Organocatalytic Asymmetric [4+2] Cycloaddition of 1-Acetylcyclopentene and 1-Acetylcyclohexene for the Synthesis of Fused Carbocycles

Article abstract of DOI:10.1002/ejoc.201701238

The first organocatalytic asymmetric [4+2]-cycloaddition reaction of 1-acetylcyclopentenes and 1-acetylcyclohexenes was developed. Enones having cyano groups were used as the dienophiles in this method. The reaction provides a useful practical route to th

Full text of DOI:10.1002/ejoc.201701238

A Journal of
Accepted Article
Title: Organocatalytic Asymmetric [4 + 2] Cycloaddition of 1-
Acetylcyclopentene and 1-Acetyl cyclohexene for the Synthesis
of Fused Carbocycles
Authors: Subhas Chandra Pan and Utpal Nath
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10.1002/ejoc.201701238
European Journal of Organic Chemistry
COMMUNICATION
Organoocatalytic Asymmetric [4 + 2] Cycloaddition of 1-
Acetylcyclopentene and 1-Acetylcyclohexene for the Synthesis of
Fused Carbocycles
Utpal Nath and Subhas Chandra Pan*[a]
Dedication ((optional))
Abstract: The first organocatalytic asymmetric [4+2] cycloaddition
reaction employing 1-acetylcyclopentene and 1-acetylcyclohexene is
described. Enones having cyano group are used as the dienophile
partner in this method. The reaction provides a useful practical route
for the synthesis of bicyclic fused carbocycles having four contiguous
stereocentres.
structures via dienamine catalytic Michael reaction followed by
1,1,3,3-tetramethylguanidine mediated cyclization where 1-
acetylcyclohexene and 1- acetylcyclopentene were employed;
however the products were obtained in moderate
enantioselectivities. Realizing the importance of fused carbocyclic
structures for the synthesis of bioactive compounds, we
embarked in direct synthesis of fused carbocycles utilizing 1-
acetylcyclopentene and 1-acetylcyclohexene. We envisaged that
strong dienophiles could undergo [4+2]-cycloaddition reaction
providing fused carbocycles. In this regard, we planned to use
electron poor olefins having cyano and keto group attached to it
(Scheme 1).
The Diels−Alder (DA) reaction is considered as one of the most
commanding, practical, and elegant synthetic approaches in
organic chemistry, which exhibits plentiful applications in the total
synthesis of natural products and drugs.[1] In recent years
dienamine[2] catalytic cycloaddition/cyclization[3] reactions has
proven to be a powerful method for the construction of cyclic
molecules. In particular, after the initial discovery by Barbas and
co-workers, cross-dienamines derived from α, β-unsaturated
ketones have been exploited tremendously with a range of
electrophiles.[4] Though this method was applied for the synthesis
of a variety of carbocycles and heterocycles, to the best of our
knowledge, it has not been used for the synthesis of fused
carbocycles.
Scheme 1. Organocatalytic intermolecular asymmetric synthesis of fused
carbocycles
Fused organic moieties such as 1-decalone, 1-decalin and
octahydro-1H-indene are present in a wide range of bioactive
compounds[5 ] such as Rapiculine,[5a] Brasilanes,[5b] Conocephale-
nols[5c] etc.Thus it is highly desirable to prepare these compounds
in economical and direct way. In 2005, MacMillan and co-workers
developed an iminium catalytic intramolecular Diels-Alder
reaction for the synthesis of fused carbocycles and
heterocycles.[6] Later in 2008, Christmann et al. demonstrated
dienamine catalytic intramolecular cyclization of tethered α, β-
unsaturated aldehydes for the synthesis of fused structures.[7]
Brenner and McGarraugh reported intermolecular synthesis of
hexahydro-1H-indene motif via double Michael reaction between
enals and β-ketoesters having cyclopentene moiety (Scheme
1).[8] Also, Chen and co-workers applied aminocatalytic domino
strategy for the synthesis of fused carbocycles with spirooxindole
motif (Scheme 1).[9] We also recently reported[10] a stepwise
synthesis of 1-decalone and hexahydro-1H-inden-4(2H)-one
Inspired by these thoughts, the investigation was started by
mixing 1-acetylcyclopentene (1a, 0.05 mmol), enone 2a (0.05
mmol), quinidine derived primary amine I (20 mol%) and 2-
fluorobenzoic acid (20 mol%) as co-catalyst in dichloromethane
as the solvent.[11] To our delight, after stirring at room temperature
for 7 days, the desired major fused bicyclic product 4-benzoyl-7-
[a]
[b]
U. Nath, and Prof. Dr. S. C. Pan
Department of Chemistry
Indian Institute of Technology Guwahati
Assam, 781039, India
E-mail: span@iitg.ernet.in
This work is supported by DST-MPI partner programme. We thank
CIF of Indian Institute of Technology Guwahati for the instrumental
facility.
