Monodeazacinchona alkaloid derivatives: Synthesis and preliminary applications as phase-transfer catalysts

Article abstract of DOI:10.1002/1099-0690(200207)2002:13<2087::AID-EJOC2087>3.0.CO;2-Z

Four analogues of cinchona alkaloids (5-8) lacking the quinoline nitrogen atom have been prepared. Quaternization afforded the phase-transfer catalysts 10a, 10b, 11a, and 12d. Other optically active catalyst salts were prepared from the cinchona alkaloids themselves (compounds 13, 14, 15). The performances of these PT catalysts and of some others were compared in three test reactions. The deazacinchona derivatives exhibited selectivities similar to or sometimes even better than those of the natural product-derived compounds, Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200207)2002:13<2087::AID-EJOC2087>3.0.CO;2-Z

FULL PAPER
Monodeazacinchona Alkaloid Derivatives: Synthesis and Preliminary
Applications as Phase-Transfer Catalysts[‡]
Eckehard Volker Dehmlow,*[a] Stephanie Düttmann,[a] Beate Neumann,[a] and
Hans-Georg Stammler[a]
Keywords: Alkaloids / Alkylation / Enantioselectivity / Epoxidation / Phase-transfer catalysis
Four analogues of cinchona alkaloids (5−8) lacking the quin-
compared in three test reactions. The deazacinchona derivat-
oline nitrogen atom have been prepared. Quaternization af- ives exhibited selectivities similar to or sometimes even
forded the phase-transfer catalysts 10a, 10b, 11a, and 12d.
Other optically active catalyst salts were prepared from the
cinchona alkaloids themselves (compounds 13, 14, 15). The
performances of these PT catalysts and of some others were
better than those of the natural product-derived compounds.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Cinchona alkaloids are of increasing interest as re- kovic’ et al. in the course of their cinchona alkaloid syn-
agents,[1] ligands, and catalysts[2] [including phase-transfer thesis.[8] Organometallic couplings with 1-lithionaphthalene
catalysis[3] (PTC)] for enantioselective reactions. Conforma- and compound 3 generated a mixture of diastereomers 5
tional studies have been used to interpret the exceptional (13% yield) and 6 (29%), which could be separated by chro-
performance of these compounds.[4] For PTC applications, matography. The purity of the isomers could be determined
common interpretations focus mainly on the ‘‘binding most easily by reference to the NMR signals of the vinylic
pocket forming’’ and sandwiching interaction between the protons on C(1ЈЈ), which gave rise to characteristic triplets
catalysts’ large flat aromatic partial structures and the sub- of doublets centered 0.26 ppm apart at δ ϭ 6.09 (5) and
strate, which are reinforced by polar effects. It is unknown 5.83 ppm (6). In addition, comparison with the equivalently
whether the polarity of the quinoline nucleus contributes positioned C(10) hydrogen atoms in cinchonine and quinid-
to this. Modification of the fundamental structure of these ine (conventional alkaloid numbering) permitted the assign-
alkaloids might aid understanding of which features of the ments of absolute configurations: the chemical shift of the
skeletons are essential for the PT catalytic action; our first C(1ЈЈ)H signal of 6 was practically identical to those of its
results in this area were published recently.[5] In this context counterparts in the two natural alkaloids. This meant that
we now became interested in the synthesis of deazacinchona 5 had to have (1R,2ЈR,4ЈS,5ЈR) stereochemistry and 6
alkaloids, transformation of these into phase transfer cata- (1S,2ЈR,4ЈS,5ЈR). This result was corroborated further by
lysts, and comparison of their performance with that of an X-ray structure determination of 6[9] (see Figure 1).
other enantioselective PT catalysts.
Thus, 6 was deaza(Naryl)cinchonine. It had a positive sign
of optical rotation, just like quinidine and cinchonine. In
contrast, compound 5 exhibited negative rotation. The
formation of 6 as the major product was in line with prefer-
ential attack from the less hindered side of 3. An analogous
observation was made by the Uskokovic’ group: they ob-
tained the natural alkaloids as main products from the
coupling of the 3/4 mixture with quinoline derivatives.[8]
When 4 was treated with lithionaphthalene analogously
to the preparation of 5 and 6 from 3, compounds 7 and 8
were obtained in 4.4 and 9% yields, respectively. Again, the
chemical shifts of the C(1ЈЈ) protons were centered at δ ϭ
5.83 (7) or 6.10 ppm (8), matching the shifts of the equiva-
lently positioned protons in quinine and cinchonidine (δ ഠ
5.86 ppm) in the case of 7. Thus, this product had to have
the (1R,2ЈS,4ЈS,5ЈR) configuration, and so was monodeaza-
(Naryl)cinchonidine. It had a negative sign of optical rota-
Deaza(Naryl)cinchona Alkaloids
Recent work by H. M. R. Hoffmann showed that quinine
and quinidine can be degraded relatively easily[6] into the
optically active 2-(hydroxymethyl)-5-vinylquinuclidine iso-
mers 1 and 2, and these have now become commercially
available (Scheme 1).[7] Swern oxidation transformed these
compounds into the aldehydes 3 and 4, respectively. A mix-
ture of epimers 3 and 4 was also prepared earlier by Usko-
[‡]
Applications of Phase Transfer Catalysis, 72. Part 71: E. V.
Dehmlow, M. Kaiser, J. Bollhöfer, New J. Chem. 2001, 25,
588Ϫ590.
[a]
Fakultät für Chemie, Universität Bielefeld,
Postfach 100131, 33501 Bielefeld, Germany
Eur. J. Org. Chem. 2002, 2087Ϫ2093  WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0713Ϫ2087 $ 20.00ϩ.50/0
2087

E. V. Dehmlow, S. Düttmann, B. Neumann, H.-G. Stammler
FULL PAPER
the organometallic reagent should produce 9. Unexpectedly,
however, this compound had a negative sign of optical rota-
tion.
Phase-Transfer Catalysts
The new compounds and other amines were quaternized
to give PT catalysts. As only limited amounts of the deazac-
inchona alkaloids were available, only representative ex-
amples of new PT catalysts (and not all possibly desirable
combinations of skeletons and residues) could be prepared.
Structural formulae of the catalysts used are given in
Scheme 2.
Scheme 1
Scheme 2. Phase-transfer catalysts used
The substituents used most widely in previous work with
the alkaloid-derived catalysts were N-benzyl and N-(p-tri-
fluoromethyl)benzyl. These were used here too, giving com-
pounds 10a, 10b and 11a. Pioneering studies by Lygo et
al.[3c] and by Corey et al.,[3i] later verified by others,[3] had
established that catalysts bearing an N-(9-anthracenylme-
thyl) group were among the most enantioselective ones.
Consequently, this residue was introduced into 8, resulting
in 12d. The known derivatives of cinchonine (13a ϭ
‘‘BCNC’’ and 13b), cinchonidine (14a ϭ ‘‘BCDC’’ and 14d)
and quinine (15a ϭ ‘‘QUIBEC‘‘) were used for comparison.
