Catalytic asymmetric direct vinylogous michael addition of deconjugated butenolides to maleimides for the construction of quaternary stereogenic centers

Article abstract of DOI:10.1002/chem.201203180

Competition under control: A practical and efficient direct asymmetric vinylogous Michael reaction of deconjugated butenolides has been developed (see scheme). The products of this reaction, highly functionalized chiral succinimides, are obtained in excel

Full text of DOI:10.1002/chem.201203180

COMMUNICATION
DOI: 10.1002/chem.201203180
Catalytic Asymmetric Direct Vinylogous Michael Addition of Deconjugated
Butenolides to Maleimides for the Construction of Quaternary Stereogenic
Centers
Madhu Sudan Manna and Santanu Mukherjee*[a]
Dedicated to Professor Benjamin List on the occasion of his 45th birthday
Chiral succinimides and functionalized pyrrolidines are
two synthetically and biologically important classes of struc-
tural motifs.[1] Conjugate addition of nucleophiles to male-
ACHTUNGTRENNUNGimACHTUNGTRENNUNGides constitutes the most straightforward route to chiral
a-substituted succinimides. Despite such impetus, the appli-
cation of maleimides in asymmetric synthesis has mostly
been limited to various cycloaddition reactions.[2] The asym-
metric Michael addition reaction to maleimides has re-
mained largely overlooked except for a few sporadic exam-
ples.[3] The realization of the full potential of this powerful
electrophile as Michael acceptor has only begun during the
past decade. The initial reports came from Hayashi and co-
workers when they disclosed a Rh-catalyzed 1,4-addition of
boronic acids to maleimides.[4] The reason for this initial
paucity of enantioselective conjugate addition reactions in-
volving maleimides probably lies in their C2v symmetry.
Unlike Michael acceptors with only one prochiral electro-
philic center (e.g., nitro-olefins, enals etc.), those containing
C2v symmetry (e.g., unsubstituted maleimides, 1,4-naphtho-
quinone etc.) pose additional challenges for developing an
asymmetric Michael addition. Here, two chemically equiva-
lent vicinal electrophilic centers are present and the diago-
nally opposite centers (related by a C2 operation) are also
stereochemically equivalent. Therefore, selective addition to
only one set of diagonally opposite centers (for example,
bottom@A or top@B, Scheme 1a) is the prerequisite for an
enantioselective process.
With the advent of organocatalysis, maleimides emerged
as a very popular electrophile and a number of reports de-
scribing the asymmetric addition of a wide range of nucleo-
philes appeared within a rather short interval.[5] However,
all these reports illustrate the addition of direct carbon-cen-
tered nucleophiles to maleimides and only one example of a
vinylogous Michael addition.[6] In 2008, Loh et al. reported
Scheme 1. Enantioselective Michael addition to unsubstituted male
ides: challenges, requirements, and strategy.
ACHTUNGTRENNUNGim-
AHCTUNGTRENNUNG
modified cinchona alkaloids as catalysts for the addition of
a,a-dicyanoolefins to N-phenyl and N-benzyl maleimides.[6]
We have recently reported a direct asymmetric vinylogous
Michael addition of g-substituted deconjugated butenolides
to nitro-olefins for the construction of quaternary stereocen-
ters.[7,8] With our continued interest in accessing compounds
containing quaternary stereocenters,[9,10] we realized that the
[a] M. S. Manna, Prof. Dr. S. Mukherjee
Department of Organic Chemistry
Indian Institute of Science
Bangalore 560 012 (India)
Fax : (+91)8023600529
E-mail: sm@orgchem.iisc.ernet.in
addition of the same nucleophile to unsubstituted male
ACHTUNGTRENNUNGim-
AHCTUNGTREGiNNNU des would, once again, result in adjacent quaternary and
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203180.
tertiary stereocenters. In this communication, we report a
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2012, 18, 15277 – 15282

highly diastereo- and enantioselective direct vinylogous[11]
Michael addition of g-substituted deconjugated butenolides
to unsubstituted maleimides.
