Chiral phosphoric acid catalyzed inverse-electron-demand aza-Diels-Alder reaction of isoeugenol derivatives

Article abstract of DOI:10.1021/ol301251h

Highly enantio- and diastereoselective three-component inverse electron-demand aza-Diels-Alder reaction of aldehydes, anilines, and isoeugenol derivatives catalyzed by a chiral phosphoric acid catalyst are reported. A wide variety of 2,3,4-trisubstituted tetrahydroquinolines containing an aryl group at the 4-position were obtained in a one-pot process with good to high yields and excellent stereoselectivities (>95:5 dr and up to >99% ee).

Full text of DOI:10.1021/ol301251h

ORGANIC
LETTERS
2012
Vol. 14, No. 12
3158–3161
Chiral Phosphoric Acid Catalyzed Inverse-
Electron-Demand Aza-DielsꢀAlder
Reaction of Isoeugenol Derivatives
ꢀ
Long He, Mathieu Bekkaye, Pascal Retailleau, and Geraldine Masson*
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, ICSN, CNRS,
91198 Gif-sur-Yvette Cedex, France
masson@icsn.cnrs-gif.fr
Received May 7, 2012
ABSTRACT
Highly enantio- and diastereoselective three-component inverse electron-demand aza-DielsꢀAlder reaction of aldehydes, anilines, and
isoeugenol derivatives catalyzed by a chiral phosphoric acid catalyst are reported. A wide variety of 2,3,4-trisubstituted tetrahydroquinolines
containing an aryl group at the 4-position were obtained in a one-pot process with good to high yields and excellent stereoselectivities (>95:5 dr
and up to >99% ee).
The inverse electron-demand aza-DielsꢀAlder reaction
(IEDDA reaction) is an important acid-catalyzed cycload-
dition allowing access to 2,3,4-trisubstituted tetrahydro-
quinolines from N-aryl imines and electron-rich alkenes.1,2
The development of a catalytic enantioselective version of
this so-called Povarov reaction has recently received con-
siderable attention due to the prevalence of these structural
motifs in many natural products and pharmaceutically
promising compounds.3 Therefore, a wide variety of dieno-
philes such as enol ethers, enecarbamates, and cyclo-
pentadienes have been successfully used in an enantio-
selective IEDDA reaction.4 Despite recent developments,
the use of simple acyclic alkenes as dienophiles for the
enantioselective formation of tetrahydroquinolines has
met with limited success. Ricci et al.5a reported the first
two-component Povarov reaction using vinylindoles as
alkene dienophiles catalyzed by a chiral phosphoric acid.5
Very recently, Feng et al.5b have disclosed that a chiral N,
N-dioxide-Sc(OTf)3 complex catalyzed an enantioselective
IEDDA reaction employing R-alkyl styrenes as dieno-
philes and N-arylimines derived from ortho-hydroxyani-
lines as dienes. Despite the aforementioned advances, no
example of an IEDDA reaction using unsymmetrically
(1) (a) Povarov, L. S.; Mikhailov, B. M. Izv. Akad. Nauk SSR, Ser.
Khim. 1963, 953. (b) Povarov, L. S. Russ. Chem. Rev. 1967, 36, 656.
(2) For a general review of inverse-electron-demand aza-DielsꢀAlder
reactions, see: (a) Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001, 57,
6099. (b) Glushkov, V. A.; Tolstikov, A. G. Russ. Chem. Rev. 2008, 77, 137.
(c) Kouznetsov, V. V. Tetrahedron 2009, 65, 2721.
(3) For an overview on the preparation and biological activity of
1,2,3,4-tetrahydroquinolines, see: (a) Katritzky, A. R.; Rachwal, S.;
Rachwal, B. Tetrahedron 1996, 52, 15031. (b) Isambert, N.; Lavilla, R.
Chem.;Eur. J. 2008, 14, 8444. (c) Sridharan, V.; Suryavanshi, P. A.;
ꢀ
Carlos Menendez, J. Chem. Rev. 2011, 111, 7157.
(4) (a) Ishitani, H.; Kobayashi, S. Tetrahedron Lett. 1996, 37, 7357.
