Scandium-bipyridine-catalyzed enantioselective aminolysis of meso-epoxides

Article abstract of DOI:10.1002/chem.200601307

The scandium-bipyridine-catalyzed enantioselective addition of anilines and O-alkyl hydroxylamines to meso-epoxides has been optimized and extended to a broad range of epoxides and amines. Whereas aromatic meso-epoxides generally furnished the corresponding 1.2-amino alcohols in Excellent enantioselectivities, aliphatic meso-epoxides only gave rise to moderate enantioselectivities in the aminolysis. The catalyst loading may be lowered to just 5 mol% with only marginal effects on yield and enantioselectivity. A strong positive nonlinear effect has been observed, pointing to aggregation phenomena of the catalyst.

Full text of DOI:10.1002/chem.200601307

FULL PAPER
DOI: 10.1002/chem.200601307
Scandium–Bipyridine-Catalyzed Enantioselective Aminolysis of meso-
Epoxides
[
a]
Enzo Mai and Christoph Schneider*
Abstract: The scandium–bipyridine-
catalyzed enantioselective addition of
anilines and O-alkyl hydroxylamines to
meso-epoxides has been optimized and
extended to a broad range of epoxides
and amines. Whereas aromatic meso-
epoxides generally furnished the corre-
sponding 1,2-amino alcohols in excel-
lent enantioselectivities, aliphatic meso-
epoxides only gave rise to moderate
enantioselectivities in the aminolysis.
The catalyst loading may be lowered to
just 5 mol% with only marginal effects
on yield and enantioselectivity.
A
strong positive nonlinear effect has
been observed, pointing to aggregation
phenomena of the catalyst.
Keywords:
amino alcohols
·
aminolysis · asymmetric catalysis ·
epoxides · scandium bipyridine
Introduction
sumably because they are able to exert their exceptional
[8,9]
Lewis acidity even in the presence of the amine.
Subsequently, Hou et al. developed a Yb(OTf) -(R)-
3
The catalytic, enantioselective ring opening of meso-epox-
ides is a valuable tool for the synthesis of 1,2-difunctional-
ized fine chemicals in a highly enantiomerically enriched
form. The chiral catalyst, typically a chiral Lewis acid, has
to differentiate between the two enantiotopic carbon atoms
of the epoxide and direct the incoming nucleophile selec-
A
H
R
U
G
BINOL-catalyst (BINOL=2,2’-dihydroxy-1,1’-binaphthyl)
which in combination with a tertiary amine catalyzed the ad-
dition of aniline to cyclohexene oxide in excellent yield and
[
1]
[10]
with 80% ee (ee=enantiomeric excess).
Whereas some
other anilines could be readily employed in this reaction
with comparable success, the substrate scope on the epoxide
part proved to be very narrow. Thus, cyclopentene oxide,
cis-2-butene oxide, and cis-stilbene oxide all gave rise to low
enantioselectivity in the reaction with aniline. Inaba et al.
utilized a chiral titanium catalyst made from equimolar
tively to one of them in a clean S 2-type pathway. In the
N
past, this strategy has been widely employed for the synthe-
[2]
[3]
sis of 1,2-azido alcohols, 1,2-halohydrins, 1,2-cyano alco-
[
4]
[5]
hols, 1,2-diol monoester and monoethers, and 1,2-mer-
capto alcohols, many of which have been obtained thus far
in good to excellent enantioselectivities. Alternatively, chiral
Ti complexes have been employed to reductively open
meso-epoxides to furnish enantiomerically enriched radical
[6]
amounts of Ti(OiPr) and (S)-BINOL (1 mol%) for the ad-
A
H
R
U
G
4
III
dition of benzyl amine to a seven-membered cyclic epoxide
containing a ketal moiety epoxide which proceeded in excel-
[11]
anions, which were then trapped with either hydrogen
lent yield and enantioselectivity.
Again, other epoxides
[7]
donors or alkenes.
failed to yield the products in good enantioselectivity. In a
formal total synthesis of 4-demethoxy daunomycin, Shibasa-
The nucleophilic addition of amines to epoxides catalyzed
by Lewis acids typically suffers from compatibility problems
between the Lewis basic amine and the Lewis acid catalyst
which tend to coordinate to one another irreversibly. A solu-
tion to this problem was first shown in the work of Crotti
ki et al. employed
a
Pr(OiPr) -(R)-BINOL-complex
A
H
R
U
G
3
(10 mol%) for the catalytic enantioselective addition of p-
anisidine to a benzo-annelated cyclohexene oxide and ob-
tained the ring-opened 1,2-amino alcohol in 75% yield and
[12]
III
who found that lanthanide triflates, such as Yb
A
H
R
U
G
50% ee.
Bartoli et al. showed that a Cr salen catalyst
3
effective catalysts for the aminolysis of 1,2-epoxides, pre-
was effective in the aminolysis of cis-stilbene oxide furnish-
ing the 1,2-amino alcohol in good yields and with 80–
[13]
9
0% ee.
Very high enantioselectivities of greater than
[
a] Dipl.-Chem. E. Mai, Prof. Dr. C. Schneider
Institut für Organische Chemie, Universität Leipzig
Johannisallee 29, 04103 Leipzig (Germany)
Fax : (+49)341-973-6599
9
0% ee were reported by Collin et al. for the aminolysis of
III
cyclic meso-epoxides with 10 mol% of the Sm iodo-(S)-
BINOL complex. Kureshy et al. reported the Ti
[14]
[15]
A
C
H
T
R
E
U
N
G
(OiPr) -
4
E-mail: schneider@chemie.uni-leipzig.de
(S)-BINOL-catalyzed aminolysis of cis-stilbene oxide and
Chem. Eur. J. 2007, 13, 2729 – 2741
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2729

cyclohexene oxide with anilines furnishing the correspond-
ing 1,2-amino alcohols in good yields and with moderate
enantioselectivities ranging from 39–78% ee.
Table 1. Influence of the metal triflate in the reactions of 1a and 1b with
aniline.
We have recently discovered the scandium–bipyridine-cat-
[16]
alyzed aminolysis of meso-epoxides. For example, cis-stil-
bene oxide (1a) was ring-opened with N-methylaniline to
furnish 1,2-amino alcohol 3 in 85% yield and with 97% ee
when catalyzed with a chiral catalyst composed of 10 mol%
of Sc(OTf) and 12 mol% of bipyridine 2 (Scheme 1). This
A
C
H
T
R
E
U
N
G
3
Entry Lewis
acid
Yield 4a
ee 4a
[%]
Yield 4b
ee 4b
[%]
[
a]
[b]
[a]
[b]
[%]
[%]
1
2
3
4
5
Sc
(OTf)
Ce(OTf)
Sm
Yb(OTf)
A
H
R
U
G
3
95
82
0
84
80
93
86
n.d.
79
71
99
94
99
97
40
29
10
9
Y
A
H
R
U
G
3
3
3
90
6
[
a] Isolated yield after chromatography. [b] Determined by HPLC on a
chiral Chiralcel OD column.
Scheme 1. Scandium–bipyridine-catalyzed aminolysis of cis-stilbene oxide
1a).
(
ring-opened with only moderate enantioselectivity with the
scandium–bipyridine catalyst at RT, which significantly de-
ligand was introduced into the field of asymmetric catalysis
by Bolm et al. in 1990. Subsequently, Kobayashi et al.
[17]
[18a]
creased with Y(OTf) –bipyridine and was almost lost with
A
H
R
U
G
3
established that just 1 mol% of this scandium–bipyridine
complex with dodecyl sulfate counterions was sufficient for
the aminolysis of epoxides in water and comparable levels
of enantioselectivity were obtained as for the reaction run in
dichloromethane.
We have nowinvestigated this process in more detail and
report here a full account and experimental details of this
work.
the other lanthanide-bipyridine catalysts. On the other hand,
in the reaction of cis-stilbene oxide (1a) with aniline, some
more lanthanide-bipyridine complexes exhibited good to
very good enantioselectivity, for example, the yttrium-, sa-
marium-, and ytterbium-complexes whereas the cerium–bi-
pyridine complex did not give rise to any product formation.
Optimization of solvent: In the related alcoholysis of epox-
[16]
ides which we developed in a parallel study,
we found
that CH Cl was optimal in terms of yield and enantioselec-
2
2
Results and Discussion
tivity.
The use of highly dipolar and coordinating solvents (THF,
Our preliminary experiments had shown that 10 mol% of
the scandium–bipyridine complex effectively catalyzed the
aminolysis of various meso-epoxides with anilines in excel-
lent yields and with up to 97% ee. To further optimize this
process and investigate scope and limitations we decided to
select the reactions of cis-stilbene oxide (1a) as an aromatic
substrate and cyclohexene oxide (1b) as an aliphatic epox-
ide with aniline as model reactions which were carefully in-
vestigated with respect to metal triflate, solvent, tempera-
ture, ligand architecture, and catalyst loading.
DMF, CH CN) resulted in no or very little product forma-
3
tion, whereas nonpolar solvents, such as diethyl ether and
toluene, led to good yields but very lowenantioselectivities
in the ring-opening event. Hence, we undertook a study of
other chlorinated solvents in our model reactions which in-
cluded CHCl and 1,2-dichloroethane under otherwise iden-
3
tical reaction conditions. Inspection of Table 2 clearly re-
veals that CH Cl remained the best solvent in terms of
2
2
yield although comparable albeit slightly lower levels of
Table 2. Optimization of solvent in the reactions of 1a and 1b with anili-
[
a]
Influence of the metal center: As Sc
A
H
R
U
G
ne.
3
with the bipyridine ligand performed very well in the ami-
nolysis of epoxides, we screened selected other rare earth
[b]
[c]
Entry
Epoxide
Solvent
CH Cl
1,2-dichloroethane
CHCl
CH Cl
1,2-dichloroethane
CHCl
Yield [%]
ee [%]
1
2
3
4
5
6
1a
1a
1a
1b
1b
1b
2
2
95
72
73
96
89
79
93
92
91
54
48
40
(
RE) metal triflates in the two model reactions with respect
to their activity and enantioselectivity. All reactions were
conducted with 10 mol% of metal triflates and 12 mol% of
bipyridine ligand 2 in CH Cl as solvent at room tempera-
3
2
2
2
2
3
ture (Table 1). While all metal triflate-bipyridine complexes
exhibited good to excellent catalytic activity in both reac-
tions, the enantioselectivity proved to be very dependent on
the metal triflate employed. Cyclohexene oxide (1b) w as
[
a] Reaction was performed with 10 mol% catalyst at RT (entries 1–3) or
208C (entries 4–6) for 24 h. The amount of aniline was 1 equiv (en-
ꢀ
tries 1–3) or 2 equiv (entries 4–6). [b] Isolated yield after chromatogra-
phy. [c] Determined by HPLC on a chiral Chiralcel OD column.
2730
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2729 – 2741

Aminolysis of meso-Epoxides
FULL PAPER
enantioselectivity were obtained with CHCl and C H Cl in
both reactions.
In the scandium–catalyzed aminolysis of epoxides, the bi-
pyridine ligand 2 was obviously superior to the other chiral
ligands so it was interesting to modify the ligand backbone
at specific sites: first, we were interested to find out if an
enantioselective catalyst required the free hydroxyl groups
in the bipyridine ligand. It turned out that the bis-O-methy-
leted bipyridine 9 formed an active but completely unselec-
tive chiral catalyst, suggesting that additional hydrogen
bonding might be involved in the transition state of the re-
action (Table 3, entry 6). Sec-
3
2
4
2
Optimization of the ligand: In our preliminary experiments,
we had investigated a number of so-called privileged chiral
ligands for the scandium–catalyzed aminolysis of cis-stilbene
oxide (1a) and cyclohexene oxide (1b), for example, bisoxa-
zoline 5, salen 6, pyridine bisoxazoline 7, and bissulfoximine
[
19]
8
.
ondly, we attempted to in-
crease the steric bulk of the
tBu groups at the chiral cen-
ters even further on the as-
sumption that this might also
increase the enantioselectivity
of the reaction. The newchiral
ligands 11 and 12 were pre-
pared along the same synthetic
route which did not exhibit,
however, any further improve-
ment in yield or enantioselec-
tivity (Table 3, entries 8 and 9).
A further point of modifica-
tion concerned the bipyridine
backbone of the ligand. From
crystal structure analyses of
[
18c]
the ScBr –bipyridine
and Y-
com-
3
A
H
R
U
G
3
[
38]
plexes
it was known that
there is a slight distortion be-
tween the two pyridine rings even in the metal complexes of
2. Accordingly, it was interesting to investigate the influence
of this torsion angle on the enantioselectivity of the reac-
tion. Chiral bipyridine 10 carrying two additional ortho
methyl groups in the pyridine rings was synthesized accord-
Scandium complexes composed of Sc(OTf) and bisoxazo-
lines and pyridine bisoxazolines are known in the literature
A
H
R
U
3
[
20a]
and have been employed in Diels–Alder reactions,
syn-
[
20b]
theses of homopropargylic alcohols and dihydrofurans,
[
20c]
[20d]
Nazarov reactions,
1,3-dipolar cycloadditions,
Friedel–
and aldol additions to glyox-
When the ligands 5–8 in combination with
(OTf) were used in our two model reactions, very low
[20e]
[21]
Crafts alkylations of indoles,
ing to a procedure established by Denmark et al. on the
[20f]
ylate esters.
Sc
expectation that they would increase the torsion angle be-
tween the pyridine rings and possibly influence the enantio-
selectivity of the reaction. It turned out, however, that the
ACHTREUNG
3
enantioselectivities were obtained (Table 3, entries 1–4).
Sc(OTf) -ligand 10 complex gave inferior results in both re-
A
H
R
U
G
3
Table 3. Optimization of ligand architecture in the model reactions of
actions: whereas the aminolysis of cis-stilbene oxide (1a)
cis-stilbene oxide (1a) and cyclohexene oxide (1b) with aniline (for li-
gands see structures 5–13).
proceeded with a slightly decreased enantioselectivity of
[
a]
8
6% ee, cyclohexene oxide (1b) was ring-opened with no
Entry Ligand Yield 4a
ee 4a
[%]
Yield 4b
[%]
ee 4b
[%]
enantioselectivity (Table 3, entry 7). The last modification of
the ligand architecture which we undertook concerned the
change from a bipyridine to a tripyridine backbone in ligand
[
b]
[c]
[b]
[c]
[%]
[
d]
1
2
3
4
5
6
7
8
9
1
5
6
7
8
2
93
62
91
–
95
63
89
81
87
60
30
0
86
96
98
71
71
80
93
91
91
93
1
14
18
6
40
0
1
3. Under the assumption of a pentagonal-bipyramidal coor-
22
–
93
0
86
89
92
51
[18c]
dination geometry around the metal center,
this five-co-
ordinate ligand should be easily accommodated in the plane
of a scandium complex. The enantioselectivity obtained with
9
10
11
12
13
0
the Sc(OTf) -ligand 13 complex was, however, lower than
A
H
R
U
G
3
36
29
6
with the parent bipyridine ligand 2 (Table 3, entry 10).
0
Catalyst loading and nonlinear effect: The practicality and
efficiency of a given catalytic process is directly related to
the catalyst loading, which should be as low as possible. To
[
a] Reactions conditions as given in Table 1. [b] Isolated yield after chro-
matography. [c] Determined by HPLC on a chiral Chiralcel OD column.
d] Compound ent-4a.
[
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2731

