New chiral iminium salt catalysts for asymmetric epoxidation

Article abstract of DOI:10.1002/ejoc.200500756

A range of enantiomerically pure 4-substituted 5-amino-1,3-dioxanes has been condensed with 2-(2-bromoethyl)benzaldehyde to produce chiral dihydroisoquinolinium salts, which are effective asymmetric catalysts for the epoxidation of simple alkenes, giving ees of up to 71 %. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500756

FULL PAPER
DOI: 10.1002/ejoc.200500756
New Chiral Iminium Salt Catalysts for Asymmetric Epoxidation
Philip C. Bulman Page,*[a] Benjamin R. Buckley,[a] Gerasimos A. Rassias,[a] and
A. John Blacker[b]
Keywords: Iminium salt / Catalyst / Catalysis / Asymmetric epoxidation
A range of enantiomerically pure 4-substituted 5-amino-1,3-
dioxanes has been condensed with 2-(2-bromoethyl)benz-
aldehyde to produce chiral dihydroisoquinolinium salts,
which are effective asymmetric catalysts for the epoxidation
of simple alkenes, giving ees of up to 71%.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Introduction
In 1976 Lusinchi reported the preparation of the first
oxaziridinium salt, in a steroidal skeleton,[1] and showed
that it behaved as an electrophilic oxygen transfer reagent
towards nucleophiles. It was, however, not until some eleven
years later that a second, racemic, oxaziridinium salt 1, de-
rived from dihydroisoquinoline, was reported;[2] it was
shown to oxidize sulfides, amines, imines and alkenes. The
first enantiomerically pure chiral oxaziridinium salt 2 was
subsequently prepared by the quaternization of a chiral ox-
aziridine, derived from (1S,2R)-(+)-norephedrine.[3] The
corresponding iminium salt induced catalytic epoxidation
of trans-stilbene in 33% ee in the presence of oxone as stoi-
chiometric oxidant. Complete retention of stereochemistry
was observed, suggesting a single-step oxygen transfer pro-
cess. Rozwadowska has reported a related system 3, derived
from thiomicamine 4.[4] Biphenyl- and binaphthalene-de-
rived iminium salts have also been reported to catalyse the
asymmetric epoxidation of simple alkenes under similar
conditions.[5,6] Armstrong has shown that even acyclic imin-
ium salts can mediate epoxidation by oxone.[7] Komatsu[8]
and Yang[9] have independently reported acyclic iminium
salt catalysts for asymmetric epoxidation.
droisoquinolinium salts 7–12 based upon the dioxane-con-
taining catalyst 6, in which the aryl substituent present in
the acetal moiety of 6 has been replaced by other groups.
We have also reported that the related biphenyl-derived di-
benzazepinium salt 13 is a much more reactive epoxidation
catalyst than is the corresponding dihydroisoquinolinium
species.[14] We also report here three new dibenzazepinium
salts 14–16, similarly related to 13, and their use as epoxid-
ation catalysts.
We have described a new type of chiral cyclic iminium
salt epoxidation catalyst, in which the enantiocontrolling
asymmetric centres are located in the exocyclic substituent
at the nitrogen atom.[10,11] We have successfully employed
these iminium salts in the catalytic asymmetric epoxidation
of simple alkenes, giving ees of up to 97% when employing
catalysts 5[12] and 6.[13] Herein we report the design, synthe-
sis and use as epoxidation catalysts of several new dihy-
[a] Department of Chemistry, Loughborough University,
Loughborough, Leicestershire LE11 3TU, England
E-mail: p.c.b.page@lboro.ac.uk
[b] Avecia LifeScience Molecules,
P. O. Box 521, Leeds Road, Huddersfield, HD2 1GA, England
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FULL PAPER
Results and Discussion
Generation of catalyst 11, in which the aryl substituent
of 6 has been replaced with a methyl group, was ac-
complished by acetonide formation from the (l)-threonine-
derived diol 17, and removal of the N-Cbz group from the
resulting acetal 18 to afford the primary amine 19 required
for cyclocondensation with 2-(2-bromoethyl)benzaldehyde
under our usual conditions (Scheme 1).
Scheme 2. Reagents and conditions: i: iPrMgCl, THF, –78 °C, 2 h,
73%; ii: TFA, DCM, –78 °C to room temp., 3 h; iii: 2,2-DMP, ace-
tone, pTsOH, room temp., 8 h, 70%: iv: 2-(2-bromoethyl)benzalde-
hyde, NaBPh4, ethanol, room temp., 24 h, 70%.
2-(2-bromoethyl)benzaldehyde proceeded smoothly, gener-
ating the corresponding iminium salt catalysts 6–9, with the
4S,5S absolute configuration, having a tetraphenylborate
anion, typically in Ͼ70% yields (Scheme 3).
Scheme 1. Reagents and conditions: i: a) NMM, iBu–O–CO–Cl,
DME, –15 °C, 1 min; b) NaBH4, H2O, –15 °C, 1 min, 70%; ii: 2,2-
DMP, acetone, pTsOH, room temp., 8 h, 85%; iii: Pd/C, H2, etha-
nol, room temp., 8 h, 90 %; iv: 2-(2-bromoethyl)benzaldehyde,
NaBPh4, ethanol, room temp., 24 h, 66%.
The corresponding isopropyl-substituted catalyst 12 was
prepared from Garner’s aldehyde 20 as shown in
Scheme 2.[15] Reaction of Garner’s aldehyde with isopro-
pylmagnesium chloride at –78 °C under the conditions de-
scribed by Joullé[16] gave the addition product 21 with high
diastereoselectivity (Ͼ14:1) and in 73% yield. Global re-
moval of the N-BOC and acetonide protecting groups with
trifluoroacetic acid gave the amino diol as its trifluoroacetic
acid salt 22, which was treated directly with 2,2-dimeth-
oxypropane in the presence of p-toluenesulfonic acid. The
resulting acetonide 23 was cyclocondensed with 2-(2-bromo-
ethyl)benzaldehyde to give 12.
The primary amines 24, 25, and 26 required for the prep-
aration of catalysts 6, 7, and 8 were prepared in good yields
from the commercially available amino diols (+)-thiomic-
Scheme 3. Reagents and conditions: i: MeOCHO, MeOH, room
temp.; ii: (Me)2C(MeO)2, acetone, CSA, room temp. (24–26) or
amine (4) and 27, using a method similar to that developed (Me)2C(MeO)2, acetone, HBr (1.0 m, cat.), 0 °C, 2.5 h (28); iii:
H2NNH2·H2O, ∆; iv: 2-(2-bromoethyl)benzaldehyde, EtOH,
NaBPh4, room temp.
by Nordin and Thomas for the synthesis of the simpler ana-
logue (+)-acetonamine 28 from the amino diol 29.[17] Aceto-
namine 28 was itself used to prepare the phenyl-substituted
catalyst 9.[11] Treatment of each amino diol with methyl for-
The 4-methoxy-substituted catalyst 10, with the opposite
mate and subsequent acetal formation with 2,2-dimeth- 4R,5R absolute configuration, was prepared from the (l)-
oxypropane afforded the formate-protected acetonide, tyrosine derivative 30 following the work of Ohfune,[18]
which was deprotected to give the amino acetals 24, 25, 26, whereby a benzylic cation is generated by treatment with
28 in 60–80% overall yield by heating with hydrazine hy- potassium persulfate (K2S2O8) and copper, and trapped by
drate. In the case of amine 24, oxidation of the sulfide to an oxygen atom of the BOC group in an intramolecular
the sulfone was accomplished in 85% yield at the formate- and highly diastereoselective manner to form the oxazolid-
protected stage with mCPBA in dichloromethane at 0 °C. inone 31 (Ն 98% R at C3) (Scheme 4). Reduction of the
Cyclocondensation of the amino acetals 24, 25, 26, 28 with methyl ester was initially achieved with lithium aluminium
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New Chiral Iminium Salt Catalysts for Asymmetric Epoxidation
FULL PAPER
hydride (77%), but sodium borohydride provided a superior of the aryl substituent with the dihydroisoquinolinium unit
yield of 91%. Hydrolysis of the oxazolidinone with 1 m so- and/or with the substrate.
dium hydroxide produced the syn-(1R,2R)-amino diol 32.
The 4-nitro substituted salt 8 gave the worst results, giv-
ing at best 42% ee for 1-phenyl-3,4-dihydronaphthalene ox-
ide (Entry 3). The sulfide 7 gave similar ee values to the
sulfone-based catalyst 6, and catalyst 7 also gave the poor-
est epoxide conversions, we believe due at least in part to
the susceptibility of the thiomethyl group to undergo oxi-
dation giving 6 during the reaction, and so consuming oxi-
dant; it is well known that oxone can oxidize sulfides to
sulfoxides or sulfones.[19] Analysis of the catalyst by 1H
NMR spectroscopy after it had been subjected to the reac-
tion conditions showed, the proton signal for the thio-
methyl group had shifted from δ = 2.42 to δ = 3.0, and
comparison of the spectrum with that of catalyst 6 con-
firmed that 7 had indeed been oxidized to the sulfone under
the epoxidation reaction conditions. No sulfoxide was ob-
served. Iminium salt 8, containing the strongly electron-
withdrawing 4-nitro group, generally gave lower conversions
than did catalysts 6, 9 and 10, all of which gave similar
conversions to epoxide. By far the most active catalysts
were 9 and 10, both of which induced complete conversion
of 1-phenylcyclohexene into the epoxide in less than 3 min-
utes. One interesting point to note is that catalysts with an
electron-withdrawing group at the 4-position (6 and 8) ep-
oxidize trans-stilbene with very poor enantioselectivity.
Undoubtedly the best catalyst for epoxidation of the
range of alkenes tested here, when using oxone as the pri-
mary oxidant, was the 4-methoxy-substituted salt 10. It im-
parted the highest enantioselectivity of this group of cata-
lysts, giving triphenylethylene oxide with 71% ee in 60%
yield in only 30 minutes. Even trans-stilbene was epoxidized
with 35% ee.
Scheme 4. Reagents and conditions: i: K2S2O8, CuSO4, H2O/
MeCN (1:1), 70 °C, 3 h, 52 %; ii: NaBH4, EtOH, 0 °C to room
temp. 45 min, 91%, iii: 1 m NaOH, ∆, 20 min, 93%; iv: MeOCHO,
MeOH, room temp. 1 h; v: (Me)2C(MeO)2, acetone, BF3·Et2O,
room temp. 45 min, 81%; vi: H2NNH2·H2O, ∆, 2.5 h, 95%; vii: 2-
(2-bromoethyl)benzaldehyde, EtOH, NaBPh4, room temp., 71%.
