Asymmetric Br?nsted acid catalyzed cycloadditions-efficient enantioselective synthesis of pyrazolidines, pyrazolines, and 1,3-diamines from N-acyl hyrazones and alkenes

Article abstract of DOI:10.1002/anie.201205813

A general, metal-free, highly enantioselective Bronsted acid catalyzed [3+2] cycloaddition between hydrazones and alkenes has been developed that affords pyrazolidine derivatives (see scheme). The resulting optically active pyrazolidines can undergo many chemical transformations which allow, for example, the enantioselective synthesis of valuable pyrazolines and 1,3-diamines. Copyright

Full text of DOI:10.1002/anie.201205813

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Angewandte
Communications
DOI: 10.1002/anie.201205813
Organocatalysis
Asymmetric Brønsted Acid Catalyzed Cycloadditions—Efficient
Enantioselective Synthesis of Pyrazolidines, Pyrazolines, and 1,3-
Diamines from N-Acyl Hyrazones and Alkenes**
Magnus Rueping,* Modhu Sudan Maji, Hatice Bas¸pınar KꢀÅꢀk, and Iuliana Atodiresei
Dedicated to Prof. Dieter Seebach on the occasion of his 75th birthday
Nitrogen-containing heterocycles constitute common struc-
tural motifs in a wide range of complex natural products.
Among them, pyrazoline and pyrazolidine derivatives are
highly important organic molecules because of their broad
spectrum of biological activity and widespread natural
occurrence.[1] They are often used as anticancer, antidepres-
sant, anti-inflamatory, antiviral, and antibacterial agents as
well as acyltransferase inhibitors.[2] Apart from these impres-
sive biological properties, which make them privileged
structures in medicinal chemistry and pharmacology, these
structures recently also attracted attention in materials
science.[3] Moreover, differently substituted enantiopure pyr-
azolidine derivatives can be used as precursors for the
preparation of chiral 1,3-diamine derivatives through cleav-
employ Lewis acid catalysts.[10–14] Given the usefulness of this
class of compounds, considerable effort has been devoted to
the development of improved methods for their synthesis. To
date, several efficient protocols are available for their
formation in a diastereoselective fashion.[10] In contrast, the
enantioselective synthesis of pyrazolidines from hydrazones is
a great challenge and there are only a few reports of this.
Kobayashi et al. showed that chiral zirconium/binol com-
plexes are efficient Lewis acid catalysts for both the intra-
molecular as well as intermolecular [3+2] cycloaddition of
hydrazones with alkenes.[11] Leighton and co-workers later
reported a related intermolecular cycloaddition between enol
ethers and acylhydrazones by using 1.5 equivalents of a chiral
silane Lewis acid.[12] Zamfir and Tsogoeva reported an
interesting approach, wherein a chiral silane derived from
a binol phosphate acted as the Lewis acid, and good
enantioselectivity was obtained for one example.[13] The
authors also described an example in which a chiral phos-
phoric acid diester was used.
À
age of the N N bond of the pyrazolidine moiety. In addition
to their broad application as chiral ligands in asymmetric
synthesis,[4] 1,3-diamines are also significant for the prepara-
tion of cytostatic cisplatin analogues for cancer therapy.[5]
Furthermore, they are also used as anti-influenza agents
(Scheme 1).[6]
Herein we describe a general and highly enantioselective
Brønsted acid catalyzed cycloaddition[15,16] between various
alkenes and N-benzoylhydrazones that leads to valuable
optically active pyrazolidine derivatives.
We started our investigation with the examination of
different binol phosphoric acid catalysts. However, low yields
of product were observed, irrespective of the reaction
conditions used. The low acidity of phosphoric acid
(pKa 13–14 in MeCN) accounted for this low reactivity.
Recent studies showed that binol-based N-triflylphosphor-
amides are not only more acidic (pKa 6–7 in MeCN), but also
more reactive catalysts.[17] From the various N-triflylphos-
phoramides tested, 4 turned out to be the best catalyst for the
[3+2] cycloaddition of hydrazones with cyclopentadiene
(Table 1). The use of hydrazones with different acyloyl
protecting groups 1a–3a had an impact on the enantioselec-
tivity of the cycloaddition (Table 1, entries 1–3). The best
result was obtained with benzoyl-protected hydrazone 3a,
with pyrazolidine 7a being isolated in a quantitative yield and
with excellent enantioselectivity (99%, 92% ee; Table 1,
entry 3).