C. Schneider and E. Mai
explore the threshold of catalytic efficiency, different cata-
lyst loadings between 1 and 10 mol% were investigated in
the reaction of cis-stilbene oxide (1a) and aniline with the
species into catalytically inactive complexes enhance the
proportion of the predominating and catalytically active cat-
alyst enantiomer.
[22]
standard Sc(OTf) –bipyridine 2 complex (Table 4).
A
C
H
T
R
E
U
N
G
3
Scope of the aminolysis: According to the optimized reac-
tion conditions discussed above, meso-epoxides 1 were treat-
ed with aniline (2 equiv) and 10 mol% of the scandium–bi-
pyridine catalyst in dichloromethane, giving rise to a broad
range of 1,2-amino alcohols 4. The results are summarized
in Table 5. In general, aromatic meso-epoxides furnished the
desired 1,2-amino alcohols 4 in good yields (76–95%) and
the highest enantioselectivities (82–97% ee) currently possi-
ble for the aminolysis of meso-epoxides (Table 5, entries 1,
Table 4. Investigation of catalyst loading.
9
–11).
[
a]
[b]
Entry
Catalyst loading [mol%]
Yield [%]
ee [%]
Aliphatic epoxides reacted with aniline in good yields and
1
2
3
4
10
5
2
95
89
92
95
93
90
80
71
only moderate enantioselectivities (entries 2–8). Epoxides
with longer side chains gave better enantioselectivities
(entry 6, 74% ee) compared to cis-butene oxide (1e)
1
(
entry 5, 60% ee), whereas epoxides with b-branched alkyl
side chains gave diminished enantioselectivities (entry 7,
9% ee). Optimal temperatures were found individually for
[
a] Isolated yield after chromatography. [b] Determined by HPLC on a
chiral Chiralcel OD column.
4
every substrate and represent a compromise between reac-
tivity and selectivity.
The reaction with a catalyst loading of 10 mol% provided
the ring-opened 1,2-amino alcohol 4a with 93% ee and in
Further investigation was directed at improving the scope
of the aminolysis of cis-stilbene oxide (1a) and cyclohexene
oxide (1b) with respect to the amines (Table 6). Sterically
hindered anilines led to a further increase in enantioselectiv-
ity. Thus, N-methyl-aniline gave the desired amino alcohol 3
in 97% ee and with 85% yield (entry 1). Also electron-defi-
cient anilines, for example, para-chloro aniline yielded 1,2-
amino alcohol 14 in 94% yield with 95% ee (entry 2). The
ring opening of cis-stilbene oxide (1a) with electron-rich
amines proceeded with slightly lower enantioselectivity at
room temperature which may, however, be compensated by
decreasing the reaction temperature. Thus, the enantioselec-
tivity of the aminolysis with para-anisidine was improved
from 82% ee at RT to 90% at 08C (entry 4). The para-me-
thoxy phenyl group had the additional advantage that it
may be oxidatively cleaved off the product with cerium am-
95% yield (Table 4, entry 1). The catalyst loading may be
lowered to 5 mol% and the enantioselectivity only dropped
slightly to 90% ee (entry 2). A further decrease of catalyst
loading to only 2 mol% led to a visibly lower enantioselec-
tivity (entry 3). With 1 mol% of catalyst, the product was
obtained in 95 and 71% ee (entry 4). Thus, by lowering the
catalyst loading below5 mol%, the enantioselectivity of the
reaction eroded, although catalytic effiency was maintained.
Furthermore, we investigated the relationship between
catalyst ee and product ee (Figure 1) as nonlinear effects
have been observed in many catalytic enantioselective pro-
cesses. Indeed, we found a strong positive nonlinear effect
in the aminolysis of cis-stilbene oxide: with only 25% ligand
ee, the product had 76% ee and with just 56% ee in the
ligand, the product was formed in almost the same enantio-
selectivity as with enantiopure ligand (90 versus 93% ee).
Apparently, aggregation of two or more monomeric catalyst
[13]
monium nitrate.
The desymmetrization of cyclohexene oxide (1b) with
electron-deficient or sterically hindered anilines was not
more selective than with aniline. The amino alcohols 18–21
were obtained in high yield and with moderate enantioselec-
tivities (entries 6–9) The reactions of cyclohexene oxide
with O-benzyl hydroxylamine and benzyl amine proceeded
in good yields but lowenantioselectivities (entries 10–11).
Conclusion
The catalytic, enantioselective ring opening of meso-epox-
ides with amines is an excellent method to furnish valuable,
enantiomerically enriched 1,2-amino alcohols. In this study,
we have developed the scandium–bipyridine-catalyzed ami-
nolysis of meso-epoxides and have optimized this process
with respect to metal, ligand, solvent, catalyst loading, epox-
Figure 1. Relationship between catalyst ee and product ee.
2732
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Chem. Eur. J. 2007, 13, 2729 – 2741

Aminolysis of meso-Epoxides
FULL PAPER
Table 5. Scope of the aminolysis with respect to the epoxide component.
Table 5. (Continued)
[
a]
[b]
[c]
Entry Epoxide Product
T [8C] Yield [%]
ee [%]
1
1
1l
RT
93
92
[
a] The absolute configuration of the products was determined by com-
parison of the rotation values with literature values or by analogy. [b] Iso-
lated yield after chromatography. [c] Determined by HPLC. [d] 48%
starting material recovered.
[
a]
[b]
[c]
Entry Epoxide Product
T [8C] Yield [%]
ee [%]
1
2
3
4
5
6
1a
1b
1c
1d
1e
1 f
RT
ꢀ20
ꢀ20
0
95
96
89
73
92
74
93
ide, and amine components. Aromatic meso-epoxides turned
out to be excellent substrates which were ring-opened with
typically >90% ee, whereas aliphatic meso-epoxides gave
rise to only moderate enantioselectivity. While most reac-
tions were conducted with 10 mol% catalyst, it was shown
that the amount can be reduced to just 5 mol% without sig-
nificant effects on yield and enantioselectivity. A significant
positive nonlinear effect was observed, pointing to aggrega-
tion phenomena of the catalyst.
54
41
10
60
74
Experimental Section
General: All reactions were performed in flame-dried glassware under
an atmosphere of dry nitrogen. The following reaction solvents were dis-
0
tilled from the indicated drying agents: dichloromethane (CaH
2
), THF
, triphenylmethane), diethyl ether (Na, benzophenone), toluene
Na, benzophenone), N,N-dimethylformamide (Acros ACS grade), aceto-
(
(
LiAlH
4
RT
nitrile (Acros ACS grade), chloroform (Acros ACS grade). Diethyl ether,
petroleum ether (b.p. 30–758C), and ethyl acetate for chromatography
were technical grade and distilled from KOH or CaCl
were monitored by TLC on precoated silica gel SIL G/UV254 plates
Machery, Nagel); spots were visualized by treatment with a solution of
vanillin (0.5 g), concd acetic acid (10 mL), and concd H SO (5 mL) in
methanol (90 mL) or molybdophosphoric acid (5 g) in ethanol (250 mL).
Flash column chromatography was performed by using Merck silica gel
2
. All reactions
(
7
8
1g
1h
RT
0
61
49
49
44
2
4
6
0 230–400 mesh. Bipyridine 2 was best prepared according to a new pro-
[
d]
[18b]
tocol developed by Kobayashi.
(Z)-1,2-Di(naphthalen-2-yl)ethene and
(
Z)-1,2-di-m-tolylethene were prepared according to literature proce-
[
23]
dures. All other chemicals were used as received from commercial sup-
1
13
pliers. H and C NMR spectra were recorded with VARIAN Gemini
00 (200 MHz), VARIAN Gemini 300 (300 MHz) spectrometers or an
Bruker Avance DRX 400 (400 MHz) spectrometer in CDCl at 258C
2
3
with TMS as internal standard. IR spectra were obtained with a FTIR
spectrometer (Genesis ATI, Mattson/Unicam). UV spectra were ob-
tained with a Beckmann DU-650 spectrometer. Melting points are uncor-
rected. Optical rotations were measured by using a Polarotronic polarom-
eter (Schmidt & Haensch). HPLC analyses were performed on a JASCO
MD-2010 plus instrument with a chiral stationary-phase column (Chiral-
cel OD purchased from Daicel). Mass spectra were measured at 70 eV
9
1i
RT
RT
76
82
(
EI) with a Finnigan MAT 95 A spectrometer. High-resolution mass
spectra (HRMS; ESI/Na) were measured with a Bruker Daltonics APEX
II FTICR spectrometer.
1
0
1k
91
93
[
24]
2
-Phenylethyltriphenylphosphonium bromide:
2-Phenylethyl bromide
(
4.63 g, 25.0 mmol) and triphenylphosphine (6.56 g, 25.0 mmol) were stir-
red neat at 1308C for 19 h in a sealed flask. The product was obtained as
white solid and used without further purification in the next step.
1
H NMR (200 MHz, CDCl
3
): d=2.98–3.13 (m, 2H; CH
2
), 4.07–4.21 (m,
Chem. Eur. J. 2007, 13, 2729 – 2741
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2733

C. Schneider and E. Mai
Table 6. Scope of the aminolysis with respect to the amine component.
ether (30 mL) and the resulting mixture was stirred for 1 h. After the ad-
dition of phenyl acetaldehyde (0.93 mL, 8.0 mmol), the mixture was stir-
red for 5 h and quenched with water. The mixture was dried over
[
a]
[c]
Entry Epoxide Amine
Product
T
Yield ee [%]
[
b]
[
8C] [%]
4
MgSO , filtered, and evaporated in vacuo. The residue was diluted with
petroleum ether and filtered. The filtrate was concentrated under re-
duced pressure and the crude product was purified by Kugelrohr distilla-
1
2
1a
1a
PhNHCH
3
RT
85
97
tion (1798C/0.5 Torr). The title compound was obtained as a colorless oil
1
(
0.92 g, 55%). H NMR (300 MHz, CDCl
3
): d=3.54 (d, J=5.5 Hz, 4H;
1
3
CH
(
2
), 5.72–5.75 (m, 2H; CH), 7.22–7.35 ppm (m, 10H; ArH); C NMR
): d=33.69, 126.1, 128.5, 128.6, 129.2, 140.9 ppm.
75 MHz, CDCl
3
[24]
4
-Cl-
2-Methylbutyltriphenylphosphonium bromide: 3-Methylbutyl bromide
(3.77 g, 25.0 mmol) and triphenylphosphine (6.56 g, 25.0 mmol) were stir-
red at 1008C for 24 h in a sealed flask. The product was obtained as a
RT
94
95
PhNH
2
2
white solid and used without further purification in the next step.
1
H NMR (200 MHz, CDCl
3
): d=0.97 (d, J=6.5 Hz, 6H; CH
3
), 1.44–1.55
),
): d=
4
-Me-
(
7
2
m, 2H; CH ), 2.01 (sept, J=6.5 Hz, 1H; CH), 3.69–3.79 (m, 2H; CH
2
2
3
4
5
1a
1a
1a
RT
RT
RT
93
93
75
87
82 (90)
86
PhNH
31
.70–7.89 ppm (m, 15H; ArH); P NMR (121 MHz, CDCl
6.18 ppm.
3
[
27]
cis-2,7-Dimethyl-4-octene:
A solution of NaHMDS in THF (2m,
1
1.0 mL) was added dropwise by syringe to a stirred suspension of 2-
4
-MeO-
[
d]
methylbutyltriphenylphosphonium bromide (8.27 g, 20.0 mmol) in diethyl
ether (30 mL), and the resulting mixture was stirred for 1.5 h. After the
addition of 3-methylbutanal (2.2 mL, 20.0 mmol), the mixture was stirred
PhNH
2
4
for 2 h and quenched with water. The mixture was dried over MgSO , fil-
tered, and concentred under reduced pressure. The residue was diluted
with petroleum ether and filtered. The filtrate was concentrated under
reduced pressure and the crude product was purified by Kugelrohr distil-
BnONH
2
lation (808C/30 mbar). The title compound was obtained as colorless oil
1
(
2.64 g, 94%). H NMR (300 MHz, CDCl
3
): d=0.89 (d, J=6.5 Hz, 12H;
), 5.39–
): d=22.41, 28.73,
6
1b
PhNHCH
3
RT
92
30
3 2
CH ), 1.59 (sept, J=6.5 Hz, 2H; CH), 1.89–1.93 (m, 4H; CH
.42 ppm (m, 2H; CH); C NMR (75 MHz, CDCl
6.46, 129.3 ppm.
1
3
5
3
3
Epoxidation of the olefins (general procedure I): Alkene (1 equiv) was
added to a stirred solution of mCPBA (mCPBA=meta-chloroperbenzoic
acid, 2.2 equiv) in dichloromethane at 08C. The reaction mixture was stir-
red overnight at RT. The white precipitate was sucked off and the organ-
ic layer was concentrated under reduced pressure. The concentrated reac-
4
-Cl-
7
8
1b
1b
ꢀ20
ꢀ10
91
89
43
52
PhNH
2
tion mixture was diluted with saturated NaHCO
extracted with diethyl ether (4”30 mL). The combined organic layers
were washed with brine (30 mL), dried over MgSO , and filtered. The
3
solution (70 mL) and
4
-Me-
PhNH
2
4
solvents were evaporated under reduced pressure. The residue was puri-
fied by flash chromatography over silica gel or by distillation.
[
28]
4
-MeO-
cis-Stilbene oxide
ACHTREUNG
(1a): Following general procedure I, cis-stilbene
9
1
1
1b
1b
1b
ꢀ20
ꢀ20
RT
83
85
92
48
26
10
PhNH
2
(2.02 g, 11.2 mmol) was treated with mCPBA (4.25 g, 24.6 mmol). Flash
chromatography (diethyl ether/petroleum ether 1:19) afforded 1a as a
colorless liquid (2.09 g, 95%) which solidified on standing. M.p. 37–388C;
1
H NMR (200 MHz, CDCl
3
): d=4.37 (s, 2H; CH), 7.18 ppm (s, 10H;
): d=59.88, 127.0, 127.6, 127.9,
1
3
0
1
BnONH
2
ArH); C NMR (50 MHz, CDCl
3
1
34.5 ppm.
[
29]
cis-Cycloheptene oxide (1d): Following general procedure I, cyclohep-
tene (1.20 mL, 10.0 mmol) was treated with mCPBA (3.97 g, 22.0 mmol).
Flash chromatography (diethyl ether/pentane 1:9) afforded 1d as a color-
[
e]
BnNH
2
1
less liquid (673 mg, 62%). H NMR (300 MHz, CDCl
3
): d=1.37–1.65 (m,
), 3.05–3.10 ppm (m, 2H; CH);
): d=24.60, 29.17, 31.18, 56.21 ppm.
6
2 2
H; CH ), 1.84–1.96 (m, 4H; CH
1
3
C NMR (50 MHz, CDCl
3
[
a] The absolute configuration of the products was determined by com-
[30]
cis-4-Octene oxide (1 f): cis-4-Octene (0.99 g, 8.80 mmol) was added to
a stirred solution of mCPBA (3.97 g, 22.0 mmol) in dichloromethane
parison of the rotation values with literature values or by analogy. [b] Iso-
lated yield after chromatography. [c] Determined by HPLC. [d] Values in
brackets refer to reactions at 08C. [e] Determined after conversion into
the Mosher ester.
(
50 mL) at RT. The reaction mixture was stirred overnight at RT. The
white precipitate was sucked off and the organic layer was concentrated
under reduced pressure. The concentrated reaction mixture was diluted
with saturated NaHCO
3
solution (70 mL) and extracted with diethyl
ether (4”30 mL). The combined organic layers were dried over MgSO
and filtered. The solvents were evaporated under reduced pressure. Ku-
4
2
H; CH
2
), 7.13–7.30 (m, 5H; ArH), 7.62–7.90 ppm (m, 15H; ArH);
3
1
P NMR (121 MHz, CDCl ): d=25.30 ppm.
3
gelrohr distillation (958C/60 mbar) afforded 1 f as a colorless liquid
[
25,26]
1
cis-1,4-Diphenyl-2-butene:
0.0 mL) was added dropwise by syringe to a stirred suspension of 2-phe-
nylethyltriphenylphosphonium bromide (4.47 g, 10.0 mmol) in diethyl
A solution of KHMDS in toluene (0.5m,
(471 mg, 46%). H NMR (300 MHz, CDCl
3
): d=0.98 (t, J=7.0 Hz, 6H;
1
3
2
CH
3
), 1.43–1.58 (m, 8H; CH
2
), 2.88–2.94 ppm (m, 2H; CH); C NMR
(50 MHz, CDCl
3
): d=14.02, 19.87, 29.82, 56.99 ppm.
2734
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2729 – 2741

