Scandium-bipyridine-catalyzed, enantioselective alcoholysis of meso-epoxides

Article abstract of DOI:10.1002/ejoc.200601101

The scandium-bipyridine-catalyzed ring-opening of meso-epoxides with aliphatic alcohols has been studied. Aromatic epoxides were ring-opened with >90 % ee furnishing valuable 1,2-diol monoethers in typically good yields whereas aliphatic epoxides gave ris

Full text of DOI:10.1002/ejoc.200601101

FULL PAPER
DOI: 10.1002/ejoc.200601101
Scandium-Bipyridine-Catalyzed, Enantioselective Alcoholysis of meso-Epoxides
Andreas Tschöp,[a] Andreas Marx,[a][‡] Anakallil R. Sreekanth,[a][‡‡] and
Christoph Schneider*[a]
Keywords: Alcohols / Asymmetric catalysis / Desymmetrization / Epoxide / Scandium-bipyridine
The scandium-bipyridine-catalyzed ring-opening of meso-
epoxides with aliphatic alcohols has been studied. Aromatic
epoxides were ring-opened with Ͼ90% ee furnishing valu-
able 1,2-diol monoethers in typically good yields whereas ali-
phatic epoxides gave rise to moderate enantioselectivities.
The catalyst loading may be lowered to 2–5 mol-% with only
marginal effects on yield and enantioselectivity. A strong
positive non-linear effect was observed pointing to aggrega-
tion phenomena of the chiral catalyst.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
We have recently shown that a scandium bipyridine com-
plex composed of Sc(OTf)3 and the chiral ligand 2 effec-
tively catalyzes the nucleophilic ring-opening of meso-epox-
ides with aliphatic alcohols.[11a] For example, cis-stilbene
oxide (1) was ring-opened with ethanol in 75% yield and
96% ee in a reaction catalyzed with 10 mol-% of the
Sc(OTf)3-bipyridine[12] complex (Scheme 1).
Introduction
The catalytic enantioselective ring-opening of meso-epox-
ides has been frequently employed in recent years for the
synthesis of valuable, highly enantiomerically enriched 1,2-
difunctionalized fine chemicals starting from achiral com-
modity compounds.[1] Azides,[2] amines,[3] acids,[4] phe-
nols,[5] thiols,[6] selenols,[7] halides,[8] cyanides,[9] and various
organometal compounds[10] have been employed as nucleo-
philes which typically ring-open the epoxides in a unified
SN2-pathway with support of a chiral Lewis acid furnishing
the corresponding β-functionalized alcohols in good to ex-
cellent enantioselectivities.
The catalytic enantioselective addition of oxygen nucleo-
philes to meso-epoxides has been the subject of only a few
reports. Actually, prior to this study there had been no re-
port on the catalytic, enantioselective addition of aliphatic
alcohols to meso-epoxides. Jacobsen et al.[4] utilized a co-
balt(III) salen complex as chiral Lewis acid in the addition
of carboxylic acids to epoxides furnishing 1,2-diol mono-
esters in excellent yield and moderate to very good enantio-
selectivities. Shibasaki et al.[5] developed a gallium-lithium-
BINOL complex which was capable of catalyzing the ad-
dition of phenols to meso-epoxides in good to excellent
enantioselectivities.
Scheme 1. Scandium-bipyridine-catalyzed ring opening of cis-stil-
bene oxide (1) with ethanol.
We have now investigated this process in more detail and
give a full account of this work.
Results and Discussion
In order to further optimize this process and investigate
scope and limitations we decided to select the reactions of
cis-stilbene oxide (1) as an aromatic epoxide and cyclohex-
ene oxide (6) as an aliphatic epoxide with either p-meth-
oxybenzyl alcohol (PMBOH) or allyl alcohol as model re-
actions which we carefully studied with respect to metal
triflate, solvent, temperature, ligand architecture, and cata-
lyst loading (Scheme 2).
[a] Institut für Organische Chemie, Universität Leipzig,
Johannisallee 29, 04103 Leipzig, Germany
Fax: +49-341-9736599
E-mail: schneider@chemie.uni-leipzig.de
[‡] New address: Technische Universität Darmstadt, Clemens-
Schöpf-Institut für Organische Chemie und Biochemie,
Petersenstraße 22, 64287 Darmstadt, Germany
[‡‡]New address: Département de Chimie, Institut de Pharmacolo-
gie, University of Sherbrooke,
Fleurimont, Québec J1H 5N4, Canada
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Enantioselective Alcoholysis of meso-Epoxides
FULL PAPER
Table 2. Screening of different metal triflates in model reaction C
(Scheme 2).
Entry
M(OTf)n
T [°C]
t
Yield (%)[a] ee (%)[b]
1
2
3
4
5
6
7
8
9
Sc(OTf)3
Y(OTf)3
–20
r.t.
r.t.
r.t.
r.t.
r.t.
0
r.t.
r.t.
r.t.
r.t.
2.5 h
2.5 d
7 d
18 h
7 d
7 d
15 d
8 d
90
56
43
47
47
44
21
43
48
48
45
54
40
0
0
11
9
La(OTf)3
Ce(OTf)3
Nd(OTf)3
Sm(OTf)3
Tb(OTf)3
Tm(OTf)3
Yb(OTf)3
Cu(OTf)2
Zn(OTf)2
4
3
8 d
2 d
8 d
12
–30[c]
–45[c]
10
12
[a] Isolated yield after flash column chromatography. [b] Deter-
mined by chiral GC analysis. [c] Negative sign indicates that the
opposite enantiomer is formed as the major product.
plexes predominantly furnished the opposite enantiomer in
low yields and 38% ee and 51% ee, respectively, which may
be attributed to their different coordination geometry com-
pared to the lanthanide metals (entries 10, 11).
A similar picture emerged in the alcoholysis of cyclohex-
ene oxide (6) (Table 2). Again, the scandium and yttrium
bipyridine complexes exhibited the highest enantio-
selectivity with up to 54% ee. The Sc(OTf)3-bipyridine com-
plex was also the most active one reaching full conversion
within 2–3 h at –20 °C. This observation nicely relates to
the well-known Lewis acidity of Sc(III) among the rare
earth metals, which, in contrast to conventional metal tri-
flates, is not affected by protic solvents or reagents.[13]
Scheme 2. Model reactions A–D selected for further optimization.
Influence of Metal Triflate
Since the scandium-bipyridine complex performed so
well in the alcoholysis of meso-epoxides, we screened other
lanthanide and metal triflates in combination with bipyri-
dine 2 in model reactions A and C and investigated their
catalytic activity and enantioselectivity. All reactions were
conducted with 10 mol-% of metal triflate and 12 mol-% of
bipyridine ligand 2 in CH2Cl2 as solvent at temperatures
between –20 °C and r.t. (Table 1 and Table 2).
Table 1. Screening of different metal triflates in model reaction A
(Scheme 2).
Optimization of Solvent
Entry
M(OTf)3
T [°C]
t
Yield (%)[a] ee (%)[b]
In earlier experiments we had found that coordinating
and highly dipolar solvents such as DMF, CH3CN, and
THF shut down the catalytic activity of the scandium-bi-
pyridine complex presumably because of coordination to
the Lewis acidic metal center. Weakly coordinating or non
coordinating solvents such as toluene and diethyl ether gave
rise to high product yields but furnished the product 1,2-
diol monoethers with no enantioselectivity. Since CH2Cl2
was initially found to be optimal, we investigated other ha-
logenated solvents in model reactions A and D (Table 3).
1
2
3
4
5
6
7
8
9
Sc(OTf)3
Y(OTf)3
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
r.t.
r.t.
r.t.
r.t.
16 h
3 d
7 d
22 h
8 d
7 d
16 d
8 d
8.5 d
3 d
82
61
3
33
14
6
97
93
32
12
26
44
26
33
La(OTf)3
Ce(OTf)3
Nd(OTf)3
Sm(OTf)3
Tb(OTf)3
Tm(OTf)3
Yb(OTf)3
Cu(OTf)2
Zn(OTf)2
9
17
23
26
15
64
10
11
–38[c]
–51[c]
8 d
[a] Isolated yield after flash column chromatography. [b] Deter-
mined by chiral HPLC analysis. [c] Negative sign indicates that the
opposite enantiomer is formed as the major product.
Table 3. Solvent optimization for model reactions A and D
(Scheme 2).
