Simple chiral pyrrolidine-pyridine-based catalysts for highly enantioselective michael addition to nitro olefins

Article abstract of DOI:10.1002/ejoc.200900716

A new class of chiral pyrrolidine-pyridine-based organocata-lysts, available from commercially available starting materi-als, have been synthesized and shown to be very effective catalysts for the asymmetric Michael addition reactions of cy-clic/acyclic/a

Full text of DOI:10.1002/ejoc.200900716

FULL PAPER
DOI: 10.1002/ejoc.200900716
Simple Chiral Pyrrolidine–Pyridine-Based Catalysts for Highly
Enantioselective Michael Addition to Nitro Olefins
Da-Zhen Xu,[a] Sen Shi,[a] and Yongmei Wang*[a]
Keywords: Asymmetric catalysis / Michael addition / Alkenes / Organocatalysis / Pyrrolidine / Catalyst design
A new class of chiral pyrrolidine–pyridine-based organocata-
lysts, available from commercially available starting materi-
als, have been synthesized and shown to be very effective
catalysts for the asymmetric Michael addition reactions of cy-
clic/acyclic/aromatic ketones and an aldehyde with nitro ole-
ties (syn/anti = 99:1), and enantioselectivities (up to 99%).
Based on the experimental results and ESI-MS analysis of
the intermediates, the mode of activity of the organocatalyst
with the substrate was deduced.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
fins, giving excellent yields (up to 99%), diastereoselectivi- Germany, 2009)
Michael addition of aromatic ketones to nitro olefins, and
Introduction
in both cases very low yields and enantioselectivities were
obtained.[4d,8d]
The Michael reaction is widely recognized as one of the
most important carbon–carbon bond-forming procedures,
and it plays an important role in organic synthesis.[1] The
development of organocatalysts that promote asymmetric
Michael reactions is an attractive area of research.[2] Thus,
it is not surprising that chemists pay considerable attention
to the development of enantioselective catalytic protocols
for this base reaction, aiming at developing more selective
and efficient catalytic systems for this synthetically useful
transformation. Over the past few years there has been a
tremendous increase in research activities directed towards
the development of organocatalysts for this asymmetric re-
action.[3] Asymmetric Michael addition reactions of ketones
or aldehydes to nitro olefins in the presence of -proline-
and pyrrolidine-based catalytic systems have been reported
to proceed with poor to good enantioselectivities,[4] and
consequently tremendous efforts have been made to find
more efficient pyrrolidine-based organocatalysts for use in
this transformation.[5]
As a result, the design and development of highly active
chiral organocatalysts for achieving good results with both
ketones and aldehydes in Michael conjugate addition reac-
tions remains a major challenge in synthetic organic chem-
istry.[8] To the best of our knowledge, there is no universal
catalyst that gives both high yield and enantioselectivity for
this reaction with cyclic/acyclic/aromatic ketones and alde-
hydes.
In this paper we report a catalyst that is compatible with
various ketones (cyclic/acyclic/aromatic) and an aldehyde,
providing excellent yields (up to 99%) and stereoselectivities
(up to syn/anti = 99:1, 99% ee). The catalysts are similar in
structure to Kotsuki pyrrolidine–pyridine-based cata-
lysts;[8b] they are composed of 2-pyrrolidinyl and 2-pyridyl
moieties linked by a methyleneoxy group instead of a meth-
Most of the catalysts used in the Michael reactions of
ketones or aldehydes with nitro olefins give excellent re-
sults,[6] but few give good enantioselectivities with both
ketones and aldehydes.[7] In nearly all cases, the Michael
products were obtained with good results, but the use of
ketones was limited to cyclohexanone. Acyclic and aromatic
ketones have been little used in this reaction. There are only
two reports of pyrrolidine-based catalysts used in the
[a] Department of Chemistry, State Key Laboratory and Institute
of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P. R. China
Fax: +86-22-2350-2654
E-mail: ymw@nankai.edu.cn
Scheme 1. Synthesis of the catalysts 3.