Aminolysis of meso-Epoxides
FULL PAPER
cis-2,7-Dimethyl-4-octene oxide (1g): Following general procedure I, cis-
dride (22 mg, 0.92 mmol) in THF (2 mL) and the solution was stirred at
RT. Methyl iodide (0.18 g, 1.30 mmol) was added after 1 h and the reac-
tion quenched with water (2 mL) after stirring overnight at RT. The
layers were separated and the aqueous layer was extracted with diethyl
ether (4”4mL). The combined organic layers were dried over MgSO4,
filtered, and concentrated under reduced pressure. The title compound
was obtained by flash chromatography over silica gel (diethyl ether/pe-
troleum ether 1:15) as white crystals (77 mg, 72%). M.p. 161–1628C;
2
,7-dimethyl-4-octene (1.40 g, 10.0 mmol) was treated with mCPBA
3.80 g, 22.0 mmol). Flash chromatography over silica gel (diethyl ether/
petroleum ether 1:19) afforded 1g as a colorless liquid (813 mg, 52%).
(
1
H NMR (200 MHz, CDCl
J=6.5 Hz, 6H; CH ), 1.32–1.48 (m, 4H; CH
CH), 2.91–2.97 ppm (m, 2H; CH); C NMR (75 MHz, CDCl
3
): d=0.97 (d, J=6.5 Hz, 6H; CH
3
), 0.99 (d,
3
2
), 1.81 (sept, J=6.5 Hz, 2H;
1
3
3
): d=22.57,
2
2.89, 26.72, 36.74, 55.72 ppm.
2
3
1
[
26]
[a] =+150.38 (c=1.1 in CH Cl ); H NMR (300 MHz, CDCl ): d=0.97
cis-2,3-Dibenzyloxirane
(1h):
1,4-Diphenyl-2-butene
(842 mg,
D
2
2
3
(
s, 18H; C
A
H
R
U
G
3
)
3
), 3.27 (s, 6H; CH
3
), 4.07 (s, 2H; CHꢀOMe), 7.38 (dd,
4
8
.00 mmol) was added to
.80 mmol) in dichloromethane (20 mL) at RT. The reaction mixture was
a stirred solution of mCPBA (1.52 g,
J=7.5, 1.3 Hz, 2H; ArH), 7.79 (dd, J=7.8, 7.5 Hz, 2H; ArH), 8.25 ppm
1
3
stirred overnight at RT. The white precipitate was sucked off and the or-
ganic layer was concentrated under reduced pressure. The concentrated
(dd, J=7.8, 1.3 Hz, 2H; ArH); C NMR (75 MHz, CDCl
3
): d=26.56,
35.82, 58.09, 93.13, 119.8, 121.9, 136.9, 155.4, 160.1 ppm; IR (KBr): n˜ =
ꢀ
1
reaction mixture was diluted with saturated NaHCO
and extracted with diethyl ether (4”25 mL). The combined organic
layers were dried over MgSO and filtered. The solvents were evaporated
3
solution (50 mL)
3448, 2969, 2863, 1571, 1436, 1392, 1101, 814, 777, 673, 631 cm ; MS
+
(70 eV, EI): m/z (%)=356 (10) [M] , 341 (5), 300 (43), 285 (47), 253
(100), 227 (15), 213 (8), 57 (8).
4
[
21]
under reduced pressure. The residue was purified by flash chromatogra-
phy over silica gel (diethyl ether/petroleum ether 1:19). The title com-
[2-(5-Methylpyridyl)]-2,2-dimethylpropanon:
A stirred solution of 2-
bromo-5-methylpyridine (4.30 g, 25.0 mmol) in diethyl ether was cooled
to ꢀ788C, then a solution of nBuLi in hexane (2.5 m, 11.0 mL) was
added slowly over 15 min. The resulting solution was stirred for 30 min at
ꢀ788C before pivalonitrile (3.30 mL, 30.0 mmol) was added. The mixture
was stirred for 1 h at ꢀ788C and then warmed up to RT. Upon adding
pound was obtained as a white solid (549 mg, 61%). M.p. 30–328C;
1
H NMR (300 MHz, CDCl
H; CH), 7.27–7.38 ppm (m, 10H; ArH); C NMR (75 MHz, CDCl
d=34.44, 57.48, 126.6, 128.6, 128.8, 137.7 ppm.
3
): d=2.94–3.09 (m, 4H; CH
2
), 3.27–3.30 (m,
1
3
2
3
):
[
31]
cis-1,2-Bis-(2’-naphthyl)ethane oxide
yl)ethene (135 mg, 0.48 mmol) was added to a stirred solution of mCPBA
183 mg, 1.06 mmol) in dichloromethane at RT. The reaction mixture was
(1i): (Z)-1,2-Di(naphthalen-2-
2 4
H SO (2n, 90 mL), the mixture was stirred at 608C for 2 h. The layers
were separated and the aqueous layer was extracted with diethyl ether
(3”25 mL). The combined organic layers were washed with saturated
(
stirred overnight at RT. The white precipitate was sucked off and the or-
ganic layer was concentrated under reduced pressure. The concentrated
2 3 4
aqueous Na CO solution, dried over MgSO , filtered, and concentrated
under reduced pressure. Purification of the crude product by flash chro-
reaction mixture was diluted with saturated NaHCO
tracted with diethyl ether. The combined organic layers were dried over
MgSO and filtered. The solvents were evaporated under reduced pres-
sure. The residue was purified by flash chromatography over silica gel
diethyl ether/petroleum ether 1:19). The title compound was obtained as
3
solution and ex-
matography over silica gel (ethyl acetate/petroleum ether 1:10) afforded
1
3.97 g (89%) of the title compound as
(200 MHz, CDCl ): d=1.45 (s, 9H; CH ), 2.38 (s, 3H; CH
(m, 1H; ArH), 7.83 (d, J=8.0 Hz, 1H; ArH), 8.43–8.44 ppm (m, 1H;
a
colorless oil. H NMR
3
), 7.55–7.60
4
3
3
1
3
(
ArH); C NMR (50 MHz, CDCl
3
): d=18.54, 27.49, 44.03, 123.3, 135.9,
1
a
white solid (90 mg, 63%). M.p. 107–1098C; H NMR (300 MHz,
CDCl ): d=4.60 (s, 2H; CH), 7.29 (dd, J=8.5, 1.5 Hz, 2H; ArH), 7.34–
.42 (m, 4H; ArH), 7.60 (d, J=8.5 Hz, 2H; ArH), 7.67–7.73 (m, 4H;
136.9, 148.1, 152.2 ppm; IR (film): n˜ =2955, 2928, 2868, 1682, 1566, 1481,
ꢀ
1
3
3
1297, 1199, 964, 849 cm ; UV/Vis (CH CN): lmax (lg e)=205 (3.691), 238
+
7
(3.916), 269 nm (3.678); MS (70 eV, EI): m/z (%): 177 (7) [M] , 162 (8),
1
3
ArH), 7.78 ppm (s, 2H; ArH); C NMR (75 MHz, CDCl
24.4, 125.8, 126.0, 126.2, 127.5, 127.6, 127.8, 131.8, 132.8 ppm.
cis-1,2-Bis-(m-tolyl)ethane oxide (1k): (Z)-1,2-Di-m-tolylethene (275 mg,
3
): d=60.24,
149 (6), 120 (7), 93 (100), 65 (15), 41 (15).
1
[21]
(
R)-1-[2-(5-Methylpyridyl)]-2,2-dimethylpropanol:
A mixture of (ꢀ)-
DipCl (DipCl = B-chlorodiisopinocampheylborane, 8.30 g, 26.0 mmol)
and the pyridyl ketone prepared above (3.10 g, 17.0 mmol) was stirred at
RT for 6 d. The mixture was dissolved in diethyl ether (80 mL), followed
by the addition of diethanolamine (5.80 g 55.0 mmol), and the resulting
mixture was stirred overnight at RT. The white precipitate was filtered
1
2
.32 mmol) was added to
.90 mmol) in dichloromethane at RT. The reaction mixture was stirred
a stirred solution of mCPBA (501 mg,
overnight at RT. The white precipitate was sucked off and the organic
layer was concentrated under reduced pressure. The concentrated reac-
tion mixture was diluted with saturated NaHCO
3
solution and extracted
through a pad of Celite and the filtrate was dried over MgSO . After fil-
4
with diethyl ether. The combined organic layers were dried over MgSO
4
tration and concentration under reduced pressure, the crude product was
and filtered. The solvents were evaporated under reduced pressure. The
residue was purified by flash chromatography over silica gel (diethyl
purified by flash chromatography over silica gel (ethyl acetate/petroleum
ether 1:5) affording 2.38 g (76%) of the title compound as a colorless oil.
2
4
1
ether/petroleum ether 1:19). The title compound was obtained as color-
[a] =+32.48 (c=1.03 in EtOH); H NMR (300 MHz, CDCl ): d=0.91
D
3
1
less oil (549 mg, 61%). H NMR (300 MHz, CDCl
3
): d=2.26 (s, 6H;
(s, 9H; C
ACHTREUNG
3
3
3
1
3
CH
3
), 4.33 (s, 2H; CH), 6.97–7.11 ppm (m, 8H; ArH); C NMR
7.08 (d, J=6.0 Hz, 1H; ArH), 7.42–7.45 (m, 1H; ArH), 8.37 ppm (s, 1H;
1
3
(
75 MHz, CDCl ): d=21.61, 60.16, 124.2, 127.9, 128.0, 128.5, 134.6,
3
ArH); C NMR (75 MHz, CDCl ): d=18.05, 25.84, 36.22, 80.07, 122.2,
3
1
37.6 ppm.
131.6, 136.1, 148.1, 157.0 ppm; IR (film): n˜ =3224, 2953, 2868, 1605, 1572,
[
32]
cis-1,2-Bis-(p-chlorophenyl)ethane oxide
(1l): A solution of tris(die-
1486, 1463, 1421, 1385, 1364, 1346, 1306, 1239, 1210, 1182, 1132, 1075,
ꢀ
1
thylamino)phosphine (4.00 mL, 15.0 mmol) in benzene/hexane (5 mL)
was added by a syringe pump to a cooled solution of p-chlorobenzalde-
hyde (5.12 g, 36.4 mmol) in benzene (2 mL) over 2 h. The reaction mix-
ture was stirred for 24 h at RT. The reaction mixture was poured onto
water (75 mL) and extracted with dichloromethane (3”75 mL). The com-
1036, 1017, 910, 835 cm ; UV/Vis (CH CN): lmax (lg e)=215 (3.744),
3
+
266 nm (3.690); MS (ESI): m/z: 179.9 [M+H] .
(R)-5-Methyl-2-(1-tert-butyldimethylsilyloxy-2,2-dimethylpropyl)pyri-
dine: TBSOTf (TBSOTF=tert-butyldimethylsilyl trifluoromethanesulfo-
nate, 4.60 mL, 20.0 mmol) and 2,6-lutidine (3.10 mL, 27.0 mmol) were
added to a stirred solution of the pyridyl carbinol prepared above (2.38 g,
4
bined organic layers were dried over MgSO , filtered, and concentrated
under reduced pressure. The cis and trans epoxide were separated by
flash chromatography over silca gel (diethyl ether/petroleum ether 1:19).
The title compound was obtained as white solid (0.61 g, 15%) after pu-
1
3.3 mmol) in dichloromethane (30 mL) at 08C. The resulting solution
was stirred for 2.5 h at RT and was then quenched with saturated aque-
ous NaHCO solution (40 mL). The layers were separated and the aque-
ous layer was extracted with dichloromethane (3”20 mL). The combined
organic layers were dried over MgSO and filtered. The residue obtained
3
rification in vacuo (1008C/10 Torr) and by a second flash chromatography
1
(
diethyl ether/petroleum ether 1:19). M.p. 90–938C; H NMR (300 MHz,
4
CDCl
J=8.5 Hz, 4H; ArH); C NMR (75 MHz, CDCl
28.2, 132.5, 133.6 ppm.
(R,R)-6,6’-Bis(1-methoxy-2,2-dimethylpropyl)-2,2’-bipyridine
pyridine 2 (0.10 g, 0.30 mmol) was added to a suspension of sodium hy-
3
): d=4.32 (s, 2H; CH), 7.08 (d, J=8.5 Hz, 4H; ArH), 7.17 ppm (d,
after removal of the solvent was purified by flash chromatography over
silica gel (ethyl acetate/petroleum ether 1:9). The title compound was ob-
1
3
3
): d=59.11, 128.1,
1
27
D
tained as a colorless oil (3.82 g, 98%). [a] =+67.28 (c=1.07 in CH
2
Cl
2
);
[
17]
1
A
C
H
T
R
E
U
N
G
(9): Bi-
H NMR (300 MHz, CDCl
3
): d=ꢀ0.34 (s, 3H; SiCH
), 0.89 (s, 9H; C(CH
3
), 0.02 (s, 3H;
SiCH
3
), 0.88 (s, 9H; SiC(CH
A
H
R
U
3
)
3
A
H
R
N
3
)
3
), 2.31 (s, 3H;
Chem. Eur. J. 2007, 13, 2729 – 2741
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2735