Scheme 1. Bioactive molecules based on pyrazolines and 1,3-diamines.
The [3+2] cycloaddition between hydrazones and alkenes
represents a convenient access to pyrazolidines.[7–14] These
cycloadditions are generally achieved by using stoichiometric
amounts of achiral Brønsted acids[8] with strong heating,[9] or
[*] Prof. Dr. M. Rueping, M. S. Maji, H. B. KꢀÅꢀk, I. Atodiresei
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
To improve the reaction further, we studied the effect of
different solvents and catalyst loadings. Chlorinated solvents
were generally found to be superior for our reaction (Table 1,
entries 3–6), with 1,2-dichloroethane giving the best results in
terms of both yield and selectivity (99%, 95% ee; Table 1,
entry 6). Furthermore, the reaction can be performed by using
E-mail: magnus.rueping@rwth-aachen.de
[**] M.S.M. thanks the Alexander von Humboldt Foundation, and
H.B.K. thanks The Council of Higher Education of Turkey for
a fellowship.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201205813.
12864
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Table 1: Optimization of the reaction conditions.[a]
Entry
R
Solvent
T [8C] 4 [mol%] Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
NO2, 1a CH2Cl2
RT
RT
RT
RT
RT
5
5
5
5
5
5
2.5
1
5
95
44
99
99
99
99
99
94
99
90
0
73
77
92
81
91
95
95
93
98
98
–
CF3, 2a
H, 3a
H, 3a
H, 3a
H, 3a
H, 3a
H, 3a
H, 3a
H, 3a
H, 3a
CH2Cl2
CH2Cl2
toluene
CHCl3
(CH2Cl)2 RT
(CH2Cl)2 RT
(CH2Cl)2 RT
(CH2Cl)2
(CH2Cl)2
CH2Cl2
9
0
0
RT
10[d]
11[e]
2.5
0
[a] Unless otherwise noted, the reactions were carried out for 18 h in the
presence of 5 mol% catalyst in a 0.05m solution of hydrazone using the
solvent and the temperature as indicated; 5a: R=NO2, 6a: R=CF3, 7a:
R=H. [b] The syn product was isolated along with its anti diastereomer
1
in a 96:4 ratio, as determined by H NMR spectroscopy. [c] The
enantioselectivity was determined by HPLC analysis on a chiral
stationary phase. [d] Reaction time 48 h. [e] Without any catalyst.
just 2.5 mol% catalyst at room temperature without affecting
either the yield or the enantioselectivity (Table 1, entry 7).
More pleasingly, the catalyst loading could be decreased
remarkably to 1 mol%, with product 7a being isolated in only
a slightly lower yield and enantiomeric excess (94%, 93% ee;
Table 1, entry 8). Finally, the effect of temperature on the
reaction outcome was also investigated. Cycloadduct 7a was
isolated in quantitative yield and with an improved enantio-
selectivity of 98% ee when the reaction was conducted at 08C
by using 5 mol% of the catalyst (Table 1, entry 9). Decreasing
the catalyst loading to 2.5 mol% at 08C resulted in the
product being isolated with the same enantioselectivity
(Table 1, entry 10). Hence, we decided to apply these
conditions (Table 1, entry 10) to reactions involving reactive
hydrazones. Reactions involving less-reactive hydrazones
were performed under the conditions described in Table 1,
entry 7.
To investigate the scope of this newly developed protocol
we prepared several hydrazones derived from aliphatic,
aromatic, and heteroaromatic aldehydes and evaluated
them under the optimized reaction conditions. The results
are summarized in Scheme 2. The reaction generally occurred
with excellent diastereoselection and the major syn diaste-
reomer was isolated along with the minor anti diastereomer.
Firstly, several hydrazones prepared from different aliphatic
aldehydes were tested. Excellent results were obtained with
the a-methylene-substituted hydrazones 3a–e, and adducts
7a–e were isolated in excellent yields and enantioselectivities
(87–99%, 96–98% ee; Scheme 2). Ethyl glyoxalate derived
hydrazone 3 f underwent a smooth reaction with cyclopenta-
diene to afford cycloadduct 7 f as a single diastereomer in
Scheme 2. Substrate scope of the organocatalytic enantioselective
[3+2] cycloaddition with cyclopentadiene. The diastereomeric ratio was
1
determined by H NMR spectroscopy when the minor diastereomer
was observed in the 1H NMR spectrum; otherwise it is reported as
>98:2. The enantiomeric excess was determined by HPLC analysis.