Inspection of Table 1 clearly reveals that the Sc(OTf)3-
bipyridine combination was the chiral catalyst of choice for
this reaction displaying the best catalytic activity and high-
est enantioselectivity (entry 1, 82% yield, 97% ee). The cor-
responding yttrium-bipyridine complex was less active and
required an extended period of reaction time, but furnished
the product in almost the same level of optical purity (entry
2, 61% yield, 93% ee). All other lanthanide triflate bipyri-
dine complexes which we investigated were significantly less
enantioselective and furnished the product in low yields.
Quite interestingly, the copper and zinc bipyridine com- sis.
Entry Solvent T [°C] t [d] Yield (%)[a]
ee (%)
A
D
A[b]
D[c]
1
2
3
4
5
CH2Cl2
CHCl3
CCl4
C2H4Cl2 –20
CHBr3 –20
–20
–20
–20
3
2
2
2
2
73
54
84
80
33
54
34
61
86
32
97
97
94
97
94
50
57
31
46
30
[a] Isolated yield after flash column chromatography. [b] Deter-
mined by chiral HPLC analysis. [c] Determined by chiral GC analy-
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A. Tschöp, A. Marx, A. R. Sreekanth, C. Schneider
FULL PAPER
1,2-Dichloroethane proved to be a good alternative to
Next we increased the size of the alkyl group at the carbi-
dichloromethane both in terms of yield and enantio- nol center and prepared ligands 10 and 11 in analogy to the
selectivity (Table 3, entry 4). In CHCl3, the ring-opening of parent bipyridine ligand. In the scandium-catalyzed reac-
cyclohexene oxide proceeded in slightly higher enantio- tion of cis-stilbene oxide (1) with allyl alcohol (reaction B)
selectivity than in CH2Cl2 but in lower yield. A similar both ligands led to almost identical enantioselectivity but in
trend of equal enantioselectivity and lower yield was ob- slightly lower yields. Cyclohexene oxide (6) was ring-opened
served for the alcoholysis of cis-stilbene oxide (entry 2). with allyl alcohol (reaction D) and either of the two chiral
CCl4 and CHBr3 turned out to be less suitable solvents es- scandium catalysts in almost the same enantioselectivity as
pecially in the ring-opening of cyclohexene oxide.
with the Sc(OTf)3-bipyridine 2 complex (entries 3 and 4).
Yet another modification concerned the ligand backbone
in that an additional pyridine ring was placed inbetween
the bipyridine yielding a tripyridine. The Sc(OTf)3-tripyrid-
ine 12 catalyst, however, did not give rise to an enantioselec-
tive catalyst furnishing 1,2-diol monoether 5 in low ee and
the 1,2-diol monoether 8 in racemic form (entry 5).
Variation of Ligand Architecture
In our preliminary experiments we had investigated a
number of so-called priviliged chiral ligands (e.g. bis-
oxazolines, pyridine bisoxazolines and salen ligands) for the
scandium-catalyzed alcoholysis of meso-epoxides none of
which gave rise to an enantioselective alcoholysis. We then
discovered the bipyridine ligand 2 which apparently offered
some important structural advantages for a highly enantio-
selective scandium complex. Thus, it was interesting to
modify the bipyridine structure at specific sites.
The first effort was to investigate the influence of the
torsion angle between the two pyridine rings in the scan-
dium-bipyridine complex. Ligand 9 was prepared in anal-
ogy to a synthetic protocol of Denmark et al.[14] and was
expected to have a significantly enhanced torsion angle in
the scandium complex because of the presence of the ortho
methyl groups. However, yields and enantioselectivities in
model reactions B and D were almost identical with both
scandium-bipyridine complexes (Table 4, entries 1, 2).
Catalyst Loading
The amount of catalyst required for a highly enantiose-
lective reaction in good yield was investigated in the reac-
tion of cis-stilbene oxide (1) and p-methoxybenzyl alcohol
(Table 5) at room temp. in CH2Cl2.
Table 5. Variation of catalyst loading in model reaction
(Scheme 2).
A
Entry
Loading [mol-%]
t [d]
Yield (%)[a]
ee (%)[b]
1
2
3
4
5
15
10
5
2
1
0.5
0.5
5
8
9
84
82
84
75
70
98
97
94
90
73
Table 4. Results for model reactions B and D performed with modi-
fied ligands 9–12 (Scheme 2).
[a] Isolated yield after flash column chromatography. [b] Deter-
mined by chiral HPLC analysis.
A catalyst loading of 10 mol-% provided 1,2-diol mono-
ether 4 in 82% yield and 97% ee within several hours. In-
creasing the catalyst loading to 15 mol-% resulted in a
slightly higher selectivity and higher yields. Lowering the
catalyst amount to 5 mol-% led to a significant increase in
reaction time. The product 4 was, however, obtained in
good yield and still excellent selectivity of 94% ee. With a
catalyst loading of only 2 mol-% the reaction time further
increased. The yield was good and the enantioselectivity
was still on a high level of 90% ee. A sharp decrease in
selectivity to only 73% ee was observed when the amount
of catalyst was further lowered to 1 mol-%. Hence, the
threshold of catalytic efficiency can be considered about
2 mol-%.
Non Linear Effect
In order to get a deeper insight into the catalyst structure
we investigated the relation between product-ee and ligand-
ee. Model reaction A in Scheme 2 was performed with li-
gands of different ee’s and the enantiomeric excess of the
product 1,2-diol monoether 4 was measured (Figure 1).
[a] Isolated yield after flash column chromatography. [b] Determined
by chiral HPLC analysis. [c] Determined by chiral GC analysis.
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Enantioselective Alcoholysis of meso-Epoxides
FULL PAPER
Table 6. Scandium-bipyridine 2 catalyzed ring-opening of aromatic
meso-epoxides with alcohols.[a]
Figure 1. Non linear effect exhibited by the scandium-bipyridine 2
complex.
With a ligand-ee of 33% we already obtained the product
with 65% ee and with 66% ligand-ee a product with 92%
ee was formed. This strong positive non-linear effect sug-
gests that two or more monomeric catalyst species form cat-
alytically inactive oligomeric aggregates thereby enhancing
the proportion of one catalytically active scandium bipyri-
dine enantiomer.[15]
Scope and Limitations
According to the optimized protocol developed above
several meso-epoxides were then tested in this scandium-
bipyridine-catalyzed alcoholysis (Table 6 and Table 7). cis-
Stilbene oxide (1) was ring-opened with various alcohols in
good yields and excellent enantioselectivities. p-Meth-
oxybenzyl alcohol performed best and gave rise to 1,2-diol
monoether 4 in 82% yield and 97% ee (Table 6, entry 1).
But also more conventional alcohols such as methanol, eth-
anol, 1-butanol, 2-propanol, allyl, and propargyl alcohol
ring-opened cis-stilbene oxide in good yields and excellent
enantioselectivities (Table 6, entries 2–7). Other aromatic
epoxides 13–15 were tested in this reaction giving rise to
good yields and high enantioselectivities, too (entries 8–10).
Aliphatic cyclic meso-epoxides 6, 23, and 24 were ring-
opened with only moderate enantioselectivity (Table 7, en-
tries 1–5). Significantly, the α-branched allylic epoxide 23
gave rise to the highest enantioselectivity in this series (en-
try 4). Acyclic meso-epoxides 25–27 underwent the
alcoholysis with varying yields and again moderate enantio-
selectivity. Apparently, α- and β-branched side chains re-
tarded the reaction rate so that no full conversion was
achieved within 2 d and side reactions set in (entries 7 and
8).
[a] Reaction conditions: 1 equiv. epoxide, 2 equiv. alcohol, 10 mol-
% Sc(OTf)3, 12 mol-% bipyridine 2, CH2Cl2, r.t., 24 h. [b] Isolated
yield after flash column chromatography. [c] Determined by chiral
HPLC analysis. [d] Assignment of absolute configuration was made
by comparison to literature values or by analogy.
Alternatively, oxidation with ceric ammonium nitrate[17]
furnished the unprotected 1,2-diol 35 in 82% yield and
Ͼ95% ee (Scheme 3).
The ring-opened products are interesting synthetic build-
ing blocks. Thus, 1,2-diol monoether 4 was converted into
the PMB-protected acyloin 34 by Swern oxidation[16] in
94% yield and almost complete retention of configuration. Scheme 3. Synthetic manipulation of 1,2-diol monoether 4.