Figure 1. ORTEP drawing of (2R,4S,5R,1ЈS)-2-[1Ј-hydroxy-1Ј-
(naphth-1-yl)methyl]-5-vinyl-1-azabicyclo[2.2.2]octane (6);[9,19,20]
numbering not in accordance with chemical nomenclature
tion, as expected. The absolute configuration of 8 Ϫ with a
positive rotation Ϫ then had to be (1S,2ЈS,4ЈS,5ЈR).
When 3 was treated with 9-lithioanthracene, a diastere-
omer mixture was again formed. This time, however, the
overall yield was much lower (ca. 5%) and only the major
isomer 9 could be isolated in pure form. Its cinchonine-like
configuration (1S,2ЈR,4ЈS,5ЈR) was again assigned from the
facts that the position of the C(1ЈЈ) proton signal matched
that of cinchonine and that preferential front side attack of Scheme 3
2088
Eur. J. Org. Chem. 2002, 2087Ϫ2093

Monodeazacinchona Alkaloid Derivatives
FULL PAPER
Table 1. Results of reactions (1), (2), and (3)
Reaction (1)
Reaction (2)
ee
(%)
Reaction (3)
Catalyst
Yield
(%)
ee
(%)
Config.
Yield
(%)
Rotation
Yield
(%)
ee
(%)
Config.
10a
60
71
50
43
(S)
(S)
62
58
71
75
80
92
65
97
55
97
69
41
50
66
32
84
42
55
52
46
71
74
39
76
(Ϫ)
(Ϫ)
(ϩ)
(Ϫ)
(Ϫ)
(Ϫ)
(Ϫ)
(ϩ)
(ϩ)
(ϩ)
(ϩ)
(ϩ)
21
56
52
37
(S)
(S)
10b
11a
12d
13a ϭ BCNC
13b
13c
14a ϭ BCDC
98
70
58
59
66
9.9
(S)
(S)
(S)
97
96
48
99
72
59
99
36
46
31
39
33
16
35
6.9
30
(S)
(S)
(S)
(R)
(R)
(R)
(R)
(R)
14c
14d
53
9.6
(R)
15a ϭ QUIBEC
15c
70
7.7
(R)
In addition, the three natural alkaloids were also quater- catalysts performed better than the derivatives of natural
nized with 9-(bromomethyl)acridine as a more polar ana- cinchona alkaloids (Table 1). Thus, the deazacinchonine
logue of the anthracenyl group. This afforded compounds derivatives 10a and 10b gave higher ee values (50 and 66%)
13c, 14c and 15c.
than the related compounds 13a (ϭ BCNC) and 13b (42
and 55% ee), while 12d gave the best ee of all catalysts. This
compound had a 9-anthracenylmethyl residue and did not
have an alkaloid-derived analogue. The configuration of the
epoxide formed with catalyst type 12 was the opposite of
that generated with the ‘‘pseudoenantiomeric’’ catalyst type
11, as was to be expected. It can furthermore be seen that
the 9-acridinylmethyl group in compounds 13c, 14c, and
15c (which are all derivatives of the natural alkaloids) gave
rise to high enantiomer ratios of up to 76%, similar to the
effects resulting from the anthracenylmethyl residue in 14d
(cf. also refs.[3c,3i]).
Test Reactions
The catalysts in Scheme 2 were evaluated in the three pre-
liminary test reactions shown in Scheme 3: (1) peroxidative
hydroxylation of 2-ethyl-1-tetralone, (2) alkaline hydrogen
peroxide epoxidation of 2-isopropyl-1,4-naphthoquinone,
and (3) benzylation of 2-(tert-butoxycarbonyl)cyclopen-
tanone.
All experiments were performed under standardized con-
ditions in order to compare the various enantioselectivities;
no attempts at optimization by variation of solvent, temper-
ature, etc. were made. Table 1 gives our results.
Reaction (1) was introduced into PTC practice by Shioiri
et al.[11] The initially formed hydroperoxide is reduced in
situ by triethyl phosphite. This conversion has repeatedly
been used to test potential enantioselective catalysts by
us[5,12] and by others.[13] Shioiri’s original ee of 72%
(achieved with catalyst 13b) has never been surpassed. Re-
sults with the present catalysts are given in Table 1. Again,
the ee value obtained with 13b was the best in our hands,
The new epimers 10a and 11a permitted the influence of
the stereochemistry of the 1-hydroxy group on enantioselec-
tion to be investigated. This cannot easily be done in the
natural products series, as the epi compounds are not read-
ily available. Compounds 10a and 11a produced opposite
configurations, although to different extents (50 vs. 32% ee).
Similarly, the reversed hydroxy group configurations in the
cinchonidinium compound 14d and the deaza derivative
12d gave rise to products with opposite configurations.
The PTC alkylation reaction (3) was introduced origin-
under conditions somewhat different from Shioiri’s. Al- ally by Manabe,[17] with ee values of a maximum of 50%
though our new deaza alkaloid derivatives 10a and 10b per- being obtained when a very unusual, special phosphonium
formed noticeably less well than 13a and 13b [50 and 43% salt catalyst was applied. Our comparisons with various
ee compared to 59 and 66%], they were far better than catalysts of type 13, 14, and 15 yielded enantiomeric ex-
many other chiral catalysts.[20]
cesses of between 7% (15a ϭ QUIBEC) and 46% (13a ϭ
The enantioselective epoxidation of naphthoquinones BCNC) (Table 1). The deaza analogues of 13a and 13b,
under PTC was first performed by Wynberg et al.[14] and compounds 10a and 10b, were both somewhat more select-
later improved by Shioiri and co-workers.[15] For reaction ive agents. With compounds 10 and 13, substitution of
(2) specifically, ee values of 31% (with QUIBEC, 15a[14]
)
more polar p-(trifluoromethyl)benzyl for benzyl as N-sub-
and 69% [with N-(1-methylnaphthyl)quinidinium chlor- stituent was not advantageous. This result is contrary to
ide[15]] were observed.[16] In this reaction, several of our new findings with other types of reactions.
Eur. J. Org. Chem. 2002, 2087Ϫ2093
2089

E. V. Dehmlow, S. Düttmann, B. Neumann, H.-G. Stammler
FULL PAPER
3230, 3075, 2933, 2869, 2802, 1729, 1685, 1637, 1560, 1456, 1375,
1203, 1054, 993, 910, 823, 757 cmϪ1. 1H NMR (250 MHz, CDCl3):
δ ϭ 1.40Ϫ1.84 (m, 4 H, 2 ϫ 7-H, 2 ϫ 3-H), 2.12Ϫ3.48 (m, 7 H, 2-
H, 4-H, 5-H, 2 ϫ 6-H, 2 ϫ 8-H), 4.93Ϫ5.11 (m, 2 H, 2 ϫ 2Ј-H),
5.66Ϫ5.97 (m, 1 H, 1Ј-H), 9.81 (d, 3J ϭ 4.40 Hz, 1 H, CHO) ppm.
13C NMR (62 MHz, CDCl3): δ ϭ 23.9, 27.1 (C-3, C-7), 27.5 (C-
4), 39.9 (C-5), 46.5, 49.0 (C-8, C-6), 57.3 (C-2), 114.6 (C-2Ј), 140.3
(C-1Ј), 203.6 (CHO). The sensitive compound must be used imme-
diately.