[a] Reaction was performed with a 5 mol% catalyst loading.
87% yield and 92% ee. Hydrazones 3g,h with alkyl substi-
tutents are also suitable substrates for the reaction, with
products 7g,h isolated in good to high yields and ee values.
Next we turned our attention to hydrazones 3i–p, which are
derived from aromatic aldehydes. We were pleased to find
that these hydrazones are also appropriate substrates for our
cycloaddition. Cycloadduct 7i was isolated from the reaction
of benzaldehyde-derived hydrazone 3i in 69% yield and
90% ee. Hydrazones bearing either electron-donating or
-withdrawing substituents on the benzene ring reacted
efficiently, and products 7j–o were isolated in good to high
yields and enantioselectivities. Importantly, substrate 3p
bearing a heteroaromatic ring also furnished the correspond-
ing adduct 7p in good yield and with an excellent enantio-
meric excess of 96% ee. The absolute configuration of
product 7l was determined as S,S,S by single-crystal X-ray
analysis (see the Supporting Information).[22]
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To show the synthetic applicability of our newly devel-
oped method, we carried out a reaction on a 0.3 g scale by
employing a catalyst loading of only 1 mol%. Pleasingly, the
reaction was highly efficient, and product 7a was isolated in
95% yield with 93% ee after 1 day. Thus, scaling-up of this
procedure is feasible.
After proving the wide substrate scope with regard to the
structure of the hydrazone in the reaction with cyclopenta-
diene, our attention turned to different alkenes for the [3+2]
cycloaddition with hydrazones, and we examined the use of a-
methylstyrenes (Scheme 3). To the best of our knowledge, the
asymmetric [3+2] cycloaddition of a-methylstyrene with
hydrazones has not been reported, although valuable pyr-
azolidine derivatives bearing a quaternary and a tertiary
stereocenter at the 3- and 5-positions would be obtained.
After optimization of the reaction conditions, we found that
a-methylstyrene and analogues are also suitable substrates
for our cycloaddition, and we were able to isolate product 8a
in 72% yield and 90% ee as
a single diastereomer
(Scheme 3). In general, different alkyl-, aryl-, and hetero-
aryl-substituted styrene derivatives as well as para-nitro-
benzoyl-protected hydrazones could be applied in this new
Brønsted acid catalyzed [3+2] cycloaddition, and the desired
pyrazolidines 8a–r were obtained in good yields and with
excellent enantioselectivities. The absolute configurations of
products 8j and 8p were determined as R,R by X-ray crystal
structure analysis (see the Supporting Information).[22]
The cycloaddition products obtained can be further
functionalized to afford synthetically valuable products. To
demonstrate their usefulness, we performed several function-
alization reactions by using products 7a and 8a as model
À
substrates. As shown in Scheme 4, oxidation of the C N bond
Scheme 4. Derivatization of the [3+2] cycloaddition products.
is of interest, as products having a pyrazoline core structure
show diverse biological activities.[1,2] Treatment of 7a with
a stoichiometric amount of cupric chloride resulted in the
oxidation occurring smoothly, and product 9 was isolated
without any loss of enantiopurity.[18] In a similar fashion,
pyrazolidine 8a was also smoothly oxidized to 10.[19] Hydro-
genation was also easily performed, and product 11 was
isolated in 96% yield without affecting the ee value. Finally,
À
we focused on the more important N N bond cleavage
reaction, as it provides valuable 1,3-diamine derivatives.
Scheme 3. Substrate scope of the organocatalytic enantioselective
[3+2] cycloaddition with a-methylstyrenes. Ar=4-NO2-Ph. The enantio-
meric excess was determined by HPLC analysis. Bn=benzyl, PMP=
p-methoxyphenyl. [a] Reactions were conducted with a 5 mol% catalyst
loading. [b] Reactions were performed at different temperatures (see
the Supporting Information).
When a methanolic solution of 7a was treated with SmI2 at
room temperature, N N bond cleavage occurred smoothly
À
and product 12 with a core structure similar to that of the anti-
influenza agent peramivir (Scheme 1) was isolated.[20,21]
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[6] a) C. M. Bromba, J. W. Mason, G. M. Brant, T. Chan, M. D.