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Eur. J. Org. Chem. 2009, 4848–4853
4848

Enantioselective Michael Addition to Nitro Olefins
ylene or ethylene spacer and are easier to synthesize and When H2O was used as the solvent, no product was ob-
more effective in the enantioselective Michael addition reac- tained. The most polar solvents, DMSO and [bmim][PF4],
tions of all kinds of ketones and an acyclic aldehyde to nitro both gave poor yields and enantioselectivities (Table 1, En-
olefins.
tries 8 and 12). The nonpolar solvent toluene gave a poor
A series of pyrrolidine–pyridine catalysts 3 were prepared yield of 82%. CHCl3 and tert-butyl alcohol gave moderate
from the “chiral pool” by using N-Boc--prolinol as the diastereoselectivities and enantioselectivities (Table 1, En-
starting material.[9] The synthetic procedures were quite tries 9 and 11). The best result was observed when THF
straightforward; N-Boc--prolinol was coupled with bro- was used as the solvent (Table 1, Entry 10: syn/anti = 97:3,
mopyridine reagents and then treated with TFA in CH2Cl2 92% ee).
to afford the product (for example, 3a) in 65% total yield
As we had obtained 92% enantioselectivity of the
Michael product in THF by using 15 mol-% of 3a, the ef-
fects of some Brønsted acids on the Michael reaction of
cyclohexanone (4a) and nitrostyrene (5a) were examined in
the hope of improving the enantioselectivity. As illustrated
in Table 2, the enantioselectivities are lower with relatively
strong acids such as TFA and pTosOH than with weak ac-
ids such as PhCOOH and C6H5OH. Finally, we found that
2-naphthol was the best weak acid in combination with cat-
alyst 3a (Table 2, Entry 9: syn/anti = 98:2, 95% ee).
from N-Boc--prolinol (Scheme 1).[10]
Results and Discussion
As can be seen from the results summarized in Table 1,
the reaction of cyclohexanone (4a) with nitrostyrene (5a)
was performed at room temperature (20 °C) with 15 mol-%
of 3 as the catalyst. All the catalysts tested exhibited good
catalytic activity with the corresponding products obtained
in excellent chemical yields (Table 1, Entries 1–5). The pyr-
rolidine–pyridine catalyst 3a promoted the Michael ad-
dition reaction with high diastereoselectivity and enantio-
selectivity (Table 1, Entry 1). Chiral catalysts 3b–3e also
gave good diastereoselectivities, but lower enantioselectivit-
ies were obtained than with 3a (Table 1, Entries 2–5). The
catalyst 3c, containing the 6-methylpyridine moiety, gave
mainly the anti Michael product, whereas the other cata-
lysts predominantly gave the syn products.
Table 2. Asymmetric Michael addition reactions of cyclohexanone
and nitrostyrene catalyzed by 3a with different additives.[a]
Entry
Additive
Time Yield syn/anti[c]
[h]
ee
[%][b]
[%][d]
1
2
3
4
5
6
7
8
9
TFA
PhCOOH
(Ϯ)-lactic acid
pTosOH
24
24
24
48
20
20
20
20
20
20
99
99
99
20
99
99
99
99
99
98
97:3
97:3
97:3
92:8
95:5
95:5
96:4
97:3
98:2
72:28
53
90
90
73
86
88
85
85
95
85
Table 1. The effect of catalysts 3 on the asymmetric Michael ad-
dition reactions of cyclohexanone and nitrostyrene.[a]
1,4-(HO)2C6H3
3,5-(H3C)2C6H3OH
C6H5OH
p-methylmandelic acid
2-naphthol
10
1-naphthol
[a] All reactions were conducted in THF (1 mL) by using 4a
(0.2 mL, 2.0 mmol), 5a (30 mg, 0.2 mmol), and catalyst 3a (5.3 mg,
0.03 mmol) in the presence of 5 mol-% of the additive. [b] Isolated
yield. [c] Determined by 1H NMR spectroscopy. [d] Determined by
HPLC analysis (Chiralcel AD-H column).
Entry Catalyst
Solvent
Time Yield syn/anti[c]
[h]
ee
[%][b]
[%][d]
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3a
3a
3a
3a
3a
3a
3a
neat
neat
neat
neat
neat
12
20
48
10
20
72
72
72
72
20
12
72
99
97
92
95
97
0
82
68
85
99
99
40
94:6
63:37
33:67
60:40
85:15
–
94:6
95:5
96:4
97:3
94:6
92:8
89
81
88
87
88
–
91
86
81
92
86
75
Having established the optimal reaction conditions, we
then examined the reactions of other nitro olefins to estab-
lish the general scope of this asymmetric transformation.