oxo-5-phenyloctahydro-1H-indene-4-carbonitrile
(3a)
was
obtained in 70% yield with 11:1 diastereomeric ratio and 59% ee
(Table 1, entry 1). Interestingly, the enantiomeric excess got
enhanced to 84% by employing epi-cinchonine amine II (entry 2).
Though slightly higher enantioselectivity was achieved with
hydroquinine derived catalyst III (entry 3) but the enantioselecti-
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201701238
European Journal of Organic Chemistry
COMMUNICATION
vity dropped using quinine derived amine IV (entry 4). Pleasingly,
cinchonidine derived amine catalyst V delivered the product 3a in
6:1 diastereomeric ratio with 94% ee (entry 5). Then, to further
improve the diastereo- and enantioselectivity of the reaction,
different solvents were screened (entries 6-8). An enantiomeric
excess of 96% was achieved with α,α,α-trifluoro toluene as the
solvent (entry 7). Finally, the best solvent turned out to be toluene
and the product 3a was isolated in 87% yield with 13:1 dr and 96%
ee (entry 8). The enantioselectivity dropped to 92% when a higher
amount of co-catalyst 2-fluorobenzoic acid was used (entry 9).
investigated (Table 2). It turned out that a variety of electron
donating, electron neutral and electron withdrawing substitutions
are well tolerated in our reaction condition. Different para-
substituted β-aryl enones were initially employed in the reaction
and excellent results were achieved (entries 2-9). For example,
products 3b and 3c having 4-methyl and 4-propan-2-yl
substitutions were isolated in high enantioselectivities and
interestingly higher diastereomeric ratio was obtained for product
3c (entries 2-3). Also products 3e-3g having different 4-halo
substitutions were obtained in high diastereo- and
enantioselectivities (entries 5-7). Biphenyl substituted enone 2h
also participated in the reaction delivering product 3h in 94% ee
(entry 8). High diastereo- and enantioselectivity was also
observed for product 3i having para-nitro substitution, however
the yield was moderate (entry 9). Then ortho- and meta-
substituted enones 2j and 2k were employed in the reaction and
Table 1: Optimization of the reaction condition
R1
OMe
NH2
NH2
N
N
N
N
Table 2: Scope of enone with varied olefin substituents
I: R1 = OMe
III
R2
O
V
catalyst (20 mol%)
1
II
: R = H
H
H
O
2-FC6H4CO2H
(20 mol%)
R
NH2
IV: R2 = OMe
V: R2 = H
+
R
COPh
N
NC
COPh
toluene, RT
7 days
NC
N
1a
2
3a-3o
dr[c]
O
catalyst (20 mol%)
2-FC6H4CO2H
(20 mol%)
O
H
Entry[a]
R
Product
3a
Yield[b]
ee[%][d]
96
Ph
+
1
Ph
87
72
67
60
89
69
87
81
39
83
65
60
55
52
40
13:1
13:1
>20:1
10:1
17:1
>20:1
19:1
16:1
>20:1
13:1
9:1
Ph
COPh
NC
COPh
H
solvent, RT
7 days
NC
1a
2a
2
4-MeC6H4
4-iPrC6H4
3b
3c
96
3a
3
95
Entry[a]
Catalyst
Solvent
Yield[b]
70
d.r[c]
11:1
7:1
ee[d]
59
84
89
76
94
94
96
96
92
4
4-OMeC6H4
4-FC6H4
3d
3e
93
1
I
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
5
98
2
II
65
6
4-ClC6H4
3f
97
3
III
IV
V
V
V
V
V
68
6:1
7
4-BrC6H4
3g
3h
3i
98
4
72
3.2:1
6:1
8
4-PhC6H4
4-NO2C6H4
3-MeC6H4
2-MeC6H4
1-Naphthyl
2,4-Cl2C6H3
94
5
72
9
94
6
mesitylene 81
9:1
10
11
12
13
14
15
3j
94
7
PhCF3
toluene
toluene
83
87
88
6:1
3k
92
8
13:1
13:1
3l
8:1
83
9[e]
3m
3n
3o
15:1
6:1
82
[a] All reactions were carried out with 0.05 mmol of 1a with 0.05 mmol of 2a in
0.5 ml solvent 20 mol% catalyst and 20 mol% 2-FC6H4CO2H at RT for 7 days.