C. Schneider and E. Mai
CH
3
), 4.43 (s, 1H; CH), 7.31 (d, J=6.0 Hz, 1H; ArH), 7.43 (dd, J=8.0,
solved in wet THF (10 mL). After addition of acetic acid (1 mL) and Zn
powder (327 mg, 5.00 mmol), the mixture was refluxed for 8 h. Ammonia
solution (25%, 30 mL) was added, the layers were separated, and the
aqueous layer was extracted with dichloromethane (4”15 mL). The com-
1
3
2
.0 Hz, 1H; ArH), 8.29 ppm (m, 1H; ArH); C NMR (75 MHz, CDCl ):
3
d=ꢀ5.32, ꢀ4.74, 18.08, 18.13, 25.86, 26.03, 36.24, 83.43, 121.9, 131.0,
1
1
2
36.0, 147.7, 160.0 ppm; IR (film): n˜ =2955, 2930, 2858, 1484, 1472, 1462,
254, 1081, 875, 836, 778 cm ; UV/Vis (CH
66 nm (3.594); MS (70 eV, EI): m/z (%): 293 (<1) [M] , 278 (9), 236
ꢀ
1
CN): lmax (lg e)=211 (3.923),
4
bined organic layers were washed with brine (50 mL), dried over MgSO ,
3
+
filtered, and concentrated under reduced pressure. The crude product
was purified by flash chromatography over silica gel (ethyl acetate/petro-
leum ether 1:2) and recrystallisation from hexane/toluene. The title com-
pound was obtained as white crystals (90 mg, 51%). M.p. 107–1108C;
(
100), 179 (62), 146 (10), 111 (20), 73 (71); elemental analysis calcd (%)
for C17 31NOSi (293.52): C 69.56, H 10.65; found: C 69.18, H 10.25.
R)-5-Methyl-2-(1-tert-butyldimethylsilyloxy-2,2-dimethylpropyl)pyridine
N-oxide: The silylated pyridyl carbinol prepared above (3.52 g,
2.0 mmol) was dissolved in dichloromethane (40 mL), treated with
H
(
2
D
4
1
[
(
8
(
1
8
(
a] =+12.08 (c=1.86 in CH
2
Cl
), 2.16 (s, 6H; CH ), 4.38 (s, 4H; CH and OH), 7.15 (d, J=
.0 Hz, 2H; ArH), 7.59 ppm (d, J=8.0 Hz, 2H; ArH); C NMR
): d=18.51, 25.93, 36.34, 79.92, 121.9, 130.5, 138.1, 155.2,
56.2 ppm; IR (KBr): n˜ =3456, 2954, 2864, 1452, 1394, 1334, 1070, 1014,
2 3
); H NMR (200 MHz, CDCl ): d=0.93
s, 18H; CH
3
3
1
1
3
mCPBA (3.12 g, 18.0 mmol) at 08C and stirred overnight at RT. The mix-
ture was quenched with cold 40% aqueous KOH solution and stirred for
50 MHz, CDCl
3
1
h. The layers were separated and the aqueous layer was extracted with
dichloromethane (4”20 mL). The combined organic layers were dried
over MgSO , filtered, and the solvent was removed under reduced pres-
sure. Purification of the crude product by flash chromatography over
silica gel (CH Cl /MeOH 20:1) afforded the title compound as colorless
oil (3.53 g, 95%). [a]D =+17.08 (c=1.14 in CH
CDCl ), 0.07 (s, 3H; SiCH
): d=ꢀ0.29 (s, 3H; SiCH
(CH ), 0.96 (s, 9H; C(CH ), 2.28 (s, 3H; CH ), 5.41 (s, 1H; CH), 7.04
d, J=8.0 Hz, 1H; ArH), 7.34 (d, J=8.0 Hz, 1H; ArH), 8.04 ppm (s, 1H;
ꢀ
1
35 cm ; UV/Vis (CH CN): lmax (lg e)=205 (4.072), 275 nm (3.913); MS
ESI): m/z: 767.5 [2M+MeOH+Na] , 735.5 [2M+Na] , 411.3
M+MeOH+Na] , 379.2 [M+Na] , 357.3 [M+H] ; HRMS (ESI): calcd
for C22
(R)-1-(6-Bromopyridin-2-yl)-2,2,3-trimethylbutanol: A stirred solution of
,6-dibromopyridine (6.72 g, 3.00 mmol) in diethyl ether (20 mL) was
3
+
+
4
+ + +
[
+
2 2
H32NaN O : 379.23560; found: 379.23586 [M+Na] .
2
2
2
7
1
2
Cl
2
); H NMR (200 MHz,
), 0.88 (s, 9H; SiC-
2
3
3
3
cooled to ꢀ788C, then a solution of nBuLi in hexane (2.5m, 12.3 mL)
was added dropwise over 15 min and stirred for 1.5 h at ꢀ788C. A solu-
tion of CuI (2.67 g, 14.0 mmol) and dimethylsulfide (12 mL) in diethyl
ether (20 mL) was added to the resulting mixture. After the reaction mix-
ture had been stirred for 1 h at ꢀ788C, 2,2,3-trimethylbutane acid chlo-
A
C
H
T
R
E
U
N
G
3
)
3
A
C
H
T
R
E
U
N
G
3
)
3
3
(
1
3
ArH); C NMR (50 MHz, CDCl
3
): d=ꢀ5.38, ꢀ5.21, 17.91, 17.95, 25.46,
2
2
5.76, 37.72, 72.56, 125.6, 125.9, 134.1, 139.0, 151.0 ppm; IR (film): n˜ =
954, 2929, 2858, 1472, 1462, 1385, 1259, 1075, 1029, 866, 841, 777 cm
ꢀ1
;
[
33]
ride was added. The mixture was stirred for 2 h at ꢀ788C and then
UV/Vis (CH
EI): m/z (%): 309 (<1) [M] , 293 (2), 278 (4), 252 (20), 236 (100), 179
339), 73 (54); HRMS (ESI): calcd for 31NNaO Si: 332.20163;
3
CN): lmax (lg e)=224 (4.422), 271 nm (4.270); MS (70 eV,
+
brought up to RT. The mixture was quenched with saturated aqueous
NH
ed. The aqueous layer was extracted with diethyl ether (3”20 mL). The
combined organic layers were washed with water, dried over MgSO , and
4
Cl solution (40 mL), stirred for 15 min, then the layers were separat-
(
C
17
H
2
+
found: 332.20177 [M+Na] .
(R,R)-3,3’-Bismethyl-6,6’-bis(1-tert-butyldimethylsilyloxy-2,2-dimethyl-
propyl)-2,2’-bipyridine bis-N-oxide: solution of nBuLi in hexane
2.5 m, 2.00 mL) was added to a solution of 2,2,6,6-tetramethylpiperidine
0.85 mL, 5.00 mmol) in THF (5 mL) and the resulting mixture was stir-
4
ACHTREUNG
filtered. After evaporation of the solvent, the residue was separated by
flash chromatography (diethyl ether/petroleum ether 1:19). The semisolid
was dissolved in hot hexane and filtered after cooling. The filtrate was
concentrated under reduced pressure and yielded 1-(6-bromopyridin-2-
yl)-2,2,3-trimethylbutanon as a colorless oil (2.62 g, 75%). The pyridyl
A
(
(
red for 3 h at 08C. This freshly prepared LiTMP (TMP=2,2,6,6-tetrame-
thylpiperidene) solution was added to a solution of the N-oxide prepared
above (1.55 g, 5.00 mmol) in diethyl ether (10 mL) at ꢀ788C. After the
reaction mixture had been stirred for 16 h at ꢀ788C, a solution of iodine
ketone was then enantioselectively hydrogenated according to the proto-
[18b]
col described by Kobayashi
and yielded the title compound as a color-
25
1
less oil (847 mg, 53%). [a]D =ꢀ32.88 (c=1.21 in CHCl
3
); H NMR
), 0.92 (d, J=
3 3
.0 Hz, 3H; CH ), 0.95 (d, J=7.0 Hz, 3H; CH ), 1.89 (sept, J=7.0 Hz,
(
0.63 g, 2.5 mmol) in THF was slowly added to the resulting deep-red
(
3 3 3
400 MHz, CDCl ): d=0.67 (s, 3H; CH ), 0.77 (s, 3H; CH
mixture at ꢀ788C. The mixture was further stirred at ꢀ788C for 2 h, then
the cooling bath was removed and the reaction mixture was brought up
to RT and stirred for 2 h. The reaction was quenched with water (5 mL),
followed by saturated aqueous NaHSO
was diluted with aqueous ammonia solution (25 mL) and the layers were
separated. The aqueous layer was extracted with dichloromethane (3”
7
1
7
H; CH), 3.52 (d, J=7.5 Hz, 1H; OH), 4.63 (d, J=7.5 Hz, 1H; CH),
.17 (d, J=7.5 Hz, 1H; ArH), 7.37 (d, J=7.5 Hz, 1H; ArH), 7.49 ppm
dd, J=7.5, 7.5 Hz, 1H; ArH); C NMR (100 MHz, CDCl
solution (5 mL). The mixture
13
3
(
): d=17.54,
3
1
1
1
2
7.59, 18.57, 18.95, 32.70, 40.98, 77.07, 121.7, 126.8, 137.8, 140.6,
62.5 ppm; IR (film): n˜ =3439, 2967, 2876, 1582, 1555, 1467, 1435, 1394,
3
0 mL). The combined organic layers were dried over MgSO
4
, filtered,
ꢀ1
368, 1159, 1123, 1045, 792, 753, 695 cm ; UV/Vis (CH
3
CN): lmax (lg e)=
and the solvents were removed under reduced pressure. Purification of
the crude product by flash chromatography over silica gel (diethyl ether/
petroleum ether 1:6) afforded the title compound as a pale-yellowsolid
02 (3.762), 210 (3.727), 268 nm (3.539); MS (ESI): m/z (%): 294.0
+
+
[
12
M+Na] , 272.0 [M+H] ; HRMS (ESI): calcd for C H18BrNNaO:
+
2
94.04640; found: 294.04656 [M+Na] .
2
D
7
(
996 mg, 65%). M.p. 67–698C; [a] =ꢀ100.48 (c=1.45 in CH
2 2
Cl );
A
H
R
U
G
3
1
H NMR (200 MHz, CDCl
3
): d=ꢀ0.23 (s, 6H; SiCH
3
), 0.02 (s, 6H;
), 2.05 (s, 6H;
), 5.47 (s, 2H; CH), 7.07 (d, J=8.0 Hz, 2H; ArH), 7.38 ppm (d, J=
(
2.02 g, 7.70 mmol) and zinc powder (137 mg, 2.10 mmol) were added to
SiCH
CH
3
), 0.87 (s, 18H; SiC
A
H
R
U
(CH
3
)
3
A
H
R
N
3 3
), 0.94 (s, 18H; C(CH )
a stirred solution of NiCl
10 mL) heated to 708C. The brown reaction mixture was stirred at 708C
for 1 h followed by addition of pyridyl carbinol prepared above (434 mg,
.60 mmol). After the reaction mixture had been stirred at 708C for 2 h,
the reaction mixture was cooled to RT. Addition of aqueous 5% NH so-
2 2
·6H 0 (451 mg, 1.90 mmol) in degassed DMF
3
(
1
3
8
.0 Hz, 2H; ArH); C NMR (50 MHz, CDCl
3
): d=ꢀ5.50, ꢀ5.10, 17.88,
2
5.75, 27.50, 37.88, 74.56, 118.5, 124.3, 124.4, 140.8, 151.3 ppm; IR (KBr):
1
n˜ =2954, 2858, 1474, 1393, 1365, 1329, 1244, 1080, 1029, 892, 858, 835,
3
ꢀ
1
8
16, 777 cm ; UV/Vis (CH
3
CN): lmax (lg e)=232 (4.556), 270 nm (4.205);
lution (10 mL) resulted in brown precipitation. The whole reaction mix-
ture was extracted with a diethyl ether/dichloromethane 1:2 mixture (5”
+ + +
MS (ESI): m/z: 1255.8 [2M+Na] , 639.4 [M+Na] , 617.4 [M+H] ; ele-
mental analysis calcd (%) for C34
found: C 65.82, H 9.46.
60 2 4 2
H N O Si (617.02): C 66.18, H 9.80;
2
5 mL). The organic layers were concentrated under reduced pressure
and diluted with dichloromethane. The organic layer was first washed
with water (5”25 mL) and second with brine (25 mL). The organic layer
A
C
H
T
R
E
U
N
G
(R,R)-3,3’-Bismethyl-6,6’-bis(1-hydroxy-2,2-dimethylpropyl)-2,2’-bipyri-
dine (10): tetrabutylammonium fluoride solution (1m, 3.0 mL,
.0 mmol) was added to a solution of the bipyridine bis-N-oxide prepared
A
was dried over MgSO and filtered. The solvents were removed under re-
4
3
duced pressure. The yellowcrude product wa s purified by flash chroma-
above (358 mg, 0.50 mmol) in THF (25 mL), and the resulting mixture
was stirred overnight over molecular sieves. The reaction was quenched
with water (10 mL), then the layers were separated and the aqueous
layer was extracted with dichloromethane (3”20 mL). The combined or-
tography over silica gel (ethyl acetate/petroleum ether 1:9!1:6). The
title compound (105 mg, 34%) was obtained after recrystallisation from
2
D
3
hexane/toluene. M.p. 170–1738C [a] =ꢀ49.48 (c=1.03 in CHCl );
3
1
H NMR (200 MHz, CDCl ): d=0.74 (s, 6H; CH ), 0.82 (s, 6H; CH ),
3
3
3
ganic layers were washed with brine (20 mL), dried over MgSO
4
, and fil-
3 3
0.96 (d, J=7.0 Hz, 6H; CH ), 1.0 (d, J=7.0 Hz, 6H; CH ), 1.96 (sept, J=
tered. The solvents were evaporated in vacuo and the residue was dis-
7.0 Hz, 2H; CH), 4.32 (d, J=7.0 Hz, 2H; OH), 4.74 (d, J=7.0 Hz, 2H;
2736
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2729 – 2741

