.82 (s, 3H), 4.04 (dd, J¼11.4, 4.3 Hz, 1H), 4.20 (dd, J¼11.4,
7.7 Hz, 1H), 5.14 (dd, J¼7.6, 4.2 Hz, 1H), 7.28e7.40 (m, 6H), 7.44 (d,
J¼8.4 Hz, 2H), 7.51e7.57 (m, 6H) ppm. 13C NMR (75 MHz, CDCl3):
59.74; H, 5.20; N, 2.27. ½a D20
ꢀ10.9 (c 3.67, CHCl3).
ꢃ
d
ꢀ2.4, 15.9, 21.9, 73.7, 78.9, 124.4 (q, JC,F¼272.0 Hz), 125.2 (q,
4.10.7. (R)-2-Propanone-O-[2-(9-methyl-9-silaxanthenyloxy)-2-
phenylethyl]oxime [(R)-61]. Colorless oil; yield: 72% (entry 12, Table
5). Rf¼0.34 (cyclohexaneetert-butylmethyl ether 10:1).GLC (SE-
JC,F¼3.8 Hz), 126.9, 127.9, 129.7 (q, JC,F¼31.7 Hz) superimposed by
130.0, 134.5, 134.6, 136.0, 136.1, 145.8, 155.2 ppm 19F NMR
(282 MHz, CDCl3):
d
ꢀ62.4 ppm. IR (ATR): 2957, 2921, 1429, 1324,
54): tR¼26.7 min.1H NMR (300 MHz, CDCl3):
d
0.61 (s, 3H),1.63 (s, 3H),
1165, 1119, 1067, 1017, 737, 700, 632 cmꢀ1. HRMS (ESI) calcd for
C25H26F3NO2SiNa [(MþNa)þ]: 480.1577. Found: 480.1563. Anal.
Calcd for C25H26F3NO2Si: C, 65.62; H, 5.73; N, 3.06. Found: C, 65.46;
1.74 (s, 3H), 3.92 (dd, J¼11.5, 3.9 Hz, 1H), 4.04 (dd, J¼11.5, 8.3 Hz, 1H),
4.87 (dd, J¼8.2, 3.9 Hz,1H), 6.89 (ddd, J¼7.3, 7.3,1.0 Hz,1H), 7.08e7.25
(m, 9H), 7.35 (ddd, J¼8.5, 7.2, 1.8 Hz, 1H), 7.46 (ddd, J¼8.5, 7.2, 1.8 Hz,
1H), 7.60 (dd, J¼7.3 Hz, 1.6 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
H, 5.78; N, 2.84. ½a D20
ꢀ12.6 (c 0.54, CHCl3).
ꢃ
d
ꢀ1.9,15.7, 21.8, 74.1, 78.5, 117.6,118.0,118.2, 122.1,122.3,126.6,127.5,
4.10.12. (R)-2-Propanone-O-[2-(2-tolyl)-2-methyldiphenylsilyloxyethyl]
oxime [(R)-66]. Colorless oil; yield: 68% (entry 3, Table 6). Rf¼0.36
(cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-54): tR¼26.0 min.
128.1, 131.7, 131.8, 134.1, 134.2,141.2,154.9, 160.4,160.5 ppm. IR (ATR):
3065, 2920, 1594, 1421, 1305, 1268, 1218, 1130, 1077, 1039, 965, 885,
775, 700, 642, 621 cmꢀ1. HRMS (ESI) calcd for C24H25NO3SiNa
1H NMR (300 MHz, CDCl3):
d 0.52 (s, 3H), 1.80 (s, 3H), 1.83 (s, 3H), 2.09
[(MþNa)þ]: 426.1496. Found: 426.1498. ½a 2D0
ꢃ
ꢀ13.0 (c 2.20, CHCl3).