[b] Isolated yield after silica gel column chromatography. [c] Determined by 1H
nmr. [d] Determined by chiral HPLC and of the major diastereomer. [e] With 30
mol% 2-FC6H4CO2H.
Thiophen-2-yl
76
(E)-Ph-CH=CH-
5.2:1
>99
[a] Unless otherwise mentioned, reactions were carried out with 0.1 mmol of 1a
with 0.1 mmol of 2 in 1 ml toluene using 20 mol% V and 20 mol% 2-FC6H4CO2H
at RT for 7 days. [b] Isolated yield after silica gel column chromatography. [c]
Determined 1H NMR. [d] Determined by chiral HPLC and of the major
diastereomer.
After finalizing the optimized conditions the scope of the reaction
was studied. Initially different enones 2 having variations of the
substitutions on the aryl group of the double bond was
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10.1002/ejoc.201701238
European Journal of Organic Chemistry
COMMUNICATION
delightfully the outcome was good (entries 10-11). The reaction
also progressed well with enone 2l having 1-naphthyl group and
The enantiomeric ratio for the minor diastereomer was also 99%.
Under this conditions, different enones having variations in the
aryl group of olefin were screened (see supporting information for
details).
slight less enenatioselectivity was detected (entry 12).
A
disubstituted aryl group containing enone was also tolerated in
our reaction displaying good result (entry 13).Importantly, enone
2n having thiophen-2-yl moiety could also be a good substrate in
the reaction albeit slight lesser enantioselectivity was observed
(entry 14). Finally, cinnamyl group containing enone 2o was
screened and excellent enantioselectivity was attained for the
corresponding product 3o (entry 15). Cyclohexyl substituted
enone was also screened but trace amount of product formation
was observed even after 15 days of stirring.
Gratifyingly, as can be seen in Table 4, the products were
obtained in high enantioselectivities irrespective of the nature of
the substitutions on the aryl group. Initially, different para-
substitions were screened and good results were observed. For
instance, 1b on reaction with 2b furnished the corresponding
cyclized product 4b in 5:1 dr with 90% ee (entry 2). Similarly
different para-halo substitutions were tolarated in the reaction
providing product 4c in high enantioselectivity (entry 3). The
reaction was sluggish with enone 2h having biphenyl moiety but
the enantiomeric excess of the corresponding product 4d was
excellent (entry 4). Besides meta-substituted enones were also
found to be good partner in this reaction and highest
diastereoselectivity (9:1 dr) was attained for product 4f (entry 6).
Finally slight slow reactivity was observed for an ortho-substituted
enone 2k delivering product 4g in 17% yield with 1.6:1 dr and 89%
ee for the major and >99% for the minor (entry 7).