It may be mentioned in passing that simple quinuclidin-
ium salts prepared by quaternization of 1 and 2[5] gave very
low ee values in these reactions, whereas lupininium salts[10]
performed somewhat better, with ee values of up to 41%.[20]
Conclusions
Although this investigation was of limited scope, some
conclusions can be drawn, particularly in the context of
published facts including our previous results.
(2S,4S,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-carbaldehyde
(4):
This compound was prepared from 2[4,5] analogously to the pre-
paration of 3 from 1. Yield: 75.0%, b.p. 80 °C/0.01 Torr. IR (KBr):
ν˜ ϭ 3264, 3073, 2946, 2871, 2812, 1725, 1637, 1456, 1421, 1317,
1089, 1070, 910, 823, 757 cmϪ1. 1H NMR (250 MHz, CDCl3): δ ϭ
1.43Ϫ1.84 (m, 4 H, 2 ϫ 3-H, 2 ϫ 7-H), 2.23Ϫ3.34 (m, 7 H, 2-H,
2 ϫ 6-H, 2 ϫ 8-H, 5-H, 4-H), 4.94Ϫ5.12 (m, 2 H, 2 ϫ 2Ј-H),
5.71Ϫ5.96 (m, 1 H, 1Ј-H), 9.81 (d, 3J ϭ 4.16 Hz, 1 H, CHO) ppm.
13C NMR (62 MHz, CDCl3): δ ϭ 20.9, 27.2 (C-3, C-7), 30.9, 39.6
(C-5, C-4), 48.65, 50.8 (C-6, C-8), 65.0 (C-2), 114.7 (C-2Ј), 139.9
(C-1Ј), 203.4 (CHO) ppm. The sensitive compound must be used
immediately.
(1) The enantioselectivities exhibited by PT catalysts are
fairly sensitive to the type of reaction. Catalysts may inter-
change their efficacy rankings in different conversions.
(2) Exchange of the quinoline residue for a naphthalene
group in such cinchona-related catalysts seems to have some
effect on the achievable asymmetric induction. In two cases
higher enantiomeric excesses were found with these less po-
lar side arms, while in the third case the optical induction
was lower. If, however, no large aromatic group was present
on the side arm, the enantioselective action of the catalyst
was very low.
(3) The presence of bulky 9-anthracenylmethyl groups on
the quinuclidine nitrogen atom of the catalysts increased the
ee values in this study, as in the literature.[3] A similar effect
was observed with the more polar 9-acridinylmethyl group
in most cases.
(1R,2R,4S,5R)-(1-Naphthyl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)-
methanol (5) and (1S,2R,4S,5R)-(1-Naphthyl)(5-vinyl-1-azabicyclo-
[2.2.2]oct-2-yl)methanol (6): Abs. ether (230 mL) and a solution of
butyllithium in hexane (1.62 , 11.0 mL, 16.8 mmol) were com-
bined and cooled to Ϫ68 °C. 1-Bromonaphthalene (4.17 g,
17.4 mmol) in abs. THF (115 mL) was added slowly at this temper-
ature. Stirring was then continued for another 30 min, and 3
(2.87 g, 17.4 mmol) in abs. ether (115 mL) was slowly added drop-
wise. The reaction was allowed to proceed for 1.5 h at Ϫ68 °C, and
was then quenched by the addition of H2O (107 mL) at Ϫ68 °C
and allowed to warm to room temp. overnight. The phases were
separated, and the aqueous one was extracted twice with 70 mL of
ether. The combined organic solutions were dried (Na2SO4), and
the solvent was removed. The residue was chromatographed on sil-
ica gel with ethyl acetate/triethylamine (9:1) to give the diastereom-
erically pure products 6 (Rf ϭ 0.21) and 5 (Rf ϭ 0.15), which were
crystallized from EtOH.
(4) The hydroxy group configuration at C(1) of the cata-
lysts had a determining influence on product configuration.
Experimental Section
General: X-ray measurement: Nonius Kappa CCD; programs used:
Siemens SHELXTL plus/SHELXL-97.[9,18,19] NMR spectra in
CDCl3 with TMS as internal standard; AC 250-P (Bruker: 1H:
250 MHz; 13C: 62.89 MHz) or DRX 500 (Bruker: 1H: 500 MHz;
13C:125.78 MHz). Polarimetry: Jasco DIP-360. IR: Genesis FT In-
strument (Mattson). HPLC determination of enantiomer ratios:
apparatus from Therma Separation Products, pump P 4000, de-
tector UV 6000 LP; chiral columns Chirasep DNBPG from Merck
A.G. [(R)-N-(3,5-dinitrobenzoylphenyl)glycine on aminopropyl-sil-
ica gel] or Chiralcel OD from Daicel Chemical Ind. Ltd. (cellulose
carbamate on silica gel). MS: VG AutoSpec from Fisons Instru-
ments. Melting points: Büchi apparatus (Dr. Tottoli). Boiling
points of kugelrohr distillations refer to air bath temperatures.
Compound 6: Yield: 1.46 g (28.6%), m.p. 212Ϫ217 °C. [α]2D3
ϩ122.95 (c ϭ 0.40, MeOH). IR (KBr): ν˜ ϭ 3388, 3067, 3050, 2923,
2862, 1637, 1590, 1445, 1345, 1320, 1093, 795 cmϪ1 1H NMR
ϭ
.
(500 MHz, [D6]DMSO): δ ϭ 1.34Ϫ1.66 (m, 4 H, 2 ϫ 3-H, 2 ϫ 7-
H), 1.89Ϫ1.93 (m, 1 H, 4-H), 2.14Ϫ2.16 (m, 1 H, 8-H), 2.51Ϫ2.65
(m, 3 H, 5-H, 6-H, 8-H), 2.98Ϫ3.03 (m, 2 H, 2-H, 6-H), 5.03Ϫ5.08
3
(m, 2 H, 2 ϫ 2ЈЈ-H), 5.30 (br. s, 1 H, OH), 5.41 (d, J ϭ 4.70 Hz,
1 H, 1Ј-H), 6.09 (ddd, J ϭ 17.6, 10.5 and 7.6, 1 H, 1ЈЈ-H),
7.43Ϫ7.52 (m, 3 H, 3-HNaph, 6-HNaph, 7-HNaph), 7.57 (d, 3J ϭ
3
7.02 Hz, 1 H, 4-HNaph), 7.78 (d, J ϭ 8.09 Hz, 1 H, 5-HNaph), 7.90
(2R,4S,5R)-5-Vinyl-1-azabicyclo[2.2.2]octane-2-carbaldehyde
(3):
(d, 3J ϭ 8.52 Hz, 1 H, 8-HNaph), 8.17 (d, 3J ϭ 8.36 Hz, 1 H, 2-
HNaph) ppm. 13C NMR (125 MHz, CDCl3): δ ϭ 21.15, 26.2 (C-3,
C-7), 28.3, 39.9 (C-5, C-4), 49.4, 49.9 (C-6, C-8), 60.0 (C-2), 72.3
(C-1Ј), 114.6 (C-1ЈЈ),123.0, 123.5, 125.3, 125.4, 126.2, 128.0, 128.9,
130.3, 133.7, 138.8, 140.4 (10 CNaph, C-2ЈЈ) ppm. C20H23NO
(293.4): calcd. C 81.87, H 7.90, N 4.77; found C 81.66, H 7.73,
N 4.75.