Eur. J. Org. Chem. 2007, 2318–2327
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A. Tschöp, A. Marx, A. R. Sreekanth, C. Schneider
FULL PAPER
Table 7. Scandium-bipyridine 2 catalyzed ring-opening of aliphatic
meso-epoxides with alcohols.[a]
Figure 2. Crystal structure of the Y(OTf)3-bipyridine 2 complex.
methylated bipyridine ligand 36 in the scandium-catalyzed
alcoholysis of cis-stilbene oxide (1) which furnished 1,2-diol
monoether 4 in 69% yield and 0% ee (Scheme 4). Ad-
ditional evidence for the supporting effect of the hydroxy
protons was obtained from the reaction of cis-stilbene oxide
(1) and p-methoxybenzyl alcohol with the scandium-bipyri-
dine catalyst which had been prepared in the presence of
2 equiv. of NaH (relative to bipyridine 2). The reaction rate
decreased dramatically and the product 4 was obtained in
only 5% yield and 83% ee after 24 h at r.t. (Scheme 4).
[a] Reaction conditions: 1 equiv. epoxide, 2 equiv. alcohol, 10 mol-
% Sc(OTf)3, 12 mol-% bipyridine 2, CH2Cl2, –20 °C, 24 h. [b] Iso-
lated yield after flash column chromatography. [c] Determined by
chiral HPLC or chiral GC analysis. [d] Assignment of absolute con-
figuration was made by comparison to literature values or by anal-
ogy. [e] Reaction was performed at r.t. [f] Reaction was performed
at 0 °C.
Mechanistic Considerations
After optimizing this process we intended to gain struc-
tural information about the chiral catalyst and make some
mechanistic proposal about the reaction path. In an unre-
lated investigation, Kobayashi et al. have reported a crystal
structure of the scandium catalyst composed of ScBr3 and
bipyridine 2 which revealed a pentagonal-bipyramidal coor-
dination geometry of the metal.[18] We successfully obtained
a crystal structure of the corresponding eight-coordinate yt-
trium-bipyridine complex which exhibited the same sense
of asymmetric induction and comparable level of enantio-
selectivity as the scandium catalyst (Figure 2). It clearly
Scheme 4.
To further shed light on this issue ESI-MS spectra of
shows that the bipyridine ligand 2 was slightly twisted along the Sc(OTf)3-bipyridine 2 complex (MW 820) in CH2Cl2/
the bipyridine axis (19.1°) and coordinated in a tetradentate CH3CN solution were recorded which showed the charac-
fashion to the metal center. Besides the tetracoordinate li- teristic isotope pattern for a [M – H]– fragment proving that
gand, two triflate groups and two water molecules were the hydroxy protons were still bound in the complex (Fig-
bound to the metal center.
ure 3).
These results clearly indicate that the hydroxy protons
What neither of the two structures could tell was the exis-
tence or nonexistence of the two hydroxy protons in the play an important role in the alcoholysis of the epoxides,
complexes. That this issue was of critical importance was possibly by hydrogen bonding to the incoming alcohol,
clear from the totally unselective performance of the bis-O- thereby guiding it to the activated Sc-bound epoxide.
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Eur. J. Org. Chem. 2007, 2318–2327

Enantioselective Alcoholysis of meso-Epoxides
FULL PAPER
ture procedures. Epoxides 13–14, 24 and 26–27 were prepared by
m-CPBA oxidation of the corresponding cis-alkenes. Bipyridine 2
was best prepared using a new procedure developed by Kobaya-
shi.[27] All other chemicals were used as received from commercial
suppliers. 1H and 13C NMR spectra were recorded with Varian
Gemini 200 and 2000 (200 MHz), Varian Gemini 300 BB
(300 MHz) or a Bruker Avance DRX 400 (400 MHz) spectrometer
in CDCl3 at 25 °C with TMS as internal standard. Melting points
were determined on a Boetius heating Table and were uncorrected.
IR spectra were obtained with a FTIR spectrometer (Genesis ATI,
Mattson/Unicam). All ESI mass spectra were recorded on a Bruker
APEX II FT-ICR. Optical rotations were measured using a Polaro-
tronic polarometer (Schmidt & Haensch). HPLC analyses were per-
formed on a JASCO MD-2010 plus instrument with a chiral sta-
tionary phase column (Chiralcel OD purchased from Daicel Co.,
Ltd.). GC analyses were performed on a HP 5890 Series II Plus
with MSD 5972 or a HP 6890 Series Plus with FID from Agilent
Technologies.
General Procedure for the Scandium-Bipyridine-Catalyzed
Alcoholysis of Epoxides: A solution of Sc(OTf)3 (0.10 mmol) and
chiral bipyridine 2 (0.12 mmol) in dichloromethane (4 mL) was
stirred under nitrogen for 10 min, after which the epoxide
(1.00 mmol) was added. The reaction mixture was cooled to the
reaction temperature mentioned in the tables and stirred for 10 min
followed by the addition of the alcohol (2.00 mmol). After stirring
at that temperature for the time mentioned in the tables the solvent
was evaporated in vacuo and the product was purified by flash
column chromatography over silica gel using mixtures of diethyl
ether/petroleum ether or ethyl acetate/petroleum ether as eluent.
All known compounds were compared with the reported data and
all new compounds were fully characterized. For authentication
Figure 3. Simulated and measured ESI-MS spectra of the
Sc(OTf)3-bipyridine 2 complex (negative mode).
Conclusions
The catalytic, enantioselective ring-opening of meso-ep-
oxides with alcohols is an excellent method to furnish valu-
able, enantiomerically enriched 1,2-diol monoethers. In this
study we have developed the scandium-bipyridine-catalyzed
alcoholysis of meso-epoxides and have optimized this pro-
cess with respect to metal, ligand, solvent, catalyst loading,
epoxide and alcohol components. Aromatic meso-epoxides purposes the racemic ring-opened products were also prepared
using an achiral scandium-bipyridine complex and the HPLC or
GC retention times compared to the enantioselective runs. The ab-
solute configuration of the products was assigned by comparison
of the optical rotation values with reported data or by analogy.
turned out to be excellent substrates which were ring-
opened with typically Ͼ90% ee whereas aliphatic meso-ep-
oxides gave rise to only moderate enantioselectivity. While
most reactions were conducted with 10 mol-% catalyst it
was shown that the amount of catalyst can be reduced to
just 5 mol-% or even less without without significant effects
on yield and enantioselectivity. A significant nonlinear ef-
fect was observed pointing to aggregation phenomena of
the catalyst.
(1R,2R)-2-Ethoxy-1,2-diphenylethanol (3): Yield 182 mg, 75%, col-
orless liquid. [α]2D5 = +58.8 (c = 1.7, CH2Cl2); ee = 96%. The enan-
tiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH, 95:5, flow
1
1 mL/min) λmax = 203 nm, (1S,2S): 7.1 min; (1R,2R): 8.1 min. H
NMR (200 MHz, CDCl3): δ = 1.23 (t, J = 7.0 Hz, 3 H, CH2CH3),
3.36–3.56 (m, 3 H, CH2CH3, OH), 4.21 (d, J = 8.5 Hz, 1 H,
CHOCH2), 4.63 (d, J = 8.5 Hz, 1 H, CHOH), 6.97–7.26 (m, 10 H,
ArH) ppm. 13C NMR (50 MHz, CDCl3): δ = 15.2, 64.5, 78.5, 87.3,
Experimental Section
127.2, 127.6, 127.7, 127.8, 127.9, 138.0, 139.1 ppm. IR (film): ν =
˜
3471, 3062, 2876, 1603, 1453, 1388, 1197, 1091 cm–1. HRMS-ESI:
General: All reactions were performed in flame-dried glassware un-
der an atmosphere of dry nitrogen. The solvents were distilled from
the indicated drying agents: dichloromethane (CaH2), tetra-
hydrofuran (LiAlH4, triphenylmethane), diethyl ether (Na, benzo-
phenone), toluene (Na, benzophenone), N,N-dimethylformamide
(Acros ACS grade), acetonitrile (Acros ACS grade), chloroform
(Acros ACS grade). Diethyl ether and petroleum ether for
chromatography were technical grade and distilled from KOH. All
reactions were monitored by thin-layer chromatography (TLC) on
precoated silica gel SIL G/UV254 plates (Machery–Nagel & Co.);
spots were visualized by treatment with a solution of vanillin
(0.5 g), conc. acetic acid (10 mL), and conc. H2SO4 (5 mL) in meth-
anol (90 mL). Flash column chromatography was performed by
m/z [M + Na]+ calcd. for C16H18O2: 265.11990; found: 265.11985.