Next, the ketone functionality of the enone was varied and the
results are summarized in Table 3. Here also, different
substitutions on the phenyl group of ketone were tolerated and
excellent results were obtained. Initially, para-substituted enones
having electron donating groups were screened and interestingly
higher enantioselectivity was detected for product 3p than 3q
(entries 1-2). Additionally, the outcome was also excellent with 4-
halo substituted enones 2r-2s (entries 3-4). Finally a meta-
substituted enone was engaged in the reaction and the product 3t
was obtained in high diastereo- and enantioselectivity (entry 5).
Acetyl substituted enone did not provide any product at room
temperature as well as at elevated temperature.
Table 4. Scope of enone having varied olefin substituents with 1-acetyl
cyclohexene
Table 3: Scope of enone with varied ketone substituents
O
catalyst V (20 mol%)
2-FC6H4CO2H
(20 mol%)
H
H
O
Ph
+
Ph
COAr
NC
COAr
toluene, RT
7 days
NC
1a
2
3p-3t
dr[c]
Entry[a]
Ar
Product
4a
Yield[b]
34
dr[c]
7:1
5:1
4:1
4:1
4:1
9:1
1.6:1
ee[%][d]
99
Entry[a]
Ar
4-MeC6H4
Product
3p
Yield[b]
ee[%][d]
94
1
2
3
4
5
6
7
Ph
1
2
3
4
5
88
64
72
54
66
17:1
20:1
12:1
10:1
8:1
4-MeC6H4
4-BrC6H4
4-PhC6H4
3-MeC6H4
3-BrC6H4
2-MeC6H4
4b
25
96
4-OMeC6H4
4-ClC6H4
4-BrC6H4
3-ClC6H4
3q
93
4c
22
96
3r
94
4d
15
95
3s
95
4e
28
95
3t
96
4f
26
95
[a] Unless otherwise mentioned, reactions were carried out with 0.1 mmol of 1a
with 0.1 mmol of 2 in 1 ml toluene using 20 mol% V and 20 mol% 2-FC6H4CO2H
at RT for 7 days. [b] Isolated yield after silica gel column chromatography. [c]
Determined 1H NMR. [d] Determined by chiral HPLC and
4g
17
89(>99)
[a] Unless otherwise mentioned, reactions were carried out with 0.15 mmol of
1b with 0.15 mmol of 2 in 1.5 ml solvent using 20 mol% V and 20 mol% 2-
FC6H4CO2H at RT for 10 days. [b] Combined yield of the isolated product. [c]
Diastereoselectivity was determined by 1H NMR. [d] Enantioselectivity was
determined by chiral HPLC and of the major diastereomer, the ee of minor
diastereomer is given in the parenthesis.
Then we became interested to employ 1-acetylcyclohexene
(1b) in our cycloaddition reaction. Initially, the reaction between
1b and enone 2a was investigated using cinchoinidine catalyst in
combination with 2-F benzoic acid. The reaction was found to be
slower than with 1a; and gratifyingly the cyclized 1-decalone
product 4a was obtained in 7:1 dr with 96 % ee. Heating the
reaction mixture was not beneficial as it provided some undesired
mixtures of products. After some optimization, it was found that
cinchonine derived primary amine II could provide the product 4a
in same diastereomeric ratio with 99% ee at room temperature.
The generality of the reaction was further demonstrated by
employing enones with varied keto functionalities (Table 5).
Gratifyingly, the reaction condition was also found to be suitable
for the enones having different keto functionalities. Though good
diastereoselectivity was achieved for product 4h (entry 1), inferior
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10.1002/ejoc.201701238
European Journal of Organic Chemistry
COMMUNICATION
diastereoselectivity was detected for the products 4i-4j derived
from enones 2r-2s (entries 2-3). But the enantioselectivity for both
the diastereomer using 2s were very good. A meta-substitutted
enone reacted slowly and less yield but high enantioselectivity
was observed for the corresponding product 4k (entry 4).
60% yield and here also both diastereo- and enantioselectivity got
preserved.
The absolute configuration of product 3f was assigned to be
(3aR,4R,5S,7aS) by X-ray crystallography.[13] The absolute
structure of other products 3 are expected to be same by analogy.