(b) Sundararajan, G.; Prabagaran, N.; Varghese, B. Org. Lett. 2001, 3,
1973. (c) Akiyama, T.; Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006,
128, 13070. (d) Liu, H.; Dagousset, G.; Masson, G.; Retailleau, P.; Zhu,
J. J. Am. Chem. Soc. 2009, 131, 4598.(e)Wang,C.;Han,Z.-Y.;Luo,H.-W.;
Gong, L.-Z. Org. Lett. 2010, 21, 2266. (f) Xie, M.-S.; Chen, X.-H.; Zhu, Y.;
Gao, B.; Lin, L.-L.; Liu, X.-H.; Feng, X.-M. Angew. Chem., Int. Ed. 2010, 49,
3799. (g) Xu, H.; Zuend, S. J.; Woll, M. G.; Tao, Y.; Jacobsen, E. N. Science
2010, 327, 986. (h) Bernardi, L.; Comes-Franchini, M.; Fochi, M.; Leo, V.;
Mazzanti, A.; Ricci, A. Adv. Synth. Catal. 2010, 352, 3399. (i) Dagousset, G.;
Zhu, J.; Masson, G. J. Am. Chem. Soc. 2011, 133, 14804.
(5) (a) Bergonzini, G.; Gramigna, L.; Mazzanti, A.; Fochi, M.;
Bernardi, L.; Ricci, A. Chem. Commun. 2010, 46, 327. (b) Xie, M.;
Liu, X.; Zhu, Y.; Zhao, X.; Xia, Y.; Lin, L.; Feng, X.-M. Chem.;Eur. J.
2011, 17, 13800. Also see: (c) Dickmeiss, G.; Jensen, K. L.; Worgull, D.;
Franke, P. T.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2011, 50, 1580.
r
10.1021/ol301251h
Published on Web 06/06/2012
2012 American Chemical Society

Table 1. Chiral Phosphoric Acid Catalyzed IEDDA Reaction
between Isoeugenols 1a and Imine 2aa
Table 2. Catalytic Enantioselective Three-Component IEDDA
Reactiona
1a/6a
yield
(%)b
2a/1a
yield
ee
entry
ratio
3 A MS
ee (%)c,d
˚
entry
R
temp ratio
solvent
(%)b (%)c
1
2
3
4
5
6
10:1
10:1
2:1
50 mg
no
80
95
1
2
3
4
C6H5 (4a)
25
25
25
25
1:1.5 CH2Cl2
1:1.5 CH2Cl2
1:1.5 CH2Cl2
1:1.5 CH2Cl2
16
16
21
13
37
47
87
79
80
96
2-naphthyl (4b)
no
72
96
1-naphthyl (4c)
3:1
no
75
94
9-anthracenyl
4:1
no
81
tracee
96
NDf
(4d)
4:1
no
5
6
7
4-ClC6H4 (4e)
25
25
25
1:1.5 CH2Cl2
1:1.5 CH2Cl2
1:1.5 CH2Cl2
15
27
35
33
59
93
4-FC6H4 (4f)
2,4,6-(iPr)3C6H5
a General conditions: (E)-Isoeugenol 1a, benzaldehyde (5a) (0.12
mmol), 4-anisidine 6a (0.10 mmol), catalyst 4g (0.01 mmol) in 1,2-
DCE (1.0 mL) for 24 to 72 h. b Yields referred to chromatographically
pure 2,3- and 3,4-trans-isomer 3a. c Ee was determined by chiral HPLC
analysis. d Dr (>95:5) was determined by 1H NMR analysis. e Catalyst
[4g]2Ca (10 mol %) used. f Not determined.
(4g)
4g
4g
4g
4g
4g
8
25
50
50
50
70
1:10
1:10
1:10
1:10
1:10
CH2Cl2
CHCl3
50
51
80
43
80
93
85
95
86
95
9
10
11
12
1,2-DCE
toluene
1,2-DCE
transformations using imines as electrophiles.7 These bi-
functional catalysts are generally known to cooperatively
activate both the electrophilic imine and the nucleophile via
H-bonding to ensure high enantioselectivities.7 Based on
this, we hypothesized that an alkene with a H-bond donor
would be a suitable dienophilic partner for an enantioselec-
tive catalytic IEDDA reaction.8 Accordingly, we selected
isoeugenol derivatives bearing a free phenol functional
group as dienophiles. In addition, this approach would
result in the efficient synthesis of optically enriched trisub-
stituted 4-aryltetrahydroquinoline derivatives possessing
potential antiparasitic and anticancer activities.3,8d,9 Herein,
we present a highly diastereo- and enantioselective one-pot,
three-component catalytic route to the synthesis of tetra-
hydroquinolines having an aryl group at the 4-position.