Aminolysis of meso-Epoxides
FULL PAPER
3
D
0
1
CH), 7.23 (d, J=8.0 Hz, 2H; ArH), 7.78 (dd, J=8.0, 8.0 Hz, 2H; ArH),
96%). M.p. 73–758C; [a] =+49.28 (c=1.00 in CH
2
Cl
2
); H NMR
1
3
8
1
1
.30 ppm (d, J=8.0 Hz, 2H; ArH); C NMR (100 MHz, CDCl
3
): d=
(200 MHz, CDCl ): d=ꢀ0.31 (s, 3H, SiCH ), 0.04 (s, 3H, SiCH ), 0.88 (s,
AHCTREUGN ACHTRENUG
3
3
3
7.70, 17.68, 18.75, 19.10, 32.80, 41.03, 77.00, 119.5, 123.2, 136.6, 153.9,
9H; SiC
3 3 3 3
(CH ) ), 0.90 (s, 9H; C(CH ) ), 4.45 (s, 1H; CH), 7.31 (dd, J=
ꢀ
1
59.8 ppm; IR (KBr): n˜ =3406, 2968, 1567, 1434, 1047, 808 cm ; UV/Vis
CN): lmax (lg e)=201 (4.211), 239 (3.783), 289 nm (4.034); MS
8.0, 1.0 Hz, 1H; ArH), 7.39 (dd, J=8.0, 1.0 Hz, 1H; ArH), 7.5 ppm (t,
1
3
(
CH
ESI): m/z (%): 407.3 [M+Na] , 385.3 [M+H] .
-(6-Bromopyridin-2-yl)-2-ethyl-2-methylbutan-1-one: A stirred suspen-
3
J=8.0 Hz, 1H; ArH); C NMR (75 MHz, CDCl ): d=ꢀ5.29, ꢀ4.65,
3
+
+
(
18.02, 25.82, 25.91, 36.37, 82.59, 121.2, 126.0, 137.7, 139.7, 164.9 ppm; IR
1
(film): n˜ =3061, 2957, 2930, 2884, 2858, 1583, 1555, 1471, 1392, 1359,
1259, 1249, 1117, 1073, 876, 777, 701 cm ; UV/Vis (CH CN): lmax (lg e)=
3
+
217 (3.671), 267 nm (3.614); MS (70 eV, EI): m/z (%): 358 (7) [M] , 237
ꢀ
1
sion of 2,6-dibromopyridine (5.00 g, 21.0 mmol) in 100 mL diethyl ether
was cooled to ꢀ788C. Then a solution of nBuLi in hexane (2.5m,
9
.90 mL, 25.0 mmol) was added to this suspension. The clear pale-yellow
(16), 188 (100), 160 (18), 102 (62), 57 (32); HRMS (ESI): calcd for
+
solution was stirred at ꢀ788C for a further 30 min followed by the addi-
tion of 2-ethyl-2-methylbutyronitrile (3.00 g, 25.0 mmol, purity 92%).
The deep-red reaction mixture was stirred at ꢀ788C for 1 h, followed by
C
16
H
29·BrNOSi: 358.11963; found: 358.11976 [M+H] .
A
H
R
U
G
2 4
warming up to RT. After addition of H SO (2n, 90 mL), the pale-yellow
THF (10 mL) was cooled to ꢀ788C, then a solution of nBuLi in hexane
reaction mixture was refluxed at 608C for 2 h. The aqueous phase was ex-
tracted with diethyl ether (3”25 mL). The combined organic layers were
(
2.5 m, 1.44 mL) was added dropwise. The resulting solution was stirred
for 30 min at ꢀ788C before a solution of ZnCl
was added and the mixture warmed to RT over 1 h. Pd
0 mol%) and 2,6-dibromopyridine (720 mg, 3.00 mmol) were added and
the mixture was heated under reflux for 4 h. EDTA/Na CO solution
75 mL) was added, the layers were separated, and the aqueous layer was
extracted with diethyl ether (3”30 mL). The combined organic layers
were dried over MgSO , filtered, and concentrated under reduced pres-
2
in THF (2 m, 7.20 mL)
rinsed with saturated Na
2 3 4
CO solution (25 mL), dried over MgSO and
A
H
E
G
3 4
)
filtered. The solvents were removed under reduced pressure. The title
1
1
compound was obtained as
300 MHz, CDCl ): d=0.76 (t, J=7.5 Hz, 6H), 1.26 (s, 3H), 1.76 (dq, J=
5.0, 7.5 Hz, 2H), 2.28 (dq, J=15.0, 7.5 Hz, 2H), 7.58 (dd, J=8.0, 1.0 Hz,
H), 7.65 (dd, J=8.0, 7.5 Hz, 1 HH), 7.83 ppm (dd, J=7.5, 1.0 Hz, 1H);
a yellow oil (5.50 g, 97%). H NMR
2
3
(
3
(
1
1
4
1
3
C NMR (75 MHz, CDCl
3
): d=8.946, 20.72, 31.14, 52.25, 122.0, 130.5,
sure. The residue which contained a mixture of the title compound and
monocoupled product was dissolved in THF (10 mL) and treated with
1
1
39.0, 139.7, 155.4, 205.0 ppm; IR (film): n˜ =2968, 2936, 2877, 1684, 1569,
ꢀ
1
+
555, 1461, 1427, 1382, 1122 cm ; MS (ESI): m/z: 292.0 [M+Na] , 270.0
nBuLi (2.5 m, 1.44 mL), ZnCl
mol%) following the procedure above. This mixture was refluxed for
4 h and then worked up as described above. The crude product was fil-
2
(2m, 7.20 mL), and Pd
A
H
R
U
G
3 4
(PPh ) (348 mg, 10
+
[
M+H] ; HRMS (ESI): calcd for C12
H
16BrNNaO: 292.03075; found:
+
2
92.03087 [M+Na] .
2
(
R)-1-(6-Bromopyridin-2-yl)-2-ethyl-2-methylbutan-1-ol: The pyridyl
tered over silica gel (diethyl ether/petroleum ether 1: 99). After evapora-
tion of the solvent, the residue was dissolved in THF (10 mL) and treated
with tetrabutylammonium fluoride solution (1m, 18 mL, 18 mmol) for
h. The reaction was quenched with water (20 mL), the layers were sepa-
rated and the aqueous layer was extracted with dichloromethane (3”
0 mL). The combined organic layers were washed with brine (20 mL),
dried over MgSO , and filtered. The solvent was removed under reduced
pressure and flash chromatography (ethyl acetate/petroleum ether 1:3)
afforded the title compound as white crystals (360 mg, 30%), which was
purified by recrystallization (hexane/toluene) (297 mg, 24%). M.p. 203–
Cl ); H NMR (300 MHz, CDCl ):
2 2 3
3 3
d=0.98 (s, 18H; C(CH ) ), 4.45 (s, 4H; CH and OH), 7.23 (d, J=7.5 Hz,
H; ArH), 7.81 (dd, J=7.5, 7.5 Hz, 2H; ArH), 7.95 (dd, J=8.0, 8.0 Hz,
H; ArH), 8.42 (d, J=8.0 Hz, 2H; ArH), 8.52 (d, J=7.5 Hz, 2H; ArH);
C NMR (75 MHz, CDCl ): d=25.91, 36.27, 80.22, 119.7, 120.9, 122.9,
3
ketone prepared above was enantioselectively hydrogenated according to
[
18b]
the protocol described by Kobayashi
and yielded the title compound
after flash chromatography over silica gel (diethyl ether/petroleum ether
4
2
D
5
1
:9) as a colorless oil (2.10 g, 52%). [a] =ꢀ26.48 (c=1.01 in CH
2 2
Cl );
1
3
H NMR (400 MHz, CDCl ): d=0.73 (s, 3H), 0.84 (t, J=7.5 Hz, 3H),
2
0
1
1
.84 (t, J=7.5 Hz, 3H), 1.18–1.34 (m, 3H), 1.55 (dq, J=15.0, 7.5 Hz,
H), 3.56 (d, J=7.5 Hz, 1H), 4.53 (d, J=7.5 Hz, 1H), 7.16 (d, J=7.5 Hz,
4
1
3
H), 7.36 (d, J=8.0, 1HH), 7.48 ppm (dd, J=8.0, 7.5 Hz, 1H); C NMR
): d=7.836, 7.868, 19.31, 26.95, 27.37, 41.07, 76.95,
21.5, 126.5, 137.8, 140.6, 162.3 ppm; IR (film): n˜ =3438, 2965, 2937, 2879,
(
100 MHz, CDCl
3
1
1
5
30
1
2
068C; [a]D =ꢀ14.48 (c=1.04 in CH
ꢀ
1
+
581, 1555, 1461, 1435, 1382, 1122 cm ; MS (ESI): m/z: 294.0 [M+Na] ,
A
H
R
U
G
+
67.1 [2M+Na] ; elemental analysis calcd (%) for C12H18BrNO: C 52.95,
2
H 6.67; found: C 52.83, H 6.81.
(R,R)-6,6’-Bis(1-hydroxy-2-ethyl-2-methylbutyl)-2,2’-bipyridine (12): The
pyridyl carbinol prepared above was reductively dimerized with
NiCl ·6H 0, PPh , and zinc powder in DMF at 708C as described for 11.
The crude product obtained was purified by flash chromatography over
silica gel (diethyl ether/petroleum ether 1:4 for separation of PPh , then
:1) and recrystallized two times from hexane. The title compound was
1
A
C
H
T
R
E
U
N
G
13
1
1
l
4
36.5, 137.8, 154.2, 154.9, 159.2 ppm; IR (film): n˜ =3375, 3060, 2962, 2665,
569, 1432, 1361, 1074, 1049, 1012, 805, 768, 632 cm ; UV/Vis (CH
max (lg e)=212 (4.442), 251 (4.458), 288 nm (4.551); MS (ESI): m/z (%):
60.2 [M+MeOH+Na] , 428.2 [M+Na] , 406.3 [M+H] ; elemental
ꢀ1
2
2
3
CN):
3
+
+
+
3
1
analysis calcd (%) for C25
73.72, H 7.77.
31 3 2
H N O (405.24): C 74.04, H 7.70; found: C
2
D
5
obtained as a white solid (587 mg, 39%). M.p. 85–878C; [a] =ꢀ40.28
1
(
c=1.12 in CHCl
3
); H NMR (200 MHz, CDCl
3
): d=0.80–0.92 (m, 18H),
Scandium–bipyridine-catalyzed aminolysis of meso-epoxides (general
procedure II): A solution of Sc(OTf) (25.0 mg, 10 mol%) and chiral bi-
pyridine 2 (17.0 mg, 10 mol%) in dichloromethane (2 mL) was stirred for
min, then the epoxide (0.5 mmol) was added. The reaction mixture was
cooled to the temperature given and the amine (1 mmol) was added.
After the reaction was completed, the solvent was evaporated and the
product was purified by flash column chromatography over silica gel.
1
2
2
7
1
1
3
3
.20–1.40 (m, 6H), 1.64 (dq, J=15.0, 7.5 Hz, 2H), 4.34 (d, J=7.0 Hz,
A
H
R
U
G
3
H), 4.65 (d, J=7.0 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.77 (t, J=8.0 Hz,
1
3
3
HH), 8.29 ppm (d, J=8.0 Hz, 2H); C NMR (50 MHz, CDCl ): d=
5
.968, 19.54, 27.13, 27.55, 41.04, 76.87, 119.4, 123.0, 136.6, 153.8,
59.6 ppm; IR (KBr): n˜ =3417, 3097, 3055, 2964, 2877, 1570, 1434, 1390,
ꢀ
1
+
+
108, 812, 767 cm ; MS (ESI): m/z: 791.5 [2M+Na] , 407.3 [M+Na] ,
+
85.3 [M+H] ; HRMS (ESI): calcd for C24
37 2 2
H N O : 385.28506; found:
+
Scandium–bipyridine-catalyzed aminolysis of meso-epoxides (general
85.28495 [M+H] .
procedure III): A solution of Sc
pyridine 2 (17.0 mg, 10 mol%) in dichloromethane (2 mL) was stirred for
min, then the epoxide (0.5 mmol) was added. The reaction mixture was
A
H
R
U
G
3
(OTf) (25.0 mg, 10 mol%) and chiral bi-
(
R)-6-Bromo-2-(1-tert-butyldimethylsilyloxy-2,2-dimethylpropyl)pyridine:
TBSOTf (3.40 mL, 15.0 mmol) and 2,6-lutidine (2.40 mL, 20.0 mmol)
were added to a stirred solution of (R)-6-bromopyridin-2-yl-2,2-dimethyl-
propan-1-ol (2.44 g, 10.0 mmol) in dichloromethane (45 mL) at 08C. The
resulting solution was stirred overnight at RT and quenched with saturat-
5
cooled to the temperature given and the amine (0.5 mmol) was added.
After the reaction was completed, the solvent was evaporated and the
product was purified by flash column chromatography over silica gel.
ed aqueous NaHCO
aqueous layer was extracted with dichloromethane (3”20 mL). The com-
bined organic layers were washed with brine (30 mL), dried over MgSO
3
solution (40 mL). The layers were separated, the
Scandium–bipyridine-catalyzed aminolysis of meso-epoxides (general
procedure IV): A solution of Sc(OTf) (25.0 mg, 10 mol%) and chiral bi-
3
A
H
R
U
G
4
and filtered. The residue obtained after removal of the solvent was puri-
fied by flash chromatography over silica gel (diethyl ether/petroleum
ether 1:19). The title compound was obtained as colorless oil (3.44 g,
pyridine 2 (20.0 mg, 12 mol%) in dichloromethane (2 mL) was stirred for
5 min, then the epoxide (0.5 mmol) was added. The reaction mixture was
cooled to the temperature given and the amine (1 mmol) was added.
Chem. Eur. J. 2007, 13, 2729 – 2741
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2737