(s, 3H), 4.01 (dd, J¼11.5, 3.2 Hz, 1H), 4.17 (dd, J¼11.5, 8.3 Hz, 1H), 5.29
(dd, J¼8.2, 3.1 Hz,1H), 7.04 (d, J¼6.6 Hz,1H), 7.16 (ddd, J¼7.4, 7.4, 1.5 Hz,
1H), 7.21 (m,1H), 7.28e7.42 (m, 6H), 7.54 (m, 4H), 7.62 (m,1H) ppm.13C
4.10.8. (R)-2-Propanone-O-[2-(9-iso-propyl-9-silaxanthenyloxy)-2-
phenylethyl]oxime [(R)-62]. Colorless oil; yield: 73% (entry 13, Table
5). Rf¼0.37 (cyclohexaneetert-butylmethylether 10:1). GLC (SE-54):
NMR (75 MHz, CDCl3):
d
ꢀ2.3, 15.9, 18.9, 20.0, 71.2, 78.6, 126.1, 127.0,
127.3, 127.7, 129.7, 129.7, 130.0, 134.1, 134.5, 134.6, 136.5, 136.7, 139.8,
154.6 ppm. IR (ATR): 3326, 1429, 1367, 1253, 1111, 1072, 964, 790, 757,
737, 698 cmꢀ1. HRMS (ESI) calcd for C25H29NO2SiNa [(MþNa)þ]:
tR¼27.6 min. 1H NMR (400 MHz, CDCl3):
1.04 (d, J¼7.5 Hz, 3H),1.04
d
(d, J¼8.0 Hz, 3H), 1.45 (m, 1H), 1.66 (s, 3H), 1.77 (s, 3H), 3.98 (dd,
J¼11.3, 3.6 Hz,1H), 4.17 (dd, J¼11.4, 7.8 Hz,1H), 4.96 (dd, J¼7.6, 3.6 Hz,
1H), 6.88 (dd, J¼7.3, 7.3 Hz,1H), 7.12e7.30 (m, 9H), 7.38 (ddd, J¼10.6,
5.0,1.8 Hz,1H), 7.46 (ddd, J¼8.5, 7.2,1.8 Hz,1H), 7.60 (dd, J¼7.3,1.6 Hz,
426.1860. Found: 426.1871. ½a D20
ꢀ14.5 (c 0.60, CHCl3).
ꢃ
4.10.13. (R)-2-Propanone-O-[2-thiophenyl-2-methyldiphenylsilyloxy-
ethyloxime [(R)-67]. Colorless oil; yield: 81% (entry 4, Table 6).
Rf¼0.18 (cyclohexaneetert-butylmethyl ether 10:1). GLC (SE-54):
1H) ppm. 13C NMR (100 MHz, CDCl3):
d 14.4,15.7,17.0, 17.1, 21.8, 74.1,
78.7, 115.7, 116.6, 118.0, 118.1, 121.8, 122.2, 126.7, 127.5, 128.1, 131.6,
131.7, 134.5, 134.5, 141.5, 154.7, 160.8 ppm. IR (ATR): 2944, 2923,
tR¼25.8 min. 1H NMR (400 MHz, CDCl3):
d 0.59 (s, 3H), 1.77 (s, 3H),

A. Weickgenannt et al. / Tetrahedron 68 (2012) 3468e3479
3479
€
10. Karatas, B.; Rendler, S.; Frohlich, R.; Oestreich, M. Org. Biomol. Chem. 2008, 6,
1435e1440.
1.83 (s, 3H), 4.14 (dd, J¼11.3, 4.1 Hz, 1H), 4.28 (dd, J¼11.3, 7.9 Hz, 1H),
5.20 (ddd, J¼7.8, 4.1, 0.6 Hz,1H), 6.86 (ddd, J¼3.5,1.2, 0.8 Hz,1H), 6.93
(dd, J¼5.0, 3.5 Hz, 1H), 7.22 (dd, J¼5.0, 1.2 Hz, 1H), 7.30e7.42 (m, 6H),
11. For a related RheH-catalyzed SieO coupling, see: Klare, H. F. T.; Oestreich, M.
Angew. Chem., Int. Ed. 2007, 46, 9335e9338.