Table 1. Catalyst evaluation and optimization of reaction conditions for
direct vinylogous Michael reaction of a-Angelica lactone 1a with N-
phenACHTNUGRTNEUNG
ylmaleimide 2a.[a]
We were aware of the potential difficulties associated
with blocking of one set of diagonally opposite prochiral
centers (Scheme 1a) and devised an alternative strategy
(Scheme 1b). We realized that Brønsted acidic activation of
the maleimide carbonyl would render only one (of the possi-
ble two) electrophilic centers “active” towards nucleophilic
attack. Under this condition, merely a face-selective ap-
proach of the nucleophile would be sufficient to bring about
enantioselective Michael addition. Such enantiofacial dis-
crimination of maleimide was thought to be achieved by
means of a chiral thiourea/tertiary-amine bifunctional cata-
lyst.[12]
We began our investigation by studying the feasibility of
the reaction between a-Angelica lactone (1a) and N-phenyl-
maleimide (2a; Table 1). As expected, no measurable prod-
uct formation was detected in the absence of any catalyst
even after 72 h when the reaction was conducted in chloro-
form at room temperature (Table 1, entry 1). However,
upon exposure to 10 mol% of the Takemoto catalyst I,[13]
complete conversion to the desired Michael adduct 3aa was
observed within one hour, albeit with only modest diastereo-
and enantioselectivity (entry 2). Quinine- and cinchonine-
derived thiourea derivatives II and III,[14] respectively, dem-
onstrated good catalytic activity, but poor enantioselectivity
(entries 3 and 4). Bifunctional squaramide derivative IV, in-
troduced by Rawal and co-workers,[15] improved the enantio-
selectivity significantly while maintaining the catalytic activi-
ty (entry 5). Excellent enantioselectivity was obtained when
the aryl moiety of the thiourea catalyst I was replaced with
a tert-leucine-derived chiral substituent.[16] The resulting cat-
alyst V afforded 3aa with d.r.=8:1 and e.r.=97:3 (entry 6).
Slight improvement in enantioselectivity was achieved when
the reaction was conducted at 08C (entry 7). With a number
of similar catalysts VI–VIII, containing various substituents
on the amide nitrogen, product was obtained with diminish-
ed d.r. and e.r. (entries 8–10), and established secondary
amide V as the optimum catalyst for this reaction. The cor-
responding diastereomeric catalyst IX, derived from (S,S)-
1,2-diaminocyclohexane turned out to possess the “mis-
matched” combination, providing the product with lower
d.r. and e.r. compared to V (entry 11 vs. 7). Interestingly,
ent-3aa was obtained as the major enantiomer with catalyst
IX and hence illustrates that the stereochemical outcome of
this Michael reaction is dictated by the 1,2-diamine moiety
and not by the chiral side chain. Lowering the reaction tem-
perature to À368C further improved the enantioselectivity
to e.r.=98:2 without compromising the reaction rate too
much (entry 12). A quick solvent screening revealed di-
chloromethane as the preferred solvent, providing the prod-
uct with excellent d.r. (13:1) and outstanding e.r. (99:1)
(entry 13). Under these reaction conditions, catalyst loading
can be reduced to 5 mol% without any deleterious effect on
the reaction selectivity (entry 16). A catalyst loading of
2 mol% provided the product with still useful level of enan-
Entry
Cat. ([mol%])
Solvent
T [8C]
t [h][b]
d.r.[c]
e.r.[d]
–
[e]
1
2
3
4
5
6
7
8
9
–
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
toluene
TBME[f]
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
25
25
25
25
25
25
0
0
0
–
–
4:1
5:1
5:1
6:1
8:1
8:1
5:1
6:1
4:1
7:1
7:1
13:1
6:1
11:1
13:1
2:1
11:1
14:1
9:1
I (10)
<1
4
4
5
<1
2
2
2
2
3
77:23
II (10)
III (10)
IV (10)
V (10)
V (10)
VI (10)
VII (10)
VIII (10)
IX (10)
V (10)
V (10)
V (10)
V (10)
V (5)
40:60
53:47
92:8
97:3
97.5:2.5
92:8
93.5:6.5
90:10
5:95
98:2
99:1
96.5:3.5
98.5:1.5
99:1
96:4
99:1
99:1
99:1
99:1
10
11
12
13
14
15
16
17
18[h]
19[h,i]
20[h,j]
21[h,k]
0
0
À36
À36
À36
À36
À36
À36
À36
À36
À36
À36
5
3
3
6
6
V (2)
V (5)
V (5)
V (5)
44[g]
8
6
11
9
V (5)
14:1
[a] Reactions were carried out using 1.0 equivalent of 1a and 1.5 equiva-
lents of 2a. [b] Time required for complete conversion of 1a. [c] Deter-
mined by H NMR analysis of crude reaction mixture. [d] Determined by
HPLC analysis using a stationary phase chiral column. Relative and ab-
solute configuration of the product was determined by X-ray diffraction
analysis. [e] No conversion after 72 h. [f] TBME: tert-Butyl methyl ether.