We have also recently reported the preparation and use
of the related catalyst 13, in which the dihydroisoquinolin-
ium moiety has been replaced by a biphenyl structure fused
to a seven-membered azepinium salt.[14] Lacour has recently
reported related catalysts containing the interesting chiral
TRISPHAT counterion.[6] We report here several new mem-
bers of this family of catalysts 14–16, generated from the
substituted amino acetals described above.
Cyclocondensation of the amines 24, 26, 28, and 33, cho-
sen from the more effective catalysts of the dihydroisoquin-
olinium salt series, with the bromoaldehyde 34, prepared
from 2,2Ј-bis(hydroxymethyl)biphenyl,[12] afforded the cor-
responding dibenzazepinium salts 13–16 in good yields
The amino diol 32 was then subjected to the synthetic
procedure outlined in Scheme 4. However, attempted acetal-
ization of the formate-protected diol to the 1,3-dioxane did
not proceed smoothly with ( )-10-camphorsulfonic acid.
Catalytic boron trifluoride–diethyl ether was thus used in-
stead, and the desired six-membered ring dioxane was pro-
duced exclusively. Subsequent deprotection afforded the
primary amine 33, which was cyclocondensed to form the
desired iminium salt catalyst 10 in 71% yield.
Catalytic Asymmetric Epoxidation
With the syntheses of catalysts 6–12 complete, we were (Scheme 5). These catalysts were tested in the asymmetric
able to test their efficiency in the catalytic asymmetric epox- epoxidation of three alkene substrates: 1-phenylcyclohex-
idation of several unfunctionalized alkenes (Table 1), using ene, α-methylstilbene and triphenylethylene (Table 2).
10 mol-% of catalyst in acetonitrile/water (1:1), at 0 °C with
oxone (2 equiv.) as stoichiometric oxidant and sodium car- ees than did their six-membered ring dihydroisoquinolinium
bonate (4 equiv.) as base. counterparts. Methoxy-substituted catalyst 16, however,
These new catalysts in general induced slightly poorer
The catalysts 11 and 12, containing alkyl group substitu- gave 1-phenylcyclohexene oxide with 63% ee (compared to
ents in the acetal moiety, while inducing efficient epoxid- 45% ee for six-membered ring catalyst 10). Disappointingly,
ation, gave less than 5% ee in the epoxidation of 1-phenyl- for reasons that at this moment remain unclear, triphenyl-
cyclohexene. These results, not included in Table 1, suggest ethylene proved to be a poor substrate with catalysts 14
that the aromatic nature of the C4 substituent of 6 is vital (11% ee), 15 (10% ee), and 16 (26% ee); we have previously
for catalyst enantioselectivity, perhaps due to interactions reported a 59% ee for triphenylethylene oxide when catalyst
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FULL PAPER
Table 1. Catalytic asymmetric epoxidation of alkenes using dihydroisoquinolinium salts.[a]
[a] Epoxidation conditions: Iminium salt (10 mol-%), oxone (2 equiv.), Na2CO3 (4 equiv.), MeCN/H2O (1:1), 0 °C, 2 h. [b] Catalyst 6–9
configuration (4S,5S); Catalyst 10 configuration (4R,5R). [c] Enantiomeric excesses were determined by 1H NMR spectroscopy in the
presence of (+)-Eu(hfc)3 (0.1 mol equiv.) or by chiral HPLC on a Chiracel OD column. [d] Conversions were evaluated from the 1H NMR
spectra by integration of alkene and epoxide signals. [e] The absolute configurations of the major enantiomers were determined by
comparison of optical rotations with those reported in the literature. [f] Isolated yields.
Scheme 5. i: a) EtOH, room temp., 12 h; b) NaBPh4.
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New Chiral Iminium Salt Catalysts for Asymmetric Epoxidation
FULL PAPER
Table 2. Catalytic asymmetric epoxidation of unfunctionalized alkenes using azepinium salts.[a]
[a] Epoxidation conditions: Iminium salt (5 mol-%), oxone (2 equiv.), Na2CO3 (4 equiv.), MeCN/H2O (1:1), 0 °C, 2 h. [b] Catalyst 13–15
configuration (4S,5S); Catalyst 16 configuration (4R,5R). [c] Enantiomeric excesses were determined by 1H NMR spectroscopy in the
presence of (+)-Eu(hfc)3 (0.1 mol equiv.). [d] Conversions were evaluated from the 1H NMR spectra by integration of alkene and epoxide
signals. [e] The absolute configurations of the major enantiomers were determined by comparison of optical rotations with those reported
in the literature. [f] Isolated yields.
national mass spectrometry service at the University of Wales,
Swansea, utilising electrospray (ES.). Analysis by GCMS utilized a
Fisons GC 8000 series (AS, 800), using a 15 m×0.25 mm DB-5
column and an electron-impact low resolution mass spectrometer.
Melting points were recorded using an Electrothermal-IA
9100 melting point instrument and are uncorrected. Optical rota-
tion values were measured with an Optical Activity-polAAar 2001
instrument, operating at λ = 589 nm, corresponding to the sodium
D line, at the temperatures indicated. Microanalyses were per-
formed on a Perkin–Elmer Elemental Analyser 2400 CHN. All
chromatographic manipulations used silica gel as the adsorbent.
Reactions were monitored using thin-layer chromatography (TLC)
on aluminium-backed plates coated with Merck Kieselgel 60 F254
silica gel. TLC plates were visualised by UV radiation at a wave-
length of 254 nm, or stained by exposure to an ethanolic solution
of phosphomolybdic acid (acidified with concentrated sulfuric
acid), followed by charring where appropriate. Reactions requiring
13 is employed. These seven-membered ring catalysts, how-
ever, provide dramatically faster reactions, providing com-
plete consumption of alkene substrates in five to ten min-
utes, as opposed to around one hour for the six-membered
ring systems under the same conditions.
Conclusions
We have discovered that the aromatic substituent present
in the acetal moiety of our catalysts is vital for asymmetric
induction during the epoxidation reaction. The new 4-meth-
oxy-substituted catalyst 10 provides promising enantio-
selectivity in the group of alkenes tested, using oxone as the
primary oxidant. The corresponding series of catalysts
based around a dibenzazepinium nucleus is highly reactive,
and all the catalysts described can be easily synthesized in anhydrous conditions were carried out using glassware dried over-
night at 150 °C, under nitrogen unless otherwise stated. Reaction
solvents were used as obtained commercially unless otherwise
stated. Light petroleum (b.p. 40–60 °C) was distilled from calcium
chloride prior to use. Ethyl acetate was distilled from over calcium
sulfate or chloride. Dichloromethane was distilled from over cal-
cium hydride. Tetrahydrofuran was distilled under nitrogen from
the sodium/benzophenone ketyl radical or from lithium aluminium
hydride. Enantiomeric excesses were determined either by proton
nuclear magnetic resonance spectroscopy in the presence of europi-
um(iii) tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphor-
ate] as the chiral shift reagent, or by chiral HPLC using a Chiracel
OD column on a TSP Thermo-Separating-Products Spectra Series
P200 instrument, with a TSP Spectra Series UV100 ultra-violet ab-
sorption detector set at 254 nm and a Chromojet integrator.
good yields. We continue to develop this catalyst motif in
order to achieve higher degrees of enantiocontrol.
Experimental Section
General: Acronyms: CSA = ( )-10-camphorsulfonic acid, DCM =
dichloromethane, mCPBA = m-chloroperbenzoic acid, 2,2-DMP =
2,2-dimethoxypropane, NMM = N-methylmorpholine. All infrared
spectra were obtained with a Perkin–Elmer Paragon 1000 FT-IR
spectrophotometer; thin film spectra were acquired using sodium
chloride plates. All 1H and 13C NMR spectra were measured at
250.13 and 62.86 MHz with a Bruker AC 250 MHz spectrometer
or at 400.13 and 100.62 MHz with a Bruker DPX 400 MHz spec-
trometer, in deuteriochloroform solution unless otherwise stated,
using TMS (tetramethylsilane) as the internal reference. Mass spec-
tra were recorded with a Jeol-SX102 instrument utilizing electron-
impact (EI), fast atom bombardment (FAB), and by the EPSRC
(2R,3R)-2-(Benzyloxycarbonylamino)butane-1,3-diol (17): N-Meth-
ylmorpholine (2.20 mL, 19.8 mmol) and isobutyl chloroformate
(2.50 mL, 19.8 mmol) were successively added to a cooled (–15 °C)
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solution of (2S,3R)-N-benzyloxycarbonyl-l-threonine (5.00 g,
19.8 mmol) in 1,2-dimethoxyethane (20 mL). After 1 min the white
precipitate was removed by filtration, washed with 1,2-dimethoxy-
ethane (2×5 mL), and the filtrate cooled using an ice/salt bath. A
solution of NaBH4 (1.13 g, 29.6 mmol) in water (50 mL) was added
in one portion. After the evolution of gas subsided, water (250 mL)
was added. The reaction mixture was extracted with ethyl acetate
(3×75 mL), the combined organic layers were washed with brine
(2×50 mL) and dried (MgSO4), and the solvents removed under
reduced pressure to give 17 as a colourless oil (3.30 g, 70%). [α]D
with brine, dried (Na2SO4), filtered, and the solvents removed un-
der reduced pressure to give a yellow solid. Column chromatog-
raphy, eluting with ethyl acetate/light petroleum (1:8), and
recrystallization (ethyl acetate/light petroleum) gave 21 as a colour-
less crystalline solid (1.2 g, 73%); m.p. 77–79 °C (ref.[16] m.p. 78–
80 °C). [α]2D0 = –52.2 (c = 1.06, CHCl3) (ref.[16] [α]D = –54.3)].
C14H27NO4 (273.37): calcd. C 61.51, H 9.96, N 5.12; found C
61.92, H 9.93, N 4.96. IR (film, cm–1): νmax 3582, 3396, 1702, 1670,
˜
1459, 1377, 1366, 1174. 1H NMR (250 MHz, CDCl3, ppm): δ =
0.90 (d, J = 6.7 Hz, 3 H), 0.98 (d, J = 6.8 Hz, 3 H), 1.44 (s, 9 H),
1.51 (s, 3 H) 1.60 (s, 3 H), 1.63–1.70 (m, 1 H), 3.45–3.49 (m, 1 H),
= –15.0 (c = 1.12, CHCl ). IR (film, cm–1): ν
= 3334, 2971,
˜
3
max
1
2360, 1698, 1522, 1456, 1251, 1069. H NMR (250 MHz, CDCl3, 3.70–3.96 (m, 1 H), 3.98–4.10 (m, 1 H). 13C NMR (100 MHz,
ppm): δ = 1.20 (d, J = 6.4 Hz, 3 H), 2.74 (br. s, 2 H), 3.51–3.61 (m,
CDCl3, ppm): δ = 14.3, 20.4, 24.4, 27.3, 28.4, 31.0, 60.6, 65.3, 78.5,
1 H), 3.81 (br. s, 2 H), 4.05–4.20 (m, 1 H), 5.11 (s, 2 H), 5.54 (d, J 81.4, 94.1, 155.7. MS: m/z = 273.1944. C14H27NO4 [M+] requires
= 8.6 Hz, 1 H), 7.25–7.47 (m, 5 H). 13C NMR (100 MHz, CDCl3,
ppm): δ = 20.2, 56.3, 64.4, 67.0, 128.1, 128.2, 128.6, 136.3, 157.2.