C. Schneider and E. Mai
After the reaction was completed, the solvent was evaporated and the
product was purified by flash column chromatography over silica gel.
(15), 77 (17); the enantiomeric assay: Chiralcel OD, isocratic (n-hexane/
ꢀ
1
iPrOH 85:15, flow1 mLmin
7.7 min; 41% ee.
(1R,2R)-2-Phenylaminocycloheptanol
) l=247, (1S,2S): 15.5 min, (1R,2R):
1
A
C
H
T
R
E
U
N
G
(1R,2R)-2-(N-Methyl-N-phenylamino)-1,2-diphenylethanol (3): Following
[
34]
general procedure IV, cis-stilbene oxide (1a) (98 mg, 0.50 mmol) was
treated with N-methyl aniline (107 mg, 1.00 mmol) at RT. Flash chroma-
tography (diethyl ether/petroleum ether 1:4) afforded 3 as a colorless
A
H
R
U
G
(4d): Following general proce-
dure IV, cycloheptene oxide (1d) (58 mL, 0.50 mmol) was treated with
aniline (91 mL, 1.00 mmol) at RT for 6.5 h. Flash chromatography (ethyl
solid (116 mg, 85%). R
f
=0.37 (diethyl ether/petroleum ether 1:2); m.p.
acetate/petroleum ether 1:4) afforded 4d as a brown viscous oil (48 mg,
2
3
1
28
5
6–608C; [a] =ꢀ184.48; (c=1.00 in CH
2
Cl
2
); H NMR (300 MHz,
47%). R
f
=0.19 (diethyl ether/petroleum ether 1:3); [a] =ꢀ7.38 (c=1.42
D
D
1
CDCl
3
): d=2.71 (s, 3H; CH
3
), 3.99 (s, 1H; OH), 4.88 (d, J=10 Hz, 1H;
in CH Cl
2
2
); H NMR (200 MHz, CDCl
3
): d=1.26–1.80 (m, 8H; CH
2
),
CH), 5.30 (d, J=10 Hz, 1H; CH), 6.91–7.04 (m, 5H; PhH), 7.15–7.32 (m,
1.87–2.08 (m, 2H; CH
3.5 Hz, 1H; CH), 3.46 (td, J=9.0, 3.5 Hz 1H; CH), 6.67–6.82 (m, 3H;
PhH), 7.15–7.24 ppm (m, 2H; PhH); C NMR (100 MHz,CDCl ): d=
3
22.14, 24.04, 27.19, 30.27, 32.83, 62.74, 76.55, 114.9, 118.7, 129.3,
147.5 ppm; IR (film): n˜ =3394, 3051, 2929, 2859, 1602, 1501, 1459, 1321,
1246, 1178, 1080, 1059, 1026, 749, 993 cm ; UV/Vis (CH
2
), 3.13 (brs, 2H; NH and OH), 3.24 (td, J=9.0,
1
3
8
H; PhH), 7.41 ppm (dd, J=8.5, 2.0 Hz, 2H; PhH); C NMR (75 MHz,
CDCl ): d=32.8, 71.6, 73.9, 117.9, 120.5, 127.5, 127.8, 127.9, 128.1, 128.4,
28.9, 129.3, 134.7, 140.8, 151.5 ppm; IR (KBr): n˜ =3419, 3028, 2883,
1
3
3
1
1
ꢀ
1
597, 1496, 1450, 1386, 1253, 1186, 1025, 754, 696 cm
;
UV/Vis
ꢀ
1
(
(
(
CH
3
CN): lmax (lg e)=200 (4.187), 208 (5.251), 255 nm (4.080); MS
3
CN): lmax (lg
+
+
+
ESI): m/z: 629.3 [2M+Na] , 326.2 [M+Na] , 304.2 [M+H] ; HRMS
ESI): calcd for C21
e)=203 (3.987), 245 (4.103), 291 nm (3.462); MS (ESI): m/z: 228.0
+
+
+
H
21NaNO: 326.15154; found: 326.15177 [M+Na] .
[M+Na] , 206.0 [M+H] ; the enantiomeric assay: Chiralcel OD, isocrat-
ꢀ
1
The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH 90:10,
ic (n-hexane/iPrOH 85:15, flow1.0 mLmin
9.9 min; (1R,2R): 11.3 min; 10% ee.
) l=243 nm, (1S,2S):
ꢀ
1
flow0.8 mLmin
7% ee.
(1R,2R)-1,2-Diphenyl-2-(phenylamino)ethanol (4a): Following general
)
l=251 nm, (1S,2S): 20.3 min; (1R,2R): 21.8 min;
9
[10]
A
H
R
U
G
(4e): Following general procedure
[
10]
A
C
H
T
R
E
U
N
G
III, cis-2,3-epoxy butane (44 mL, 0.50 mmol) was treated with aniline
(46 mL, 0.50 mmol) at 08C. Flash chromatography (diethyl ether/petrole-
um ether 1:2) afforded 4e as a colorless liquid (76 mg, 92%). R
procedure III, cis-stilbene oxide (1a) (98 mg, 0.50 mmol) was treated
with aniline (46 mL, 0.50 mmol) at RT. Flash chromatography (diethyl
ether/petroleum ether 1:8) afforded 4a as a colorless solid (138 mg,
f
=0.14
Cl );
2
D
3
(diethyl ether/petroleum ether 1:2); [a] =ꢀ58.88 (c=0.93 in CH
2
2
1
9
5%). R
f
=0.27 (diethyl ether/petroleum ether 1:2); m.p. 100–1038C;
3 3
H NMR (300 MHz, CDCl ): d=1.16 (d, J=6.5 Hz, 3H; CH ), 1.27 (d,
2
3
1
[
(
a] =+48.68 (c=0.53 in CH
2
Cl
brs, 1H; NH), 4.60 (d, J=6.9 Hz, 1H; CH), 4.76 (brs, 1H; OH), 4.91 (d,
J=6.0 Hz, 1H; CH), 6.60–6.64 (m, 2H; PhH), 6.72–6.78 (m, 1H; PhH),
2
); H NMR (300 MHz, CDCl
3
): d=2.75
J=6.5 Hz, 3H; CH
3
), 2.70 (brs, 1H; NH), 3.34 (quint, J=6.5 Hz, 2H;
D
CH and OH), 3.65 (quint, J=6.5 Hz, 1H; CH), 6.67–6.78 (m, 3H; PhH),
7.16–7.23 ppm (m, 2H; PhH); C NMR (75 MHz, CDCl
56.1, 71.4, 114.4, 118.3, 129.4, 147.9 ppm; IR (film): n˜ =3398, 3050, 2972,
1
3
3
): d=17.4, 19.6,
1
3
7
(
1
3
.16–7.19 (m, 2H; PhH), 7.26–7.40 ppm (m, 10H; PhH); C NMR
75 MHz, CDCl ): d=64.8, 78.1, 114.2, 118.0, 126.7, 127.4, 127.6, 128.0,
28.3, 128.6, 129.1, 140.3, 140.6, 147.3 ppm; IR (KBr): n˜ =3545, 3406,
ꢀ1
3
2927, 2357, 1601, 1504, 1452, 1315, 1253, 1170, 1091, 748, 692 cm ; UV/
Vis (CH CN): lmax (lg e)=200 (3.989), 205 (4.044), 248 (4.112), 297 nm
(3.317); MS (70 eV, EI): m/z (%): 165 (9) [M] , 120 (100), 93 (6), 77
(15), 51 (6); HRMS (ESI): calcd for C22 24NO: 318.18524; found:
3
ꢀ1
+
031, 2879, 2846, 1601, 1498, 1450, 1427, 1319, 1034, 758, 700 cm ; UV/
CN): lmax (lg e)=201 (4.167), 210 (4.196), 247 (4.102), 295 nm
Vis (CH
3
H
+
+
(
3.292); MS (70 eV, EI): m/z (%): 289 (1) [M] , 182 (100), 104 (20), 86
318.18521 [M+H] ; the enantiomeric assay: Chiralcel OD, isocratic (n-
+
ꢀ1
(
79), 84 (99), 77 (30), 51 (5); MS (ESI): m/z: 601.3 [2M+Na] , 312.1
hexane/iPrOH 95:5, flow1 mLmin
(2R,3R): 18.6 min; 60% ee.
) l=247 nm, (2S,3S): 17.2 min;
+
+
[
M+Na] , 290.2 [M+H] ; the enantiomeric assay: Chiralcel OD, isocrat-
ꢀ
1
ic (n-hexane/iPrOH 85:15, flow1 mLmin
) l=247 nm, (1R,2R):
A
H
R
U
G
1
3.6 min; (1S,2S): 17.5 min; 93% ee.
(1R,2R)-2-(Phenylamino)cyclohexanol
dure II, cyclohexene oxide (51 mL, 0.50 mmol) was treated with aniline
91 mL, 1.00 mmol) at ꢀ208C. Flash chromatography (diethyl ether/petro-
leum ether 1:2) afforded 4b as a pale-yellowsolid (92 mg, 96%).
IV, cis-4-octene oxide (1 f) (64 mg, 0.50 mmol) was treated with aniline
(91 mL, 1.00 mmol) at RT. Flash chromatography (diethyl ether/petrole-
um ether 1:3) afforded 4 f as a pale brown oil (82 mg, 74%). R
[
10]
A
C
H
T
R
E
U
N
G
(4b): Following general proce-
f
=0.27 (di-
Cl );
2
D
3
(
ethyl ether/petroleum ether 1:3); [a] =ꢀ0.958 (c=1.05 in CH
2
2
1
R
f
=
3 3
H NMR (300 MHz, CDCl ): d=0.89 (d, J=7.0 Hz, 3H; CH ), 0.93 (d,
2
3
0
.12 (diethyl ether/petroleum ether 1:2); m.p. 57–598C; [a] =ꢀ37.78
J=7.0 Hz, 3H; CH
3 2
), 1.29–1.67 (m, 8H; CH ), 2.17 (brs, 1H, NH), 3.28
D
1
(
c=0.54 in CH
2
Cl
2
); H NMR (300 MHz, CDCl
3
): d=1.03–1.08 (m, 1H),
(dt, J=7.5, 5.0 Hz 1H; CH), 3.56–3.62 (m, 2H; CH, OH), 6.63–6.71 (m,
3H; PhH), 7.13–7.18 ppm (m, 2H; PhH); C NMR (75 MHz,CDCl ): d=
3
14.11, 14.19, 19.12, 19.43, 34.85, 36.20, 58.03, 73.21, 113.4, 117.4, 129.3,
148.6 ppm; IR (film): n˜ =3405, 3052, 3020, 2957, 2932, 2871, 1602, 1505,
1
3
1
3
3
.27–1.43 (m, 3H), 1.71–1.81 (m, 2H), 2.11–2.15 (m, 2H), 3.10–3.18 (m,
H; CH, NH, OH), 3.35 (td, J=10.0, 4.5 Hz, 1H; CH), 6.71–6.79 (m,
1
3
H; PhH), 7.17–7.22 ppm (m, 2H; PhH); C NMR (50 MHz, CDCl
3
):
ꢀ
1
d=24.6, 25.2, 31.8, 33.5, 60.3, 74.7, 114.6, 129.6, 148.2 ppm; IR (KBr): n˜ =
1464, 1431, 1320, 1259, 747, 692 cm ; UV/Vis (CH
3
CN): lmax (lg e)=201
ꢀ1
3
390, 3049, 2931, 2856, 1600, 1502, 1448, 1068, 748 cm
; UV/Vis
(4.148), 207 (4.150), 250 (4.284), 299 nm (3.489); MS (ESI): m/z: 244.1
+
+
(
CH CN): lmax (lg e)=201 (4.036), 205 (4.030), 248 (4.049), 296 nm
3
[M+Na] , 222.1 [M+H] ; HRMS (ESI): calcd for C14
H
24NO: 222.18524;
+
+
(
3.252); MS (70 eV, EI): m/z (%): 191 (39) [M] , 148 (14), 132 (100), 118
found: 222.18532 [M+H] ; the enantiomeric assay: Chiralcel OD, iso-
cratic (n-hexane/iPrOH 95:5, flow0.8 mLmin ) l=247 nm, (3R,4R):
10.8 min; (3S,4S): 12.3 min; 74% ee.
ꢀ1
(
25), 106 (40), 93 (15), 77 (23); the enantiomeric assay: Chiralcel OD, iso-
ꢀ1
cratic (n-hexane/iPrOH 85:15, flow1 mLmin
) l=247 nm, (1S,2S):
1
0.3 min; (1R,2R): 11.9 min; 54% ee.
(1R,2R)-2-(Phenylamino)cyclopentanol (4c): Following general proce-
dure II, cyclopentene oxide (44 mL, 0.50 mmol) was treated with aniline
91 mL, 1.00 mmol) at ꢀ208C. Flash chromatography (diethyl ether/petro-
leum ether 1:2) afforded 4c as a pale-yellowsolid (79 mg, 89%).
A
H
R
U
G
[
10]
A
C
H
T
R
E
U
N
G
al procedure IV, cis-2,7-dimethyl-4-octene oxide (1g) (78 mg, 0.50 mmol)
was treated with aniline (91 mL, 1.00 mmol) at RT. Flash chromatography
(diethyl ether/petroleum ether 1:3) afforded 4g as a colorless oil (76 mg,
61%). R
0.73 in CH
CH
(d, J=6.5 Hz, 3H; CH
(sept, J=7.0 Hz, 1H), 1.76–1.89 (m, 1H), 2.10 (brs, 1H; NH), 3.27–3.33
(m, 1H; CH), 3.48 (brs, 1H; OH), 3.59–3.65 (m, 1H; CH), 6.63–6.71 (m,
3H; PhH), 7.15–7.18 ppm (m, 2H; PhH); C NMR (75 MHz,CDCl
(
R
f
=
2
3
0
.18 (diethyl ether/petroleum ether 1:2); m.p. 52–568C; [a] =ꢀ12.88
D
1
(
c=0.55 in CH
2
Cl
2
); H NMR (300 MHz, CDCl
3
): d=1.36–1.46 (m, 1H;
CH
1
3
2
), 1.59–1.72 (m, 1H; CH
), 2.22–2.34 (m, 1H; CH
.64 (m, 1H; CH), 4.06 (dt, J=4.5, 6.0 Hz, 1H; CH), 6.65–6.75 (m, 3H;
2
), 1.72–1.88 (m, 2H; CH
2
), 1.90–2.04 (m,
H; CH
2
2
), 2.71 (brs, 2H; OH and NH), 3.58–
1
3
PhH), 7.15–7.22 ppm (m, 2H; PhH); C NMR (75 MHz, CDCl
3
): d=
2
1.14, 31.31, 32.99, 62.19, 78.36, 113.4, 117.6, 129.4, 147.9 ppm; IR (KBr):
21.89, 22.45, 23.33, 23.70, 24.80, 24.88, 42.31, 43.37, 56.81, 71.89, 113.3,
ꢀ1
n˜ =3527, 3373, 2958, 1601, 1502, 1315, 1105, 750 cm ; UV/Vis (CH
l
3
CN):
117.4, 129.3, 148.7 ppm; IR (film): n˜ =3404, 3053, 3020, 2956, 2869, 1602,
ꢀ
1
max (lg e)=203 (3.962), 206 (3.961), 249 (4.089), 297 nm (3.355); MS
1504, 1467, 747, 692 cm ; UV/Vis (CH
3
CN): lmax (lg e)=204 (3.949), 251
+
+
+
(
70 eV, EI): m/z (%): 177 (52) [M] , 132 (100), 118 (14), 106 (44), 93
(4.099), 299 nm (3.299); MS (ESI): m/z: 272.1 [M+Na] , 250.1 [M+H ];
2738
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2729 – 2741