[g] 85% conversion after 44 h. [h] 1.1 equivalents of 2a was used. [i] Re-
action concentration of 0.25m. [j] Reaction concentration of 1.0m. [k] Re-
action concentration of 0.1m.
1
tioselectivity (e.r.=96:4), but both the reaction rate and the
diastereoselectivity were curtailed severely (entry 17).
Therefore, 5 mol% of the catalyst V was used for all subse-
quent optimization studies. Diastereoselectivity was slightly
improved to d.r.=14:1 when the reaction concentration was
reduced to 0.25m (entry 19). However, no beneficial effect
could be achieved by further diluting the reaction mixture
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Chem. Eur. J. 2012, 18, 15277 – 15282

Vinylogous Michael Addition
COMMUNICATION
Table 3. Scope of the maleimide N-substitution in the asymmetric vinylo-
gous Michael reaction.[a]
to 0.1m (entry 21). It must be noted that our optimized reac-
tion conditions (entry 19) utilize only small excess
(1.1 equiv) of maleimide 2a.
Having optimized the catalyst structure and reaction con-
ditions (Table 1, entry 19), we examined the influence of
structural diversity of the deconjugated butenolide on the
reaction outcome. The results are summarized in Table 2.
Entry Ar
t [h]
3
Yield [%][b] d.r.[c] e.r.[d]
1
2
3
4
5
6
7
8
4-BrC6H4 (2b)
6
4
5
4
12
6
3ab 93
3ac 95
3ad 90
3ae 93
3af 94
3ag 97
3ah 96
3ai 88
5:1
6:1
10:1
18:1 >99:1
15:1
5:1
98:2
98:2
96.5:3.5
Table 2. Scope of deconjugated butenolides in the asymmetric vinylogous
Michael reaction.[a]
4-ClC6H4 (2c)
4-CF3C6H4 (2d)
4-MeC6H4 (2e)
4-OMeC6H4 (2 f)
3-ClC6H4 (2g)
3-MeC6H4 (2h)
99:1
97.5:2.5
4
10:1 >99:1
15:1 98:2
2,4-(OMe)2C6H3 (2i) 16
[a] Reactions were carried out using 1.0 equivalent of 1a and 1.1 equiva-
lents of 2 under an argon atmosphere. [b] Isolated yield of the products
after column chromatography. [c] Determined by 1H NMR analysis of
the crude reaction mixture. [d] Determined by HPLC analysis using a sta-
tionary phase chiral column (see the Supporting Information).
Entry
R
t [h]
3
Yield [%][b]
d.r.[c]
e.r.[d]
1
2
3
4
5
6
7
Me (1a)
Et (1b)
6
8
5
4
5
5
4
3aa
3ba
3ca
3da
3ea
3 fa
3ga
99
92
96
96
97
94
91
14:1
14:1
14:1
13:1
10:1
18:1
15:1
>99:1
99.5:0.5
98:2
nPr (1c)
nPent (1d)
iBu (1e)
iPr (1 f)
Bn (1g)
98:2
>99:1
97.5:2.5
98.5:1.5
[a] Reactions were carried out using 1.0 equivalent of 1 and 1.1 equiva-
lents of 2a under an argon atmosphere. [b] Isolated yield of the products
after column chromatography. [c] Determined by 1H NMR analysis of
the crude reaction mixture. [d] Determined by HPLC analysis using a sta-
tionary phase chiral column (see the Supporting Information).