We initiated our investigations using (E)-isoeugenol
(1a), preformed arylimine 2a, and 10 mol % of chiral
phosphoric acid derived from (R)-BINOL 4 in CH2Cl2 at
rt in the presence of 3 A molecular sieves (Table 1). All
catalysts tested afforded high diastereoselectivity (95:5) in
favor of 2,3- and 3,4-trans tetrahydroquinoline 3a. Cata-
lyst 4g, with a bulky 2,4,6-triisopropyl phenyl group in the
3,30-position of (R)-BINOL,10 furnished the cycloadduct
with the highest enantioselectivity but with a low yield. To
further optimize the procedure, this IEDDA reaction was
chosen for a survey of different solvents and temperatures.
a General conditions: (E)-Isoeugenol 1a, imine 2a (0.10 mmol),
catalyst 4 (0.01 mmol) in solvent (1.0 mL) with 3 A MS (50 mg) for 48
to 96 h. b Yields referred to chromatographically pure 2,3-and 3,4-trans-
isomer 3a. In each case, the ratio of “all trans”/“all cis” stereomers was
higher than 95/5 by 1H NMR. c Ee was determined by chiral HPLC
analysis.
β-substituted alkenes for the preparation of optically
active tetrahydroquinolines with three contiguous stereo-
centers has been reported yet.
The past decade has witnessed the emergence of chiral
phosphoric acids, pioneered by Akiyama and Terada’s
groups,6 as efficient catalysts for numerous enantioselective
(6) For first reports on the use of binol-derived phosphoric acids in
enantioselective transformations, see: (a) Akiyama, T.; Itoh, J.; Yokota,
K.; Fuchibe, K. Angew. Chem., Int. Ed. 2004, 43, 1566. (b) Uraguchi, D.;
Terada, M. J. Am. Chem. Soc. 2004, 126, 5356.
(7) For recent reviews on Brønsted acid catalysis, see: (a) Yamamoto,
H.; Payette, N. In Hydrogen Bonding in Organic Synthesis; Pihko, P. M.,
Ed.; Wiley-VCH: Weinheim, 2009; p 73. (b) Doyle, A. G.; Jacobsen, E. N.
Chem. Rev. 2007, 107, 5713. (c) Yu, X.; Wang, W. Chem.;Asian J. 2008,
3, 516. (d) Kampen, D.; Reisinger, C. M.; List, B. Top. Curr. Chem. 2010,
291, 395. For recent reviews on chiral phosphoric acid catalysis, see:
(e) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348, 999.
(f) Akiyama, T. Chem. Rev. 2007, 107, 5744. (g) Terada, M. Chem.
Commun. 2008, 4097. (h) Terada, M. Synthesis 2010, 1929. (i) Terada, M.
Bull. Chem. Soc. Jpn. 2010, 83, 101. (j) Kampen, D.; Reisinger, C. M.;
List, B. Top. Curr. Chem. 2010, 291, 395. (k) Terada, M. Curr. Org.
Chem. 2011, 15, 2227. (l) Rueping, M.; Kuenkel, A.; Atodiresei, I. Chem.
Soc. Rev. 2011, 40, 4539.
(8) For selected racemic examples with isoeugenols as dienophiles,
ꢀ
(9) (a) Gerlach, M.; Przewosny, M.; Englberger, W.; Reissmueller,
E.; Bloms-Funke, P.; Maul, C.; Jagusch, U.-P. U.S. Patent 0087926 A1,
see: (a) Kouznetsov, V. V.; Romero Bohorquez, A. R.; Stashenko, E. E.
Tetrahedron Lett. 2007, 48, 8855. (b) Kouznetsov, V. V.; Merchan
ꢀ
2003. (b) Gomez-Barrio, A.; Montero-Pereira, D.; Nogal-Ruiz, J. J.; Escario,
ꢀ
Arenas, D. R.; Romero Bohorquez, A. R. Tetrahedron Lett. 2008, 49,
3097. (c) Kouznetsov, V. V.; Bello Forero, J. S.; Amado Torres, D. F.