As shown in Table 3 (Entries 1–10), high isolated yields
were obtained for all the products, regardless of the elec-
tronic nature of the aromatic substituents, and in most of
the cases we obtained the syn products with high diastereo-
selectivities (Ͼ96% syn/anti) and enantioselectivities (92–
99% ee).
Other ketones, including cyclic and acyclic ketones, were
also examined in the 3a-catalyzed Michael addition reac-
tion with 5a, and the products (Table 4, Entries 1–5) were
isolated in good yields and with good to excellent enantio-
H2O
toluene
DMSO
CHCl3
THF
(CH3)3COH
[bmim][PF4]
10
11
12
[a] All reactions were conducted in solvent (1 mL) by using 4a
(0.2 mL, 2.0 mmol) and 5a (30 mg, 0.2 mmol) in the presence of
15 mol-% of the catalyst. [b] Isolated yield. [c] Determined by H
NMR spectroscopy. [d] Determined by HPLC analysis (Chiralcel
AD-H column).
1
Catalyst 3a was used as the catalyst of choice and evalu- selectivities. Cycloheptanone is reported to be less active as
ated in different solvents (Table 1, Entries 6–12). The yields a substrate, and the products of Michael reactions with ni-
and enantioselectivities of the product differed significantly. tro olefins have always been obtained in very low yields
Eur. J. Org. Chem. 2009, 4848–4853
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D.-Z. Xu, S. Shi, Y. Wang
FULL PAPER
Table 3. Asymmetric Michael addition reactions of cyclohexanone and enantioselectivities;[7b,8d,11] however, in this work the
and nitro olefins catalyzed by 3a.[a]
highest enantioselectivity was obtained for the reaction with
cycloheptanone in the presence of the catalyst 3a (Table 4,
Entry 1). The use of aliphatic ketones in the reaction with
nitrostyrene gave similar results (Table 4, Entries 2–4).
Table 4. Asymmetric Michael addition reactions of ketones and ni-
trostyrene catalyzed by 3a.[a]
[a] Reaction conditions: ketone
4 (2.0 mmol), nitro olefin
(0.2 mmol), 15 mol-% 3a, 5 mol-% 2-naphthol, and THF (1 mL).
[b] Isolated yield. [c] Determined by 1H NMR spectroscopy. [d]
Determined by HPLC analysis (Chiralcel AD-H or OD-H col-
umn).
The results of a preliminary study demonstrated that 3a
also catalyzed the Michael addition reaction of an aromatic
ketone to nitrostyrene (Table 4, Entry 5). Under the reac-
tion conditions described above, the addition of acetophe-
none to nitrostyrene (5a) resulted in the formation of the
product in 53% yield and 85% ee. This is the best result
obtained for the reaction between acetophenone and nitro-
styrene catalyzed by a pyrrolidine-based catalyst.[4d,8d] Pre-
viously, highly enantioselective Michael additions of aro-
matic ketones to nitro olefins were only achieved by using
chiral bifunctional primary amine–thiourea catalysts.[12]
An aldehyde was also found to be compatible with 3a
under the optimized conditions; the addition of isobutyral-
dehyde to nitrostyrene (5a) gave the desired product in good
yield and 81% ee (Table 4, Entry 6).
The stereochemistries of the major products 6 were de-
termined to be (2S,3R) by comparison of their optical rota-
tions with other previous studies.[4–8] The absolute stereo-
chemical results can be explained by an acyclic synclinal
transition state, as proposed by Seebach and Golinski.[13] It
is accepted that when primary or secondary chiral amines
are used as organocatalysts, the reaction proceeds by an
enamine pathway. As shown in Scheme 2, the catalyst 3a
[a] Reaction conditions: ketone 4a (196 mg, 2.0 mmol), nitro olefin
(0.2 mmol), 15 mol-% 3a, 5 mol-% 2-naphthol, and THF (1 mL).
[b] Isolated yield. [c] Determined by 1H NMR spectroscopy. [d]
Determined by HPLC analysis (Chiralcel AD-H or OD-H col-
umn).