We were delighted to find that the butenolide structure has
little impact on the overall performance of this direct vinylo-
gous Michael protocol. For butenolides with either linear
alkyl chains (Me: 1a, Et: 1b, nPr: 1c, nPent: 1d; entries 1–
4), branched alkyl groups (iBu 1e, iPr 1 f; entries 5 and 6),
or alkyl chain with an aromatic moiety (Bn 1g; entry 7),
products were obtained in uniformly high yield with excel-
lent diastereoselectivity and outstanding enantioselectivity.
With the generality of the butenolide g-substituent al-
ready established, we next turned our attention to the effect
of maleimide N-substitution on the selectivity of the reac-
tion. As can be seen from Table 3, a wide range of aromatic
substituents are tolerated and the Michael adducts are gen-
erally obtained in excellent yield and enantioselectivity with
high d.r. However, the substituents do influence the reaction
rate depending on their electronic nature. The reactions are
found to be slower for maleimides with electron-rich aro-
matic substituents (entries 5 and 8). Nevertheless, the level
of diastereo- and enantioselectivity remained impervious to
the electronic nature of the substituents. Our preliminary
studies on maleimides with non-aromatic N-substituents
showed a significant decrease in both reaction rate and se-
lectivity, leaving room for future improvement.
Figure 1. Relative and absolute stereochemistry of 3ac and its X-ray
structure.
Table 2 and 3 were tentatively assigned the same by assum-
ing that a similar catalytic mechanism was followed.
The practicality of this protocol was demonstrated by a
same-pot catalyst recycling experiment (Table 4) in which
new batches of substrates (both 1a and 2a) were added
once the reaction was judged complete by TLC without sep-
aration of the products formed. Each reaction cycle was
conducted on a 0.25 mmol scale. It is clear from Table 4,
that the d.r. and e.r. of the product remained consistent over
three reaction cycles. The slight erosion of the overall prod-
uct yield compared to a single catalytic experiment (Table 2,
entry 1) and the longer reaction times for the second and
third cycle are due to the loss of effective catalyst amount
while extracting sample for analysis. In addition, a gradual
decrease in reaction concentration with each cycle and com-
petitive product inhibition of catalyst might also have con-
tributed towards the attrition of the reaction rate.
Both the relative and absolute stereochemistry of 3ac
were determined by X-ray diffraction analysis (Figure 1).[17]
The configuration of the other Michael adducts shown in
Chem. Eur. J. 2012, 18, 15277 – 15282
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www.chemeurj.org
15279

S. Mukherjee and M. S. Manna
Table 4. One-pot catalyst-recycling experiment.[a]
requirement for the development of asymmetric Michael re-
action to maleimides (see Scheme 1). The X-ray structure of
catalyst V (Figure 2)[17] supports the role of the bulky ada-
mantyl group in the desired face selectivity.
At this point we speculated that if this mechanistic model
is operative, then a catalyst consisting of the tert-leucine-de-
rived component as the sole chiral element should be able
to promote a similar face-selective Michael addition. This
assumption was indeed found to be true when X was used
as the catalyst for reaction between 1a and 2a under our op-
timized reaction conditions. The same product stereoisomer
3aa was obtained with rather impressive enantioselectivity
(Scheme 2). This experiment provides strong evidence in
support of our proposed stereochemical model.
Cycles
Conc. of 1a [M]
t [h]
d.r.[b]
e.r.[c]
Overall yield[d]
84%
1st
2nd
3rd
0.25
0.17
0.12
6
22
50
14:1
14:1
14:1
99:1
99:1
99:1
[a] Reactions were carried out using 1.0 equivalent of 1a and 1.1 equiva-
lents of 2a under an argon atmosphere. [b] Determined by 1H NMR anal-
ysis of the crude reaction mixture. [c] Determined by HPLC analysis
using a stationary phase chiral column (see the Supporting Information).
[d] Isolated yield of the products after column chromatography.