DMSO (13.2 g, 169 mmol) in dry CH2Cl2 (19.0 mL) was cooled to
Ϫ45 °C, and oxalyl chloride (3.36 g, 26.3 mmol) in CH2Cl2 (36.0
mL) was added slowly whilst stirring, over 50 min. After a further
30 min at Ϫ45 °C, (2R,4S,5R)-2-(hydroxymethyl)-5-vinylquinuclid-
ine[4,5] (1, 8.0 g, 48.3 mmol) in dry CH2Cl2 (80.0 mL) was added
dropwise over 1.0 h at Ϫ45 °C. The mixture was stirred for an addi-
tional 1 h at this temperature, and then treated with triethylamine
(43.2 mL). Warming to room temp. was followed by stirring for Compound 5: Yield: 677 mg (13.2%), [α]2D3 ϭ Ϫ47.2 (c ϭ 0.42,
30 min. H2O (80.0 mL) was added, the mixture was kept overnight,
and the phases were separated. The organic layer was washed thrice
MeOH). IR (KBr): ν˜ ϭ 3412, 3065, 2945, 2867, 1633, 1454, 1378,
1261, 1110, 1023, 788 cmϪ1. 1H NMR (500 MHz, [D6]DMSO): δ ϭ
with 30.0 mL of H2O, dried with Na2SO4, and filtered. Solvents 1.62Ϫ1.70 (m, 4 H, 2 ϫ 3-H, 2 ϫ 7-H), 2.17 (br. s, 1 H, OH),
were removed, and the residue was distilled in a kugelrohr appar-
atus. Yield: 5.74 g (72.0%); b.p. 140 °C/0.26 Torr. IR (KBr): ν˜ ϭ
2.35Ϫ2.40 (m, 2 H, 8-H, 5-H), 2.82Ϫ2.84 (m, 1 H, 5-H), 2.85Ϫ2.87
(m, 1 H, 8-H), 3.05Ϫ3.07 (m, 1 H, 6-H), 3.33Ϫ3.31 (m, 2 H, 2-H,
2090
Eur. J. Org. Chem. 2002, 2087Ϫ2093

Monodeazacinchona Alkaloid Derivatives
6-H), 4.90Ϫ4.98 (m, 2 H, 2 ϫ 2ЈЈ-H), 5.26 (d, J ϭ 6.63 Hz, 1 H, 2 H, 2-H, 6-H), 5.18Ϫ5.32 (m, 3 H, 1-H, 2 ϫ 2ЈЈ-H), 5.99Ϫ6.12
FULL PAPER
3
1-H), 5.83 (ddd, J ϭ 17.4, 10.3, 7.6, 1 H, 1ЈЈ-H), 7.43Ϫ7.52 (m, 3
(ddd, J ϭ 17.1, 9.64, 7.11 Hz, 1 H, 1ЈЈ-H),7.44Ϫ7.48 (m, 4 H,
H, 3-HNaph3, 6-HNaph, 7-HNaph), 7.57 (d, 3J ϭ 6.77 Hz, 1 H, 4- HAnth), 8.03Ϫ8.05 (m, 4 H, HAnth), 8.46 (s, 1 H, HAnth) ppm. 13C
HNaph), 7.78 (d, 3J ϭ 8.10 Hz, 1 H, 5-HNaph), 7.91 (d, 3J ϭ 8.90 Hz, NMR (62 MHz, CDCl3): δ ϭ 21.7, 24.2 (C-3, C-7) 27.9, 48.6 (C-
8-HNaph), 8.21 (d, 3J ϭ 8.30 Hz, 1 H, 2-HNaph) ppm. 13C NMR 5, C-4), 49.2, 58.8 (C-6, C-8), 62.2 (C-2), 71.2 (C-1), 116.6 (C-
(125 MHz, [D6]DMSO): δ ϭ 23.35, 26.4 (C-3, C-7), 27.85, 48.4 (C-
2ЈЈ),122.3, 124.7, 125.0, 125.8, 126.1, 127.2, 128.5, 129.2, 130.45,
5, C-4), 49.2, 52.3 (C-6, C-8), 60.5 (C-2), 71.8 (C-1Ј), 114.1 (C- 131.55, 131.8, 133.5, 133.9, 134.1, 137.7 (14 CAnth, C-1ЈЈ).
2ЈЈ),123.6, 123.9, 125.0, 125.2, 125.5, 126.8, 128.5, 130.6, 133.25,
C24H25NO (343.5): calcd. C 83.92, H 7.34, N 4.08; found C 84.02,
141.1, 141.4 (10 CNaph, C-1ЈЈ) ppm. C20H23NO (293.4): calcd. C H 7.51, N 4.13.
81.87, H 7.90, N 4.77; found C 81.80, H 7.69, N 4.72.
Preparation of the Catalysts: This was performed by stirring the
bases with the appropriate halides in MeCN/CHCl3 at room temp.
for 24Ϫ72 h (compounds 10a, 10b, 11a), by stirring in that mixture
for 24 h and then heating at 45 °C for 5Ϫ8 h (compounds 13c, 14c,
15c), by heating under reflux for 2 h in toluene (compound 12d),
or by boiling for 2Ϫ24 h in MeCN (compounds 18).
(1S,2S,4S,5R)-(1-Naphthyl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)-
methanol (7) and (1R,2S,4S,5R)-(1-Naphthyl)(5-vinyl-1-azabicyclo-
[2.2.2]oct-2-yl)methanol (8): These compounds were prepared from
4 and 1-bromonaphthalene, similarly to the production of 5 and 6
from 3. The crude mixture was separated by column chromato-
graphy on silica gel with ethyl acetate/triethylamine (9:1). Com-
pound 7 was eluted first (Rf ϭ 0.20), and 8 (Rf ϭ 0.16) second.
The compounds were recrystallized from ethyl acetate.