ꢀ
J. A.; Muelas-Serrano, S.; Kouznetsov, V. V.; Vargas Mendez, L. Y.; Urbina
ꢀ
Gonzales, J. M.; Ochoa, C. Acta Parasitol. 2006, 51, 73.
Tetrahedron Lett. 2008, 49, 5855. (d) Kouznetsov, V. V.; Merchan
~
Arenas, D. R.; Arvelo, F.; Bello Forero, J. S.; Sojo, F.; Munoz, A. Lett.
ꢀ
(10) (R)-TRIP catalyst 4g was easily prepared from (R)-BINOL; see:
(a) Akiyama, T. U.S. Patent 0276329 A1, Dec 7, 2006. (b) Klussmann, M.;
Ratjen, L.; Hoffmann, S.; Wakchaure, V.; Goddard, R.; List, B. Synlett 2010,
2189.
Drug Des. Discovery 2010, 7, 632. (e) Romero Bohorquez, A. R.;
Kouznetsov, V. V. Synlett 2010, 970. (f) Merchan Arenas, D. R.; Rojas
Ruız, F. A.; Kouznetsov, V. V. Tetrahedron Lett. 2011, 52, 1388.
Org. Lett., Vol. 14, No. 12, 2012
3159

(entry 10). When higher temperatures were used, however,
no improvement in the final yield was observed (entry 12).
To simplify the process and to avoid the use of a
preformed N-arylimine, a three-component reaction of
benzaldehyde (5a), 4-methoxyaniline (6a), and isoeugenol
(1a) was investigated next.11 To our pleasure, the reaction
proceeded smoothly to afford 3a with 80% yield and 95%
ee (Table 2, entry 1). In addition, the presence of molecular
sieves was not essential for this cycloaddition.12 In an
attempt to reduce the amount of isoeugenol dienophile
1a, we found that 4 equiv of 1a gave the best result in terms
of yield and enantioselectivity (entry 5). Chiral BINOL
phosphate salts have proven to be the catalysts of choice
for some transformations since their initial report by
Ishihara et al.13 and later exploited by others.14 This result
led us to examine the chiral calcium phosphate [4g]2Ca at
50 °C in 1,2-DCE. However, only trace amounts of the
desired product was isolated after 96 h (Table 2, entry 6).
This showed that only metal-free chiral phosphoric acid
appears able to catalyze the Povarov reaction.
With the reaction parameters for the IEDDA reaction
optimized, we extended it to a selection of aldehydes,
arylamines, and isoeugenol derivatives. The results of the
enantioselective multicomponent IEDDA reaction are
shown in Table 3. Gratefully, aromatic aldehydes with
electronwithdrawing substituents(entries 1ꢀ10), aswellas
electrondonatingsubstituents(entries 11, 14, 15, and 17) in
ortho- meta-, and para-positions were appropriate sub-
strates, affording the products in good yields with excellent
diastereo- and enantioselectivity (up to 99% ee). Cyclo-
hexanecarboxaldehyde gave the three-component product
3m in 61% yield and 90% ee (entry 12). However, a
complex mixture was observed with linear aliphatic alde-
hydes. Both electron-rich (entries lꢀ12) and -deficient
(entries 13ꢀ23) para-substituted anilines participated with
good yield and enantioselectivity. Interestingly, when a
substituent in the meta-position was present on the aniline,
the cycloaddition led only to the formation of the more
congested regioisomer 3y (entry 24). The absolute config-
uration of 3p was unequivocally determined to be 2S, 3S,
4R by single-crystal X-ray diffraction experiments (cf.