(1R,2R)-2-(4-Methoxybenzyloxy)-1,2-diphenylethanol (4):[23] Yield
234 mg, 70%, white solid, m.p. 85–86 °C. [α]2D5 = –41.6 (c = 0.72,
CH2Cl2); ee = 97%. The enantiomeric assay: Chiralcel OD, iso-
cratic (n-hexane/iPrOH, 90:10, flow 1 mL/min) λmax = 199 nm,
(1S,2S): 10.3 min, (1R,2R): 11.7 min. 1H NMR (300 MHz, CDCl3):
δ = 3.54 (d, J = 1.0 Hz, 1 H, OH), 3.82 (s, 3 H, OCH3), 4.27 (d, J
= 11.0 Hz, 1 H, OCHAHB), 4.33 (d, J = 8.5 Hz, 1 H, CHOCH2),
4.47 (d, J = 11.0 Hz, 1 H, OCHAHB), 4.70 (dd, J = 8.5, 1.0 Hz, 1
H, CHOH), 6.88–6.91 (m, 2 H, ArH), 7.00–7.25 (m, 12 H, ArH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 55.4, 70.6, 78.7, 86.7, 114.0,
using Merck silica gel 60 230–400 mesh (0.040–0.063 mm). (Z)-1,2- 127.4, 127.8, 127.9, 128.0, 128.2, 129.7, 137.8, 139.3, 159.5 ppm.
Bis(naphthalen-2-yl)ethene,[19] (Z)-1,2-di-m-tolylethene,[19] cis-1,2-
bis(p-chlorophenyl)ethane oxide[20] and 1,4-dimethylidene-2,3-ep-
oxy-2,3-dihydronaphthalene[10e] were prepared according to litera-
IR (KBr): ν = 3521, 3432, 2865, 1610, 1509, 1241, 1195, 1022 cm–1.
˜
HRMS-ESI: m/z [M + Na]+ calcd. for C22H22O3: 357.14587; found:
357.14612.
Eur. J. Org. Chem. 2007, 2318–2327
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2323

A. Tschöp, A. Marx, A. R. Sreekanth, C. Schneider
FULL PAPER
(1R,2R)-2-(Allyloxy)-1,2-diphenylethanol (5):[22] Yield 198 mg,
78%, colorless liquid. [α]2D5 = –27.2 (c = 1.1, CH2Cl2); ee = 95%.
The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH,
97:3, flow 1 mL/min) λmax = 203 nm, (1S,2S): 8.9 min, (1R,2R):
CDCl3): δ = 14.0, 19.5, 32.0, 69.0, 78.8, 87.7, 127.4, 127.7, 127.8,
127.9, 128.0, 128.1, 138.1, 139.3 ppm. IR (KBr): ν = 3525, 3029,
˜
1490, 1386, 1257, 1025 cm–1. HRMS-ESI: m/z [M + Na]+ calcd.
for C18H22O2: 293.15120; found: 293.15114.
1
10.6 min. H NMR (200 MHz, CDCl3): δ = 3.61 (d, J = 1.0 Hz, 1
(1R,2R)-2-Isopropyloxy-1,2-diphenylethanol (18): Yield 185 mg,
72%, colorless liquid. [α]2D5 = +11.7 (c = 0.85, CH2Cl2); ee = 89%.
The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH,
97:3, flow 1 mL/min) λmax = 203 nm, (1S,2S): 6.5 min; (1R,2R):
H, OH), 3.87 (ddt, J = 12.5, 5.5, 1.5 Hz, 1 H, OCHAHB), 4.04 (ddt,
J = 12.5, 5.5, 1.5 Hz, 1 H, OCHAHB), 4.33 (d, J = 8.5 Hz, 1 H,
CHOCH2), 4.73 (dd, J = 8.5, 1.0 Hz, 1 H, CHOH), 5.19–5.34 (m,
2 H, CH=CH2), 5.86–5.98 (m, 1 H, CH=CH2), 7.01–7.28 (m, 10
H, ArH) ppm. 13C NMR (50 MHz, CDCl3): δ = 69.7, 78.6, 86.8,
105.4, 117.3, 127.3, 127.7, 127.8, 128.0, 128.1, 134.3, 137.6, 139.2
1
7.7 min. H NMR (200 MHz, CDCl3): δ = 1.12 (d, J = 6.0 Hz, 3
H, CH3), 1.20 (d, J = 6.0 Hz, 3 H, CH3), 1.57 (br. s, 1 H, OH),
3.57 (hept, J = 6.0 Hz, 1 H, CH(CH3)2), 4.30 (d, J = 8.5 Hz, 1 H,
CHOCH), 4.59 (d, J = 8.5 Hz, 1 H, CHOH), 6.98–7.25 (m, 10 H,
ArH) ppm. 13C NMR (50 MHz, CDCl3): δ = 21.2, 23.5, 69.7, 78.5,
84.8, 127.2, 127.5, 127.6, 127.7, 127.8, 138.6, 139.3 ppm. IR (film):
ppm. IR (film): ν = 3455, 3031, 2867, 1647, 1453, 1339, 1196,
˜
1074 cm–1. HRMS-ESI: m/z [M + Na]+ calcd. for C17H18O2:
277.11990; found: 277.11978.
ν = 3550, 2971, 2887, 1603, 1453, 1383, 1196, 1122 cm–1. HRMS-
(1R,2R)-2-(4-Methoxybenzyloxy)cyclohexanol (7):[23] Yield 213 mg,
90%, colorless liquid. [α]2D5 = –25.0 (c = 1.6, CH2Cl2); ee = 54%.
The enantiomeric assay: Chiral GC analysis 15 m (2,6-Me-3-pen-
tyl-γ-CD), 135° (50% in OV 1701). (1R,2R): 38.2 min, (1S,2S):
39.1 min. 1H NMR (300 MHz, CDCl3): δ = 1.20–1.26 (m, 4 H,
CH2), 1.69–1.77 (m, 2 H, CH2), 1.95–2.21 (m, 2 H, CH2), 2.68 (s,
1 H, OH), 3.10–3.22 (m, 1 H, CHOCH2), 3.40–3.52 (m, 1 H,
CHOH), 3.80 (s, 3 H, OCH3), 4.39 (d, J = 11.0 Hz, 1 H, OCHAHB),
4.63 (d, J = 11.0 Hz, 1 H, OCHAHB), 6.89 (d, J = 8.5 Hz, 2 H,
ArH), 7.27 (d, J = 8.5 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 23.9, 24.2, 29.2, 32.0, 55.2, 70.4, 73.7, 83.1, 113.8,
˜
ESI: m/z [M + Na]+ calcd. for C17H20O2: 279.13555; found:
279.13552.
(1R,2R)-1,2-Diphenyl-2-(prop-2-ynyloxy)ethanol (19): Yield 184 mg,
73%, colorless liquid. [α]2D5 = –69.2 (c = 1.3, CH2Cl2); ee = 91%.
The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH,
90:10, flow 0.8 mL/min) λmax = 207 nm, (1S,2S): 11.4 min, (1R,2R):
1
13.4 min. H NMR (300 MHz, CDCl3): δ = 2.46 (t, J = 2.5 Hz, 1
H, alkyne-CH), 3.46 (d, J = 1.5 Hz, 1 H, OH), 3.93 (dd, J = 15.5,
2.5 Hz, 1 H, OCHAHB), 4.21 (dd, J = 15.5, 2.5 Hz, 1 H, OCHAHB),
4.50 (d, J = 8.5 Hz, 1 H, CHOCH2), 4.72 (dd, J = 8.5, 1.5 Hz, 1
H, CHOH), 7.00–7.25 (m, 10 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 56.2, 75.2, 78.5, 79.5, 86.4, 127.6, 128.0, 128.1, 128.2,
129.3, 130.7, 159.2 ppm. IR (film): ν = 3438, 2998, 2861, 1610,
˜
1511, 1299, 1079, 1033 cm–1. HRMS-ESI: m/z [M + Na]+ calcd.
for C14H20O3: 259.13047; found: 259.13064.
128.4, 128.6, 136.7, 139.1 ppm. IR (film): ν = 3453, 3031, 1603,
˜
1454, 1196, 1082 cm–1. HRMS-ESI: m/z [M + Na]+ calcd. for
(1R,2R)-2-(Allyloxy)cyclohexanol (8):[26] Yield 84 mg, 54%, color-
less liquid. [α]2D5 = –20.5 (c = 1.2, CH2Cl2); ee = 50%. The enantio-
meric assay: Chiral GC analysis 25 m (FS-Hydrodex β-3-P).