(1S,2R,4S,5R)-1-Benzyl-2-[(hydroxy)(1-naphthyl)methyl]-5-vinyl-
quinuclidinium Bromide (10a): M.p. 262Ϫ264 °C, [α]2D5 ϭ ϩ114.7
(c ϭ 0.86, MeOH). IR (KBr): ν˜ ϭ 3410, 3200, 2945, 1632, 1454,
1405, 1212, 1165, 1058, 1001, 783, 766 cmϪ1. 1H NMR (500 MHz,
[D6]DMSO): δ ϭ 1.05Ϫ1.78 (m, 4 H, 2 ϫ 3-H, 2 ϫ 7-H),),
2.26Ϫ2.36 (m, 1 H, 4-H), 2.63Ϫ2.66 (m, 1 H, 5-H), 2.90Ϫ3.01 (m,
1 H, 8-H), 3.43Ϫ3.50 (m, 1 H, 8-H), 3.81Ϫ3.95 (m, 2 H, 6-H, 2-
H), 4.18Ϫ4.32 (m, 1 H, 2-H), 4.90 (d, 1 H, CH2), 5.06 (d, 1 H,
CH2), 5.20Ϫ5.23 (m, 2 H, 2ЈЈ-H), 5.99 (ddd, 1 H, 1ЈЈ-H), 6.47 (br.
s, 1 H, OH), 6.59 (d, 1 H, 1Ј-H), 7.56Ϫ7.62 (m, 5 H, 3-HNaph, 6-
HNaph, 7-HNaph, 2 ϫ HBz), 7.66 (t, 1 H, HBz), 7.71Ϫ7.73 (m, 2 H,
2 ϫ HBz), 7.87 (d, 1 H, 5-HNaph), 7.95 (d, 1 H, 4-HNaph), 8.01 (d,
1 H, 8-HNaph), 8.24 (d, 1 H, 2-HNaph) ppm. 13C NMR (62 MHz,
[D6]DMSO): δ ϭ 21.3, 23.0 (C-3, C-7), 26.2, 36.5 (C-5, C-4), 53.9,
55.8 (C-6, C-8), 61.1 (CH2), 65.1, 67.9 (C-1Ј, C-2), 116.9 (C-2ЈЈ),
122.55, 123.0, 123.1, 123.8, 124.7, 125.2, 125.3, 125.6, 126.7, 128.4,
128.7, 129.0, 130.5, 133.0, 133.1, 134.7, 134.8 (16 Carom, C-1ЈЈ)
ppm. C27H30BrNO·1H2O (372.5): calcd. C 67.22, H 6.69, N 2.90;
found C 67.19, H 6.60, N 2.88.
Compound 7: Yield 9%, m.p. 94Ϫ95 °C, [α]2D5 ϭ ϩ221.0 (c ϭ 0.55,
MeOH). IR (KBr): ν˜ ϭ 3473, 3411, 3070, 2948, 2875, 1635, 1500,
1457, 1388, 1353, 1322, 1248, 1106, 1027, 784 cmϪ1 1H NMR
.
(250 MHz, [D6]DMSO): δ ϭ 1.31Ϫ1.97 (m, 5 H, 4-H, 2 ϫ 3-H,
2 ϫ 7-H), 2.12Ϫ2.22 (m, 1 H, 8-H), 2.47Ϫ2.70 (m, 3 H, 6-H, 5-H,
8-H), 2.96Ϫ3.07 (m, 2 H, 2-H, 6-H), 3.31 (br. s, 1 H, OH),
3
5.04Ϫ5.18 (m, 2 H, 2 ϫ 2ЈЈ-H),5.32 (d, J ϭ 6.64 Hz, 1 H, 1Ј-H),
6.10 (ddd, 3J ϭ 17.3, 3J ϭ 10.4, 3J ϭ 7.57 Hz, 1ЈЈ-H),7.43Ϫ7.52
3
(m, 3 H, 3-HNaph, 6-HNaph, 7-HNaph), 7.57 (d, J ϭ 7.02 Hz, 1 H,
5-HNaph), 7.78 (d, 3J ϭ 8.09 Hz, 1 H, 4-HNaph), 7.90 (d, 3J ϭ
3
8.37 Hz, 1 H, 8-HNaph), 8.17 (d, J ϭ 8.13 Hz, 1 H, 2-HNaph) ppm.
13C NMR (62 MHz, [D6]DMSO): δ ϭ 23.5, 26.6 (C-3, C-7), 27.8,
48.45 (C-5, C-4), 49.2, 52.4 (C-6, C-8), 60.5 (C-2), 71.9 (C-1Ј), 114.3
(C-2ЈЈ),123.5, 124.0, 125.0, 125.1, 125.4, 126.4, 128.65, 130.9, 134.0,
141.2, 141.8 (10 CNaph, C-1ЈЈ) ppm. C20H23NO (293.4): calcd. C
81.87, H 7.90, N 4.77; found C 81.62, H 7.77, N 4.85.
(1S,2R,4S,5R)-2-[(Hydroxy)(1-naphthyl)methyl]-1-(4-tri-
fluoromethylbenzyl)-5-vinylquinuclidinium Bromide (10b): M.p.
265Ϫ267 °C, [α]2D5 ϭ ϩ80.0 (c ϭ 0.10, MeOH). C28H29BrNOF3
(532.4): calcd. C 63.16, H 5.49, N 2.63; C 62.83, H 5.66, N 2.73.
Compound 8: Yield 4.4%, m.p. 94Ϫ95 °C, [α]2D5 ϭ Ϫ72.9 (c ϭ 0.40,
MeOH). IR (KBr): ν˜ ϭ 3392, 3075, 3046, 2917, 2863, 1637, 1594,
1
1448, 1376, 1376, 1322, 1294, 1097, 995, 914, 792 cmϪ1. H NMR
(250 MHz, [D6]DMSO): δ ϭ 1.42Ϫ1.88 (m, 6 H, 8-H, 4-H, 2 ϫ 3-
H, 2 ϫ 7-H), 2.18Ϫ3.19 (m, 5 H, 2-H, 2 ϫ 6-H, 5-H, 8-H),
(1R,2R,4S,5R)-1-Benzyl-2-[(hydroxy)(1-naphthyl)methyl]-5-vinyl-
quinuclidinium Bromide (11a): M.p. 173Ϫ176 °C, [α]2D5 ϭ-43.3 (c ϭ
0.24, MeOH). IR (KBr): ν˜ ϭ 3411, 3272, 3204, 2937, 1637, 1457,
1407, 1311, 1214, 1160, 1118, 1058, 1035, 1002, 921, 784, 765, 703
3
4.90Ϫ5.00 (m, 2 H, 2 ϫ 2ЈЈ-H), 5.28 (d, J ϭ 6.63 Hz, 1 H, 1Ј-H),
5.85 (ddd, 3J ϭ 17.5, 3J ϭ 10.3, 3J ϭ 7.56 Hz, 1 H, 1ЈЈ-H),7.59 (d,
3J ϭ 6.25 Hz, 1 H, 5-HNaph), 7.79 (d, 3J ϭ 8.02 Hz, 1 H, 4-HNaph),
3
3
7.92 (d, J ϭ 9.47 Hz, 1 H, 8-HNaph), 8.22 (d, J ϭ 7.42 Hz, 1 H,
2-HNaph) ppm. 13C NMR (62 MHz, [D6]DMSO): δ ϭ 21.5, 26.1
(C-3, C-7), 29.0, 39.3 (C-5, C-4), 38.5, 50.0 (C-6, C-8), 60.3 (C-2),
72.0 (C-1Ј), 114.5 (C-2ЈЈ), 123.0, 123.4, 125.3, 125.8, 126.2, 128.0,
128.9, 130.2, 133.8, 138.1, 140.6 (10 CNaph, C-1ЈЈ) ppm. C20H23NO
(293.4): calcd. C 81.87, H 7.90, N 4.77; found C 81.91, H 7.95,
N 4.75.