Also, the absolute structure of product 4 can be proposed to be
opposite as cinchonine and cinchonidine used to provide
enantiomeric products.[14]
Table 5. Scope of enone having varied keto substituents with 1-acetyl
cyclohexene
In summary, we have developed the first catalytic asymmetric
[4+2]-cycloaddition reaction of 1-acetylcyclopentene and 1-
acetylcyclohexene providing bicyclic fused frameworks. Electron
deficient olefins having simultaneous cyano and keto groups were
identified as the most suitable dienophile and cinchona alkaloid
derived primary amines were found to be the best catalysts. The
bicyclic products having four contiguous stereogenic centres
including one quaternary centre are obtained in high diastereo-
and enantioselectivities and also valuable synthetic
transformations including triazole synthesis has been
demonstrated. Thus our methodology is useful to prepare such
bicyclic skeletons in a simple and efficient way.
Entry[a]
Ar
Product
Yield[b]
22
dr[c]
8:1
ee[%][d]
94
1
2
3
4
4-MeC6H4
4-ClC6H4
4-BrC6H4
3-ClC6H4
4h
4i
26
2:1
90 (56%)
>99 (93%)
99
4j
28
1.6:1
4:1
4k
17
Experimental Section
General procedure for the formation of 3a-3t: In a 5 ml round bottomed
flusk enone 2 (0.1 mmols), epi-cinchonidine amine V (20 mol%, 0.02
mmols, 5.9 mg), 2-fluoro benzoic acid (20 mol%, 0.02 mmols, 2.8 mg) was
taken and 1-aectyl cyclopentene (0.1 mmols, 11 mg) and 1 mL toluene
was added and the reaction mixture was stirred at room temperaure for 7
days. The reaction mixture then directly employed to column
chromatographic separation using 4% ethyl acetate/hexane as eluent to
obtain pure product 3.
[a] Unless otherwise mentioned, reactions were carried out with 0.15 mmol of
1b with 0.15 mmol of 2 in 1.5 ml solvent using 20 mol% V and 20 mol% 2-
FC6H4CO2H at RT for 10 days. [b] Combined yield of the isolated product. [c]
Diastereoselectivity was determined by 1H NMR. [d] Enantioselectivity was
determined by chiral HPLC and of the major diastereomer.
To illustrate the utility of our method, few reactions were carried
out on 3a and 3q (Scheme 2). Initially copper mediated triazole
synthesis[12] was envisaged from 3a. For this, first 3a was
converted to tosylhydrazone 5 which upon treatment with aniline,
copper acetate and pivalic acid delivered triazole 6 in 54% overall
General procedure for the formation of 4a-4k: In a 5ml round bottomed
flusk enone 2 (0.15 mmols), epi-cinchonine amine II (20 mol%, 0.03 mmols,
8.9 mg), 2-fluoro benzoic acid (20 mol%, 0.03 mmoles, 4.2 mg) was taken
and 1-aectyl cyclohexene (0.15 mmols, 18.6 mg) and 1.5 mL toluene was
added and the reaction mixture was stirred at room temperaure for 10 days.
The reaction mixture then directly employed to column chromatographic
separation using 3% ethyl acetate/hexane as eluent to obtain pure product
4.
Scheme 2: Synthetic transformation of 3a and 3q
NHTs
N
N
N
O
H
H
H
PhNH2
Cu(OAc)2
N
Ph
TsNHNH2
Ph
Ph
COPh
NC
Ph
COPh
PivOH
H
H
H
NC COPh
NC
Acknowledgements ((optional))
54% over
two steps
3a
5
6
13:1 d.r, 96% ee
13:1 d.r, 96% ee
This work is supported by Board of Research in Nuclear Sciences,
India, (Grant no. 2012/20/37c/05/BRNS). We also thank CIF,
Indian Institute of Technology Guwahati for the instrumental
facility and Gobinda Dolai for starting material preparations.