MS: m/z = 239.1152. C12H17NO4 [M+] requires 239.1158.
273.1940.
(4S,5S)-2,2-Dimethyl-4-(1-methylethyl)-1,3-dioxan-5-amine (23):
(4S)-N-tert-Butoxycarbonyl-4-[(1S)-hydroxy-2-methylpropyl]-2,2-
(4R,5R)-5-(Benzyloxycarbonylamino)-2,2,4-trimethyl-1,3-dioxane dimethyloxazolidine (21) (0.10 g, 0.37 mmol) was dissolved in
(18): (2R,3R)-2-(benzyloxycarbonylamino)butane-1,3-diol (17)
(0.20 g, 0.87 mmol) was dissolved in acetone (20.0 mL) and 2,2-
dimethoxypropane (1.10 mL, 8.70 mmol). A catalytic amount of p-
toluenesulfonic acid (10 mol-%, 0.016 g, 0.09 mmol) was added and
the reaction stirred overnight at room temperature. The solvent was
evaporated under reduced pressure. The residue was dissolved in
ethyl acetate, and the solution washed with sodium hydrogen car-
bonate (50%) (2×20 mL) and brine (2×20 mL). The organic layers
were combined, dried (Mg2SO4), and the solvents removed under
reduced pressure to give 18 as a colourless oil (0.24 g, 85%), [α]D
dichloromethane (1 mL), and the solution cooled using an ice bath.
Trifluroacetic acid (0.50 mL, 6.50 mmol) was added dropwise. The
mixture was stirred for 1.5 hours in an ice bath; the ice bath was
removed, and the mixture stirred for a further 1.5 hours while
reaching room temperature. The solvents were removed under re-
duced pressure and the residue dissolved in acetone (25 mL) and
2,2-dimethoxypropane (0.45 mL, 3.70 mmol), together with a cata-
lytic amount of p-toluenesulfonic acid. The mixture was stirred
overnight at room temperature. The solvents were removed under
reduced pressure, and the dark oil dissolved in dichloromethane.
= –8.2 (c = 1.04, CHCl3). C15H21NO4 (279.33): calcd. C 64.50, H The solution was washed with saturated aqueous sodium hydrogen
7.58, N 5.01; found C 64.27, H 7.46, 4.61. IR (film, cm–1): ν
=
carbonate, dried (MgSO4), and the solvents removed under reduced
˜
max
1
2360, 1716, 1505, 1455, 1381. H NMR (400 MHz, CDCl3, ppm):
δ = 1.60 (d, J = 6.3 Hz, 3 H), 1.40 (s, 3 H), 1.48 (s, 3 H), 3.53 (dq,
J = 9.8, 1.9 Hz, 1 H), 3.78 (dd, J = 12.0, 1.8 Hz, 1 H), 4.09 (dd, J
= 12.0, 2.0 Hz, 1 H), 4.15 (ddd, J = 6.3, 1.9 Hz, 1 H), 5.16 (s, 2
H), 5.58 (d, J = 9.8 Hz, 1 H), 7.27–7.44 (m, 5 H). 13C NMR
(100 MHz, CDCl3, ppm): δ = 18.2, 18.9, 30.1, 50.0, 65.3, 67.2, 67.4,
99.4, 127.3, 128.5, 128.9, 136.9, 156.8. MS: m/z = 279.1471.
C15H21NO4 [M+] requires 279.1471.
pressure to give 23 as a pale yellow oil (0.045 g, 70%). IR (film,
cm–1): νmax 3583, 2966, 2361, 2306, 1675, 1471, 1265, 1138. [α]2D0
=
˜
1
+32.2 (c = 1.02, CHCl3). H NMR (250 MHz, CDCl3, ppm): δ =
0.86 (d, J = 6.7 Hz, 3 H), 0.95 (d, J = 6.5 Hz, 3 H), 1.41 (s, 3 H),
1.42 (s, 3 H), 1.69–1.87 (m, 1 H), 2.20 (br. s, 2 H), 2.65 (dd, J =
3.8, 2.0 Hz, 1 H), 3.32 (dd, J = 9.6, 1.6 Hz, 1 H), 3.72 (dd, J =
11.9, 2.0 Hz, 1 H), 4.06 (dd, J = 11.8, 2.1 Hz, 1 H). 13C NMR
(100 MHz, CDCl3, ppm): δ = 19.0, 19.1, 27.6, 28.1, 32.5, 63.1, 64.3,
84.1, 94.6. MS: m/z = 173.1419. C9H19NO2 [M+] requires 173.1416.
(4R,5R)-5-Amino-2,2,4-trimethyl-1,3-dioxane (19): (4R,5R)-5-(Ben-
zyloxycarbonylamino)-2,2,4-trimethyl-1,3-dioxane (18) (1.30 g,
4.7 mmol) was dissolved in ethanol under a slight positive pressure
of hydrogen. Palladium (10% on carbon) (0.10 g) was added. The
mixture was stirred at room temperature for 12 h, filtered through
a pad of celite, and the ethanol removed under reduced pressure to
give 19 as a colourless oil (0.61 g, 90%), [α]D = –26.7 (c = 1.05,
General Procedure for the Formation of 5-Amino-1,3-dioxanes from
Amino Diols: The amino diol (1.0 equiv.) was dissolved in methanol
(10 mL/g), and methyl formate (1.1 equiv.) added together with so-
dium methoxide (10 mol-%). The mixture was stirred for 3.5 h and
the solvent removed under reduced pressure. The crude yellow oil
was dissolved in acetone (50 mL/g), and CSA (10 mol-%) and 2,2-
CHCl ). IR (film, cm–1): νmax = 3580, 2959, 1605, 1473, 1262, 1140. dimethoxypropane (10.0 equiv.) added. The mixture was stirred for
˜
3
1H NMR (250 MHz, CDCl3, ppm): δ = 1.16 (d, J = 6.4 Hz, 3 H),
1.41 (s, 3 H), 1.46 (s, 3 H), 1.60 (br. s, 2 H), 2.42 (q, J = 4.0, 2.0 Hz,
1 H), 3.72 (dd, J = 11.8, 2.0 Hz, 1 H), 4.11 (dd, J = 11.8, 2.0 Hz,
1 H), 4.09 (m, 1 H). 13C NMR (100 MHz, CDCl3, ppm): δ = 18.3,
19.0, 30.1, 49.2, 67.4, 68.0, 99.1. MS: m/z = 145.1100. C7H15NO2
[M+] requires 145.1103.
up to 4 h and monitored by TLC. Upon completion, the solvents
were removed under reduced pressure and the residue redissolved
in ethyl acetate. The solution was washed with saturated aqueous
sodium hydrogen carbonate, dried (MgSO4), and the solvents re-
moved under reduced pressure to give the formate-protected 1,3-
dioxane, which was dissolved in aqueous hydrazine hydrate (85%)
(20 mL/g) and the solution heated under reflux for 2.5 h. The solu-
tion was cooled to room temperature and extracted with ethyl ace-
tate (3×20 mL/g). The combined organic solutions were washed
with water (2×20 mL/g), dried (MgSO4), and the solvents removed
under reduced pressure.
(4S)-N-tert-Butoxycarbonyl-4-[(1S)-hydroxy-2-methylpropyl]-2,2-di-
methyloxazolidine (21): A solution of isopropylmagnesium chloride
(2 m in THF, 8.60 mL, 17.2 mmol) was added dropwise over 30 min
to a pre-cooled solution of Garner’s aldehyde, (4S)-N-tert-butoxy-
carbonyl-2,2-dimethyloxazolidine-4-carbaldehyde (20) (1.20 g,
5.2 mmol) in tetrahydrofuran (50 mL) at –78 °C, under a stream (4S,5S)-5-Formylamino-2,2-dimethyl-4-[4-(methylsulfonyl)phenyl]-
of nitrogen. The resulting dark yellow solution was stirred for an
additional 2 h at –78 °C, and warmed to 0 °C. The reaction mixture
was diluted with diethyl ether (50 mL), and saturated aqueous am-
monium chloride (10 mL) added. The organic layer was washed
1,3-dioxane: (4S,5S)-5-formylamino-2,2-dimethyl-4-[4-(methylthio)-
phenyl]-1,3-dioxane (4.00 g, 14.2 mmol) was dissolved in dichloro-
methane (100 mL) and the solution cooled to 0 °C. A solution of
mCPBA (2.2 equiv., 7.03 g, 31.0 mmol) in chloroform (20 mL) was
808
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Eur. J. Org. Chem. 2006, 803–813

New Chiral Iminium Salt Catalysts for Asymmetric Epoxidation
FULL PAPER
added dropwise over 10 min. The reaction was then stirred for 2 h,
washed with saturated aqueous sodium hydrogen carbonate
(2×40 mL) and brine (2×40 mL), and dried (MgSO4). The sol-
vents were removed under reduced pressure to give a colourless oil.
Crystallization from chloroform/diethyl ether gave the product as
a colourless crystalline solid (3.80 g, 85%); m.p. 146–147 °C. [α]D
1.7 Hz, 1 H), 4.24 (dd, J = 12.1, 1.8 Hz, 1 H), 4.34–4.44 (m, 1 H),
5.26 (d, J = 1.0 Hz, 1 H), 7.50 (d, J = 8.9 Hz, 2 H), 7.91 (s, 1 H),
8.15 (d, J = 8.9 Hz, 2 H). 13C NMR (62.5 MHz, CDCl3, ppm): δ
= 18.8, 29.3, 45.4, 64.9, 71.9, 100.7, 123.7, 126.8, 145.8, 147.8,
160.6. MS: m/z = 298.1399. C13H16N2O5 [M+ + NH4] requires
298.1403.