1
cmϪ1. H NMR (250 MHz, [D6]DMSO): δ ϭ 1.26Ϫ2.69 (m, 7 H,
8-H, 5-H, 4-H, 2 ϫ 3-H, 2 ϫ 7-H), 3.35Ϫ3.91 (m, 3 H, 6-H, 2-H,
2
8-H), 4.09Ϫ4.29 (m, 1 H, 6-H), 4.97 (d, J ϭ 11.9 Hz, 1 H, CH2),
2
5.15 (d, J ϭ 12.0 Hz, 1 H, CH2), 5.17Ϫ5.26 (m, 2 H, 2 ϫ 2ЈЈ-H),
5.67 (ddd, 3J ϭ 17.1, 3J ϭ 10.5, 3J ϭ 6.44 Hz, 1 H, 1ЈЈ-H), 6.50
(br. s, 1 H, 1Ј-H), 7.57Ϫ7.85 (m, 8 H, 5 ϫ HBz, 3 ϫ HNaph), 7.87
(d, 3J ϭ 6.97 Hz, 1 H, 5-HNaph), 7.96 (d, 3J ϭ 8.11 Hz, 1 H, 4-
HNaph), 8.03 (d, 3J ϭ 7.87 Hz, 1 H, 8-HNaph), 8.23 (d, 3J ϭ 8.24 Hz,
1 H, 2-HNaph) ppm. 13C NMR (62 MHz, [D6]DMSO): δ ϭ 20.8,
23.4 (C-3, C-7), 26.1, 36.5 (C-5, C-4), 55.8, 53.9, 54.5 (CH2, C-6,
C-8), 66.0, 67.4 (C-1Ј, C-2), 116.7 (C-2ЈЈ), 120.0, 123.6, 124.1,
124.5, 124.8, 125.3, 125.9, 126.2, 126.7, 127.6, 128.4, 129.6, 132.9,
131.0, 133.55, 134.2, 136.4 (16 Carom, C-1ЈЈ) ppm. C27H30BrNO
(464.4): calcd. C 69.82, H 6.51, C 3.02; found C 70.12, H 6.37,
N 3.00.
(1S,2R,4S,5R)-(1-Anthracenyl)(5-vinyl-1-azabicyclo[2.2.2]oct-2-yl)-
methanol (9) [and Its (1R,2R,4S,5R) Diastereomer]: These were pre-
pared from 3 and 9-bromoanthracene, analogously to the forma-
tion of 5 and 6 from 3. Although the presence of the diastereomer
was apparent by TLC, only 9 could be isolated by preparative
HPLC (LiChrospher Si; ethyl acetate/triethylamine, 9:1; flow
10 mL/min); Rf ϭ 0.19 on TLC plates. Yield 5%, [α]2D3 ϭ Ϫ19.0
(c ϭ 0.10, MeOH). IR (KBr): ν˜ ϭ 3422, 3056, 2955, 2868, 1631,
1454, 1378, 1267, 1110, 1023, 783 cmϪ1
.
1H NMR (250 MHz,
(1S,2S,4S,5R)-1-(9-Anthracenylmethyl)-2-[(Hydroxy)(1-naph-
thyl)methyl]-5-vinylquinuclidinium Chloride (12d): M.p. 217Ϫ218
CDCl3): δ ϭ 1.43Ϫ1.96 (m, 4 H, 2 ϫ 3-H, 2 ϫ 7-H), 2.48Ϫ2.55 (m,
2 H, 8-H, 5-H), 2.62Ϫ2.67 (m, 1 H, 5-H), 2.89Ϫ2.94 (m, 1 H, 8- °C, [α]2D5 ϭϩ56.0 (c ϭ 0.10, MeOH). IR (KBr): ν˜ ϭ 3075, 3050,
H), 3.11Ϫ3.20 (m, 1 H, 6-H), 3.28 (br. s, 1 H, OH), 3.51Ϫ3.68 (m, 3006, 2950, 2885, 1625, 1509, 1450, 1419, 1261, 1166, 1124, 995,
Eur. J. Org. Chem. 2002, 2087Ϫ2093
2091

E. V. Dehmlow, S. Düttmann, B. Neumann, H.-G. Stammler
FULL PAPER
917, 821, 784, 734 cmϪ1
.
1H NMR (250 MHz, [D6]DMSO): δ ϭ ether (b.p.30Ϫ60 °C)/ether (3:1), and the slightly orange colored
0.97Ϫ1.75 (m, 4 H, 2 ϫ 3-H, 2 ϫ 7-H), 2.30Ϫ2.33 (m, 2 H, 8-H,
fraction of Rf ഠ 0.33 (containing the product and sometimes a
4-H), 2.70Ϫ2.74 (m, 1 H, 5-H), 2.95Ϫ3.04 (m, 1 H, 8-H), 8.97 (s, little starting material) was concentrated to dryness and weighed.
1 H, 10-HAnth), 4.24Ϫ4.40 (m, 3 H, 2-H, 2 ϫ 6-H), 4.99Ϫ5.17 (m,
Relative yields were determined by 1H NMR, eeЈs by HPLC. 1H
2
3
2 H, 2 ϫ 2ЈЈ-H), 5.87Ϫ5.96 (m, 1 H, 1ЈЈ-H), 6.05 (d, J ϭ 14.1 Hz, NMR (250 MHz, CDCl3): δ ϭ, 1.04 (d, J ϭ 6.96 Hz, 3 H, CH3),
2
3
3
1 H, CH2), 6.37 (d, J ϭ 14.1 Hz, 1 H, CH2), 6.93 (br. s, 1 H, 1- 1.15 (d, J ϭ 6.84 Hz, 3 H, CH3), 2.77 (sept, J ϭ 6.90 Hz, 1 H,
H), 7.25Ϫ7.84 (m, 7 H, 7 ϫ Harom), 7.98Ϫ8.06 (m, 3 H, 3 ϫ Harom),
CH), 3.86 (s, 1 H, CHϪO), 7.70Ϫ7.78 (m, 2 H, 2 ϫ Harom),
7.91Ϫ7.99 (m, 1 H, Harom), 8.01Ϫ8.05 (m, 1 H, Harom) ppm. 13C
3
8.29 (d, J ϭ 7.85 Hz, 2 H, 2 ϫ Harom), 8.61 (m, 2 H, 2 ϫ Harom),
8.93 (d, 3J ϭ 9.66 Hz, 1 H, Harom) ppm. 13C NMR (62 MHz, NMR (62 MHz, CDCl3): δ ϭ 16.3, 18.8 (2 CH3). 25.7 (CH), 58.0
[D6]DMSO): δ ϭ 21.5, 23.5 (C-3, C-7), 25.5, 37.0 (C-5, C-4), 54.1,
54.5, 56.5 (CH2, C-6, C-8), 66.0, 67.3 (C-1Ј, C-2), 116.7 (C-2ЈЈ),
(CHϪO), 67.1 (CϪO), 126.7, 127.5, 131.3, 133.0, 134.3, 134.6 (6
Carom), 191.5 (CO), 192.3 (CO) ppm. HPLC (Chiralcel OD; hexane/
119.2, 123.6, 124.1, 124.5, 124.8, 125.3, 125.5, 125.8, 126.2, 126.7, 2-propanol, 500:1; flow 0.5 mL/min): (ϩ) enantiomer: 40.5 min;
127.4, 127.6, 128.4, 128.6, 129.3, 129.5, 129.6, 131.0, 131.1, 131.9, (Ϫ) enantiomer: 42.7 min.