In conclusion, we have developed a general metal-free
highly enantioselective cycloaddition between hydrazones
and alkenes that affords pyrazolidine and pyrazoline deriv-
atives, which are valuable compounds with important biolog-
ical activity. In contrast to the less acidic binol-derived
phosphoric acids, the much more acidic N-triflylphosphor-
amide Brønsted acids proved to be very effective catalysts and
promoted the highly enantioselective cycloaddition. The
reaction can be performed with a broad range of hydrazones
and alkenes and leads to high yields and excellent diastereo-
and enantioselectivities. Notably, the resulting optically active
pyrazolidines can undergo many chemical transformations,
including the enantioselective synthesis of valuable 1,3-
diamines.
Lunke, M. Petric, M. J. Boulanger, J. E. Wulff, Bioorg. Med.
Chem. Lett. 2011, 21, 7137 – 7141; b) D. M. Andrews, P. C.
Cherry, D. C. Humber, P. S. Jones, S. P. Kelling, P. F. Martin,
C. D. Shaw, S. Swanson, Eur. J. Med. Chem. 1999, 34, 563 – 574;
c) P. Chand, P. L. Kotian, A. Dehghni, Y.-E. Kattan, T.-H. Lin,
T. L. Hutchison, Y. S. Babu, S. Bantia, A. J. Elliot, J. A.
Montgomery, J. Med. Chem. 2001, 44, 4379 – 4392.
[7] For achiral Brønsted acid mediated [3+2] cycloadditions, see
a) K.-D. Hesse, Justus Liebigs Ann. Chem. 1970, 743, 50 – 56;
b) G. Le Fevre, S. Sinbandhit, J. Hamelin, Tetrahedron 1979, 35,
1821 – 1824; c) B. Fouchet, M. Joucla, J. Hamelin, Tetrahedron
Lett. 1981, 22, 1333 – 1336; d) T. Shimizu, Y. Hayashi, Y. Kitora,
K. Teramura, Bull. Chem. Soc. Jpn. 1982, 55, 2450 – 2455; e) T.
Shimizu, Y. Hayashi, M. Miki, K. Teramura, J. Org. Chem. 1987,
52, 2277 – 2285; f) L. O. Davis, W. F. M. Daniel, S. L. Tobey,
Tetrahedron Lett. 2012, 53, 522 – 525.
Received: July 23, 2012
Published online: November 19, 2012
[8] For recent reviews on 1,3-dipolar cycloadditions, see a) H.
Pellissier, Tetrahedron 2007, 63, 3235 – 3285; b) V. Nair, T. D.
Suja, Tetrahedron 2007, 63, 12247 – 12275.
[9] For [3+2] cycloadditions under thermal conditions, see a) R.
Grigg, J. Kemp, N. Thompson, Tetrahedron Lett. 1978, 19, 2827 –
2830; b) G. Le Fevre, J. Hamelin, Tetrahedron Lett. 1979, 20,
1757 – 1760; c) B. B. Snider, R. S. E. Conn, S. Sealfon, J. Org.
Chem. 1979, 44, 218 – 221; d) R. Grigg, M. Dowling, M. W.
Jordan, V. Sridharan, Tetrahedron 1987, 43, 5873 – 5886; e) V. V.
Khau, M. J. Martinelli, Tetrahedron Lett. 1996, 37, 4323 – 4326.
[10] For Lewis acid catalyzed [3+2] cycloadditions with hydrazones,
see a) S. Kobayashi, R. Hirabayashi, H. Shimizu, H. Ishitani, Y.
Yamashita, Tetrahedron Lett. 2003, 44, 3351 – 3354; b) E. Frank,
Z. Mucsi, I. Zupko, B. Rethy, G. Falkay, G. Schneider, J.
Wolfling, J. Am. Chem. Soc. 2009, 131, 3894 – 3904; c) A. Zamfir,
S. Schenker, W. Bauer, T. Clark, S. B. Tsogoeva, Eur. J. Org.
Chem. 2011, 3706 – 3709; d) H. Xie, J. Zhu, Z. Chen, S. Li, Y. Wu,
Synthesis 2011, 2767 – 2774.
Keywords: heterocycles · homogeneous catalysis · hydrazones ·
hydrogen bonding · ion pairs
.