O
H
O
H
m-CPBA
Ph
Ph
Na2HPO4
H
H
O
NC
O
NC
OMe
60%
O
OMe
3q
7
>20:1 d.r, 93% ee
>20:1 d.r, 93% ee
Keywords: [4+2] cycloaddition • dienamine catalysis•
carbocycle• organocatalysis • enantioselecitivity
yield. It is delighting that both the diastereo- and enantiopurity got
retained in this process (Scheme 2). Then a Baeyer Villiger
oxidation reaction was performed on 3q having a 4-anisyl group.
The reaction progressed smoothly affording the ester product 7 in
[1]
a) E. J. Corey, Angew. Chem. Int. Ed. 2002, 41, 1650; b) K. C. Nicolaou,
S. A. Snyder, T. Montagnon, G. Vassilikogiannakis, Angew. Chem. Int.
Ed. 2002, 41, 1668; c) K. Takao, R. Munakata, K. Tadano, Chem. Rev.
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10.1002/ejoc.201701238
European Journal of Organic Chemistry
COMMUNICATION
2005, 105, 4779. For reviews on organocatalytic Diels-Alder reaction,
see: d) J. Shen and C.-H. Tan, Org. Biomol. Chem. 2008, 6, 3229; e) P.
Merino, E. Marqués-López, T. Tejero, R. P. Herrera, Synthesis 2010, 1.
J. Chem. Soc. Perkin Trans. 1 1995, 593. For selected examples, see:
d) P. A. Wender, L. J. Letendre, J. Org. Chem. 1980, 45, 367; e) Y. Sato,
M. Sodeoka, M. Shibasaki, J. Org. Chem. 1989, 54, 4738; f) S. H. Lim,
M. D. Curtis, P. Beak, Org. Lett. 2001, 3, 711; g) L. Barriault, I. Denissova,
Org. Lett. 2002, 4, 1371; h) Shaik Anwar, Hui-Ju Chang, Kwunmin Chen,
Org. Lett. 2011, 13, 2200; i) S. C. Butler, C. J. Forsyth, J. Org. Chem.
2013, 78, 3895. j) For a review on natural products having decalin motif,
see: G. Li, S. Kusari, M. Spiteller, Nat. Prod. Rep. 2014, 31, 1175. k) For
a review on the synthesis of cis-decalins, see: V. Singh, S. R. Iyer, S. Pal,
Tetrahedron 2005, 61, 9197.
[2]
For reviews, see: a) D. B. Ramachary, Y. V. Reddy Eur. J. Org. Chem.
2012, 865; b) M. Christmann, Asymmetric Dienamine Activation, In
Asymmetric Synthesis: More Methods and Applications; M. Christmann,
S. Bräse, Eds. Wiley-VCH: Weinheim, 2012, 43; c) I. D. Jurberg, I.
Chatterjee, R. Tannert, P. Melchiorre, Chem. Commun. 2013, 49, 4869.
For selected reviews, see: a) A. Moyano, R. Rios, Chem. Rev., 2011,
111, 4703; b) G. Masson, C. Lalli, M. Benohoud, G. Dagousset, Chem.
Soc. Rev. 2013, 42, 902; c) C. M. R. Volla, L. Atodiresei, M. Rueping,
Chem. Rev. 2014, 114, 2390.
[3]
[4]
[6]
[7]
R. M. Wilson, W. S. Jen, D. W. C. MacMillan, J. Am. Chem. Soc. 2005,
127, 11616.
For selected examples on cross-dienamine mediated reactions, a) D. B.
Ramachary, N. S. Chowdari, C. F. Barbas, Angew. Chem. Int. Ed. 2003,
42, 4233; b) Y. Yamamoto, N. Momiyama, H. Yamamoto, J. Am. Chem.
Soc. 2004, 126, 5962; c) H. Sundén, I. Ibrahem, L. Eriksson, A. Córdova,
Angew. Chem. Int. Ed. 2005, 44, 4877; d) L. -Y. Wu, G. Bencivenni, M.
Miancinelli, A. Mazzanti, G. Bartoli, P. Melchiorre, Angew. Chem. Int. Ed.