4850
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Eur. J. Org. Chem. 2009, 4848–4853

Enantioselective Michael Addition to Nitro Olefins
first forms a chiral enamine I with cyclohexanone (4a), and
then a Michael reaction between the enamine-activated I
and the nitro olefin 5 leads to the formation of the corre-
sponding product 6 via transition state A. The catalyst 3a
is regenerated for use in the subsequent catalytic cycle. The
existence of the intermediates I and II in the reaction mix-
ture was confirmed by ESI-MS (Figure 1).
Conclusions
We have developed a new class of chiral pyrrolidine–pyr-
idine-based organocatalysts that are capable of catalyzing
highly enantioselective and diastereoselective nitro-Michael
addition reactions. The chiral pyrrolidine–pyridine catalysts
were easily prepared from commercially available -prolinol
in only two steps. An exceptionally broad range of ketones
(cyclic/acyclic/aromatic), an aldehyde, and a variety of nitro
olefins are tolerated in this system. These are the first uni-
versal catalysts that can be employed in the Michael ad-
dition reactions of all kinds of ketones and nitro olefins to
give high yields and good to excellent diastereoselectivities
and enantioselectivities. Further investigation into the ap-
plications of this organocatalyst in asymmetric catalysis is
in progress.
Experimental Section
General: All solvents were purified according to standard pro-
1
cedures. H NMR spectra were recorded at 300 or 400 MHz, and
13C NMR spectra were recorded at 75 or 100 MHz with Bruker
DPX-300 or AV400 spectrometers. Chemical shifts (δ) were cal-
ibrated relative to tetramethylsilane as external reference and are
reported in ppm. Coupling constants (J) are given in Hz. The fol-
lowing abbreviations are used to indicate the multiplicity: s, singlet;
d, doublet: t, triplet; m, multiplet. HRMS data were recorded with
an IonSpec FT-ICR mass spectrometer with ESI source. Melting
points were measured with a RY-I apparatus and are reported un-
corrected. Optical rotations were measured with a Perkin–Elmer
341 polarimeter at 20 °C. HPLC analysis was performed with a
Scheme 2. Proposed mechanism for the 3a-catalyzed Michael ad-
dition reaction.
Figure 1. ESI-MS (+) spectra of the intermediates I and II in the reaction cycle.
Eur. J. Org. Chem. 2009, 4848–4853
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4851

D.-Z. Xu, S. Shi, Y. Wang
FULL PAPER
Shimadzu CTO-10AS by using a Chiralpak AD-H or an OD-H
column purchased from Daicel Chemical Industries.
162.02 ppm. HRMS: calcd. for C11H16N2OH+ [M + H]+ 193.1335;
found 193.1339. [α]2D0 = –20.0 (c = 0.5, CH2Cl2). C11H16N2O
(192.26): calcd. C 68.72, H 8.39, N 14.57; found C 68.65, H 8.34,
N 14.53.
General Procedure for the Synthesis of Catalysts
(2S)-2-[(2-Pyridyloxy)methyl]pyrrolidine (3a):
A solution of 1
(2S)-2-{[4-(Trifluoromethyl)-2-pyridyloxy]methyl}pyrrolidine (3d):
Catalyst 3d was prepared according to the General Procedure to
afford the product as a colorless oil; yield 98%. 1H NMR
(400 MHz, CDCl3): δ = 1.48–1.56 (m, 1 H, CH2 pyrrolidine), 1.70–
1.97 (m, 3 H, CH2 pyrrolidine), 2.23 (br., 1 H, NH), 2.91–3.04 (m,
2 H, CH2 pyrrolidine), 3.49–3.56 (m, 1 H, CH pyrrolidine), 4.19
(dd, J1 = 7.6, J2 = 10.4 Hz, 1 H, OCH2), 4.33 (dd, J1 = 4.4, J2 =
10.8 Hz, 1 H, OCH2), 6.98 (s, 1 H, pyridine), 7.04 (d, J = 5.2 Hz,
1 H, pyridine), 8.27 (d, J = 5.2 Hz, 1 H, pyridine) ppm. 13C NMR
(100 MHz, CDCl3): δ = 25.36, 27.91, 46.59, 56.95, 69.80, 107.82,
112.18, 123.97, 140.95, 148.18, 164.21 ppm. HRMS: calcd. for
C11H13F3N2OH+ [M + H]+ 247.1053; found 247.1056. [α]2D0 = +9.6
(c = 0.5, CH2Cl2). C11H13F3N2O (246.23): calcd. C 53.66, H 5.32,
N 11.38; found C 53.71, H 5.38, N 11.42.