[1] L. C. Behr, R. Fusco, C. H. Jarboe, Pyrazoles, Pyrazolines,
Pyrazolidines, Indazoles and Condensed Rings, The Chemistry of
Heterocyclic Compounds 22, Interscience Publishers, New York,
1967.
[2] a) A. Gꢀrspy, S. Demirayak, G. Capan, K. Erol, K. Vural, Eur. J.
Med. Chem. 2000, 35, 359 – 364; b) Y. J. Prasad, A. L. Rao, L.
Prasoona, K. Murali, P. R. Kumar, Bioorg. Med. Chem. Lett.
2005, 15, 5030 – 5034; c) T.-S. Jeong, K. S. Kim, S.-J. An, K.-H.
Cho, S. Lee, W. S. Lee, Bioorg. Med. Chem. Lett. 2004, 14, 2715 –
2717; d) A. ꢁzdemir, G. Turan-Zitouni, Z. A. Kaplancıkli, G.
Revial, K. Guven, Eur. J. Med. Chem. 2007, 42, 403 – 409; e) Z.
Brzozowski, F. Saczewski, M. Gdaniec, Eur. J. Med. Chem. 2000,
35, 1053 – 1064; f) Z. ꢁzdemir, H. B. Kandilci, B. Gumusel, U.
Calis, A. A. Bilgin, Eur. J. Med. Chem. 2007, 42, 373 – 379; g) X.
Zhang, X. Li, G. F. Allan, T. Sbriscia, O. Linton, S. G. Lundeen,
Z. Sui, J. Med. Chem. 2007, 50, 3857 – 3869; h) M. E. Camacho, J.
Leon, A. Entrena, G. Velasco, M. D. Carrion, G. Escames, A.
Vivo, D. Acuna-Castroviejo, M. A. Gallo, A, Espinosa, J. Med.
Chem. 2004, 47, 5641 – 5650; i) J. R. Goodell, F. Puig-Basagoiti,
B. M. Forshey, P.-Y. Shi, D. M. Ferguson, J. Med. Chem. 2006, 49,
2127 – 2137.
[3] a) X. C. Gao, H. Cao, L. Q. Zhang, B. W. Zhang, Y. Cao, C. H.
Huang, J. Mater. Chem. 1999, 9, 1077 – 1080; b) H. B. Fu, J. N.
Yao, J. Am. Chem. Soc. 2001, 123, 1434 – 1439; c) S. W. Oh, D. R.
Zhang, Y. S. Kang, Mater. Sci. Eng. C 2004, 24, 131 – 134.
[4] For the application of 1,3-diamines in asymmetric catalysis, see
a) W. P. Hems, M. Groarke, A. Zanotti-Gerosa, G. A. Grasa,
Acc. Chem. Res. 2007, 40, 1340 – 1347; b) K. Kodama, K.
Sugawara, T. Hirose, Chem. Eur. J. 2011, 17, 13584 – 13592;
c) T. Kano, Y. Yamaguchi, K. Maruoka, Angew. Chem. 2009, 121,
1870 – 1872; Angew. Chem. Int. Ed. 2009, 48, 1838 – 1840; d) Y.
Yamashita, K. Odashima, K. Koga, Tetrahedron Lett. 1999, 40,
2803 – 2806; e) Y. Yamashita, Y. Emura, K. Odashima, K. Koga,
Tetrahedron Lett. 2000, 41, 209 – 213; f) E. Vedejs, A. W. Kruger,
J. Org. Chem. 1998, 63, 2792 – 2793; g) D. Pini, A. Mastantuono,
G. Uccello-Barretta, Tetrahedron 1993, 49, 9613 – 9624; h) Q. J.
Yao, Z. M. A. Judeh, Tetrahedron 2011, 67, 4086 – 4092.
[5] a) J. E. Shurig, W. T. Brandner, J. B. Huflutalen, G. J. Doyle,
J. A. Gylys, Cisplatin, Academic Press, New York, 1980, 227;
b) W. L. Armarego, T. Kobayashi, J. Chem. Soc. 1970, 1597 –
1600.
[11] a) S. Kobayashi, H. Shimizu, Y. Yamashita, H. Ishitani, J.
Kobayashi, J. Am. Chem. Soc. 2002, 124, 13678 – 13679; b) Y.
Yamashita, S. Kobayashi, J. Am. Chem. Soc. 2004, 126, 11279 –
11282.