2009, 48, 7196; e) D.-Q. Xu, A.-B. Xia, S.-P. Luo, J. Tang, S. Zhang, J.-
R. Jiang, Z.-Y. Xu, Angew. Chem. Int. Ed. 2009, 48, 3821; f) X. Feng, Z.
Zhou, R. Zhou, Q.-Q. Zhou, L. Dong, Y.-C. Chen, J. Am. Chem. Soc.
2012, 134, 19942; g) M. P. Lalonde, M. A. McGowan, N. S. Rajapaksa,
E. N. Jacobsen, J. Am. Chem. Soc. 2013, 135, 1891; h) X. Wu, M.-L. Li,
D.-F. Chen, S.-S. Chen, J. Org. Chem. 2014, 79, 4743; i) E. Masalo, M.
Benaglia, R. Annunziata, A. Palmieri, G. Celentano, A. Forni, Adv. Synth.
Catal. 2014, 356, 493; j) H. Hu, C. Meng, Y. Dong, X. Li, J. Ye, ACS Catal.
2015, 5, 3700; k) J. Fei, Q. Qian, X. Sun, X. Gu, C. Zou, J. Ye, Org. Lett.
2015, 17, 5296; l) D. B. Ramachary, P. M. Krishna, Asian J. Org. Chem.
2016, 5, 729.
R. M. de Figueiredo, R. Fröhlich, M. Christmann, Angew. Chem. Int. Ed.
2008, 47, 1450.
[8]
[9]
P. G. McGarraugh, S. E. Brenner, Org. Lett. 2009, 11, 5654.
K. Jiang, Z.-J. Jia, X. Yin, Y.-C. Chen, Org. Lett. 2010, 12, 2766.
[10] U. Nath, A. Banerjee, B. Ghosh and S. C. Pan, Org. Biomol. Chem. 2015,
13, 7076.
[11] For initial reports of aminocatalytic reactions with these catalysts, see: a)
S. H. McCooey, S. J. Connon, Org. Lett. 2007, 9, 599; b) W. Chen, W.
Du, L. Yue, R. Li, Y. Wu, L.-S. Ding, Y.-C. Chen, Org. Biomol. Chem.
2007, 5, 816; c) G. Bartoli, M. Bosco, A. Carlone, F. Pesciaioli, L. Sambri,
P. Melchiorre, Org. Lett. 2007, 9, 1403.
[12] Z. Chen, Q. Yan, Z. Liu, Y. Xu and Y. Zhang, Angew. Chem. Int. Ed. 2013,
52, 13324.
[13] CCDC 1546626 contains the crystallographic data of 3f.
[14] For an example of opposite enantiomer formation, see: X. Xu, K. Wang,
S. G. Nelson, J. Am. Chem. Soc. 2007, 129, 11690.
[5]
a) K. Nozawa, S. Nakajima, S.-I. Udagawa, K.-I. Kawai, J. Chem. Soc.
Perkin Trans. 1 1991, 537; b) M. Tori, K. Nakashima, M. Seike, Y.
Asakawa, Tetrahedron Lett. 1994, 35, 3105; c) M. Tori, K. Nakashima, Y.
Asakawa, J. D. Connolly, L. J. Harrison, D. S. Rycroft, J. Singh, N. Woods,
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10.1002/ejoc.201701238
European Journal of Organic Chemistry
COMMUNICATION
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COMMUNICATION
A highly diastereo- and
Utpal Nath, Subhas Chandra Pan*
enantioselective [4+2] cycloaddition of
1-acetylcyclopentene and 1-
acetylcyclohexene with cyano group
containing enones is described. With
20 mol% chiral primary amine catalyst
and 2-flurobenzoic acid as additive,
high yields and good to excellent
enantioselectivities have been
achieved.
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Organoocatalytic Asymmetric [4 + 2]
Cycloaddition of 1-
Acetylcyclopentene and 1-Acetyl
cyclohexene for the Synthesis of
Fused Carbocycles
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This article is protected by copyright. All rights reserved.