= –11.6 (c = 1.21, CHCl ). IR (film, cm–1): ν
3054, 2993, 1675,
˜
3
max
(4S,5S)-5-Amino-2,2-dimethyl-4-(4-nitrophenyl)-1,3-dioxane (26):
Prepared according to the general procedure from (4S,5S)-5-for-
mylamino-2,2-dimethyl-4-(4-nitrophenyl)-1,3-dioxane (4.00 g,
14.9 mmol), and purified by chromatography, eluting with ethyl
1516, 1382, 1300, 1239, 1202, 1149, 1086, 948. C14H19NO5S
(313.37): calcd. C 53.66, H 6.11, N 4.47; found C 52.68, H 6.12, N
4.33. 1H NMR (400 MHz, CDCl3, ppm): δ = 1.54 (s, 3 H), 1.57 (s,
3 H), 3.01 (s, 3 H), 3.82 (dd, J = 12.0, 2.0 Hz, 1 H), 4.33 (dd, J =
12.0, 1.6 Hz, 1 H), 4.37 (dd, J = 10.0, 1.6 Hz, 1 H), 5.25 (s, 1 H),
6.51 (d, J = 9.2 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 2 H), 7.85 (d, J =
8.0 Hz, 2 H), 7.89 (s, 1 H). 13C NMR (100 MHz, CDCl3, ppm): δ
= 18.9, 29.9, 44.8, 45.4, 64.9, 71.9, 100.4, 127.0, 127.5, 140.0, 145.0,
160.9. MS: m/z = 314.1058. C14H19NO5S [M+ + H] requires
314.1062.
acetate. Pale yellow plates (2.80 g, 78%); m.p. 117–119 °C. [α]2D0
=
+66.2 (c = 1.13, CHCl3). C12H16N2O4 (252.27): calcd. C 57.13, H
6.39, N 11.10; found C 57.05, H 6.51, N 10.77. IR (film, cm–1):
ν
˜
max = 1605, 1520, 1350, 1196, 1080, 941, 856. 1H NMR (250 MHz,
CDCl3, ppm): δ = 1.56 (s, 6 H), 2.84 (q, J = 1.9 Hz, 1 H), 3.86 (dd,
J = 11.8, 1.9 Hz, 1 H), 4.31 (dd, J = 11.8, 2.3 Hz, 1 H), 5.17 (d, J
= 0.7 Hz, 1 H), 7.49 (d, J = 7.5 Hz, 2 H), 8.22 (d, J = 7.5 Hz, 2
H). 13C NMR (100 MHz, CDCl3, ppm): δ = 18.6, 29.7, 49.4, 66.3,
73.4, 99.6, 123.6, 126.7, 147.2, 147.3. MS: m/z = 253.1191.
C12H16N2O4 [M + H] requires 253.1188.
(4S,5S)-5-Amino-2,2-dimethyl-4-[4-(methylsulfonyl)phenyl]-1,3-di-
oxane (24): Prepared according to the general procedure from
(4S,5S)-5-formylamino-2,2-dimethyl-4-[4-(methylsulfonyl)phenyl]-
1,3-dioxane (1.80 g, 5.8 mmol), isolated as a colourless oil, and
crystallized from diethyl ether/ethyl acetate. Colourless crystals
(1.59 g, 96%); m.p. 120–122 °C. [α]2D0 = +50.0 (c = 1.00, CHCl3).
C13H19NO4S (285.36): calcd. C 54.72, H 6.71, N 4.91; found C
(4R,5R)-5-Formylamino-2,2-dimethyl-4-(4-methoxyphenyl)-1,3-di-
oxane: (1R,2R)-(–)-2-Amino-1-(4-methoxyphenyl)-1,3-propanediol
(1.20 g, 6.1 mmol) was dissolved in methanol (25 mL), and methyl
formate (0.45 mL, 7.3 mmol) added together with sodium methox-
ide (0.1 mL). The mixture was stirred for 3.5 h, and the solvent
removed under reduced pressure. The crude yellow oil was dis-
solved in acetone (60 mL) and 2,2-dimethoxypropane (10 equiv.),
and boron trifluoride–diethyl ether added until pale yellow colour
persisted (ca. 0.2 mL). The reaction was then stirred for 45 min.
The solvents were removed under reduced pressure and the residue
dissolved in ethyl acetate. The solution was washed with saturated
aqueous sodium hydrogen carbonate, dried (MgSO4), and the sol-
vents removed to give a pale yellow oil (1.21 g, 75%). [α]D = –2.7
54.64, H 6.69, N 4.83. IR (film, cm–1): ν
= 3372, 2991, 1601,
˜
max
1380, 1198, 1077, 949. 1H NMR (400 MHz, CDCl3, ppm): δ = 1.56
(s, 6 H), 2.82–3.00 (m, 1 H), 3.06 (s, 3 H), 3.88 (dd, J = 11.6,
2.0 Hz, 1 H), 3.24 (dd, J = 11.6, 2.4 Hz, 1 H), 5.10–5.19 (m, 1 H),
7.55 (d, J = 8.0 Hz, 2 H), 7.95 (d, J = 8.0 Hz, 2 H). 13C NMR
(100 MHz, CDCl3, ppm): δ = 19.0, 30.0, 44.9, 49.8, 66.8, 73.9, 99.9,
127.2, 127.9, 139.9, 146.6. MS: m/z = 285.1028. C13H19NO4S [M+]
requires 285.1035.
(4S,5S)-5-Formylamino-2,2-dimethyl-4-[4-(methylthio)phenyl]-1,3-
dioxane: Prepared according to the general procedure from (1S,2S)-
(+)-2-amino-1-(4-methylthiophenyl)-1,3-propandiol (5.00 g, 1248, 1199, 1084, 1032, 949. H NMR (250 MHz, CDCl3, ppm): δ
(c = 1.20, CHCl ). IR (film, cm–1): ν
= 2992, 1668, 1515, 1381,
˜
3
max
1
23.4 mmol). Colourless oil (5.50 g, 84%). [α]D = +1.3 (c = 1.27,
= 1.54 (s, 3 H), 1.58 (s, 3 H), 3.78 (s, 3 H), 3.87 (dd, J = 12.25,
CHCl ). IR (film, cm–1): νmax = 3315, 2988, 2362, 1667, 1494, 1380, 1.95 Hz, 1 H), 4.20–4.33 (m, 2 H), 5.16 (s, 1 H), 6.19 (d, J =
˜
3
1
1197, 1084, 947. H NMR (250 MHz, CDCl3, ppm): δ = 1.54 (s, 3
H), 1.58 (s, 3 H), 2.45 (s, 3 H), 3.87 (dd, J = 7.5, 1.0 Hz, 1 H), 4.24
(dd, J = 7.5, 1.0 Hz, 1 H), 4.21–4.33 (m, 1 H), 5.16 (d, J = 1.3 Hz,
8.55 Hz, 1 H), 6.85 (d, J = 8.90 Hz, 2 H), 7.23 (d, J = 8.90 Hz, 2
H), 8.00 (s, 1 H). 13C NMR (100 MHz, CDCl3, ppm): δ = 18.6,
29.6, 45.6, 55.3, 64.6, 71.4, 99.7, 113.7, 126.5, 130.1, 159.0, 160.5.
1 H), 6.27 (d, J = 5.8 Hz, 1 H), 7.20 (s, 4 H), 7.97 (s, 1 H). 13C MS: m/z = 266.1390. C14H19NO4 [M + H] requires 266.1392.
NMR (100 MHz, CDCl3, ppm): δ = 15.8, 18.5, 29.7, 45.3, 64.6,
(4R,5R)-5-Amino-2,2-dimethyl-4-(4-methoxyphenyl)-1,3-dioxane
71.4, 99.7, 125.8, 126.6, 135.0, 137.8, 160.5. MS: m/z = 281.1081.
(33): Prepared according to the general procedure from (4R,5R)-5-
C14H19NO3S [M+] requires 281.1085.
formylamino-4-(4-methoxyphenyl)-2,2-dimethyl-1,3-dioxane
(4S,5S)-5-Amino-2,2-dimethyl-4-[4-(methylthio)phenyl]-1,3-dioxane
(25): Prepared according to the general procedure from (4S,5S)-5-
(0.70 g, 2.6 mmol). Colourless oil. (0.59 g, 95%). [α]2D0 = –28.9 (c =
1.08, CHCl ). IR (film, cm–1): νmax = 3050, 2991, 2925, 1612, 1515,
˜
3
formylamino-2,2-dimethyl-4-[4-(methylthio)phenyl]-1,3-dioxane 1458, 1380, 1249, 1199, 1129, 1079, 948, 850. 1H NMR (250 MHz,
(1.50 g, 5.34 mmol). Colourless oil (1.28 g, 95%). [α]2D0 = +44.7 (c
= 1.20, CHCl ). IR (film, cm–1): ν
= 3369, 2990, 1599, 1495,
CDCl3, ppm): δ = 1.53 (s, 3 H), 1.55 (s, 3 H), 2.72 (q, 1 H, 2.0 Hz,
1 H), 3.81 (s, 3 H), 3.89 (dd, J = 13.4, 1.7 Hz, 1 H), 4.29 (dd, J =
˜
3
max
1379, 1198, 1076, 947. 1H NMR (400 MHz, CDCl3, ppm): δ = 1.53 11.7, 2.3 Hz, 1 H), 5.05 (d, J = 1.9 Hz, 1 H), 6.89 (d, J = 8.8 Hz,
(s, 3 H), 1.54 (s, 3 H), 2.47 (s, 3 H), 2.72 (q, J = 2.0 Hz, 1 H), 3.88
(dd, J = 12.0, 2.0 Hz, 1 H), 4.27 (dd, J = 12.0, 2.4 Hz, 1 H), 5.05
1 H), 7.24 (d, J = 8.8 Hz, 2 H). 13C NMR (100 MHz, CDCl3, ppm):
δ = 19.0, 30.1, 50.2, 55.7, 66.4, 73.9, 99.5, 114.3, 127.2, 132.1, 159.3.
(d, J = 1.6 Hz, 1 H), 7.23–7.28 (m, 4 H). 13C NMR (100 MHz, MS: m/z = 238.1443. C13H19NO3 [M + H] requires 238.1443.
CDCl3, ppm): δ = 16.0, 18.6, 29.7, 49.6, 66.1, 73.5, 99.2, 126.4,
N-tert-Butoxycarbonyl-O-methyl-L-tyrosine Methyl Ester (30): A
126.8, 136.6, 137.4. MS: m/z = 253.1137. C13H19NO2S [M+] re-
quires 253.1137.
solution of N-tert-butoxycarbonyl-l-tyrosine (8.00 g, 28.5 mmol) in
dimethyl formamide (80 mL) was cooled using an ice bath, treated
with freshly ground potassium hydroxide (1.72 g, 31.3 mmol), and
a cooled solution of iodomethane (1.95 mL, 31.3 mmol) in di-
methyl formamide (20 mL) added dropwise over 5 min. The mix-
ture was stirred at room temperature for 30 min, cooled using an
(4S,5S)-5-Formylmino-2,2-dimethyl-4-(4-nitrophenyl)-1,3-dioxane:
Prepared according to the general procedure from (1S,2S)-(+)-2-
amino-1-(4-nitrophenyl)-1,3-propandiol (27) (1.00 g, 4.71 mmol).