Based on the observed stereochemistry of the Michael
adduct (Figure 1) and the well-documented activation mode
involving this type of bifunctional catalysts,[18] a plausible
transition state model is proposed. As shown in Figure 2, nu-
cleophilic addition of the butenolide occurs via its corre-
sponding aromatic enol form, activated by the tertiary
amine group of the catalyst by means of a general base cat-
alysis. Dual hydrogen bonding from thiourea to the male
ACHTUNGERTNiNUNG m-
ACHTUNGTRENNUNGide not only reduces its LUMO energy, but also orients the
maleimide for a face-selective nucleophilic attack, a prime
Scheme 2. Asymmetric vinylogous Michael reaction between 1a and 2a
using catalyst X.
In conclusion, we have developed a highly diastereo- and
enantioselective protocol for the direct vinylogous Michael
addition of deconjugated butenolides to maleimides using a
tertiary-amine/thiourea-based bifunctional catalyst. This op-
erationally simple protocol should be synthetically useful
due to the mild reaction conditions, low catalyst loading,
and excellent level of product stereoselectivity. We are cur-
rently working on extending the scope of the reaction to in-
clude N-alkyl and substituted maleimides.
Experimental Section
Typical procedure for the direct asymmetric vinylogous Michael reaction
between 1a and 2a: In an oven and vacuum dried Schlenk tube, N-phen-
AHCTUNGTERGyNNUN lmaleimide 2a (48.5 mg, 0.280 mmol; 1.1 equiv) and the catalyst V
(5.7 mg, 0.012 mmol; 0.05 equiv) were taken under argon. Freshly distil-
led CH2Cl2 (0.5 mL) was added and the solution was cooled to À368C
under a positive argon pressure. A solution of a-Angelica lactone 1a
(25.0 mg, 0.254 mmol; 1.0 equiv) in CH2Cl2 (0.5 mL) was added and the
resulting mixture was stirred at À368C until TLC (1:1 petroleum
ether:CH2Cl2) revealed complete conversion of 1a. The reaction mixture
was then brought to room temperature, solvent was removed in vacuo,
and the residue was purified by column chromatography on silica gel
(100–200 mesh) using 1:1 EtOAc in petroleum ether to afford 3aa as a
colorless foam (68.1 mg, 0.251 mmol; 99%).
Figure 2. X-ray structure of the catalyst V and rationalization for the
stereoACHTUNGTRENNUNGchemical outcome of the vinylogous Michael addition.
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Vinylogous Michael Addition
COMMUNICATION
Chem. Eur. J. 2010, 16, 9884–9889; k) X. Li, S. Hu, Z. Xi, L. Zhang,
S. Luo, J.-P. Cheng, J. Org. Chem. 2010, 75, 8697–8700; l) F. Xue, L.
Liu, S. Zhang, W. Duan, W. Wang, Chem. Eur. J. 2010, 16, 8537;
m) F. Yu, Z. Jin, H. Huang, T. Ye, X. Liang, J. Ye, Org. Biomol.
Chem. 2010, 8, 4767–4774; n) F. Yu, X. Sun, Z. Jin, S. Wen, X.
Liang, J. Ye, Chem. Commun. 2010, 46, 4589–4591; o) Y.-H. Liao,
X.-L. Liu, Z.-J. Wu, L.-F. Cun, X.-M. Zhang, W.-C. Yuan, Org. Lett.
2010, 12, 2896–2899; p) A. Zea, G. Valero, A.-N. R. Alba, A.
Moyano, R. Rios, Adv. Synth. Catal. 2010, 352, 1102–1106; q) Z.
Jiang, Y. Pan, Y. Zhao, T. Ma, R. Lee, Y. Yang, K.-W. Huang, M. W.
Wong, C.-H. Tan, Angew. Chem. 2009, 121, 3681–3685; Angew.
Chem. Int. Ed. 2009, 48, 3627–3631; r) Z. Jiang, W. Ye, Y. Yang, C.-
H. Tan, Adv. Synth. Catal. 2008, 350, 2345–2351; s) W. Ye, Z. Jiang,
Y. Zhao, S. L. M. Goh, D. Leow, Y.-T. Soh, C.-H. Tana, Adv. Synth.
Catal. 2007, 349, 2454–2458; t) L. Zu, H. Xie, H. Li, J. Wang, W.