Supporting Information (SI)).15 As the IEDDA reaction
Table 3. Chiral Brønsted Acid Catalyzed IEDDA Reactiona
yield
(%)b
ee
(%)c
entry
R1
R2
1
3
1
4-BrC6H4
4-NO2C6H4
4-CNC6H4
4-FC6H4
3-FC6H4
3-ClC6H4
3-NO2C6H4
3-BrC6H4
2-FC6H4
2-BrC6H4
4-iPrC6H4
Cyclohexyl-
3-CF3C6H4
1-naphthyl
4-PhC6H4
4-ClC6H4
4-CH3C6H4
4-CF3C6H4
C6H5
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-Cl
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
3b
3c
79d
92
70
66
86
71
93
83
74
93
65
61e
73
70
79
72
79
89
81
74
82
75
77
91
75
78
<10
11
61
53
97
98
96
94
96
96
96
96
96
96
94
90
91
94
>99
93
96
96
96
96
97
95
95
96
94
97
91
85g
73
45h
2
3
3d
3e
3f
4
5
6
3g
3h
3i
7
8
9
3j
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27f
28
29
30
3k
3l
3m
3n
3o
3p
3q
3r
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
3s
4-Cl
3t
C6H5
4-Br
3u
3v
3w
3x
3y
3z
C6H5
4-NO2
4-CF3
4-F
C6H5
C6H5
C6H5
3-Cl
C6H5
H
C6H5
4-CH3
4-OMe
H
3aa
3ab
3z
C6H5
C6H5
C6H5
4-OMe
4-OMe
3ac
3ad
C6H5
a General conditions: Isoeugenol derivatives 1 (0.40 mmol), aldehyde
5 (0.12 mmol), arylamine 6 (0.10 mmol), catalyst 4g (0.01 mmol) in 1,2-
DCE (1.0 mL) for 24 to 96 h. b Yields referred to chromatographically
pure product, and the ratio of “all trans”/“all cis” stereomers was higher
than 95/5 unless indicated otherwise. c Ee was determined by chiral
HPLC analysis. d 15/1 dr. e 10/1 dr. f Reaction at 70 °C. g 2/1 dr in favor
of “all cis-isomer”. h 7/1 dr.
(12) It was found that addition of MS to the Povarov reaction has an
impact on the ee’s of the products obtained; see ref 4b.
(13) Hatano, M.; Moriyama, K.; Maki, T.; Ishihara, K. Angew.
Chem., Int. Ed. 2010, 49, 3823.
(14) For selected examples, see: (a) Hatano, M.; Ikeno, T.; Matsumura,
T.; Torii, S.; Ishihara, K. Adv. Synth. Catal. 2008, 350, 1776. (b) Klussmann,
M.; Ratjen, L.; Hoffmann, S.; Wakchaure, V.; Goddard, R.; List, B. Synlett
2010, 2189. (c) Zheng, W.; Zhang, Z.; Kaplan, M. J.; Antilla, J. C. J. Am.
Chem. Soc. 2011, 133, 3339. (d) Larson, S. E.; Li, G.; Rowland, G. B.;
Junge, D.; Huang, R.; Woodcock, H. L.; Antilla, J. C. Org. Lett. 2011, 13,
2188. (e) Zhang, Z.; Zheng, W.; Antilla, J. C. Angew. Chem., Int. Ed. 2011,
50, 1135. (f) Drouet, F.; Lalli, C.; Liu, H.; Masson, G.; Zhu, J. Org. Lett.
2011, 13, 94. (g) Terada, M.; Kanomata, K. Synlett 2011, 1255. For
examples of phosphoramide/calcium complex, see: (h) Rueping, M.;
Theissmann, T.; Kuenkel, A.; Koenigs, R. M. Angew. Chem., Int. Ed.
2008, 47, 6798. (i) Rueping, M.; Nachtsheim, B. J.; Koenigs, R. M.;
Ieawsuwan, W. Chem.;Eur. J. 2010, 16, 13116. For recent reviews, see:
(j) Zhong, C.; Shi, X. Eur. J. Org. Chem. 2010, 2999. (k) Rueping, M.;
Koenigs, R. M.; Atodiresei, I. Chem.;Eur. J. 2010, 16, 9350. For a general
review on the calcium complex in homogeneous catalysis, see: (l) Harder, S.
Chem. Rev. 2010, 110, 3852.
To our delight, when the reaction was carried out at 50 °C
in 1,2-dichloroethane (1,2-DCE), the desired tetrahydro-
quinoline 3a was isolated in 80% yield and with 95% ee
(11) (a) Seayad, J.; List, B. Catalytic Asymmetric Multicomponent
ꢀ
Reactions. In Multicomponent Reaction; Zhu, J., Bienayme, H., Eds.;
ꢀ
Wiley-VCH: Weinheim, 2005; p 227. (b) Ramon, D. J.; Yus, M. Angew.