(1S,2S): 20.81 min, (1R,2R): 21.13 min. 1H NMR (300 MHz,
CDCl3): δ = 1.05–1.40 (m, 4 H, CH2), 1.60–1.80 (m, 2 H, CH2),
1.95–2.15 (m, 2 H, CH2), 2.75 (s, 1 H, OH), 3.04–3.14 (m, 1 H,
CHOCH2), 3.40–3.52 (m, 1 H, CHOH), 3.97 (ddt, J = 12.5, 5.5,
1.5 Hz, 1 H, OCHAHB), 4.17 (ddt, J = 12.5, 5.5, 1.5 Hz, 1 H, OCH-
AHB), 5.18 (dq, J = 10.5, 1.5 Hz, 1 H, CH=CHAHB), 5.29 (dd, J =
17.0, 1.5 Hz, 1 H, CH=CHAHB), 5.95 (ddt, J = 17.0, 10.5, 5.5 Hz, 1
H, CH = CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 23.9, 24.2,
C17H16O2: 275.10425; found: 275.10349.
(1R,2R)-2-Methoxy-2-(naphthalen-3-yl)-1-(naphthalen-6-yl)ethanol
(20): Yield 273 mg, 83%, white solid, m.p. 98–99 °C. [α]2D5 = +184.6
(c = 0.65, CH2Cl2); ee = 98%. The enantiomeric assay: Chiralcel
OD, isocratic (n-hexane/iPrOH, 95:5, flow 0.8 mL/min) λmax
=
210 nm, (1R,2R): 29.5 min, (1S,2S): 31.1 min. 1H NMR (200 MHz,
CDCl3): δ = 3.38 (s, 3 H, OCH3), 3.75 (d, J = 1.0 Hz, 1 H, OH),
4.42 (d, J = 8.5 Hz, 1 H, CHOCH3), 4.99 (dd, J = 8.5, 1.0 Hz, 1
H, CHOH), 7.09–7.20 (m, 2 H, ArH), 7.39–7.82 (m, 12 H, ArH)
ppm. 13C NMR (50 MHz, CDCl3): δ = 57.1, 78.6, 89.2, 125.3,
125.4, 125.8, 126.1, 126.4, 127.3, 127.5, 127.6, 127.7, 128.0, 133.0,
29.2, 32.0, 69.7, 73.7, 83.2, 116.9, 135.1 ppm. IR (film): ν = 3439,
˜
2933, 2861, 1647, 1451, 1302, 1233, 1882 cm–1. MS (ESI): m/z =
135.0, 136.8 ppm. IR (KBr): ν = 3444, 3019, 2890, 1600, 1506,
˜
179.1 [M + Na]+, 335.2 [2M + Na]+.
1361, 1268, 1162, 1062 cm–1. HRMS-ESI: m/z [M + Na]+ calcd.
(1R,2R)-2-Methoxy-1,2-diphenylethanol (16):[21] Yield 185 mg,
81%, white solid, m.p. 69–70 °C. [α]2D5 = +53.3 (c = 1.5, CHCl3); ee
= 92%. The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/
iPrOH, 90:10, flow 0.8 mL/min) λmax = 203 nm, (1S,2S): 7.8 min;
for C23H20O2: 351.13555; found: 351.13527.
(1R,2R)-2-Methoxy-1,2-di-m-tolylethanol (21): Yield 197 mg, 77%,
colorless liquid. [α]2D5 = +70.0 (c = 1.0, CH2Cl2); ee = 96%. The
enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH, 95:5,
flow 0.8 mL/min) λmax = 203 nm, (1S,2S): 9.8 min, (1R,2R):
10.9 min. 1H NMR (300 MHz, CDCl3): δ = 2.24 (s, 3 H, CH3),
2.26 (s, 3 H, CH3), 3.31 (s, 3 H, OCH3), 3.47 (s, 1 H, OH), 4.08 (d,
J = 8.5 Hz, 1 H, CHOCH3), 4.61 (d, J = 8.5 Hz, 1 H, CHOH),
6.77–7.20 (m, 8 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ =
21.6, 57.2, 78.7, 89.3, 124.7, 125.2, 127.8, 128.1, 128.6, 128.9, 137.5,
1
(1R,2R): 8.7 min. H NMR (200 MHz, CDCl3): δ = 3.31 (s, 3 H,
OCH3), 3.51 (s, 1 H, OH), 4.12 (d, J = 8.5 Hz, 1 H, CHOCH3),
4.65 (d, J = 8.5 Hz, 1 H, CHOH), 6.97–7.23 (m, 10 H, ArH) ppm.
13C NMR (50 MHz, CDCl3): δ = 56.8, 78.6, 89.1, 127.2, 127.6,
127.7, 127.8, 128.0, 137.3, 139.1 ppm. IR (KBr): ν = 3405, 3061,
˜
1492, 1453, 1337, 1201, 1102, 1059 cm–1. HRMS-ESI: m/z [M +
Na]+ calcd. for C15H16O2: 251.10425; found: 251.10446.
137.7, 137.8, 139.5 ppm. IR (film): ν = 3463, 2979, 2823, 1606,
˜
1508, 1382, 1182, 973 cm–1. HRMS-ESI: m/z [M + Na]+ calcd. for
(1R,2R)-2-Butoxy-1,2-diphenylethanol (17): Yield 216 mg, 80%,
white solid, m.p. 55–56 °C. [α]2D5 = +31.2 (c = 1.6, CH2Cl2); ee =
94%. The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/
C17H20O2: 279.13555; found: 279.13561.
(1R,2R)-1,2-Bis(4-chlorophenyl)-2-(4-methoxybenzyloxy)ethanol
iPrOH, 95:5, flow 1 mL/min) λmax = 203 nm, (1S,2S): 6.3 min, (22): Yield 303 mg, 75%, white solid, m.p. 72–74 °C. [α]2D5 = +28.8
(1R,2R): 7.1 min. 1H NMR (200 MHz, CDCl3): δ = 0.94 (t, J =
7.0 Hz, 3 H, CH3), 1.41–1.51 (m, 2 H, CH2), 1.58–1.71 (m, 2 H,
CH2), 3.35–3.47 (m, 2 H, OCH2), 3.67 (d, J = 1.0 Hz, 1 H, OH),
4.23 (d, J = 8.5 Hz, 1 H, CHOCH2), 4.68 (dd, J = 8.5, 1.0 Hz, 1
H, CHOH), 7.00–7.25 (m, 10 H, ArH) ppm. 13C NMR (50 MHz,
(c = 1.2, CHCl3); ee = 92%. The enantiomeric assay: Chiralcel OD,
isocratic (n-hexane/iPrOH, 95:5, flow 1.0 mL/min) λmax = 203 nm,
(1S,2S): 19.8 min, (1R,2R): 22.3 min. 1H NMR (300 MHz, CDCl3):
δ = 3.47 (s, 1 H, OH), 3.82 (s, 3 H, OCH3), 4.24 (d, J = 8.5 Hz, 1
H, CHOCH2), 4.24 (d, J = 11.0 Hz, 1 H, OCHAHB), 4.44 (d, J =
2324
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2318–2327

Enantioselective Alcoholysis of meso-Epoxides
FULL PAPER
11.0 Hz, 1 H, OCHAHB), 4.63 (d, J = 8.5 Hz, 1 H, CHOH), 6.88–
7.00 (m, 6 H, ArH), 7.14–7.25 (m, 6 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 55.3, 70.6, 77.8, 85.7, 114.0, 128.1, 128.5,
128.6, 129.2, 129.3, 129.7, 133.5, 134.0, 135.9, 137.4, 159.5 ppm.
(1R,2R)-5-(4-Methoxybenzyloxy)octan-4-ol (32): Yield 67 mg, 25%,
colorless oil. [α]2D5 = –5.0 (c = 0.94, CHCl3); ee = 44%. The enantio-
meric assay: Chiralcel OD, isocratic (n-hexane/iPrOH, 99.5:0.5,
flow 1.0 mL/min) λmax = 203 nm, (1S,2S): 23.6 min, (1R,2R):
1
IR (KBr): ν = 3536, 2959, 2875, 2857, 1614, 1515, 1488, 1255, 1190,
25.0 min. H NMR (200 MHz, CDCl3): δ = 0.92 (t, J = 7.0 Hz, 3
˜
1010 cm–1. MS (ESI): m/z = 425.0 [M + Na]+. C22H20Cl2O3: calcd.