Aminolysis of meso-Epoxides
FULL PAPER
+
HRMS (ESI): calcd for C16
H
28NO: 250.21654; found: 250.21657 [M+H] .
(p-chlorophenyl)ethane oxide (1l) (66 mg, 0.25 mmol) was added. The re-
sulting solution was stirred for 5 min, then aniline (46 mL, 0.50 mmol) was
added. After 1 d of stirring, the solvent was evaporated. The product was
purified by flash column chromatography over silica gel (diethyl ether/
petroleum ether 1:4) affording 4l as a pale-yellowviscous oil (83 mg,
The enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH 95:5,
ꢀ
1
flow0.8 mLmin
9% ee.
(2R,3R)-1,4-Diphenyl-3-N-phenylamino-2-butanol (4h): Following gener-
) l=247 nm, (3R,4R): 8.3 min; (3S,4S): 10.5 min;
4
ACHTREUNG
2
5
al procedure IV, cis-dibenzyloxirane (1h) (112 mg, 0.50 mmol) was treat-
ed with aniline (91 mL, 1.00 mmol) at 08C. Flash chromatography (diethyl
ether/petroleum ether 2:3) afforded 4h as a pale-yellowviscous oil
93%). R
1.26 in CH
f
=0.31 (diethyl ether/petroleum ether 1:2); [a]
D
=+34.38 (c=
1
2
Cl
2
); H NMR (400 MHz, CDCl
3
): d=2.62 (brs, 1H; NH),
4.28 brs, 1H; OH), 4.44 (d, J=6.5 Hz, 1H; CH), 4.78 (d, J=6.5 Hz, 1H;
2
5
(
78 mg, 49%). R
f
=0.21 (diethyl ether/petroleum ether 1:3); [a] =+
CH), 6.50–6.52 (m, 2H; ArH), 6.67–6.71 (m, 1H; ArH), 7.06–7.17 (m,
D
1
13
1
1
1
1.48 (c=0.91 in CH
H; NH), 2.81–3.02 (m, 4H; CH
2
Cl
2
); H NMR (300 MHz, CDCl
3
): d=1.78 (brs,
), 3.62–3.67 (m 1H; CH), 3.90–3.95 (m,
H; CH), 4.14 (brs, 1H; OH), 6.66–6.76 (m, 3H; PhH), 7.13–7.32 ppm
6H; ArH), 7.22–7.27 ppm (m, 4H; ArH); C NMR (100 MHz, CDCl
3
):
d=64.27, 77.35, 114.2, 118.4, 128.0, 128.5, 128.6, 128.8, 129.1, 133.3, 133.8,
138.4, 138.8, 146.7 ppm; IR (film): n˜ =3400, 3052, 3026, 2923, 1601, 1489,
2
1
3
(
m, 12H; PhH); C NMR (75 MHz, CDCl
1.96, 113.4, 117.3, 126.3, 126.5, 128.5, 128.6, 129.2, 129.3, 129.4, 138.1,
38.6 ppm; IR (film): n˜ =3564, 3406, 3083, 3058, 3025, 2853, 1600, 1504,
3
): d=37.63, 40.84, 57.18,
1431, 1316, 1091, 1013, 834, 752, 733, 692 cm; UV/Vis (CH
3
CN): lmax (lg
7
1
1
2
2
e)=202 (4.339), 209 (4.303), 224 (4.372), 243 (4.220), 292 nm (3.490); MS
+
+
(ESI): m/z: 380.0 [M+Na] , 358.0 [M+H] ; HRMS (ESI): calcd for
ꢀ
1
+
391, 746 cm ; UV/Vis (CH
3
CN): lmax (lg e)=212 (4.223), 253 (4.244),
98 nm (3.419); MS (70 eV, EI): m/z (%): 317 (3) [M] , 299 (2), 252 (4),
26 (91), 196 (93), 104 (100), 91 (100), 77 (99); the enantiomeric assay:
Chiralcel OD, isocratic (n-hexane/iPrOH 90:10, flow0.8 mLmin ) l=
47 nm, (1R,2R): 13.2 min; (1S,2S): 15.5 min; 44% ee.
(1R,2R)-1,2-Bis(2’-naphthyl)-2-(phenylamino)ethanol (4i): A solution of
Sc(OTf) (8 mg, 10 mol%) and chiral bipyridine 2 (7 mg, 12 mol%) in di-
C H Cl NO: 358.07600; found: 358.07612 [M+H] ; the enantiomeric
2
0
18
2
+
assay: Chiralcel OD, isocratic (n-hexane/iPrOH 85:15, flow:
ꢀ
1
1.0 mLmin ) l=209 nm, (1R,2R): 15.8 min; (1S,2S): 23.6 min; 92% ee.
ꢀ1
[35]
A
H
R
U
G
(14): Following
2
general procedure IV, cis-stilbene oxide (1a) (98 mg, 0.50 mmol) was
treated with p-chloro aniline (128 mg, 1.00 mmol) at RT. Flash chroma-
tography (diethyl ether/petroleum ether 1:2) afforded 14 as a pale-yellow
ACHTREUNG
A
C
H
T
R
E
U
N
G
3
chloromethane (1 mL) was stirred for 10 min at RT. Then cis-1,2-bis(2’-
naphthyl)ethane oxide (1i) (50.0 mg, 0.17 mmol) was added. The result-
ing solution was stirred for 5 min, then aniline (31 mL, 0.34 mmol) was
added. After 8 h of stirring the solvent was evaporated. The product was
purified by flash column chromatography over silica gel (dichlorome-
thane/petroleum ether 9:1), affording 4i as a white solid (50 mg, 76%).
viscous oil (153 mg, 95%). R
f
=0.29 (diethyl ether/petroleum ether 1:2);
23
1
[
a]D =+34.28 (c=1.09 in CH
2
Cl
2
); H NMR (300 MHz, CDCl
3
): d=2.43
(
brs, 1H; NH), 4.48 (d, J=5.5 Hz; CH), 4.75 (brs, 1H; OH); 4.87 (d, J=
5
7
1
.5 Hz; CH), 6.43 (d, J=9.0 Hz; ArH), 7.00 (d, J=9.0 Hz; ArH), 7.19–
.31 ppm (m, 10H; ArH); C NMR (75 MHz, CDCl
15.1, 122.4, 126.4, 127.2, 127.6, 128.0, 128.3, 128.6, 128.8, 139.7, 140.4,
13
3
): d=64.62, 77.92,
2
3
R
f
=0.37 (CH
2
Cl
2
); m.p. 147–1508C; [a] =+109.48 (c=0.89 in CH
2
Cl
2
);
D
146 ppm; IR (film in CCl ): n˜ =3405, 3063, 3030, 2888, 1599, 1497, 1454,
4
1
H NMR (300 MHz, CDCl
3
): d=2.80 (brs, 1H; NH), 4.84 (d, J=5.5 Hz,
ꢀ1
1
2
3
315, 816, 788, 766, 700 cm ; UV/Vis (CH
3
CN): lmax (lg e)=202 (4.331),
2
7
7
H; CH, OH), 5.13 (d, J=5.5 Hz, 1H; CH), 6.58–6.7 (m, 3H; ArH),
+
10 (4.366), 255 (4.399), 306 nm (3.464); Ms (ESI): m/z: 346.0 [M+Na] ,
24.1 [M+H] ; the enantiomeric assay: Chiralcel OD, isocratic (n-
.04–7.11 (m, 2H; ArH), 7.38 (ddd, J=8.5, 6.5, 2.0 Hz, 2H; ArH), 7.44–
+
1
3
.53 (m, 4H; ArH), 7.74–7.85 ppm (m, 8H; ArH); C NMR (75 MHz,
): d=64.7, 78.0, 114.3, 118.1, 124.5, 125.4, 125.7, 126.0, 126.1, 126.2,
26.3, 126.3, 127.8, 128.1, 128.2, 128.5, 129.2, 133.1, 133.2, 133.2, 133.5,
37.9, 138.1, 147.3 ppm; IR (KBr): n˜ =3415, 3053, 2924, 1600, 1502,
ꢀ1
hexane/iPrOH 85:15, flow1.0 mLmin ) l=247 nm, (1S,2S): 15.7 min;
CDCl
3
(
1R,2R): 17.7 min. 95% ee.
1
1
7
[
35]
AHCTREUNG
(1R,2R)-2-(4-Methylphenylamino)-1,2-diphenylethanol (15): Following
ꢀ
1
general procedure IV, cis-stilbene oxide (1a) (98 mg, 0.50 mmol) was
treated with p-toluidine (107 mg, 1.00 mmol) at RT. Flash chromatogra-
phy (diethyl ether/petroleum ether 1:3) afforded 15 as a solid (153 mg,
3
50 cm ; UV/Vis (CH CN): lmax (lg e)=203 (4.417), 230 (4.603), 350 nm
(
(
3
2.504); MS (70 eV, EI): m/z (%): 371 (2), 267 (1), 232 (100), 155 (5), 127
+
+
6), 104 (23), 77 (22); MS (ESI): m/z: 801.3 [2M+Na] , 412.2 [M+Na] ,
+
95%). R =0.25 (diethyl ether/petroleum ether 1:3); m.p. 83–868C;
90.2 [M+H] ; HRMS (ESI): calcd for C28
H
24NO: 412.16719; found:
f
2
5
1
+
D
2 2 3
[a] =+31.48 (c=1.54 in CH Cl ); H NMR (300 MHz, CDCl ): d=2.20
4
12.16698 [M+H] ; the enantiomeric assay: Chiralcel OD, isocratic (n-
ꢀ
1
3
(s, 3H; CH ), 2.61 (brs, 1H; NH), 4.48 (brd, J=6.0 Hz, 2H; CH, OH),
hexane/iPrOH 90:10, flow: 0.8 mLmin ) l=227 nm, (1S,2S): 31.9 min;
1R,2R): 38.7 min; 82% ee.
(1R,2R)-2-(Phenylamino)-1,2-bis
(OTf) (11 mg, 10 mol%) and chiral bipyridine 2 (9 mg, 12 mol%) in di-
4
8
.84 (d, J=6.0 Hz, 1H; CH), 6.46 (d, J=8.0 Hz, 2H; ArH), 6.87 (d, J=
.0 Hz, 2H; ArH), 7.20–7.25 ppm (m, 10H; ArH);
(
1
3
C NMR
A
C
H
T
R
E
U
N
G
A
H
R
U
G
(
75 MHz,CDCl
3
): d=20.32, 65.18, 78.03, 114.3, 126.6, 127.2, 127.3, 127.4,
A
C
H
T
R
E
U
N
G
3
1
3
6
27.8, 128.2, 128.5, 129.5, 140.2, 140.5, 144.9 ppm; IR (KBr): n˜ =3611,
chloromethane (1 mL) was stirred for 5 min at RT. Then cis-1,2-bis-(m-
tolyl)ethane oxide (1k) (50 mg, 0.22 mmol) was added. The resulting so-
lution was stirred for 5 min, then aniline (40 mL, 0.44 mmol) was added.
After 7 h of stirring the solvent was evaporated. The product was purified
by flash column chromatography over silica gel (diethyl ether/petroleum
390, 3061, 3026, 2871, 1815, 1519, 1454, 1317, 1260, 1038, 1022, 805, 766,
ꢀ
1
3
97 cm ; UV/Vis (CH CN): lmax (lg e)=205 (4.336), 215 (4.316), 251
+
(
4.313), 281 nm (3.699); MS (ESI): m/z: 304.1 [M+H] ; the enantiomeric
ꢀ
1
assay: Chiralcel OD, isocratic (n-hexane/iPrOH 94:6, flow: 0.8 mLmin
l=247 nm, (1S,2S): 37.9 min; (1R,2R): 40.2 min; 87% ee.
)
ether 1:4), affording 4k as a pale-yellowviscous oil (65 mg, 93%).
f
R =
2
3
[35]
0
CH
CH
.3 (diethyl ether/petroleum ether 1:2); [a] =+50.28 (c=0.89 in
A
H
R
U
G
(16): Follow-
D
1
Cl
2
); H NMR (300 MHz, CDCl
3
): d=2.33 (s, 3H; CH
3
), 2.36 (s, 3H;
ing general procedure IV, cis-stilbene oxide (1a) (98 mg, 0.50 mmol) was
treated with p-anisidine (123 mg, 1.00 mmol) at 08C. Flash chromatogra-
phy (diethyl ether/petroleum ether 1:3) afforded 16 as a brown solid
2
3
), 2.57 (brs, 1H; NH), 4.52 (d, J=5.0 Hz, 1H; CH), 4.68 (brs, 1H;
OH), 4.86 (d, J=5.0 Hz, 1H; CH), 6.57 (dd, J=8.5, 1.0 Hz, 2H; ArH),
6
.69 (dd, J=7.5, 7.5 Hz, 1H; ArH), 7.07–7.24 ppm (m, 10H; ArH);
(139 mg, 87%). R
958C; [a]D =+25.18 (c=0.61 in CH Cl ); H NMR (200 MHz, CDCl ):
f
=0.4 (diethyl ether/petroleum ether 1:1); m.p. 91–
1
3
23
1
C NMR (75 MHz,CDCl
3
): d=21.5, 21.6, 54.6, 78.0, 114.1, 117.8, 123.6,
2
2
3
1
1
7
28.0, 128.2, 128.4, 128.5, 128.6, 129.1, 137.9, 138.2, 140.4, 140.6,
d=3.66 (s, 3H; OCH ), 4.40 (d, J=6.5 Hz, 1H; CH), 4.81 (d, J=6.5 Hz,
3
47.5 ppm; IR (film): n˜ =3398, 3024, 2920, 1601, 1502, 1313, 1105,
1H; CH), 6.51 (d, J=9.0 Hz, 2H; ArH), 6.66 ppm (d, J=9.0 Hz, 1H;
ꢀ
1
13
94 cm ; UV/Vis (CH
3
CN): lmax (lg e)=212 (4.262), 248 (4.144), 295 nm
ArH), 7.17–7.25 (m, 10H; ArH); C NMR (75 MHz, CDCl ): d=55.8,
3
+
+
(
3.292); MS (ESI): m/z: 657.3 [2M+Na] , 340.2 [M+Na] , 318.2
66.3, 78.2, 114.8, 115.9, 126.8, 127.5, 127.9, 128.2, 128.5, 140.3, 140.7,
+
[
M+H] ; HRMS (ESI): calcd for
C
22
H
23NaNO: 340.16719; found:
141.4 ppm; IR (KBr): n˜ =3479, 3428, 3027, 2933, 2831, 1807, 1510, 1452,
+
ꢀ1
3
40.16711 [M+Na] ; the enantiomeric assay: Chiralcel OD, isocratic (n-
1240, 1030, 820, 762, 698 cm ; UV/Vis (CH CN): l (lg e)=200 (4.139),
3
max
ꢀ
1
hexane/iPrOH 90:10, flow: 0.8 mLmin ) l=199 nm, (1R,2R): 15.9 min;
1S,2S): 21.1 min; 91% ee.
(1R,2R)-1,2-Di(p-chlorophenyl)-2-(phenylamino)ethanol (4l): A solution
of Sc(OTf) (12 mg, 10 mol%) and chiral bipyridine 2 (10 mg, 12 mol%)
in dichloromethane (1 mL) was stirred for 5 min at RT. Then cis-1,2-bis-
208 (4.250), 246 (4.072), 314 nm (3.403); MS (70 eV, EI): m/z (%): 319
+
(
(
1) [M] , 301 (1), 212 (100), 168 (8), 134 (10), 91 (5), 77 (9); MS (ESI):
+ + +
A
C
H
T
R
E
U
N
G
m/z: 661.3 [2M+Na] , 342.1 [M+Na] , 320.2 [M+H] ; the enantiomeric
assay: Chiralcel OD, isocratic (n-hexane/iPrOH 90:10, flow:
0.8 mLmin ) l=243 nm, (1S,2S): 31.9 min; (1R,2R): 38.7 min; 90% ee.
A
C
H
T
R
E
U
N
G
3
ꢀ
1
Chem. Eur. J. 2007, 13, 2729 – 2741
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2739