Colourless oil (1.12 g, 85%). [α]D = +3.5 (c = 1.02, CHCl3). IR
(film, cm–1): ν
= 1674, 1520, 1346, 856. 1H NMR (250 MHz, ice bath, and additional potassium hydroxide (1.72 g, 31.3 mmol)
˜
max
CDCl3, ppm): δ = 1.55 (s, 3 H), 1.59 (s, 3 H), 3.83 (dd, J = 12.1,
and a cooled solution of iodomethane (1.95 mL, 31.3 mmol) in di-
Eur. J. Org. Chem. 2006, 803–813
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P. C. Bulman Page, B. R. Buckley, G. A. Rassias, A. J. Blacker
FULL PAPER
methyl formamide (20 mL) added. The mixture was stirred for 3 h,
poured onto ice (150 mL), and extracted with ethyl acetate
(3 × 75 mL). The organic layers were washed with water
(3×50 mL), brine (2×50 mL) and dried (MgSO4). The solvent was
removed under reduced pressure to afford a colourless oil.
Crystallization was achieved from ethyl acetate/light petroleum, to
give 30 as colourless crystals (6.5 g, 74%); m.p. 52–53 °C. IR (film,
was recrystallized from methanol/diethyl ether (1.33 g, 91%); m.p.
132–134 °C. [α]2D0 = –28.3 (c = 1.06, 2 m aq. HCl). C10H15NO3
(197.23): calcd. C 60.90, H 7.67; N 7.10; found C 61.14, H 7.51; N
6.96. IR (nujol, cm–1): νmax = 3338, 1615, 1583, 1515, 1459, 1376,
˜
1253, 1064, 873. 1H NMR (400 MHz, CD3OD, ppm): δ = 2.86–
2.98 (m, 1 H), 3.32 (dd, J = 10.8, 4.4 Hz, 1 H), 3.42 (dd, J = 10.8,
4.4 Hz, 1 H), 3.80 (s, 3 H), 4.49 (d, J = 7.2 Hz, 1 H), 4.90 (br. s, 2
cm–1): νmax = 2976, 1746, 1716, 1612, 1515, 1391, 1366, 1248, 1175, H), 6.90 (d, J = 8.8 Hz, 2 H), 7.29 (d, J = 8.8 Hz, 2 H). 13C NMR
˜
1
1058, 1034. H NMR (250 MHz, CDCl3, ppm): δ = 1.42 (s, 9 H), (100 MHz, CD3OD, ppm): δ = 56.1, 60.3, 64.4, 75.8, 115.2, 129.2,
3.01–3.11 (m, 2 H), 3.71 (s, 3 H), 3.78 (s, 3 H), 4.53 (q, J = 5.7 Hz, 136.4, 161.1. MS: m/z = 198.1125. C10H16NO3 [M+ + H] requires
1 H), 5.00 (d, J = 6.7 Hz, 1 H), 6.82 (d, J = 8.7 Hz, 2 H), 7.03 (d,
J = 8.7 Hz, 2 H). 13C NMR (100 MHz, CDCl3, ppm): δ = 28.3,
37.6, 52.7, 54.7, 55.3, 79.9, 114.1, 128.1, 130.3, 155.1, 158.8, 172.4.
MS: m/z = 309.1578. C16H23NO5 requires 309.1576.
198.1130.
General Procedure for the Preparation of Dihydroisoquinolinium
Salts from 2-(2-Bromoethyl)benzaldehyde and Primary Amines: 2-
(2-Bromoethyl)benzaldehyde (1.60 equiv., 1.10 if freshly distilled)
Methyl (4S,5R)-5-(4-Methoxyphenyl)-2-oxo-1,3-oxazolidine-4-car- was cooled using an ice bath, and a solution of the amine in ethanol
boxylate (31): A solution of N-tert-butoxycarbonyl-O-methyl-l-ty-
rosine methyl ester (30) (5.00 g, 16.2 mmol) in CH3CN (200 mL)
was treated with a solution of K2S2O8 (8.75 g, 32.4 mmol) in water
(210 mL) and a solution of CuSO4 (0.52 g, 3.2 mmol) in water
(50 mL). The mixture was heated to 70 °C for 3 h under a blanket
of N2, cooled, and extracted with ethyl acetate (3×150 mL). The
combined organic solutions were dried (MgSO4) and concentrated
under reduced pressure to give a dark yellow oil. Column
chromatography, eluting with ethyl acetate/light petroleum (1:10 to
1:1), afforded a colourless solid, which was recrystallized from ethyl
acetate/light petroleum to give 31 as a colourless crystalline solid
(2.10 g, 52%); m.p. 94–96 °C. [α]2D0 = +83.5 (c = 1.15, CHCl3). IR
(10 mL per g of amine) was added dropwise. After the addition
was complete, the ice bath was removed and the reaction mixture
stoppered to retain HBr and stirred overnight. A solution of so-
dium tetraphenylborate or other anion-exchanging salt (1.10 equiv.)
in the minimum amount of acetonitrile was added in one portion
to the reaction mixture. After stirring for 5 min, the organic sol-
vents were removed under reduced pressure. Ethanol was added to
the residue, followed by water. The resulting precipitate was col-
lected by filtration and washed with additional ethanol followed by
diethyl ether. If no solid materialized after the addition of the water,
the mixture was allowed to settle and the ethanol/water phase was
decanted. The gummy residue was triturated in hot ethanol or
methanol, inducing precipitation of the organic salt immediately or
upon slow cooling of the hot alcoholic solution. Small quantities
(film, cm–1): νmax = 3316, 2956, 2362, 2337, 1762, 1613, 1515, 1382,
˜
1
1250, 1224, 1026, 834, 763. H NMR (400 MHz, CDCl3, ppm): δ
= 3.81 (s, 3 H), 3.83 (s, 3 H), 4.31 (d, J = 5.2 Hz, 1 H), 5.56 (d, J of acetonitrile may be added during this process to aid solubility.
= 5.2 Hz, 1 H), 6.81 (s, 1 H), 6.93 (d, J = 4.8 Hz, 2 H), 7.33 (d, 2
(+)-N-{(4S,5S)-2,2-Dimethyl-4-[4-(methylsulfonyl)phenyl]-1,3-di-
H, 4.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3, ppm): δ = 53.5,
oxan-5-yl}-3,4-dihydroisoquinolinium Tetraphenylborate (6): Pre-
55.7, 61.8, 79.9, 114.7, 127.5, 130.3, 158.6, 160.6, 170.7. MS: m/z =
pared according to the general procedure from (4S,5S)-5-amino-
2,2-dimethyl-4-[4-(methylsulfonyl)phenyl]-1,3-dioxane (24) (0.75 g,
251.0794. C12H13NO5 [M+] requires 251.0794.
(1R,2R)-(–)-2-Amino-1-(4-methoxyphenyl)propane-1,3-diol (32):
Methyl (4S,5R)-5-[4-methoxyphenyl]-2-oxo-1,3-oxazolidine-4-car-
boxylate (31) (2.20 g, 8.8 mmol) was dissolved in ethanol (25 mL)
and the solution cooled using an ice bath. A solution of NaBH4
2.96 mmol), and purified by recrystallization from CH2Cl2/hexane
to give 6 as yellow plates (1.55 g, 73%); m.p. 199–201 °C (dec.).
[α]D20 = +126.7 (c = 1.20, acetone). C46H46BNO4S·0.5H2O (anhydrate:
719.74): calcd. C 75.79, H 6.50, N 1.92; found C 75.62, H 6.32, N
(0.70 g, 19.3 mmol) in ethanol (8 mL) was added dropwise with 1.84. IR (film, cm–1): ν
= 1636, 1603, 1572, 1478, 1383, 1314,
˜
max
stirring. After the addition was complete the ice bath was removed
and the mixture stirred for 45 min. The mixture was cooled to 0 °C
and concd. HCl (1.5 mL) added, followed by water (15 mL). The
ethanol was removed under reduced pressure and the remaining
aqueous solution extracted with ethyl acetate (3 ×50 mL). The
combined organic solutions were dried (MgSO4), and the solvents
removed to afford an off-white solid, which was recrystallized from
ethyl acetate/light petroleum to give (4R,5R)-4-hydroxymethyl-5-(4-
methoxyphenyl)-1,3-oxazolidin-2-one as a colourless crystalline so-
lid (1.75 g, 90%); m.p. 140–142 °C. [α]2D0 = +74.8 (c = 1.08,
1266, 1202, 1150, 1076, 1032, 956. 1H NMR (400 MHz; [D6]ace-
tone, ppm): δ = 1.69 (s, 3 H), 1.72 (s, 3 H), 2.60–2.69 (m, 1 H),
2.85–2.96 (m, 1 H), 3.00 (s, 3 H), 3.65–3.72 (m, 1 H), 4.12–4.20 (m,
1 H), 4.49 (d, J = 13.6 Hz, 1 H), 4.57 (m, 1 H), 4.77 (dd, J = 13.6,
2.8 Hz, 1 H), 6.05 (d, J = 2.8 Hz, 1 H), 6.80 (t, J = 7.2 Hz, 4 H),
6.92 (t, J = 7.2 Hz, 8 H), 7.33 (m, 8 H), 7.49 (t, J = 7.6 Hz, 1 H),
7.73–7.83 (m, 3 H), 7.82 (d, J = 8.2 Hz, 2 H), 7.95 (d, J = 8.2 Hz,
2 H), 9.28 (s, 1 H). 13C NMR (100 MHz; [D6]acetone, ppm): δ =
18.8, 25.4, 29.5, 44.3, 52.3 62.9, 66.1, 71.5, 101.7, 122.3, 125.3,
126.1, 127.6, 128.8, 129.3, 129.4, 135.4, 137.0, 137.0, 137.9, 142.4,
143.2, 165.0, 168.9. MS: m/z = 400.1586. C22H26NO4S (cation) re-
CH3COCH3). IR (nujol, cm–1): ν
= 3239, 1725, 1614, 1514,
˜
max
1459, 1376, 1251, 1174, 1062, 1016, 828. 1H NMR (250 MHz; [D6]- quires 400.1583.
acetone, ppm): δ = 3.71–3.87 (m, 3 H), 3.86 (s, 3 H), 5.35 (d, J =
(+)-N-{(4S,5S)-2,2-Dimethyl-4-[4-(methylthio)phenyl]-1,3-dioxan-5-
5.3 Hz, 1 H), 7.01 (d, J = 8.6 Hz, 2 H), 7.41 (d, J = 8.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3, ppm): δ = 56.0, 63.1, 64.2, 80.4,
115.4, 128.7, 133.2, 159.6, 161.3. MS: m/z = 223.0842. C11H13NO4
[M+] requires 223.0845.