H, CH3), 0.94 (t, J = 7.0 Hz, 3 H, CH3), 1.32–1.64 (m, 8 H, CH2),
2.27 (br. s, 1 H, OH), 3.25 (q, J = 5.5 Hz, 1 H, CHOCH2), 3.46–
3.58 (m, 1 H, CHOH), 3.81 (s, 3 H, OCH3), 4.42 (d, J = 11.0 Hz,
1 H, OCHAHB), 4.59 (d, J = 11.0 Hz, 1 H, OCHAHB), 6.88 (d, J
= 8.5 Hz, 2 H, ArH), 7.27 (d, J = 8.5 Hz, 2 H, ArH) ppm. 13C
NMR (50 MHz, CDCl3): δ = 14.1, 14.4, 18.5, 19.0, 32.7, 35.6, 55.3,
C 65.52, H 5.00; found C 65.48, H 5.08.
(1R,2R)-2-Methoxycyclohexanol (28):[25] Yield 120 mg, 92%, color-
less liquid. [α]2D5 = –23.5 (c = 1.7, CH2Cl2); ee = 45%. The enantio-
meric assay: Chiral GC analysis 25 m (FS-Hydrodex β-3-P).
(1S,2S): 18.0 min, (1R,2R): 18.6 min. 1H NMR (300 MHz, CDCl3):
δ = 0.98–1.24 (m, 4 H, CH2), 1.60–1.65 (m, 2 H, CH2), 1.88–2.06
(m, 2 H, CH2), 2.80–2.92 (m, 1 H, CHOCH3), 3.06 (br. s, 1 H,
OH), 3.30–3.45 (m, 1 H, CHOH), 3.35 (s, 3 H, OCH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 24.0, 24.1, 28.4, 32.1, 56.3, 73.7, 85.0
72.1, 72.5, 82.0, 113.9, 129.4, 130.6, 159.3 ppm. IR (film): ν = 3444,
˜
2957, 2933, 2871, 1613, 1586, 1514, 1464, 1380, 1110, 822 cm–1.
HRMS-ESI: m/z [M + Na]+ calcd. for C16H26O3: 289.17742; found:
289.17745.
ppm. IR (film): ν = 3432, 2861, 1452, 1301, 1232, 1095 cm–1. MS
˜
(1R,2R)-5-(4-Methoxybenzyloxy)-2,7-dimethyloctan-4-ol (33): Yield
97 mg, 33%, colorless oil. [α]2D5 = +1.1 (c = 1.5, CHCl3); ee = 45%.
The enantiomeric assay: Mosher ester of the product. 1H NMR
(400 MHz, CDCl3): δ = 0.90–0.95 (m, 12 H, CH3), 1.18–1.26 (m,
1 H, CH(CH3)2), 1.36–1.52 (m, 3 H, CH(CH3)2, CH2), 1.71–1.86
(m, 2 H, CH2), 2.16 (br. s, 1 H, OH), 3.29 (dt, J = 7.0, 5.0 Hz, 1
H, CHOCH2), 3.55–3.60 (m, 1 H, CHOH), 3.80 (s, 3 H, OCH3),
4.46 (d, J = 11.0 Hz, 1 H, OCHAHB), 4.58 (d, J = 11.0 Hz, 1 H,
OCHAHB), 6.88 (d, J = 8.5 Hz, 2 H, ArH), 7.26 (d, J = 8.5 Hz, 2
H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.8, 22.7, 23.4,
23.7, 24.6, 24.7, 40.1, 42.8, 55.3, 71.3, 72.3, 80.7, 113.9, 129.4,
(ESI): m/z = 283.2 [2M + Na]+.
(2R,3R)-3-(4-Methoxybenzyloxy)-1,4-dimethylene-1,2,3,4-tetra-
hydronaphthalen-2-ol (29): Yield 225 mg, 73 %, colorless liquid.
[α]2D3 = –73.9 (c = 1.4, CHCl3); ee = 62%. The enantiomeric assay:
Chiralcel OD, isocratic (n-hexane/iPrOH, 90:10, flow 1.0 mL/min)
λmax = 262 nm, (1R,2R): 13.5 min, (1S,2S): 15.2 min. 1H NMR
(400 MHz, CDCl3): δ = 2.52 (d, J = 3 Hz, 1 H, OH), 3.81 (s, 3 H,
OCH3), 4.12 (d, J = 8.0 Hz, 1 H, CHOCH2), 4.40 (d, J = 8.0 Hz,
1 H, CHOH), 4.53 (d, J = 11.5 Hz, 1 H, OCHAHB), 4.74 (d, J =
11.5 Hz, 1 H, OCHAHB), 5.43 (s, 1 H, C=CH2), 5.52 (s, 1 H,
C=CH2), 5.72 (s, 1 H, C=CH2), 5.79 (s, 1 H, C=CH2), 6.89 (d, J
= 8.5 Hz, 2 H, ArH), 7.29 (d, J = 8.5 Hz, 2 H, ArH), 7.27–7.32
(m, 2 H, ArH), 7.60–7.62 (m, 1 H, ArH), 7.68–7.71 (m, 1 H, ArH)
ppm. 13C NMR (50 MHz, CDCl3): δ = 55.3, 71.9, 73.8, 81.9, 111.0,
111.8, 113.9, 124.6, 125.2, 128.5, 128.6, 129.5, 129.9, 131.8, 132.5,
130.6, 159.3 ppm. IR (film): ν = 3422, 2955, 2868, 1612, 1584, 1513,
˜
1467, 1383, 1075, 817 cm–1. HRMS-ESI: m/z [M + Na]+ calcd. for
C18H30O3: 317.20872; found: 317.20881.
(R)-2-(4-Methoxybenzyloxy)-1,2-diphenylethanone (34): To a stirred
solution of oxalyl chloride (0.022 mL, 0.25 mmol) in CH2Cl2
(0.5 mL) under nitrogen at –78 °C was added a solution of DMSO
(30 µL, 0.42 mmol) in CH2Cl2 (0.2 mL). After 10 min, a solution
of alcohol 4 (56 mg, 0.17 mmol) in CH2Cl2 (1 mL) was added drop-
wise over a period of 5 min at the same temperature. After stirring
for 15 min at –78 °C, Et3N (0.11 mL, 0.84 mmol) was added and
further stirred for 10 min at –78 °C and warmed to room temp. and
stirred for 30 min. Water was added to quench the reaction, the
layers were separated, and the aqueous phase was extracted with
CH2Cl2. The organic phases were washed with brine, 1% H2SO4,
water and 5% NaHCO3 solution, dried with MgSO4, filtered, and
the solvents evaporated in vacuo. Flash chromatography over silica
gel with diethyl ether/petroleum ether, 1:3 afforded 52 mg (94%) of
the title compound as a colorless oil. [α]2D5 = –36.8 (c = 1.9,
CH2Cl2); ee = 95%. The enantiomeric assay: Chiralcel OD, iso-
cratic (n-hexane/iPrOH, 95:5, flow 0.8 mL/min) λmax = 203 nm, (S):
141.6, 142.8, 159.4 ppm. IR (film): ν = 3435, 3063, 3032, 2998,
˜
2933, 2870, 2835, 1612, 1585, 1513, 1455, 1248, 1173, 1090, 787,
763 cm–1. HRMS-ESI: m/z [M + Na]+ calcd. for C13H18O3:
331.13047; found: 331.13022.