12. Weickgenannt, A.; Mewald, M.; Muesmann, T. W. T.; Oestreich, M. Angew. Chem.,
Int. Ed. 2010, 49, 2223e2226 and cited references.
13. Oestreich, M. Synlett 2007, 1629e1643.
14. For the kinetic resolution of related N-Boc-protected b-hydroxyhydroxylamines
by enzymatic acylation, see: Buchalska, E.; Plenkiewicz, J. Synth. Commun. 2002,
32, 2591e2599.
15. (a) Buchalska, E.; Plenkiewicz, J. J. Mol. Catal. B: Enzym. 2001,11, 255e263; (b) Rad,
M. N. S.; Behrouz, S.; Dianat, M. Synthesis 2008, 2055e2064; (c) Luisa, M.; Wang,
E. Y.; Cockerill, K.; Linnik, M. D.; Victoria, E. J. WO 2006/094201 A2; (d) Bachman,
G. B.; Hokama, T. J. Am. Chem. Soc. 1959, 81, 4223e4225.
16. Atobe, M.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 2004, 69, 5595e5607.
17. Cardillo, G.; Gentilucci, L.; Bastardas, I. R.; Tolomelli, A. Tetrahedron 1998, 54,
8217e8222.
18. Dhanak, D.; Reese, C. B.; Romana, S.; Zappia, G. J. Chem. Soc., Chem. Commun.
1986, 903e904.
7.58 (dd, J¼7.8, 1.4 Hz, 4H) ppm. 13C NMR (100 MHz, CDCl3):
d
ꢀ2.4,
15.9, 21.9, 70.3, 79.0, 124.1, 124.6, 126.5, 127.8, 127.8, 129.8, 129.9,
134.6, 134.7, 136.2, 136.4, 145.6, 155.1 ppm. IR (ATR): 3069, 2919,
1428, 1367, 1254, 1111, 1077, 1036, 961, 791, 736, 695 cmꢀ1. HRMS
(ESI) calcd for C22H25NO2SSi [(MþNa)þ]: 418.1267. Found: 418.1263.
½
a 2D0
ꢃ
ꢀ15.5 (c 0.49, CHCl3).
Acknowledgements
This research was supported by the Deutsche For-
schungsgemeinschaft (Oe 249/4-1) and the Fonds der Chemischen
Industrie (predoctoral fellowship to A.W., 2008e2010).
19. (a) Rendler, S.; Auer, G.; Keller, M.; Oestreich, M. Adv. Synth. Catal. 2006, 348,
€
1171e1182; (b) Konigs, C. D. F.; Oestreich, M. Synthesis 2011, 2062e2065.
20. Selectivity factors were determined according to Kagan: Kagan, H. B.; Fiaud, J.
C. In Topics in Stereochemistry; Eliel, E. L., Wilen, S. H., Eds.; Wiley: New York,
NY, 1988; Vol. 18, pp 249e330.
Supplementary data
21. (a) The selectivity factor of the reagent-controlled kinetic resolution with
a chiral silane is indirectly calculated from the experiment in the racemic series.
The drrac (diastereomeric ratio) or derac (diastereomeric excess) in the racemic
series corresponds to the ee (enantiomeric excess) of the recovered alcohol in
the enantiomeric series at exactly 50% conversion (provided that both follow
identical kinetics). That theoretical selectivity factor stheo is useful if the
enantioimpure silane is only available. stheo is calculated from s¼ln[(1e0.
5)(1ederac)]/ln[(1e0.5)(1þderac)] where derac¼derac/100. The apparent selec-
tivity factor sapp when using an enantioimpure chiral silane is calculated from
sapp¼ln[(1eC)(1eee)]/ln[(1eC)(1þee) where ee ¼ ee/100 of the slow-reacting
alcohol and C is conversion/100; (b) The selectivity factor s of the catalyst-
controlled kinetic resolution with an achiral silane is directly calculated from
s¼ln[(1eC)(1eee)]/ln[(1eC)(1þee) where ee¼ee/100 of the slow-reacting en-
antiomer and C¼conversion/100.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.06.102.