yl}-3,4-dihydroisoquinolinium Tetraphenylborate (7): Prepared ac-
cording to the general procedure from (4S,5S)-5-amino-2,2-di-
methyl-4-[4-(methylthio)phenyl]-1,3-dioxane (25) (0.50 g,
2.0 mmol), and purified by recrystallization from CH2Cl2/hexane
(4R,5R)-4-Hydroxymethyl-5-(4-methoxyphenyl)-1,3-oxazolidin-2- to give 7 as yellow plates (1.00 g, 73%); m.p. 146–148 °C (dec.).
one (1.65 g, 7.4 mmol) was suspended in aqueous NaOH (1 m,
40 mL) and heated under reflux for 30 min. The mixture was co-
oled to room temperature and extracted with ethyl acetate
(8×30 mL). The combined organic solutions were dried (MgSO4),
and the solvents removed to give 32 as a colourless solid, which
[α]D20 = +115.9 (c = 1.41, acetone). C46H46BNO2S·0.5H2O (anhydrate:
687.74): calcd. C 79.27, H 6.66, N 2.01; found C 79.05, H 6.59, N
1.93. IR (film, cm–1): ν
= 3053, 2996, 2360, 2341, 1634, 1603,
˜
max
1571, 1478, 1265, 1201, 1162, 1108, 1075. 1H NMR (250 MHz;
[D6]acetone, ppm): δ = 1.66 (s, 3 H), 1.72 (s, 3 H), 2.42 (s, 3 H),
810
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 803–813

New Chiral Iminium Salt Catalysts for Asymmetric Epoxidation
FULL PAPER
2.66–2.84 (m, 1 H), 2.90–3.03 (m, 1 H), 3.62–3.74 (m, 1 H), 4.13–
4.26 (m, 1 H), 4.53 (m, 2 H), 4.78 (dd, J = 13.8, 3.1 Hz, 1 H), 5.91
(d, J = 2.6 Hz, 1 H), 6.78 (t, J = 7.2 Hz, 4 H), 6.92 (t, J = 7.40 Hz,
8 H), 7.34 (m, 8 H), 7.40–7.56 (m, 6 H), 7.76–7.87 (m, 2 H), 9.30
(s, 1 H). 13C NMR (100 MHz; [D6]acetone, ppm): δ = 15.4, 18.8,
25.4, 30.0, 52.3, 62.7, 66.5, 71.5, 101.4, 122.3, 125.3, 126.1, 126.9,
127.4, 129.2, 129.3, 133.9, 135.2, 137.0, 137.8, 139.5, 140.5, 165.0,
168.5. MS: m/z = 368.1682. C22H26NO2S (cation) requires
368.1684.
61.9, 64.9, 70.5, 100.4, 114.4, 122.2, 123.7, 125.9, 127.3, 127.9,
128.7, 129.5, 134.0, 134.7, 136.2, 138.8, 159.8, 163.8, 169.5. MS: m/
z = 352.1915. C22H26NO3 (cation) requires 352.1913.
(–)-N-[(4R,5R)-2,2,4-Trimethyl-1,3-dioxan-5-yl]-3,4-dihydroisoquin-
olinium Tetraphenylborate (11): Prepared according to the general
procedure from (4R,5R)-5-amino-2,2,4-trimethyl-1,3-dioxane (19)
(0.75 g, 2.96 mmol), and purified by recrystallization from DCM/
hexane to give 11 as yellow plates (1.13 g, 66%); m.p. 164–165 °C
(dec.). [α]2D0 –22.3 (c = 1.05, acetone). IR (film, cm–1): νmax = 3054,
˜
1636, 1604, 1576, 1477, 1268, 1201, 1180. 1H NMR (400 MHz,
CD3CN, ppm): δ = 1.26 (d, J = 6.4 Hz, 3 H), 1.46 (s, 3 H), 1.55 (s,
3 H), 3.25 (t, J = 8.0 Hz, 2 H), 3.89 (t, 1 H, 2.4 Hz, 1 H), 4.23 (dd,
J = 13.6, 0.8 Hz, 1 H), 4.27–4.36 (m, 2 H), 4.46 (dd, J = 14.0,
3.2 Hz, 1 H), 4.63 (dq, J = 6.4, 2.8 Hz, 1 H), 6.83 (t, J = 7.2 Hz, 4
H), 6.93 (t, J = 7.6 Hz, 8 H), 7.22–7.33 (m, 8 H), 7.45 (d, J =
7.6 Hz, 1 H), 7.53 (t, J = 7.6 Hz, 1 H), 7.80 (dt, J = 7.6, 1.2 Hz, 1
H), 7.86 (d, J = 7.6 Hz, 1 H), 9.05 (s, 1 H). 13C NMR (100 MHz;
[D6]acetone, ppm): δ = 17.7, 18.7, 25.6, 51.7, 62.9, 66.1, 66.5, 100.6,
122.3, 125.7, 126.1, 129.3, 136.0, 137.0 138.2, 139.4, 164.9, 168.7.
MS: m/z = 260.1655. C16H22NO2 (cation) requires 260.1651.
(+)-N-[(4S,5S)-2,2-Dimethyl-4-(4-nitrophenyl)-1,3-dioxan-5-yl]-3,4-
dihydroisoquinolinium Tetraphenylborate (8): Prepared according to
the general procedure from (+)-(4S,5S)-5-amino-2,2-dimethyl-4-(4-
nitrophenyl)-1,3-dioxane (26) (0.19 g, 0.8 mmol), and purified by
recrystallization from CH2Cl2/hexane to give 8 as yellow plates
(0.36 g, 74%); m.p. 176–178 °C (dec.). [α]2D0 = +107.7 (c = 1.30,
acetone). C45H43BN2O4·0.5H2O (anhydrate: 686.64): calcd. C
77.66, H 6.38, N 4.03; found C 77.73, H 6.23, N 4.00. IR (film,
cm–1): νmax = 1635, 1604, 1571, 1524, 1478, 1384, 1202, 1163, 1107,
˜
1032. 1H NMR (400 MHz; [D6]acetone, ppm): δ = 1.72 (s, 3 H,
CH3, C7), 1.76 (s, 3 H), 2.70–2.80 (m, 1 H), 2.88–2.96 (m, 1 H),
3.65–3.74 (m, 1 H), 4.19–4.23 (m, 1 H), 4.54 (d, J = 13.6 Hz, 1 H),
4.65 (m, 1 H), 4.82 (dd, J = 13.6, 2.8 Hz, 1 H), 6.11 (d, J = 2.4 Hz,
1 H), 6.80 (t, J = 6.8 Hz, 4 H), 6.94 (t, J = 7.2 Hz, 8 H), 7.36 (m,
8 H), 7.51 (t, J = 7.6 Hz, 1 H), 7.59–7.88 (m, 3 H), 7.85 (d, J =
8.4 Hz, 2 H), 7.95 (d, J = 8.8 Hz, 2 H), 9.28 (s, 1 H). 13C NMR
(100 MHz; [D6]acetone, ppm): δ = 19.2, 25.9, 30.0, 52.8, 63.4, 66.4,
71.9, 102.2, 122.7, 125.3, 125.8, 126.4, 128.3, 129.7, 129.8, 135.9,
137.4, 138.4, 140.1, 145.0, 149.0, 165.0, 169.5. MS: m/z = 367.1658.
C21H23N2O4 (cation) requires 367.1658.
(+)-N-[(4S,5S)-4-Isopropyl-2,2-dimethyl-1,3-dioxan-5-yl]-3,4-dihy-
droisoquinolinium Tetraphenylborate (12): Prepared according to the
general procedure from (4S,5S)-5-amino-4-isopropyl-2,2-dimethyl-
1,3-dioxane (23) (0.05 g, 0.29 mmol), and purified by recrystalli-
zation from acetone/diethyl ether to give 12 as yellow plates
(0.120 g, 70%); m.p. 166–167 °C (dec.). [α]2D0 = +31.7 (c = 1.16,
acetone). IR (film, cm–1): ν
= 3055, 1637, 1604, 1574, 1479,
˜
max
1
1265, 1202, 1152, 1088. H NMR (400 MHz, CD3CN, ppm): δ =
0.89 (d, J = 7.8 Hz, 3 H), 0.97 (d, J = 6.4 Hz, 3 H), 1.48 (s, 3 H),
1.51 (s, 3 H) 1.69–1.75 (m, 1 H), 3.14–3.22 (m, 2 H), 3.89 (m, 2 H),
4.06 (m, 2 H), 4.33 (m, 2 H), 6.84 (t, J = 7.1 Hz, 4 H), 6.99 (t, J =
7.4 Hz, 8 H), 7.23–7.29 (m, 8 H), 7.44 (d, J = 7.4 Hz, 1 H), 7.51
(t, J = 7.6 Hz, 1 H), 7.80 (m, 2 H), 9.13 (s, 1 H). 13C NMR
(100 MHz, CD3CN, ppm): δ = 17.0, 17.4, 17.9, 24.5, 28.3, 28.6,
50.6, 62.0, 62.3, 74.8, 99.9, 121.5, 124.4, 125.3, 128.6, 129.2, 134.2,
135.4, 137.0, 138.4, 163.5, 167.8. MS: m/z = 288.1959. C18H26NO2
(cation) requires 288.1964.
(+)-N-[(4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl]-3,4-dihy-
droisoquinolinium Tetraphenylborate (9):[11] Prepared according to
the general procedure from (4S,5S)-5-amino-2,2-dimethyl-4-
phenyl-1,3-dioxane 28 (3.00 g, 14.4 mmol), and purified by
recrystallization from acetone/diethyl ether to give 9 as a yellow
solid (6.93 g, 75%), m.p. 169–170 °C. [α]2D0 = +38.6 (c = 2.70,
CH CN). IR (nujol, cm–1): νmax = 1637, 1603, 1571, 1480, 1266,
˜
3
1
1202, 1166, 1108, 1073. H NMR (250 MHz, CD3CN, ppm): δ =
1.65 (s, 3 H), 1.94 (s, 3 H), 2.39–2.48 (m, 1 H), 2.70–2.82 (m, 1 H),
3.25–3.40 (m, 1 H), 3.81–3.97 (m, 1 H), 4.06 (m, 1 H), 4.30 (d, J
= 13.7 Hz, 1 H), 4.58 (dd, J = 13.7, 3.1 Hz, 1 H), 5.70 (d, J =
2.8 Hz, 1 H), 6.81 (t, J = 7.2 Hz, 4 H), 7.35–7.40 (m, 6 H), 7.46 (t,
J = 7.3 Hz, 1 H), 7.65–7.74 (m, 2 H), 8.92 (s, 1 H). 13C NMR
(62.50 MHz, CD3CN, ppm): δ = 17.9, 24.1, 28.7, 51.6, 61.4, 65.5,
70.7, 104.9, 121.9, 124.3, 125.4, 125.7, 128.1, 128.5, 128.6, 128.0,
134.4, 135.8, 137.0, 137.7, 138.7, 163.5, 167.5. MS: m/z = 322.1809.