(1R,2R)-2-(4-Methoxybenzyloxy)cycloheptanol (30): Yield 115 mg,
46%, colorless oil. [α]2D5 = –8.3 (c = 1.0, CHCl3); ee = 53%. The
1
enantiomeric assay: NMR of the corresponding Mosher ester. H
NMR (300 MHz, CDCl3): δ = 1.39–1.58 (m, 6 H, CH2), 1.62–1.75
(m, 2 H, CH2), 1.86–2.03 (m, 2 H, CH2), 2.73 (br. s, 1 H, OH),
3.23 (td, J = 8.5, 3.5 Hz, 1 H, CHOCH2), 3.56 (td, J = 8.5, 3.5 Hz,
1 H, CHOH), 3.80 (s, 3 H, OCH3), 4.37 (d, J = 11.0 Hz, 1 H,
CHAHB), 4.62 (d, J = 11.0 Hz, 1 H, CHAHB), 6.89 (d, J = 8.5 Hz, 2
H, ArH), 7.27 (d, J = 8.5 Hz, 2 H, ArH) ppm. 13C NMR (50 MHz,
CDCl3): δ = 22.2, 22.5, 27.0, 28.4, 31.5, 55.3, 70.7, 75.9, 85.7, 113.9,
129.4, 130.4, 159.3 ppm. IR (film): ν = 3444, 2932, 2864, 1612,
˜
1
1572, 1513, 1440, 1070, 787 cm–1. HRMS-ESI: m/z [M + Na]+
13.1 min, (R): 14.4 min. H NMR (300 MHz, CDCl3): δ = 3.81 (s,
3 H, OCH3), 4.55 (d, J = 8.5 Hz, 1 H, CHAHB), 4.58 (d, J = 8.5 Hz,
1 H, CHAHB), 5.63 (s, 1 H, CHOCH2), 6.87 (d, J = 8.5 Hz, 2 H,
ArH), 7.24–7.49 (m, 10 H, ArH), 7.94 (d, J = 8.5 Hz, 2 H, ArH)
ppm. 13C NMR (75 MHz, CDCl3): δ = 55.3, 71.0, 83.4, 113.9,
127.7, 128.5, 128.9, 129.2, 129.4, 129.9, 133.3, 135.1, 136.3, 159.5,
calcd. for C15H22O3: 273.14612; found: 273.14617.
(2R,3R)-3-(4-Methoxybenzyloxy)butan-2-ol (31):[23] Yield 196 mg,
93%, colorless liquid. [α]2D5 = –33.3 (c = 2.4, CH2Cl2); ee = 49%.
The enantiomeric assay: Chiral GC analysis 25 m (6T-2,3-Me-β-
CD), 120° (50% in OV 1701). (1R,2R): 37.9 min, (1S,2S): 38.8 min.
1H NMR (300 MHz, CDCl3): δ = 1.17 (d, J = 6.5 Hz, 3 H, CH3),
1.18 (d, J = 6.5 Hz, 3 H, CH3), 2.30 (d, J = 4.5 Hz, 1 H, OH), 3.28
(qd, J = 6.5, 3.5 Hz, 1 H, CHOCH2), 3.84 (s, 3 H, OCH3), 3.84–
197.5 ppm. IR (film): ν = 2929, 1641, 1450, 1301, 1178, 1070,
˜
962 cm–1. HRMS-ESI: m/z [M + Na]+ calcd. for C22H20O3:
355.13047; found: 355.12996.
3.98 (m, 1 H, CHOH), 4.47 (d, J = 11.0 Hz, 1 H, OCHAHB), 4.59 (1R,2R)-1,2-Diphenylethane-1,2-diol (35):[24] To a stirred solution of
(d, J = 11.0 Hz, 1 H, OCHAHB), 6.92 (d, J = 8.5 Hz, 2 H, ArH),
alcohol 4 (56 mg, 0.17 mmol) in CH3CN/H2O (2 mL/0.5 mL) at
room temp. was added CAN (0.37 g, 0.67 mmol) and the reaction
7.31 (d, J = 8.5 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 13.5, 17.7, 55.3, 69.2, 70.4, 77.9, 113.8, 129.3, 130.7, 159.2 ppm. mixture was stirred for 30 min. The reaction was quenched by the
IR (film): ν = 3415, 2931, 2873, 1612, 1511, 1245, 1085, 819 cm–1.
addition of 3 mL of 6  HCl, the layers were separated, and the
aqueous phase was extracted with CH2Cl2 (3ϫ10 mL). The or-
ganic phases were washed with water and brine, dried with MgSO4,
˜
HRMS-ESI: m/z [M + Na]+ calcd. for C12H18O3: 233.11482; found:
233.11504.
Eur. J. Org. Chem. 2007, 2318–2327
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2325

A. Tschöp, A. Marx, A. R. Sreekanth, C. Schneider
FULL PAPER
S. H. R. Abdi, S. Agrawal, V. J. Mayani, R. V. Jasra, Tetrahe-
dron Lett. 2006, 47, 5277–5279.
E. N. Jacobsen, F. Kakiuchi, R. G. Konsler, J. F. Larrow, M.
filtered, and the solvents evaporated in vacuo. Flash chromatog-
raphy over silica gel with diethyl ether/petroleum ether, 1:1 afforded
29 mg (82%) of the title compound as a colorless solid. M.p. 148–
[4]
[5]
Tokunaga, Tetrahedron Lett. 1997, 38, 773–776.
150 °C. [α]2D5
= +91.9 (c = 0.87, EtOH); ee = 96% (lit.
S. Matsunaga, J. Das, J. Roels, E. M. Vogl, N. Yamamoto, T.
Iida, K. Yamaguchi, M. Shibasaki, J. Am. Chem. Soc. 2000,
122, 2252–2260.
a) T. Iida, N. Yamamoto, H. Sasai, M. Shibasaki, J. Am. Chem.
Soc. 1997, 119, 4783–4784; b) M. H. Wu, E. N. Jacobsen, J.
Org. Chem. 1998, 63, 5252–5254; c) S. Y. Ko, K. B. Sharpless,
J. Org. Chem. 1986, 51, 5413–5415; d) J. Wu, X. L. Hou, L. X.
Dai, L. J. Xia, M. H. Tang, Tetrahedron: Asymmetry 1998, 9,
3431–3436.
[α]2D5 = +95 (c = 0.87, EtOH)).[22] 1H NMR (300 MHz, CDCl3): δ
= 2.85 (s, 2 H, OH), 4.71 (s, 2 H, CHOH), 7.11–7.25 (m, 10 H,
ArH) ppm. 13C NMR (50 MHz, CDCl3): δ = 79.2, 127.0, 128.0,
[6]
128.2, 139.9 ppm. IR (KBr): ν = 3498, 2921, 1650, 1384, 1078 cm–1.
˜
HRMS-ESI: m/z [M + Na]+ calcd. for C14H14O2: 237.08860; found:
237.08868.
Crystal Data for the Y(OTf)3/bipyridine 2 Complex: Empirical for-
mula C23H32F9N2O13S3Y·0.5CH2Cl2. M = 973.06, T = 180(2) K,
λ = 0.71073 Å, crystal system: monoclinic, space group: P2(1). Unit
cell dimensions: a = 11.7963(3), b = 13.5670(3), c = 24.6087(7) Å,
α = γ = 90°, β = 103.618(2), V = 3827.67(17) Å3, Z = 4. ρ(calcul-
ated) = 1.636 g/cm3, absorption coefficient 1.859 mm–1. F(000) =
1908. Crystal size: 0.50ϫ0.08ϫ0.06 mm. Θ = 3.13 to 26.00°. Index
ranges: –14ՅhՅ14, –16ՅkՅ16, –30ՅlՅ30. Reflections col-
lected: 51515. Independent reflections: 14973 [Rint = 0.0526]. Com-
pleteness to 2Θ = 26.00°: 99.7%. Refinement method: Full-matrix
least-squares on F2. Data/restraints/parameters: 14973/1/986.
[7]
[8]
M. Yang, C. Zhu, F. Yuan, Y. Huang, Y. Pan, Org. Lett. 2005,
7, 1927–1930.
a) W. A. Nugent, J. Am. Chem. Soc. 1998, 120, 7139–7140; b)
S. E. Denmark, P. A. Barsanti, K. T. Wong, R. A. Stavenger, J.
Org. Chem. 1998, 63, 2428–2429; c) B. Tao, M. M. C. Lo, G. C.
Fu, J. Am. Chem. Soc. 2001, 123, 353–354; d) M. Nakaijama,
M. Saito, M. Uemura, S. Hashimoto, Tetrahedron Lett. 2002,
43, 8827–8829; e) E. Tokuoka, S. Kotani, H. Matsunaga, T.
Ishizuka, S. Hashimoto, M. Nakaijama, Tetrahedron: Asym-
metry 2005, 16, 2391–2392; f) S. Bruns, G. Haufe, J. Fluorine
Chem. 2000, 104, 247–254; g) G. Haufe, S. Bruns, Adv. Synth.
Catal. 2002, 344, 165–171.
a) B. M. Cole, K. D. Shimizu, C. A. Krueger, J. P. A. Harrity,
M. L. Snapper, A. H. Hoveyda, Angew. Chem. 1996, 108, 1776–
1779; Angew. Chem. Int. Ed. Engl. 1996, 35, 1668–1671; b)
K. D. Shimizu, B. M. Cole, C. A. Krueger, K. W. Kuntz, M. L.
Snapper, A. H. Hoveyda, Angew. Chem. 1997, 109, 1782–1785;
Angew. Chem. Int. Ed. Engl. 1997, 36, 1704–1707; c) S. E.