132.9, 133.15, 133.2, 135.4, 137.2 (24 Carom
C35H34ClNO (520.1): calcd. C 80.83, H 6.59, N 2.69; found C
80.96, H 6.33, N 2.75.
, C-1ЈЈ) ppm.
PTC Benzylation of 2-(tert-Butoxycarbonyl)cyclopentanone (Reac-
tion 3): 2-(tert-Butoxycarbonyl)cyclopentanone (184 mg,
1.00 mmol) and the PT catalyst (5 mol %) were stirred in toluene
(10.0 mL) and sat. aq. K2CO3 (6.00 mL) for 5 min at room temp.
Benzyl bromide (0.18 mL, 1.52 mmol) was added, and the mixture
was stirred for 26 h at room temp. The reaction was then quenched
by addition of H2O (40.0 mL) and sat. aq. NaBr (15.0 mL). The
phases were separated, and the aqueous one was extracted with
CH2Cl2 (10.0 mL). The combined organic layers were dried
(Na2SO4), and the solvent was removed. The residue was taken up
in petroleum ether (b.p. 30Ϫ60 °C)/ether (25:1) and chromato-
graphed on silica gel. The fraction with Rf ϭ 0.03 contained 2-
benzyl-2-(tert-butoxycarbonyl)cyclopentanone and sometimes re-
N-(9-Acridinylmethyl)cinchoninium Bromide (13c): M.p.158Ϫ160
°C. [α]2D5 ϭ ϩ173.2 (c ϭ 0.73, MeOH). C33H32BrN3O·1H2O
(584.56): calcd. C 67.81, H 5.86, N 7.19; found C 68.01, H 5.88,
N 7.08.
N-(9-Acridinylmethyl)cinchonidinium Bromide (14c): M.p.153Ϫ154
°C. [α]2D3 ϭ Ϫ191.5 (c ϭ 0.43, MeOH). C33H32BrN3O·1H2O
(584.56): calcd. C 67.81, H 5.86, N 7.19; found C 67.61, H 5.82,
N 7.18.
N-(9-Acridinylmethyl)quininium Bromide (15c): M.p. 144Ϫ146 °C,
[α]2D3 ϭ Ϫ333.1 (c ϭ 0.50, MeOH). C33H34BrN3O2·1H2O (596.6): sidual benzyl bromide. The solvent was removed and the residue
C 66.45, H 5.90, N 6.84; found C 66.38, H 5.85, N 6.73.
weighed. Relative yields were determined by 1H NMR spectro-
scopy, ee values by HPLC. 1H NMR (250 MHz, CDCl3): δ ϭ
7.28Ϫ7.12 (m, 5 H, 5 HAr), 3.12 (s, 2 H, CH2Ph), 2.41Ϫ2.28 (m, 2
H, 2 ϫ 5-H), 2.03Ϫ1.82 (m, 3 H, 2 ϫ 4-H, 3-H), 1.59Ϫ1.51 (m, 1
H, 3-H), 1.43 (s, 9 H, 3 CH3) ppm. 13C NMR (62 MHz, CDCl3):
δ ϭ 19.85 (C-4), 28.5 (3 CH3), 32.3 (C-3), 38.4 (C-5), 38.9 (Cq),
62.3 (CH2), 82.3 (CϪO), 127.3, 129.1, 130.7, 136.9 (Carom), 170.7
(COO), 215.6 (CO) ppm. HPLC (Chiralcel OD; hexane/2-pro-
panol, 1000:1; flow 0.5 mL/min): (S)-2-benzyl-2-(tert-butoxycar-
bonyl)cyclopentanone: 18.5 min; (R) isomer: 20.4 min.
PTC Oxidation of 2-Ethyl-1-tetralone (Reaction 1): Aq. NaOH
(50%, 2.5 mL), toluene (7.5 mL), triethyl phosphite (239 mg, 0.25
mL, 1.44 mmol), 2-ethyl-1-tetralone (174 mg, 1.00 mmol), and the
PT catalyst (5 mol %) were placed in a micro-hydrogenation appar-
atus connected to a balloon containing oxygen. The mixture was
stirred vigorously for 42 h at room temp. H2O (20.0 mL) and tolu-
ene (10.0 mL) were then added, the phases were separated, and the
aqueous phase was extracted with toluene (10 mL). The combined
organic solutions were washed with HCl (10%, 10.0 mL), H2O (10
mL), and sat. aq. NaCl (10 mL), and dried with Na2SO4. The solv-
ent was removed, and the residue was chromatographed on silica
gel with petroleum ether (b.p.30Ϫ60 °C)/ethyl acetate (10:1). The
fraction with Rf Ն 0.10, a yellowish oil, contained 2-ethyl-2-hy-
droxy-1-tetralone and occasionally still some starting material. It
was concentrated to dryness and weighed. Relative yields were de-
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(Project De173/20-1,2) and the Fonds der Chemischen Industrie.
Thanks are due to Prof. P. Jutzi of this faculty for allowing access
to and manpower for his X-ray equipment.
1
1
termined by H NMR, enantiomeric excesses by HPLC. H NMR
(250 MHz, CDCl3): δ ϭ 0.96 (t, 3J ϭ 7.50 Hz, 3 H, CH3),
1.56Ϫ1.80 (m, 2 H, CH2), 2.00Ϫ2.35 (m, 2 H, 2 ϫ 3-H), 2.92Ϫ3.17
[1]
For a spectacular example see: H. Wynberg, A. G. Staring, J.
3
(m, 2 H, 2 ϫ 4-H), 3.75 (br. s, 1 H, OH), 7.24 (d, J ϭ 8.30 Hz, 1
Am. Chem. Soc. 1982, 104, 166Ϫ168.
H, 1 Harom), 7.30 (t, 3J ϭ 7.56 Hz, 1 H, 1 Harom), 7.56 (dt, 3J ϭ
7.56, 4J ϭ 1.40 Hz, 1 H, 1 Harom), 8.00 (dd, 3J ϭ 7.83, 4J ϭ 1.33 Hz,
1 H, 1 Harom) ppm. HPLC (Chirasep DNBPG; hexane/2-propanol,
500:1; flow 0.5 mL/min): (R)-2-ethyl-2-hydroxy-1-tetralone:
36.8 min.; (S) isomer: 38.2 min.
[2]
Examples: [2a] H. C. Kolb, M. S. Van Nieuwenhze, K. B. Sharp-
[2b]
less, Chem. Rev. 1994, 94, 2483Ϫ2547.
E. J. Corey, M. C.
Noe, J. Am. Chem. Soc. 1996, 118, 11038Ϫ11053.
[3]
[3a]
Selected leading references:
D. L. Hughes, U. H. Dolling,
K. M. Ryan, E. F. Schoenewaldt, E. J. Grabowski, J. Org.
[3b]
Chem. 1987, 52, 4745Ϫ4752.