References and notes
1. (a) Vedejs, E.; Jure, M. Angew. Chem., Int. Ed. 2005, 44, 3974e4001; (b) Keith, J.
M.; Larrow, J. F.; Jacobsen, E. N. Adv. Synth. Catal. 2001, 343, 5e26.
2. Somfai, P. Angew. Chem., Int. Ed. 1997, 36, 2731e2733.
3. (a) Ebner, D. C.; Bagdanoff, J. T.; Ferreira, E. M.; McFadden, R. M.; Caspi, D. D.;
Trend, R. M.; Stoltz, B. M. Chem.dEur. J. 2009, 15, 12978e12992; (b) Sigman, M.
S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221e229.
4. (a) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups in Organic Synthesis,
ꢀ
22. Kadyrov, R.; Koenigs, R. M.; Brinkmann, C.; Voigtlaender, D.; Rueping, M. An-
gew. Chem., Int. Ed. 2009, 48, 7556e7559.
4th ed.; Wiley: New York, NY, 2007, pp 165e221; (b) Kociensky, P. J. Protecting
Groups, 3rd ed.; Thieme: Stuttgart, 2004, pp 188e230.
23. (a) Denmark, S. E.; Jacobs, R. T.; Dai-Ho, G.; Wilson, S. Organometallics 1990, 9,
3015e3019; (b) Myers, A. G.; Kephart, S. E.; Chen, H. J. Am. Chem. Soc. 1992, 114,
7922e7923; (c) Matsumoto, K.; Oshima, K.; Utimoto, K. J. Org. Chem. 1994, 59,
7152e7155.
5. (a) Weickgenannt, A.; Mewald, M.; Oestreich, M. Org. Biomol. Chem. 2010, 8,
1497e1504; (b) Rendler, S.; Oestreich, M. Angew. Chem., Int. Ed. 2008, 47, 248e250.
6. Isobe, T.; Fukuda, K.; Araki, Y.; Ishikawa, T. Chem. Commun. 2001, 243e244.
7. Zhao, Y.; Mitra, A. W.; Hoveyda, A. H.; Snapper, M. L. Angew. Chem., Int. Ed. 2007,
46, 8471e8474.
24. Corey, J. Y.; Chang, L. S. J. Organomet. Chem. 1986, 307, 7e14.
25. Weickgenannt, A.; Oestreich, M. Chem.dAsian J. 2009, 4, 406e410.
8. (a) Zhao, Y.; Rodrigo, J.; Hoveyda, A. H.; Snapper, M. L. Nature 2006, 443, 67e70;
(b) You, Z.; Hoveyda, A. H.; Snapper, M. L. Angew. Chem., Int. Ed. 2009, 48, 547e550.
9. (a) Rendler, S.; Auer, G.; Oestreich, M. Angew. Chem., Int. Ed. 2005, 44,
€
26. Mewald, M.; Weickgenannt, A.; Frohlich, R.; Oestreich, M. Tetrahedron: Asym-
metry 2010, 21, 1232e1237.
€
€
27. Niikura, K.; Kamitani, R.; Kurogochi, M.; Uematsu, R.; Shinohara, Y.; Nakagawa,
H.; Deguchi, K.; Monde, K.; Kondo, H.; Nishimura, S.-I. Chem.dEur. J. 2005, 11,
3825e3834.
7620e7624; (b) Rendler, S.; Plefka, O.; Karatas, B.; Auer, G.; Frohlich, R.; Muck-
Lichtenfeld, C.; Grimme, S.; Oestreich, M. Chem.dEur. J. 2008, 14, 11512e11528;
(c) Steves, A.; Oestreich, M. Org. Biomol. Chem. 2009, 7, 4464e4469.