Schaus, E. N. Jacobsen, Org. Lett. 2000, 2, 1001–1004; d) C.
Zhu, F. Yuan, W. Gu, Y. Pan, Chem. Commun. 2003, 692–693.
a) M. Mizuno, M. Kanai, A. Iida, K. Tomioka, Tetrahedron:
Asymmetry 1996, 7, 2483–2484; b) A. Alexakis, E. Vrancken,
P. Mangeney, Synlett 1998, 1165–1167; E. Vrancken, A.
Alexakis, P. Mangeney, Eur. J. Org. Chem. 2005, 1354–1366; c)
N. Oguni, Y. Miyagi, K. Itoh, Tetrahedron Lett. 1998, 39, 9023–
9026; d) C. Zhu, M. Yang, J. Sun, Y. Zhu, Y. Pan, Synlett 2004,
465–468; e) F. Bertozzi, P. Crotti, F. Macchia, M. Pineschi, A.
Arnold, B. L. Feringa, Org. Lett. 2000, 2, 933–936; f) F.
Bertozzi, P. Crotti, F. Del Moro, V. Di Bussolo, F. Macchia, M.
Pineschi, Eur. J. Org. Chem. 2003, 1264–1270; g) F. Del Moro,
P. Crotti, V. Di Bussolo, F. Macchia, M. Pineschi, Org. Lett.
2003, 5, 1971–1974; h) F. Bertozzi, P. Crotti, F. Del Moro, B. L.
Feringa, F. Macchia, M. Pineschi, Chem. Commun. 2001,
2606–2607.
Goodness-of-fit on F2: 1.094. Final R indices [IϾ2σ(I)]: R1
0.0429, wR2 = 0.0923. R indices (all data): R1 = 0.0492, wR2
0.0950. Absolute structure parameter: –0.008(3).
=
=
[9]
CCDC-617014 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[10]
Acknowledgments
Support of this work by the Deutsche Forschungsgemeinschaft
(DFG) (Schn 441/3-2) is most gratefully acknowledged. We would
like to thank Prof. Harald Krautscheid and Dr. Claudia Birkeme-
yer (University of Leipzig) for solving the X-ray structure of the
yttrium-bipyridine complex and recording the ESI-MS spectra of
the scandium bipyridine complex, respectively. Wacker AG is grate-
fully acknowledged for the donation of chemicals.
[11]
a) C. Schneider, A. R. Sreekanth, E. Mai, Angew. Chem. 2004,
116, 5809–5812; Angew. Chem. Int. Ed. 2004, 43, 5691–5694;
for some recent nonenantioselective metal-catalyzed alcohol
additions to epoxides see; b) P. R. Lihkar, M. P. Kumar, A. K.
Bandyopadhyay, Synlett 2001, 836–838; c) J. Barluenga, H.
Vazquez-Villa, A. Ballesteros, J. M. Gonzalez, Org. Lett. 2002,
4, 2817–2819; d) A. Berkessel, E. Ashkenazi, M. R. M. And-
reae, Appl. Catal., A 2003, 27; e) B. M. Choudary, K. Jyothi,
S. Mahdi, M. L. Kantam, Synlett 2004, 231–234.
For the first synthesis and application of bipyridine 2 in asym-
metric catalysis see a) C. Bolm, M. Zehnder, D. Bur, Angew.
Chem. 1990, 102, 206–208; Angew. Chem. Int. Ed. Engl. 1990,
29, 191–193; b) C. Bolm, M. Ewald, M. Zehnder, M. A. Neu-
burger, Chem. Ber. 1992, 125, 453–458.
Reviews: a) S. Kobayashi, Eur. J. Org. Chem. 1999, 15–27; b)
S. Kobayashi, M. Sugiura, H. Kitagawa, W. W. L. Lam, Chem.
Rev. 2002, 102, 2227–2302.
S. E. Denmark, Y. Fan, J. Am. Chem. Soc. 2002, 124, 4233–
4235.
Excellent review about nonlinear effects: H. Kagan, C. Girard,
Angew. Chem. 1998, 110, 3088–3127; Angew. Chem. Int. Ed.
1998, 37, 2922–2959.
[1] Most recent and comprehensive reviews: a) C. Schneider, Syn-
thesis 2006, 3919–3944; b) I. M. Pastor, M. Yus, Curr. Org.
Chem. 2005, 9, 1–29.
[2] a) H. Yamashita, Bull. Chem. Soc. Jpn. 1988, 61, 1213–1220;
b) M. Hayashi, K. Kohmura, N. Oguni, Synlett 1991, 774–776;
c) W. A. Nugent, J. Am. Chem. Soc. 1992, 114, 2768–2769; d)
L. E. Martinez, J. L. Leighton, D. H. Carsten, E. N. Jacobsen,
J. Am. Chem. Soc. 1995, 117, 5897–5898; e) R. G. Konsler, J.
Karl, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120, 10780–
10781; f) H. Adolfsson, C. Moberg, Tetrahedron: Asymmetry
1995, 6, 2023–2031.
[3] a) X. L. Hou, J. Wu, L. X. Dai, L. J. Xia, M. H. Tang, Tetrahe-
dron: Asymmetry 1998, 9, 1747–1752; b) S. Sagawa, H. Abe, Y.
Hase, T. Inaba, J. Org. Chem. 1999, 64, 4962–4965; c) A. Sek-
ine, T. Ohshima, M. Shibasaki, Tetrahedron 2002, 58, 75–82;
d) S. Azoulay, K. Manabe, S. Kobayashi, Org. Lett. 2005, 7,
4593–4595; e) for a Bi(OTf)3-bipyridine-catalyzed aminolysis
of meso-epoxides see:C. Ogawa, S. Azoulay, S. Kobayashi, Het-
erocycles 2005, 66, 201–206; f) F. Carree, R. Gil, J. Collin, Org.
Lett. 2005, 7, 1023–1026; F. Carree, R. Gil, J. Collin, Tetrahe-
dron Lett. 2004, 45, 7749–7751; g) R. V. Jasra, R. I. Kureshy,
S. Singh, N. H. Khan, S. H. R. Abdi, E. Suresh, Eur. J. Org.
Chem. 2006, 1303–1309; ; R. I. Kureshy, S. Singh, N. Khan,
[12]
[13]
[14]
[15]
[16]
A. J. Manusco, D. Swern, Synthesis 1981, 165–184.
2326
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2318–2327

Enantioselective Alcoholysis of meso-Epoxides
FULL PAPER
[17] a) R. Johansson, B. Samuelsson, J. Chem. Soc., Perkin Trans.
1 1984, 2371; b) G. I. Georg, P. M. Mashava, E. Akgün, M. W.
Milstead, Tetrahedron Lett. 1991, 32, 3151–3154.
[18] S. Ishikawa, T. Hamada, K. Manabe, S. Kobayashi, J. Am.
Chem. Soc. 2004, 126, 12236–12237.
[19] H. Shechter, B. K. Ravi Shankar, Tetrahedron Lett. 1982, 23,
2277–2280.
[20] L. Zhao, B. Han, Z. Huang, M. Miller, H. Huang, D. Malash-
ock, Z. Zhu, A. Milan, D. E. Robertson, D. P. Weiner, M. J.
Burk, J. Am. Chem. Soc. 2004, 126, 11156–11157.
[21] K. Tomioka, A. Iida, M. Kanai, M. Mizuno, Tetrahedron 1997,
53, 10699–10708.
[22] J. Aube, C. J. Mossman, S. Dickey, Tetrahedron 1992, 48, 9819–
9826.
[23] S. Kobayashi, M. Shiro, S. Nagayama, S. Ishikawa, K. Manabe,
T. Hamada, J. Am. Chem. Soc. 2003, 125, 2989–2996.
[24] K. B. Sharpless, Z.-M. Wang, J. Org. Chem. 1994, 59, 8302–
8303.
[25] H. Hönig, P. Seufer-Wasserthal, Synthesis 1990, 1137–1140.
[26] S. C. Jha, N. N. Joshi, J. Org. Chem. 2002, 67, 3897–3899.
[27] S. Ishikawa, T. Hamada, K. Manabe, S. Kobayashi, Synthesis
2005, 2176–2182.
Received: December 19, 2006
Published Online: March 14, 2007
Eur. J. Org. Chem. 2007, 2318–2327
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2327