C21H24NO2 (cation) requires 322.1807.
General Procedure for the Preparation of 5H-Dibenzo[c,e]azepinium
Salts from 2-[2-(Bromomethyl)phenyl]benzaldehyde and Primary
Amines: A solution of 2-[2-(bromomethyl)phenyl]benzaldehyde
(1.10 equiv.) in ethanol (10 mL/g aldehyde) was cooled using an ice
bath. A solution of the amine in ethanol (10 mL per g of amine, 1
equiv.) was added dropwise. After the addition was complete, the
ice bath was removed and the reaction mixture stoppered to retain
HBr and stirred overnight. A solution of sodium tetraphenylborate
or other anion exchanging salt (1.10 equiv.) in the minimum
amount of acetonitrile was added in one portion. After stirring for
5 min, the organic solvents were removed under reduced pressure.
Ethanol was added to the residue, followed by water. The resulting
solid was collected by filtration and washed with additional ethanol
followed by diethyl ether. If no solid materialized after the addition
of the water, the mixture was allowed to settle and the ethanol/
water phase decanted. The gummy residue was triturated in hot
ethanol or methanol, inducing precipitation of the organic salt im-
mediately or upon slow cooling of the hot alcoholic solution. Small
quantities of acetonitrile may be added during this process to aid
solubility.
(–)-N-[(4R,5R)-2,2-Dimethyl-4-(4-methoxyphenyl)-1,3-dioxan-5-yl]-
3,4-dihydroisoquinolinium Tetraphenylborate (10): Prepared accord-
ing to the general procedure from (–)-(4R,5R)-5-amino-4-(4-meth-
oxyphenyl)-2,2-dimethyl-1,3-dioxane (33) (0.40 g, 1.7 mmol), and
purified by recrystallization from CH2Cl2/hexane to give 10 as yel-
low plates (0.83 g, 74%); m.p. 171–173 °C (dec.). [α]2D0 –108.6 (c =
1.40, acetone). IR (film, cm–1): νmax = 1639, 1604, 1573, 1514, 1382,
˜
1254, 1202, 1107, 1031. C46H46BNO3·0.5Et2O (anhydrate: 671.67):
1
calcd. C 77.92, H 6.54, N 1.98; found C 77.70, H 6.50, N 1.88. H
NMR (400 MHz, CDCl3, ppm): δ = 1.51 (s, 3 H), 1.52 (s, 3 H),
2.20–2.25 (m, 1 H), 2.31–2.35 (m, 1 H), 2.85–2.90 (m, 1 H), 3.00–
3.10 (m, 1 H), 3.04 (m, 1 H), 3.56 (d, J = 14.4 Hz, 1 H), 3.72 (s, 3
H), 3.90 (dd, J = 14.0, 2.8 Hz, 1 H), 5.11 (d, J = 2.4 Hz, 1 H), 6.79
(–)-N-[(4S,5S)-2,2-Dimethyl-4-phenyl-1,3-dioxan-5-yl]-5H-dibenzo-
[c,e]azepinium Tetraphenylborate (13): Prepared according to the ge-
(d, J = 2.0 Hz, 2 H), 6.87 (m, 2 H), 7.02 (t, J = 7.6 Hz, 8 H), 7.23 neral procedure from (+)-(4S,5S)-5-amino-2,2-dimethyl-4-phenyl-
(m, 2 H) 7.24 (m, 1 H), 7.41 (m, 8 H), 7.57 (m, 1 H), 8.25 (s, 1 H). 1,3-dioxane (28) (3.85 g, 18.8 mmol). The product was isolated as
13C NMR (100 MHz, CDCl3, ppm): δ = 18.4, 24.6, 29.4, 50.5, 55.4,
yellow plates (9.00 g, 68%); m.p. 187–188 °C (dec.). [α]2D0 = –44.0
Eur. J. Org. Chem. 2006, 803–813
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
811

P. C. Bulman Page, B. R. Buckley, G. A. Rassias, A. J. Blacker
FULL PAPER
(c = 1.01, CH3CN). C50H46BNO2 (703.72): calcd. C 85.34, H 6.59,
1031, 966. 1H NMR (400 MHz; [D6]DMSO, 100 °C, ppm): δ = 1.66
(s, 3 H), 1.68 (s, 3 H), 3.60 (s, 3 H), 4.28 (dd, J = 14.4, 2.0 Hz, 1
H), 4.43 (d, 1 H, 14.0 Hz, 1 H), 4.65 (m, 2 H), 5.02 (d, J = 14.0 Hz,
N 1.99; found C 85.23, H 6.52, N 1.96. IR (film, cm–1): ν
=
˜
max
3055, 3038, 2999, 1633, 1579, 1480, 1451, 1385, 1203, 1114, 848,
735, 706. 1H NMR (400 MHz; [D6]DMSO, 115 °C, ppm): δ = 1.71 1 H), 5.70 (d, J = 2.8 Hz, 1 H), 6.63 (d, J = 8.6 Hz, 2 H), 6.72 (t,
(s, 3 H), 1.74 (s, 3 H), 4.32 (d, J = 21.8 Hz, 1 H), 4.49 (d, J =
J = 7.4 Hz, 4 H), 6.86 (t, J = 7.4 Hz, 8 H), 7.08 (d, J = 8.6 Hz, 2
21.6 Hz, 1 H), 4.68–4.77 (m, 1 H), 4.72 (dd, J = 5.2, 21.8 Hz, 1 H), H), 7.18 (m, 8 H), 7.52 (m, 3 H), 7.65 (m, 3 H), 7.91 (m, 2 H), 9.00
5.15 (d, J = 22.2 Hz, 1 H), 5.82 (d, J = 4.1 Hz, 1 H), 6.75 (t, J =
11.4 Hz, 4 H), 6.88 (t, J = 11.5 Hz, 8 H), 7.11–7.16 (m, 5 H), 7.20–
7.25 (m, 8 H), 7.55–7.63 (m, 3 H), 7.64–7.69 (m, 3 H), 7.92–7.94
(m, 2 H), 9.03 (s, 1 H). 13C NMR (100 MHz; [D6]DMSO, 120 °C,
ppm): δ = 18.1, 28.4, 55.8, 60.8, 66.1, 70.5, 99.9, 120.4, 124.1, 124.2,
124.2, 124.4, 127.3, 127.6, 127.7, 128.2, 128.3, 129.0, 129.3, 129.4,
132.6, 133.6, 135.0, 135.2, 140.5, 163.3, 170.1. MS: m/z = 384.1968.
C26H26NO2 (cation) requires 384.1964.
(s, 1 H). 13C NMR (100 MHz; [D6]DMSO, 100 °C, ppm): δ = 18.3,
28.8, 54.8, 56.1, 60.9, 66.42, 70.5, 100.0, 113.8, 120.8, 124.6, 125.6,
125.9, 127.5, 128.0, 128.5, 128.5, 129.4, 129.6, 129.7, 132.9, 133.9,
135.2, 135.5, 136.2, 140.7, 158.7, 163.3, 170.2. MS: m/z = 414.2063.
C27H28NO3 (cation) requires 414.2069.
General Procedure for the Catalytic Asymmetric Epoxidation of Al-
kenes Mediated by Iminium Salts Using Oxone: Oxone (2 equiv.
with respect to alkene) was added with stirring to an ice-cooled
solution of sodium carbonate (4 equiv.) in water (12 mL per 1.50 g
of sodium carbonate), and the resulting foaming solution was
stirred for 5–10 minutes, until most of the initial effervescence sub-
sided. A solution of the iminium salt (10 mol-% with respect to
alkene) in acetonitrile (6 mL per 1.50 g of sodium carbonate used)
was added, followed by a solution of the alkene substrate in aceto-
nitrile (6 mL per 1.50 g of sodium carbonate used). The suspension
was stirred with ice bath cooling until the substrate was completely
consumed according to TLC. The reaction mixture was then di-
luted with ice-cooled diethyl ether (20 mL per 100 mg substrate)
and the same volume of water added immediately. The aqueous
phase was washed four times with diethyl ether and the combined
organic solutions washed with brine and dried (MgSO4). Filtration
and removal of the solvents gave a yellow or light brown residue,
which was purified by column chromatography, typically using
ethyl acetate/light petroleum (1:99) to provide the pure epoxide.
(–)-N-[(4S,5S)-2,2-Dimethyl-4-(4-nitrophenyl)-1,3-dioxan-5-yl]-5H-
dibenzo[c,e]azepinium Tetraphenylborate (14): Prepared according
to the general procedure from (+)-(4S,5S)-5-amino-2,2-dimethyl-4-
(4-nitrophenyl)-1,3-dioxane (26) (0.30 g, 1.19 mmol). The product
was isolated as yellow plates (0.57 g, 64%); m.p. 209–210 °C (dec.).
[α]2D0 –68.0 (c = 1.17, acetone). C50H45BN2O4 (748.35): calcd. C
80.21, H 6.06, N 3.74; found C 80.43, H 6.09, N 3.72. IR (film,
cm–1): νmax = 3055, 2998, 1633, 1600, 1579, 1523, 1480, 1451, 1385,
˜
1349, 1204, 1106, 969, 852. 1H NMR (400 MHz; [D6]DMSO,
100 °C, ppm): δ = 1.67 (s, 3 H), 1.71 (s, 3 H), 4.35 (d, J = 13.2 Hz,
1 H), 4.49 (d, J = 12.8 Hz, 1 H), 4.66 (d, J = 13.2 Hz, 1 H), 4.82
(s, 1 H), 4.99 (d, J = 12.8 Hz, 1 H), 5.91 (s, 1 H), 6.71 (t, J =
6.8 Hz, 4 H), 6.85 (t, J = 6.8 Hz, 8 H), 7.17 (m, 8 H), 7.44 (m, 4
H), 7.56–7.75 (m, 4 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.88 (m, 2 H),
9.19 (s, 1 H). 13C NMR (100 MHz; [D6]DMSO, 100 °C, ppm): δ =
19.7, 30.1, 58.0, 62.7, 67.1, 71.6, 101.8, 122.2, 124.2, 125.9, 126.9,
127.5, 129.5, 129.9, 130.0, 130.8, 130.9, 134.1, 135.8, 136.6, 137.1,
137.4, 142.1, 144.0, 164.6, 172.0. MS: m/z = 429.1815. C26H25N2O4
(cation) requires 429.1814.