(3.02 g, 15 mmol) in dry THF (30 mL) under N2 was cooled to
0 °C and stirred for 10 min. NaH (2.16 g, 90 mmol) was added, and
the mixture was stirred for 20 min. The mixture was warmed to
room temperature and stirred overnight, and then a solution of 2-
bromopyridine (1.7 g, 15 mmol) in THF (5 mL) was added. The
mixture was heated at reflux for 24 h. After evaporation of the
THF, ethyl acetate (80 mL) was added, and the solution was
washed with water (30 mL) and brine (30 mL), and dried with
Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by chromatography with petroleum
ether/ethyl acetate (8:1) to afford 2.9 g (71%) of 2a as a colorless
oil. TFA (8 mL) was added dropwise to a solution of 2a (1.0 g,
3.6 mmol) in CH2Cl2 (10 mL) at 0 °C. The mixture was warmed to
room temperature and stirred overnight. After removal of the or-
ganic solvents under vacuum, the residue was dissolved in CH2Cl2
(10 mL) and then treated with saturated Na2CO3 solution (30 mL)
at room temperature for 1 h. The aqueous layer was extracted with
CH2Cl2 (3ϫ15 mL), and the combined extracts were washed with
brine (15 mL) and dried with anhydrous Na2SO4. Concentration in
(2S)-2-[(4-Pyridyloxy)methyl]pyrrolidine (3e): Catalyst 3e was pre-
pared according to the General Procedure to afford the product as
a yellow liquid; yield 91%. 1H NMR (300 MHz, CDCl3): δ = 1.48–
1.60 (m, 1 H, CH2 pyrrolidine), 1.73–1.87 (m, 2 H, CH2 pyrroli-
dine), 1.92–2.01 (m, 1 H, CH2 pyrrolidine), 2.34 (br., 1 H, NH),
2.92–3.02 (m, 2 H, CH2 pyrrolidine), 3.49–3.58 (m, 1 H, CH pyr-
rolidine), 3.85–3.97 (m, 2 H, OCH2), 6.79–6.81 (m, 2 H, pyridine),
8.40–8.42 (m, 2 H, pyridine) ppm. 13C NMR (75 MHz, CDCl3):
δ = 25.28, 27.97, 46.60, 56.78, 71.28, 110.23, 151.01, 164.89 ppm.
HRMS: calcd. for C10H14N2ONa+ [M + Na]+ 201.0998; found
201.0999. [α]2D0 = +9.6 (c = 0.5, CH2Cl2). C10H14N2O (178.23):
calcd. C 67.39, H 7.92, N 15.72; found C 67.33, H 7.87, N 15.66.
1
vacuo after filtration gave 3a as a colorless oil (587 mg, 92%). H
NMR (400 MHz, CDCl3): δ = 1.72–1.81 (m, 1 H, CH2 pyrrolidine),
1.90–1.97 (m, 2 H, CH2 pyrrolidine), 2.04–2.13 (m, 1 H, CH2 pyr-
rolidine), 3.09–3.23 (m, 2 H, CH2 pyrrolidine), 3.81–3.87 (m, 1 H,
CH pyrrolidine), 4.31 (dd, J1 = 6.8, J2 = 11.6 Hz, 1 H, OCH2),
4.51 (dd, J1 = 3.6, J2 = 11.6 Hz, 1 H, OCH2), 6.79 (d, J = 8.4 Hz,
1 H, pyridine), 6.89–6.92 (m, 1 H, pyridine), 7.57–7.62 (m, 1 H,
pyridine), 8.10–8.12 (m, 1 H, pyridine) ppm. 13C NMR (100 MHz,
CDCl3): δ = 24.29, 27.02, 45.48, 58.25, 65.84, 111.23, 117.49,
139.08, 146.51, 162.98 ppm. HRMS: calcd. for C10H14N2ONa+ [M
+ Na]+ 201.0998; found 201.0992. [α]2D0 = +33.6 (c = 0.5, CH2Cl2).
C10H14N2O (178.23): calcd. C 67.39, H 7.92, N 15.72; found C
67.45, H 7.88, N 15.67.