C. Schneider and E. Mai
A
C
H
T
R
E
U
N
G
(1R,2R)-2-(Benzyloxyamino)-1,2-diphenylethanol (17): Following general
meric assay: Chiralcel OD, isocratic (n-hexane/iPrOH 85:15, flow:
0.8 mLmin ) l=247 nm, (1S,2S): 9.2 min; (1R,2R): 15.1 min; 52% ee.
ꢀ
1
procedure IV, cis-stilbene oxide (1a) (98 mg, 0.50 mmol) was treated with
O-benzyl hydroxylamine (123 mL, 1.00 mmol) at RT. Flash chromatogra-
phy (diethyl ether/petroleum ether 1:4) afforded 17 as a colorless solid
(
4
[
10]
A
H
R
U
G
(21): Following gen-
eral procedure IV, cyclohexene oxide (1b) (51 mL, 0.50 mmol) was treat-
ed with p-anisidine (123 mg, 1.00 mmol) at ꢀ208C. Flash chromatography
(diethyl ether/petroleum ether 1:2) afforded 21 as a pale-brown solid
120 mg, 75%). R
78C; [a] =+42.68 (c=0.98 in CH
f
=0.25 (diethyl ether/petroleum ether 1:2); m.p. 44–
2
3
1
2
Cl
2
); H NMR (300 MHz, CDCl
3
):
D
d=3.22 (brs, 1H; NH), 4.17 (d, J=9.0 Hz, 1H; CH), 4.62 (d, J=11.5 Hz,
(92 mg, 83%). R =0.24 (diethyl ether/petroleum ether 1:1); m.p. 66–
f
2
3
1
1
6
H; CH
.34 (brs, 1H; OH), 7.07–7.37 ppm (m, 15H; ArH); C NMR (75 MHz,
): d=71.9, 76.4, 76.7, 127.0, 127.7, 127.8, 128.1, 128.1, 128.2, 128.5,
28.6, 128.7, 137.4, 138.5, 140.9 ppm; IR (KBr): n˜ =3421, 2358, 2330,
2
), 4.67 (d, J=11.5 Hz, 1H; CH
2
), 4.83 (d, J=9.0 Hz, 1H; CH),
698C; [a] =ꢀ36.68 (c=0.72 in CH Cl ); H NMR (300 MHz, CDCl ):
D
2
2
3
1
3
d=0.94–1.07 (m, 1H; CH
2
), 1.25–1.45 (m, 3H; CH
2
), 1.67–1.79 (m, 2H;
CDCl
1
1
3
CH
2
), 2.06–2.16 (m, 2H; CH
2
), 2.92–3.04 (m, 3H; CH, OH and NH), 3.32
), 6.66–6.72 (m, 2H;
ArH), 6.76–6.81 ppm (m, 2H; ArH); C NMR (75 MHz, CDCl ): d=
(td, J=10.0, 5.0 Hz, 1H; CH), 3.75 (s, 3H; CH
3
ꢀ
1
13
630, 1450, 1028, 754, 698, 575 cm ; UV/Vis (CH
3
CN): lmax (lg e)=206
3
(
4.096), 212 (4.133), 258 nm (3.137); MS (70 eV, EI): m/z (%): 320 (1)
24.57, 25.38, 31.81, 33.37, 56.02, 61.97, 74.68, 115.1, 116.6, 141.9,
+
[
M+1] , 302 (1), 274 (0,5), 212 (95), 107 (11), 91 (100), 77 (28); MS
153.2 ppm; IR (KBr): n˜ =3388, 2929, 2859, 1514, 1448, 1331, 1302, 1246,
ꢀ
1
+
+
+
1180, 1035, 812 cm ; UV/Vis (CH CN): l
max
(lg e)=202 (3.933), 205
(
ESI): m/z: 661.3 [2M+Na] , 342.1 [M+Na] , 320.2 [M+H] ; HRMS
3
+
(3.922), 246 (3.956), 314 nm (3.241); MS (70 eV, EI): m/z (%): 221 (86)
(
ESI): calcd for C21H22NO: 342.14645; found: 342.14598 [M+H] ; the en-
+
[
M] , 162 (100), 136 (43), 149 (21), 108 (18), 91 (43), 77 (7), 41 (12); the
antiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH 90:10, flow:
0
ꢀ
1
enantiomeric assay: Chiralcel OD, isocratic (n-hexane/iPrOH 85:15, flow
.8 mLmin ) l=203 nm, (1R,2R): 20.6 min; (1S,2S): 25.7 min; 86% ee.
ꢀ
1
1
.0 mLmin ) l=243 nm, (1S,2S): 10.2 min; (1R,2R): 13.9 min; 48% ee.
[
34]
A
C
H
T
R
E
U
N
G
(1R,2R)-2-(N-Methyl-N-phenylamino)-cyclohexanol
(18): Following
[
37]
A
H
R
U
G
general procedure IV, cyclohexene oxide (1b) (51 mL, 0.50 mmol) was
treated with N-methyl aniline (0.11 mL, 1.00 mmol) at RT. Flash chroma-
tography (diethyl ether/petroleum ether 1:4) afforded 18 as a colorless oil
cedure IV, cyclohexene oxide (1b) (51 mL, 0.50 mmol) was treated with
O-benzyl hydroxylamine (123 mg, 1.00 mmol) at ꢀ208C. Flash chroma-
2
D
3
tography (diethyl ether/petroleum ether 1:1) afforded 22 as a colorless oil
(
95 mg, 93%).
R
f
=0.22 (diethyl ether/petroleum ether 1:2); [a]
=
23
D
1
(94 mg, 85%). R
c=1.05 in CH Cl
CH ), 1.70 (m, 2H; CH
CH), 3.11 (brs, 1H; NH), 3.40–3.48 (m, 1H; CH), 4.71 (s, 2H; CH
f
=0.15 (diethyl ether/petroleum ether 1:1); [a]
=ꢀ6.68
+
24.88 (c=1.16 in CH
2
Cl
2
); H NMR (200 MHz, CDCl
3
): d=1.21–1.44
), 2.17 (m, 1H; CH ), 2.76 (s, 3H;
), 2.80 (brs, 1H; OH), 3.35–3.47 (m, 1H; CH), 3.65 (td, J=10.0,
1
(
2
2
); H NMR (300 MHz, CDCl
3
): d=1.20–1.28 (m, 4H;
), 2.63–2.71 (m, 1H,
), 5.80
brs, 1H; OH), 7.30–7.36 ppm (m, 5H; ArH); C NMR (75 MHz,
(
m, 4H; CH
2
), 1.68–1.77 (m, 3H; CH
2
2
2
2
), 1.91–2.02 (m, 2H; CH
2
CH
4
2
3
2
.5 Hz 1H; CH), 6.83 (dd, J=8.0, 8.0 Hz 1H; PhH), 6.94 (d, J=8.0 Hz,
13
(
1
3
H; PhH), 7.25 ppm (dd, J=8.0, 8.0 Hz, 2H; PhH); C NMR (50 MHz,
): d=24.45, 25.60, 26.15, 31.22, 33.47, 67.14, 70.13, 115.7, 118.7,
29.2, 151.5 ppm; IR (film): n˜ =3433, 2929, 2858, 1597, 1500, 1450, 1296,
3
CDCl ): d=24.30, 24.77, 28.96, 33.80, 65.64, 72.38, 77.80, 128.0, 128.3,
CDCl
3
1
1
28.4, 128.5, 128.5, 137.6 ppm; IR (film): l=3419, 3030, 2931, 2858, 1361,
1
1
2
ꢀ1
045, 991, 734, 696 cm ; UV/Vis (CH CN): lmax (lg e)=205 nm (3.636);
3
ꢀ
1
072, 748 cm ; UV/Vis (CH
3
CN): lmax (lg e)=198 (3.998), 204 (4.018),
+
MS (70 eV, EI): m/z (%): 221 (36) [M] , 186 (7), 129 (11), 91 (100), 77
07 (4.023), 256 (4.116), 301 (3.238), 346 nm (0.499); MS (70 eV, EI): m/z
(
32), 41(32); the enantiomeric assay: Chiralcel OD, isocratic (n-hexane/
+
(
(
%): 205 (32) [M] , 146 (100), 132 (19), 120 (30), 106 (9), 91 (10), 77
16), 51 (5); the enantiomeric assay: Chiralcel OD, isocratic (n-hexane/
ꢀ1
iPrOH 90:10, flow0.8 mLmin ) l=209 nm, (1R,2R): 11.1 min; (1S,2S):
1
3.0 min; 26% ee.
ꢀ1
iPrOH 95:5, flow: 1.0 mLmin ) l=251 nm, (1S,2S): 11.2 min; (1R,2R):
2.4 min; 30% ee.
(1R,2R)-2-(4-Chlorophenylamino)cyclohexanol (19): Following general
[36]
A
H
R
U
G
(23): Following general proce-
1
dure IV, cyclohexene oxide (1b) (58 mL, 0.50 mmol) was treated with
benzylamine (110 mL, 1.00 mmol) at RT for 2 d. Flash chromatography
[
10]
ACHTREUNG
procedure IV, cyclohexene oxide (1b) (51 mL, 0.50 mmol) was treated
with p-chloro aniline (128 mg, 1.00 mmol) at ꢀ208C. Flash chromatogra-
phy (dichloromethane/ethyl acetate 25:1) afforded 19 as a pale-brown
(
ethyl acetate/dichloromethane 1:1 5% NEt
3
) afforded 23 as a pale-
yellowsolid (94 mg, 92%). R =0.35 (ethyl acetate/dichloromethane 1:1
f
2
7
1
10% NEt ); m.p. 52–548C; [a] =ꢀ14.58 (c=1.15 in CH Cl ); H NMR
3
2
2
D
solid (103 mg, 91%). R
f
=0.25 (dichloromethane/ethyl acetate 25:1); m.p.
3 2 2
(200 MHz, CDCl ): d=0.88–1.07 (m, 1H; CH ), 1.17–1.32 (m, 3H; CH ),
3
0
1
9
3–948C; [a] =ꢀ28.58 (c=1.32 in CH
2
Cl
2
); H NMR (300 MHz,
2 2
1.68–1.76 (m, 2H; CH ), 1.99–2.35 (m, 3H; CH and CH), 3.20 (td, J=
9.5, 5.0 Hz, 1H; CH), 3.69 (d, J=13.0 Hz; CH ), 3.96 (d, J=13.0 Hz;
2
CH ), 7.23–7.38 ppm (m, 5H; ArH); C NMR (75 MHz,CDCl ): d=
2 3
24.29, 25.05, 30.44, 33.30, 50.72, 63.03, 73.70, 126.9, 128.0, 128.3,
140.5 ppm; IR (KBr): n=3295, 3060, 3023, 2928, 2853, 1450, 1430, 1100,
1060, 1029, 748, 700 cm ; UV/Vis (CH CN): lmax (lg e)=208 (3.911),
270 nm (3.905); MS (ESI): m/z: 206.0 [M+H] ; the enantiomeric assay:
Mosher ester, 10% ee.
D
CDCl
3
): d=1.02–1.10 (m, 1H; CH
2
), 1.23–1.40 (m, 3H; CH
), 3.04–3.12 (m, 1H; CH), 3.35 (td,
J=9.5, 4.0 Hz, 1H; CH), 6.64 (d, J=9.0 Hz, 2H; ArH), 7.12 ppm (d, J=
2
), 1.71–1.80
1
3
(
m, 2H; CH
2
), 2.07–2.13 (m, 2H; CH
2
1
3
9
3
2
.0 Hz, 2H; ArH); C NMR (75 MHz, CDCl
3
): d=24.18, 24.87, 31.44,
ꢀ1
3.19, 60.25, 74.43, 115.3, 122.7, 129.1, 146.4 ppm; IR (KBr): n˜ =3389,
3
ꢀ1
+
922, 2856, 1597, 1507, 1490, 1323, 1058, 1038, 808 cm
;
UV/Vis
(
CH
3
CN): lmax (lg e)=206 (3.954), 257 (4.061), 308 nm (3.169); MS
+
+
(
ESI): m/z: 248.0 [M+Na] 226.0 [M+H] ; the enantiomeric assay: Chir-
ꢀ
1
alcel OD, isocratic (n-hexane/iPrOH 90:10, flow: 1.0 mLmin
) l=
2
43 nm, (1S,2S): 10.9 min; (1R,2R): 18.2 min; 43% ee.
[
36]
A
C
H
T
R
E
U
N
G
(1R,2R)-2-(4-Methylphenylamino)cyclohexanol
(20): Following gener-
Acknowledgements
al procedure IV, cyclohexene oxide (1b) (51 mL, 0.50 mmol) was treated
with p-toluidine (107 mg, 1.00 mmol) at ꢀ108C. Flash chromatography
Support of this work through the Deutsche Forschungsgemeinschaft
Schn 441/3–2) is most gratefully acknowledged. We thank Wacker AG
for the generous donation of TBSCl and Prof. Michael Reggelin (TU
Darmstadt) for providing the bissulfoximine ligand 8.
(
(
5
dichloromethane/ethyl acetate 25:1) afforded 20 as a pale-brown solid
(
91 mg, 89%). R
f
=0.20 (dichloromethane/ethyl acetate 50:1); m.p. 50–
2
5
1
38C; [a] =ꢀ42.88 (c=1.04 in CH
2
Cl
2
); H NMR (300 MHz, CDCl
3
):
), 1.70–1.79 (m, 2H;
), 3.04 (s, 2H; NH and
OH), 3.05–3.13 (m, 1H; CH), 3.33 (td, J=9.5, 4.0 Hz, 1H; CH), 6.65 (d,
D
2 2
d=0.98–1.09 (m, 1H; CH ), 1.27–1.42 (m, 3H; CH
2 2 3
CH ), 2.09–2.14 (m, 2H; CH ), 2.25 (s, 3H; CH
[
1] Reviews: a) D. M. Hodgson, A. R. Gibbs, G. P. Lee, Tetrahedron
1996, 52, 14361; b) E. N. Jacobsen, M. H. Wu, Comprehensive Asym-
metric Catalysis, Vol. 3 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamo-
to), 1999, p. 1309; c) C. Schneider, Synthesis 2006, 3919.
[2] For example: a) H. Yamashita, Bull. Chem. Soc. Jpn. 1988, 61, 1213;
b) W. M. Nugent, J. Am. Chem. Soc. 1992, 114, 2768; c) L. E. Marti-
nez, J. L. Leighton, D. H. Carsten, E. N. Jacobsen, J. Am. Chem.
1
3
J=9.0 Hz, 2H; ArH), 7.00 ppm (d, J=9.0 Hz, 2H; ArH); C NMR
75 MHz, CDCl ): d=20.35, 24.24, 25.04, 31.51, 33.04, 60.63, 74.43, 114.7,
27.7, 129.8, 145.3 ppm; IR (KBr): n˜ =3518, 3357, 2919, 2854, 1618, 1523,
CN): lmax (lg e)=206 (4.093), 249 (4.118),
02 nm (3.324); MS (70 eV, EI): m/z (%): 205 (43) [M] , 183 (16), 158
(
3
1
1
3
ꢀ
1
066, 805 cm ; UV/Vis (CH
3
+
(
8), 146 (92), 120 (31), 106 (100), 91 (36), 77 (23), 67 (40); the enantio-
2740
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2729 – 2741

Aminolysis of meso-Epoxides
FULL PAPER
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ently developed this chiral catalyst for Mukaiyama aldol reactions in
aqueous solution.
2
000, 33, 421.
[
3] a) S. E. Denmark, P. A. Barsanti, K. T. Wong, R. A. Stavenger, J.
Org. Chem. 1998, 63, 2428; b) W. A. Nugent, J. Am. Chem. Soc.
1
2
998, 120, 7139; c) B. Tao, M. M. C. Lo, G. C. Fu, J. Am. Chem. Soc.
001, 123, 353; d) M. Nakajima, M. Saito, M. Uemura, S. Hashimo-
[19] M. Reggelin, H. Weinberger, V. Spohr, Adv. Synth. Catal. 2004, 346,
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[20] See for example: a) H. C. Aspinall, Chem. Rev. 2002, 102, 1807;
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Fandrick, H. W. Lam, J. Wu, J. Am. Chem. Soc. 2003, 125, 10780;
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[21] S. E. Denmark, Y. Fan, J. Am. Chem. Soc. 2002, 124, 4233.
[22] Excellent reviewabout nonlinear effects: H. Kagan, C. Girard,
Angew. Chem. 1998, 110, 3088; Angew. Chem. Int. Ed. 1998, 37,
2922.
[
4] 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; Angew.
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C. A. Krueger, K. W. Kuntz, M. L. Snapper, A. H. Hoveyda, Angew.
Chem. 1997, 109, 1782; Angew. Chem. Int. Ed. Engl. 1997, 36, 1703;
c) S. E. Schaus, E. N. Jacobsen, Org. Lett. 2000, 2, 1001.
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Roels, E. M. Vogl, N. Yamamoto, T. Iida, K. Yamaguchi, M. Shiba-
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[
[
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Received: September 11, 2006
Published online: December 13, 2006
Chem. Eur. J. 2007, 13, 2729 – 2741
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2741