M. J. OЈDonnell, F. Delgado,
PTC Epoxidation of 2-Isopropyl-1,4-naphthoquinone (Reaction 2): A
mixture of 2-isopropyl-1,4-naphthoquinone (201 mg, 1.00 mmol),
CHCl3 (3.00 mL), and aq. H2O2 (30%, 1.00 mL) was stirred for 3
min at 0 °C. LiOH (37.0 mg, 2.0 mmol) and the PT catalyst (5
mol %) were then added, and the mixture was stirred for 5 h at 0
°C and for12 h at room temp. Quenching was performed by the
addition of HCl (1 , 10 mL) and the phases were separated. The
aqueous layer was extracted thrice with 10 mL of ether. The com-
bined extracts were dried (Na2SO4), and the solvent was removed.
The residue was chromatographed on silica gel with petroleum
R. S. Pottorf, Tetrahedron 1999, 55, 6347Ϫ6362. [3c] B. Lygo, P.
[3d]
G. Wainwright, Tetrahedron Lett. 1997, 38, 8595Ϫ8598.
B.
Lygo, P. G. Wainwright, Tetrahedron Lett. 1998, 39,
[3e]
1599Ϫ1602.
B. Lygo, P. G. Wainwright, Tetrahedron 1999,
[3f]
55, 6289Ϫ6300.
S. Arai, Y. Shirai, T. Ishida, T. Shioiri, Tet-
rahedron 1999, 55, 6375Ϫ6386. [3g] S. Arai, Y. Shirai, T. Ishida,
T. Shioiri, Chem. Commun. 1999, 49Ϫ50. [3h] S. Arai, Y. Shirai,
[3i]
T. Ishida, T. Shioiri, J. Org. Chem. 1998, 63, 9572Ϫ9575.
Arai, T. Shioiri, Tetrahedron Lett. 1998, 39, 2145Ϫ2137.
J. Corey, F. Xu, M. C. Noe, Tetrahedron Lett. 1998, 39,
S.
E.
[3j]
[3k]
5347Ϫ5350.
E. J. Corey, F.-Y. Zhang, Angew. Chem. 1999,
Eur. J. Org. Chem. 2002, 2087Ϫ2093
2092

Monodeazacinchona Alkaloid Derivatives
FULL PAPER
S. Arai, M. Oku, M. Miura, T. Shioiri, Synlett 1998,
1201Ϫ1202.
Epoxidations of (E)-enones have been performed with hypo-
chlorite and cinchona alkaloid derived catalysts in up to 90%
ee, but the opposite enantiomer to that produced in the H2O2
reactions was obtained.[3e]
[15]
[16]
111, 2057Ϫ2059; Angew. Chem. Int. Ed. 1999, 38, 1931Ϫ1934.
[3l]
E. J. Corey, Y. Bo, J. Busch-Petersen, J. Am. Chem. Soc.
1998, 120, 13000Ϫ13001.
[4] [4a]
G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. S.
Svendsen, I. Marko, K. B. Sharpless, J. Am. Chem. Soc. 1989,
[4b]
111, 8069Ϫ8076.
E. J. Corey, F. Xu, M. C. Noe, J. Am.
[17]
[18]
[4c]
K. Manabe, Tetrahedron 1998, 42, 14465Ϫ14476; Tetrahedron
Chem. Soc. 1997, 119, 12414Ϫ12415.
W. M. Braje, J. Holz-
Lett. 1998, 39, 5807Ϫ5810.
grefe, R. Wartchow, H. M. R. Hoffmann, Angew. Chem. 2000,
112, 2165Ϫ2167; Angew. Chem. Int. Ed. 2000, 39, 2085Ϫ2087.
E. V. Dehmlow, S. Wagner, A. Müller, Tetrahedron 1999, 55,
6335Ϫ6346.
H. M. R. Hoffmann, T. Plessner, C. von Riesen, Synlett 1996,
690Ϫ692.
Buchler GmbH, Braunschweig, Germany.
G. Grethe, H. L. Lee, T. Mitt, M. R. UskokovicЈ, J. Am. Chem.
Soc. 1978, 100, 581Ϫ588 and 589Ϫ593.
Crystal data and structure refinement parameters: Formula
mass: 293.39; crystal size: 0.1 ϫ 0.15 ϫ 0.3 mm; colorless
needles; crystal system, space group: trigonal, P31; unit cell
[5]
[6]
˚
˚
dimensions: a ϭ 11.8100(8) A, b ϭ 11.8100(10) A, c ϭ
3
˚
˚
9.9270(10) A; volume: 1199.08(18) A ; Z ϭ 3; Dcalcd. ϭ 1.219
Mg/m3; F(000) ϭ 474; absorption coefficient: 0.074 mmϪ1; θ
range for data collection: 2.86Ϫ27.5°; index ranges: Ϫ15 Յ h
Յ12, Ϫ15 Յ k Յ 15, Ϫ12 Յ l Յ12; reflections collected/unique:
8113/3205 [R(int) ϭ 0.0891]; completeness to θ ϭ 27.49°:
88.8%; absorption correction: none; refinement method: full-
matrix, least squares on F2; data/restraints/parameters: 3205/1/
199; goodness-of-fit on F2: 1.059; final R indices [I Ն 2σ(I)]:
R1 ϭ 0.0577, wR2 ϭ 0.1051; R indices (all data): R1 ϭ 0.0928,
wR2 ϭ 0.1212; largest diff. peak and hole: 0.306 and Ϫ0.209 e
[7]
[8]
[9]
X-ray work was performed by B. Neumann and H.-G.
Stammler.
[10]
[11]
[12]
E. V. Dehmlow, R. Klauck, B. Neumann, H.-G. Stammler, J.
Prakt. Chem. 1998, 340, 572Ϫ575.
M. Masui, A. Ando, T. Shioiri, Tetrahedron Lett. 1988, 29,
2835Ϫ2838.
E. V. Dehmlow, V. Knufinke, Liebigs Ann. Chem. 1992,
283Ϫ285; E. V. Dehmlow, I. Nachstedt, J. Prakt. Chem. 1993,
335, 371Ϫ374; E. V. Dehmlow, M. S. Romeo, J. Chem. Res.
(S) 1992, 400Ϫ401; E. V. Dehmlow, S. Schrader, Pol. J. Chem.
1994, 68, 2199Ϫ2208.
E. F. L. de Vries, L. Ploeg, M. Calao, J. Brussee, A. Van der
Gen, Tetrahedron: Asymmetry 1995, 6, 1123Ϫ1132.
R. Helder, J. C. Hummelen, R. W. P. M. Laane, J. S. Wiering,
H. Wynberg, Tetrahedron Lett. 1976, 21, 1831Ϫ1834; H. Pluim,
H. Wynberg, J. Org. Chem. 1980, 45, 2388Ϫ2502.
˚
A
Ϫ3. The absolute configuration could not be determined reli-
ably but follows from the known one of the starting material.
CCDC-172080 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cam-
bridge Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB2 1EZ, UK [Fax: (internat.) ϩ 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
[19]
[20]
[13]
[14]
Details: S. Düttmann, Dissertation, Universität Bielefeld, 2001.
Received December 17, 2001
[O010586]
Eur. J. Org. Chem. 2002, 2087Ϫ2093
2093