Typical Experimental Procedure for Asymmetric Michael Addition
to Nitro Olefins: 2-Naphthol (1.5 mg, 0.01 mmol) was added to a
mixture of catalyst 3a (5.4 mg, 0.03 mmol) in THF (0.5 mL) at
room temperature under air. The reaction mixture was stirred for
10 min, and then cyclohexanone (4a; 208 µL, 2.0 mmol) and (E)-β-
nitrostyrene (5a; 30 mg, 0.2 mmol) were added. The homogeneous
reaction mixture was stirred at room temperature for 18 h. The
reaction mixture was directly loaded onto a silica gel column to
afford the Michael adduct 6a (49 mg, 99%) as a white solid (m.p.
(2S)-2-[(4-Methyl-2-pyridyloxy)methyl]pyrrolidine (3b): Catalyst 3b
was prepared according to the General Procedure to afford the
product as a light-yellow solid; yield 92%; m.p. 58–59 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.52–1.63 (m, 1 H, CH2 pyrrolidine), 1.71–
2.01 (m, 2 H, CH2 pyrrolidine), 2.28 (s, 3 H, CH3), 2.95–3.08 (m,
2 H, CH2 pyrrolidine), 3.54–3.66 (m, 1 H, CH pyrrolidine), 3.83–
3.89 (m, 1 H, CH2 pyrrolidine), 4.16 (dd, J1 = 10, J2 = 14.4 Hz, 1
H, OCH2), 4.33 (dd, J1 = 5.2, J2 = 14 Hz, 1 H, OCH2), 6.58 (s, 1 H,
pyridine), 6.70 (d, J = 6.8 Hz, 1 H, pyridine), 7.98 (d, J = 7.2 Hz, 1
H, pyridine) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.90, 25.19,
27.77, 46.34, 57.41, 68.46, 111.17, 118.45, 146.24, 150.00,
164.04 ppm. HRMS: calcd. for C11H16N2O5Na+ [M + Na]+
215.1155; found 215.1162. [α]2D0 = +14.1 (c = 0.5, CH2Cl2).
C11H16N2O (192.26): calcd. C 68.72, H 8.39, N 14.57; found C
68.78, H 8.33, N 14.59.
1
129–130 °C) in a syn/anti ratio of 98:2 (by H NMR). The ee was
determined by HPLC analysis [Chiralpak AD-H, iPrOH/hexane
(10:90), 0.5 mL/min, 254 nm, tr(minor)
= 21.8, tr(major) =
27.0 min] to be 96% ee. [α]2D5 = –33.7 (c = 0.80, CHCl3).
Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (grant no. 20672061) and 863 Project
(no. 2007AA05Z102). We also thank the Nankai University State
Key Laboratory of Elemento-Organic Chemistry for support.
(2S)-2-[(6-Methyl-2-pyridyloxy)methyl]pyrrolidine (3c): Catalyst 3c
[1] P. Perlmutter, Conjugate Addition Reactions in Organic Synthe-
sis, Pergamon Press, Oxford, 1992.
was prepared according to the General Procedure to afford the
1
[2] a) N. Krause, A. Hoffmann-Röder, Synthesis 2001, 171–196; b)
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product as a brown oil; yield 95%. H NMR (400 MHz, CDCl3):
δ = 1.65–1.74 (m, 1 H, CH2 pyrrolidine), 1.85–1.92 (m, 2 H, CH2
pyrrolidine), 1.97–2.07 (m, 1 H, CH2 pyrrolidine), 2.43 (s, 3 H,
CH3), 3.03–3.15 (m, 2 H, CH2 pyrrolidine), 3.66–3.77 (m, 1 H, CH
pyrrolidine), 4.24 (dd, J1 = 6.8, J2 = 11.6 Hz, 1 H, OCH2), 4.41
(dd, J1 = 3.6, J2 = 11.6 Hz, 1 H, OCH2), 6.57 (d, J = 8.0 Hz, 1 H,
pyridine), 6.74 (d, J = 7.2 Hz, 1 H, pyridine), 7.47 (t, J = 8 Hz, 1
H, pyridine) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.99, 24.05,
26.38, 44.88, 56.86, 66.86, 106.59, 115.37, 138.31, 155.06,
[3] For reviews, see: a) P. L. Dalko, L. Moisan, Angew. Chem.
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4852
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Published Online: ᭿
Eur. J. Org. Chem. 2009, 4848–4853
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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