[12] S. Shirakawa, P. J. Lombardi, J. L. Leighton, J. Am. Chem. Soc.
2005, 127, 9974 – 9975.
[13] A. Zamfir, S. B. Tsogoeva, Synthesis 2011, 1988 – 1992.
[14] For recent catalytic asymmetric syntheses of pyrazolines and
pyrazolidines, see a) R. L. LaLonde, Z. J. Wang, M. Mba, A. D.
Lackner, F. D. Toste, Angew. Chem. 2010, 122, 608 – 611; Angew.
Chem. Int. Ed. 2010, 49, 598 – 601; b) T. Hashimoto, Y. Maeda,
M. Omote, H. Nakatsu, K. Maruoka, J. Am. Chem. Soc. 2010,
132, 4076 – 4077; c) T. Hashimoto, M. Omote, K. Maruoka,
Angew. Chem. 2011, 123, 3551 – 3554; Angew. Chem. Int. Ed.
2011, 50, 3489 – 3492; d) M. Fernꢂndez, E. Reyes, J. L. Vicario,
D. Badꢃa, L. Carrillo, Adv. Synth. Catal. 2012, 354, 371 – 376;
e) T. Hashimoto, H. Kimura, Y. Kawamata, K. Maruoka, Nat.
Chem. 2011, 3, 642 – 646; f) L. Deiana, G.-L. Zhao, H. Leijon-
marck, J. Sun, C. W. Lehmann, A. Cꢄrdova, ChemistryOpen
2012, 1, 134 – 139.
[15] For reviews on Brønsted acid catalysis, see a) T. Akiyama, Chem.
Rev. 2007, 107, 5744 – 5758; b) T. Akiyama, J. Itoh, K. Fuchibe,
Adv. Synth. Catal. 2006, 348, 999 – 1010; c) M. S. Taylor, E. N.
Jacobsen, Angew. Chem. 2006, 118, 1550 – 1573; Angew. Chem.
Int. Ed. 2006, 45, 1520 – 1543; d) H. Yamamoto, N. Payette, in
Hydrogen Bonding in Organic Synthesis (Ed.: P. M. Pihko),
Wiley-VCH, Weinheim, 2009, pp. 73 – 140; e) M. Terada, Chem.
Commun. 2008, 4097 – 4112; f) M. Terada, Synthesis 2010, 1929 –
1982; g) M. Terada, Bull. Chem. Soc. Jpn. 2010, 83, 101 – 119;
h) A. Zamfir, S. Schenker, M. Freund, S. B. Tsogoeva, Org.
Biomol. Chem. 2010, 8, 5262 – 5276; i) D. Kampen, C. M. Rei-
singer, B. List, Top Curr. Chem. 2010, 291, 395 – 456; j) M.
Angew. Chem. Int. Ed. 2012, 51, 12864 –12868
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 12867

.
Angewandte
Communications
Rueping, E. Sugiono, F. R. Schoepke, Synlett 2010, 852 – 865;
k) M. Rueping, A. Kuenkel, I. Atodiresei, Chem. Soc. Rev. 2011,
40, 4539 – 4549.
Nachtsheim, R. M. Koenigs, W. Ieawsuwan, Chem. Eur. J.
2010, 16, 13116 – 13126; j) M. Rueping, M.-Y. Lin, Chem. Eur.
J. 2010, 16, 4169 – 4172; k) M. Rueping, B. J. Nachtsheim, Synlett
2010, 119 – 122; l) M. Rueping, E. Merino, R. M. Koenigs, Adv.
Synth. Catal. 2010, 352, 2629 – 2634; m) C. H. Cheon, H.
Yamamoto, Org. Lett. 2010, 12, 2476 – 2479; n) M. Rueping, U.
Uria, M.-Y. Lin, I. Atodiresei, J. Am. Chem. Soc. 2011, 133,
3732 – 3735; o) T. Hashimoto, H. Nakatsu, K. Yamamoto, K.
Maruoka, J. Am. Chem. Soc. 2011, 133, 9730 – 9733; p) M.
Rueping, W. Ieawsuwan, Chem. Commun. 2011, 47, 11450 –
11452.
[16] For other Brønsted acid catalyzed 1,3-dipolar cycloadditions, see
a) P. Jiao, D. Nakashima, H. Yamamoto, Angew. Chem. 2008,
120, 2445 – 2447; Angew. Chem. Int. Ed. 2008, 47, 2411 – 2413;
b) X.-H. Chen, W.-Q. Zhang, L.-Z. Gong, J. Am. Chem. Soc.