€
Chem., Int. Ed. 2005, 44, 1602. (c) Enders, D.; Grondal, C.; Huttl,
M. R. M. Angew. Chem., Int. Ed. 2007, 46, 1570. (d) Guillena, G.;
ꢀ
Ramon, D. J.; Yus, M. Tetrahedron: Asymmetry 2007, 18, 693. (e) Gong,
L.-Z.; Chen, X.-H.; Xu, X.-Y. Chem.;Eur. J. 2007, 13, 8920.
(f) Dandapani, S.; Marcaurelle, L. A. Curr. Opin. Chem. Biol. 2010,
14, 362. (g) Yu, J.; Shi, F.; Gong, L.-Z. Acc. Chem. Res. 2011, 44, 1156.
(15) See the Supporting Information for details.
3160
Org. Lett., Vol. 14, No. 12, 2012

can be sensitive to dienophile geometry, we examined the
reaction witha Z-dienophile. (Z)-1cgeneratedthe cycload-
duct as a 2:1 mixture of diastereomer with only an 11%
yield (entry 28). In this case, the major 2,3- and 3,4-cis
cycloadduct was isolated as a racemic product, whereas the
minor all trans product was obtained with 85% ee. Mean-
while, the (Z)-1d afforded the 2,3- and 3,4-trans product
3ac with 73% ee (cf. SI).
The IEDDA reactions16 proceed through either a
concerted4g,17 or stepwise mechanism4d,h,i,18,19 via a catio-
nic intermediate according to the nature of the dienophile
used. As the possibility of isomerization of Z-dienophiles
(entries 28ꢀ29, Table 3), occurring under our experimental
conditions, had been ruled out by control experiments (cf.
SI), we thought that a stepwise mechanism could account
for the nonstereoselective issue of the reaction involving
Z-dienophiles (1cꢀd). Thus, the reaction would be viewed as
a nucleophilic-type attack of isoeugenol to the N-arylimine
with a concomitant cyclization with formation of zwitter-
ionic intermediates.
importance of the position of phenol on the isoeugenol
derivatives was supported by the low enantioselectivity in
the case of (E)-2-hydroxystyrene 1e (45% ee, entry 30). In
addition, a control experiment, in which (E)-1-methoxy-4-
propenylbenzene 1b (Table 3, entry 27) was subjected to this
three-component reaction, afforded the corresponding pro-
duct 3ab in very low yield (<10%) but with good enantio-
selectivity (91% ee). This indicates that the free hydroxyl
group in the para-position of the dienophile appears to be
crucial for reactivity, but not for enantioselectivity.
Scheme 1. Activation Model and Possible Reaction Mechanism
Based on the above experimental results, a tentative
transition state model 7 wherein the phosphoric acid forms
H-bonds with the phenol and imine was proposed to
explain the stereochemical outcome of the enantioselective
IEDDA reaction (Scheme 1). Then the cycloaddition occurs
to form (2S,3S,4R)-tetrahydroquinoline 3 exclusively. The
In summary, we have developed an efficient enantiose-
lective IEDDA reaction with isoeugenol derivatives as the
dienophiles catalyzed by chiral phosphoric acids. This
cycloaddition is applicable to a wide range of aldehydes
and anilines, providing a highly diastereo- and enantiose-
lective method to 2,3,4-trisubstituted 4-aryl-tetrahydro-
quinolines.3,8d,9 Further investigations into the mechanism
of the IEDDA reaction, as well as application to the
synthesis of biologically active compounds, are currently
underway in our laboratory.
ꢀ
(16) Bello, D.; Ramon; Lavilla, R. Curr. Org. Chem. 2010, 14, 332.
(17) (a) Beifuss, U.; Ledderhose, S.; Ondrus, V. ARKIVOC 2005, 147.
(b) Stevenson, P. J.; Nieuwenhuyzen, M.; Osborne, D. ARKIVOC 2007,
12. See also: (c) McCarrick, M. A.; Wu, Y.-D.; Houk, K. N. J. Org.
Chem. 1993, 58, 3330. (d) Whiting, A.; Windsor, C. M. Tetrahedron
ꢀ
ꢀ
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Acknowledgment. We thank ICSN and CNRS for fi-
nancial support and ANR for postdoctoral fellowships to
L.H. We also acknowledge Prof. Jieping Zhu (EPFL) for
his unwavering support.
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Supporting Information Available. Experimental de-
tails, characterization data, HPLC enantiomer analysis,
and 1H and 13C NMR spectra for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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The authors declare no competing financial interest.
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