General Procedure for the Formation of Racemic Epoxides: The al-
kene was dissolved in CH2Cl2 (10 mL/g) and the solution cooled
using an ice bath. A solution of mCPBA (2 equiv.) in CH2Cl2
(10 mL/g, pre-dried with MgSO4) was added. The reaction was al-
lowed to attain ambient temperature and stirred until complete
consumption of the substrate was observed by TLC. Saturated
aqueous NaHCO3 (10 mL/g) was added and the layers separated.
The organic layer was washed with saturated aqueous NaOH
(1.0 m, 10 mL/g) and dried (MgSO4). The solvents were removed
under reduced pressure, and the residue purified by column
chromatography, typically eluting with ethyl acetate/light petroleum
(1:99), to give pure epoxide.
(–)-N-{(4S,5S)-2,2-Dimethyl-4-[4-(methylsulfonyl)phenyl]-1,3-di-
oxan-5-yl}-5H-dibenzo[c,e]azepinium Tetraphenylborate (15): Pre-
pared according to the general procedure from (+)-(4S,5S)-5-
amino-2,2-dimethyl-4-[4-(methylsulfonyl)phenyl]-1,3-dioxane (24)
(0.30 g, 1.05 mmol). The product was isolated as yellow plates
(0.54 g, 66%); m.p. 162–165 °C (dec.). [α]2D0 = –50.3 (c = 1.09, ace-
tone). C51H48BNO4S·2.0H2O (anhydrate: 781.81): calcd. C 74.87,
H 6.29, N 1.71; found C 75.14, H 5.89, N 1.75. IR (film, cm–1):
ν
max = 3052, 2997, 1636, 1599, 1551, 1479, 1454, 1385, 1304, 1205,
˜
1148, 1090, 947.6, 844. 1H NMR (400 MHz; [D6]DMSO, 100 °C,
ppm): δ = 1.79 (s, 3 H), 2.01 (s, 3 H), 3.01 (s, 3 H), 4.40 (d, J =
13.6 Hz, 1 H), 4.56 (d, J = 13.2 Hz, 1 H), 4.66 (dd, J = 13.6 Hz, 1
H), 4.88 (br. s, 1 H), 5.15 (d, J = 12.8 Hz, 1 H), 5.91 (d, J = 2.8 Hz,
1 H), 6.79 (t, J = 6.8 Hz, 4 H), 6.92 (t, J = 7.6 Hz, 8 H), 7.17 (m,
8 H), 7.52–7.58 (m, 4 H), 7.65–7.74 (m, 4 H), 7.91–7.97 (m, 2 H),
9.16 (s, 1 H). 13C NMR (100 MHz; [D6]DMSO, 100 °C, ppm): δ =
19.3, 29.7, 44.2, 57.0, 62.1, 66.8, 71.4, 101.3, 121.8, 125.5, 126.4,
126.8, 127.4, 128.6, 129.0, 129.5, 129.6, 130.4, 130.6, 130.8, 135.1,
136.2, 136.7, 137.1, 141.5, 141.7, 142.0, 164.1, 171.6. MS: m/z =
462.1739. C27H28NO4S (cation) requires 462.1739.
α-Methylstyrene Oxide:[20] Colourless oil. IR (neat, cm–1): ν
=
˜
max
3034, 2958, 2929, 2872, 1604, 1496, 1447, 1381, 1343, 1061, 1027,
860, 759, 699. 1H NMR (250 MHz, CDCl3, ppm): δ = 0.86 (d, J =
6.6 Hz, 3 H), 2.79 (dd, J = 0.8, 5.4 Hz, 1 H), 2.96 (d, J = 5.4 Hz,
1 H), 7.24–7.38 (m, 5 H). 13C NMR (62.5 MHz, CDCl3, ppm): δ
= 21.7, 56.7, 56.9, 125.2, 127.4, 128.3, 129.0.
trans-α-Methylstilbene Oxide:[21] Colourless oil. IR (neat, cm–1):
ν
max = 3061, 1602, 1495, 1449, 1381, 1279, 1157, 1118, 1065, 1027,
˜
1
980. H NMR (400 MHz, CDCl3, ppm): δ = 1.46 (s, 3 H), 3.96 (s,
1 H), 7.30–7.46 (m, 10 H). 13C NMR (100 MHz, CDCl3, ppm): δ
= 17.1, 63.5, 67.5, 125.6, 126.9, 127.7, 127.9, 128.6, 129.2, 136.4,
142.8.
(+)-N-[(4S,5S)-2,2-Dimethyl-4-(4-methoxyphenyl)-1,3-dioxan-5-yl]-
5H-dibenzo[c,e]azepinium Tetraphenylborate (16): Prepared accord-
ing to the general procedure from (–)-(4R,5R)-5-amino-4-(4-meth-
oxyphenyl)-2,2-dimethyl-1,3-dioxane (33) (0.13 g, 0.48 mmol). The
product was isolated as yellow plates (0.23 g, 64 %); m.p.
Triphenylethylene Oxide:[22] Colourless oil which slowly solidified,
m.p. 66–67 °C (ref. m.p. 75 °C). IR (neat, cm–1): νmax = 3062, 3030,
˜
2957, 2925, 2856, 1605, 1596, 1499, 1471, 1448, 1262, 1221, 741,
698, 621. 1H NMR (250 MHz, CDCl3, ppm): δ = 4.40 (m, 1 H),
7.10–7.47 (m, 15 H). 13C NMR (62.5 MHz, CDCl3, ppm): δ = 68.0,
68.3, 126.3, 126.8, 127.5, 127.6, 127.7, 127.8 128.0, 128.2, 128.6,
135.4, 135.9, 141.1.
207–209 °C (dec.). [α]2D0
C51H48BNO3·3.5H2O (anhydrate: 733.74): calcd. C 76.84, H 6.52,
N 1.76; found C 76.58, H 6.02, N 1.84. IR (film, cm–1): ν
=
+37.8 (c
=
1.09, acetone).
=
˜
max
3055, 2998, 1633, 1613, 1579, 1557, 1514, 1480, 1384, 1253, 1202,
812
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 803–813

New Chiral Iminium Salt Catalysts for Asymmetric Epoxidation
FULL PAPER
1-Phenylcyclohexene Oxide:[23] Colourless oil. IR (neat, cm–1):
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43, 8257; J. Vachon, C. Pérollier, D. Monchaud, C. Marsol, K.
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1997, 1075; A. Armstrong, G. Ahmed, I. Garnett, K. Gioaco-
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Lett. 2001, 3, 2587.
ν
max = 3084, 1602, 1495, 1446, 1359, 1249, 1173, 1132, 1079, 1030,
˜
1
993, 974. H NMR (250 MHz, CDCl3, ppm): δ = 1.22–1.35 (m, 1
H), 1.53–1.64 (3 H m), 1.99–2.06 (m, 2 H) 2.16–2.18 (m, 1 H),
2.26–2.32 (m, 1 H), 3.10 (t, J = 2.0 Hz, 1 H), 7.28–7.44 (m, 5 H).
13C NMR (62.5 MHz, CDCl3, ppm): δ = 19.8, 20.1, 24.7, 28.2,
60.1, 61.8, 125.3, 127.1, 128.2, 142.8.
1-Phenyl-3,4-dihydronaphthalene Oxide:[23] Pale yellow solid; m.p.
104–106 °C (ref.[24] m.p. 94–97 °C). IR (nujol, cm–1): ν
= 1602,
˜
max
1486, 1307, 1155, 1074, 1042, 953. 1H NMR (250 MHz, CDCl3,
ppm): δ = 2.10 (td, J = 5.8, 13.7 Hz, 1 H), 2.49–2.60 (m, 1 H), 2.77
(dd, J = 5.6, 15.5 Hz, 1 H), 2.98–3.06 (m, 1 H), 3.71 (d, J = 3.1 Hz,
1 H), 7.11–7.31 (m, 4 H), 7.45–7.61 (m, 5 H). 13C NMR (62.5 MHz,
CDCl3, ppm): δ = 22.1, 25.4, 60.9, 63.0, 126.0, 127.7, 127.9, 128.1,
128.2, 128.6, 129.8, 135.0, 137.5, 138.8.
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ling, J. Chem. Soc. Perkin Trans. 1 2000, 3325.
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ley, D. Bethell, T. A. D. Smith, A. M. Z. Slawin, J. Org. Chem.
2001, 66, 6926.
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1543.
trans-Stilbene Oxide:[25] Colourless solid; m.p. 66–67 °C (ref.[26]
[13] P. C. B. Page, B. R. Buckley, H. Heaney, A. J. Blacker, Org.
Lett. 2005, 7, 375.
[14] P. C. B. Page, G. A. Rassias, D. Barros, A. Ardakani, D. Beth-
ell, E. Merifield, Synlett 2002, 4, 580; P. C. B. Page, D. Barros,
B. R. Buckley, A. Ardakani, B. A. Marples, J. Org. Chem. 2004,
69, 3595.
m.p. 61–63 °C). IR (neat, cm–1): νmax = 1601, 1492, 1284, 1176,
˜
1157, 1094, 1072, 1025. 1H NMR (400 MHz, CDCl3, ppm): δ =
3.84 (s, 2 H), 7.28–7.37 (10 H m). 13C NMR (100 MHz, CDCl3,
ppm): δ = 63.3, 126.0, 128.6, 129.3, 137.6.
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[16] L. Williams, Z. Zhang, F. Shao, P. J. Carroll, M. M. Joullé,
Tetrahedron 1996, 52, 11673.
1,2-Dihydronaphthalene Oxide: Colourless oil. IR (neat, cm–1):
ν
max = 3059, 3028, 2930, 2850, 1602, 1493, 1316, 1129, 1088, 1030,
˜
964. 1H NMR (400 MHz, CDCl3, ppm): δ = 1.67 (m, 1 H), 2.33
(m, 1 H), 2.45 (dd, J = 15.6, 5.6 Hz, 1 H), 2.67 (m, 1 H), 3.65 (t,
J = 4.0 Hz, 1 H), 3.78 (d, J = 4.4 Hz, 1 H), 7.01 (d, J = 7.2 Hz, 1
H), 7.17 (m, 2 H), 7.33 (d, J = 7.2 Hz, 1 H). 13C NMR (100 MHz,
CDCl3, ppm): δ = 22.2, 24.8, 55.2, 55.5, 126.5, 128.8, 128.8, 129.9,
132.9, 137.1.
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Acknowledgments
This investigation has enjoyed the support of the EPSRC, the Le-
verhulme Trust, and Avecia Life Science Molecules. We are in-
debted to the EPSRC Mass Spectrometry Unit, Swansea.
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Received: October 3, 2005
Published Online: November 21, 2005
Eur. J. Org. Chem. 2006, 803–813
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
813