2008, 130, 5652 – 5653; c) W.-J. Liu, X.-H. Chen, L.-Z. Gong,
Org. Lett. 2008, 10, 5357 – 5360; d) J. Yu, L. He, X.-H. Chen, J.
Song, W.-J. Chen, L.-Z. Gong, Org. Lett. 2009, 11, 4946 – 4949;
e) X.-H. Chen, Q. Wei, S.-W. Luo, H. Xiao, L.-Z. Gong, J. Am.
Chem. Soc. 2009, 131, 13819 – 13825; f) L. He, X.-H. Chen, D.-N.
Wang, S.-W. Luo, W.-Q. Zhang, J. Yu, L. Ren, L.-Z. Gong, J. Am.
Chem. Soc. 2011, 133, 13504 – 13518.
[17] For pioneering work in the field of chiral binol-based N-
triflylphosphoramides, see a) S. A. Yamamoto, D. Nakashima,
H. Yamamoto, J. Am. Chem. Soc. 2006, 128, 9626 – 9627; for an
overview, see b) M. Rueping, B. J. Nachtsheim, W. Ieawsuwan, I.
Atodiresei, Angew. Chem. 2011, 123, 6838 – 6853; Angew. Chem.
Int. Ed. 2011, 50, 6706 – 6720; for further examples, see c) M.
Rueping, W. Ieawsuwan, A. P. Antonchick, B. J. Nachtsheim,
Angew. Chem. 2007, 119, 2143 – 2146; Angew. Chem. Int. Ed.
2007, 46, 2097 – 2100; d) M. Rueping, B. J. Nachtsheim, S. A.
Moreth, M. Bolte, Angew. Chem. 2008, 120, 603 – 606; Angew.
Chem. Int. Ed. 2008, 47, 593 – 596; e) M. Rueping, T. Theiss-
mann, A. Kuenkel, R. M. Koenigs, Angew. Chem. 2008, 120,
6903 – 6906; Angew. Chem. Int. Ed. 2008, 47, 6798 – 6801; f) D.
Enders, A. A. Narine, F. Toulgoat, T. Bisschops, Angew. Chem.
2008, 120, 5744 – 5748; Angew. Chem. Int. Ed. 2008, 47, 5661 –
5665; g) M. Zeng, Q. Kang, Q.-L. He, S.-L. You, Adv. Synth.
Catal. 2008, 350, 2169 – 2173; h) M. Rueping, W. Ieawsuwan,
Adv. Synth. Catal. 2009, 351, 78 – 84; i) M. Rueping, B. J.
[18] M. A. Badawy, S. A. El-Bahaie, A. M. Kadry, Y. A. Ibrahim,
Heterocycles 1988, 27, 7 – 10.
[19] For the enantioselective synthesis of 3,5-disubstituted pyrazo-
lines, see a) S. Mꢀller, B. List, Angew. Chem. 2009, 121, 10160 –
10163; Angew. Chem. Int. Ed. 2009, 48, 9975 – 9978; b) O. Mahꢅ,
I. Dez, V. Levacher, J.-F. Briꢆre, Angew. Chem. 2010, 122, 7226 –
7229; Angew. Chem. Int. Ed. 2010, 49, 7072 – 7075; c) O. Mahꢅ, I.
Dez, V. Levacher, J.-F. Briꢆre, Org. Biomol. Chem. 2012, 10,
3946 – 3954; d) J.-R. Chen, W.-R. Dong, M. Candy, F.-F. Pan, M.
Jçrres, C. Bolm, J. Am. Chem. Soc. 2012, 134, 6924 – 6927.
[20] M. J. Burk, J. E. Feaster, J. Am. Chem. Soc. 1992, 114, 6266 –
6267.
[21] For reviews on organocatalysis in the synthesis of natural
products and bioactive compounds, see a) E. Marquꢅs-Lꢄpez,
R. P. Herrera, M. Christmann, Nat. Prod. Rep. 2010, 27, 1138;
b) R. M. de Figueiredo, M. Christmann, Eur. J. Org. Chem. 2007,
2575.
[22] CCDC 909012 (7l), 909013 (8j) and 909014 (8p) contains the
supplementary crystallographic data for this paper. The data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
12868 www.angewandte.org
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