Jiang, W. Wang, Adv. Synth. Catal. 2007, 349, 1882–1886; u) G.-L.
Zhao, Y. Xu, H. Sundꢄn, L. Eriksson, M. Sayaha, A. Cꢁrdova,
Chem. Commun. 2007, 734–735; v) G. Bartoli, M. Bosco, A. Car-
lone, A. Cavalli, M. Locatelli, A. Mazzanti, P. Ricci, L. Sambri, P.
Melchiorre, Angew. Chem. 2006, 118, 5088–5092; Angew. Chem. Int.
Ed. 2006, 45, 4966–4970.
Acknowledgements
Generous financial support from Indian Institute of Science, Bangalore,
in the form of start-up grant is gratefully acknowledged. This research
program is funded by the Department of Science and Technology (DST),
New Delhi (Grant No. SR/FT/CS-90/2010) and the Council of Scientific
and Industrial Research (CSIR), New Delhi (Grant No.01ACTHNUTRGNEUG(N 2505)/11/
EMR-II). M.S.M. thanks CSIR for a doctoral fellowship. We thank
Pavan M.S. and Vijith Shetty (Solid State and Structural Chemistry Unit,
IISc, Bangalore) for their help with the X-ray diffraction analysis. We
wish to thank Soumya Jyoti Singha Roy for helpful discussion.
Keywords: asymmetric
catalysis
·
butyrolactone
·
maleimide · Michael addition · thiourea
[1] a) R. M. de Figueiredo, R. Frçhlich, M. Christmann, Angew. Chem.
2007, 119, 2941–2944; Angew. Chem. Int. Ed. 2007, 46, 2883–2886;
b) R. M. de Figueiredo, M. Voith, R. Frçhlich, M. Christmann, Syn-
lett 2007, 391–394; c) J. Pohlmann, T. Lampe, M. Shimada, P. G.
Nell, J. Pernerstorfer, N. Svenstrup, N. A. Brunner, G. Schiffer, C.
Freiberg, Bioorg. Med. Chem. Lett. 2005, 15, 1189–1192; d) R. Balli-
ni, G. Bosica, G. Cioci, D. Fiorini, M. Petrini, Tetrahedron 2003, 59,
3603–3608; e) M. L. Curtin, R. B. Garland, H. R. Heyman, R. R.
Frey, M. R. Michaelides, J. Li, L. J. Pease, K. B. Glaser, P. A. Mar-
cotte, S. K. Davidsen, Bioorg. Med. Chem. Lett. 2002, 12, 2919–
2923; f) A. Mitchenson, A. Nadin, J. Chem. Soc. Perkin Trans. 1
2000, 2862–2892; g) S. Ahmed, Drug Des. Discovery 1996, 14, 77–
89.
[2] For selected reports on cycloaddition reaction using maleimides,
see: a) Y. Wang, L. Liu, T. Zhang, N.-J. Zhong, D. Wang, Y.-J. Chen,
J. Org. Chem. 2012, 77, 4143–4147; b) F. Zhong, G.-Y. Chen, X.
Han, W. Yao, Y. Lu, Org. Lett. 2012, 14, 3764–3767; c) Q. Zhao, X.
Han, Y. Wei, M. Shi, Y. Lu, Chem. Commun. 2012, 48, 970–972;
d) S. Mukherjee, E. J. Corey, Org. Lett. 2010, 12, 632–635; e) L.-Y.
Wu, G. Bencivenni, M. Mancinelli, A. Mazzanti, G. Bartoli, P. Mel-
chiorre, Angew. Chem. 2009, 121, 7332–7335; Angew. Chem. Int.
Ed. 2009, 48, 7196–7199; f) J. Y.-T. Soh, C.-H. Tan, J. Am. Chem.
Soc. 2009, 131, 6904–6905; g) C. Gioia, A. Hauville, L. Bernardi, F.
Fini, A. Ricci, Angew. Chem. 2008, 120, 9376–9379; Angew. Chem.
Int. Ed. 2008, 47, 9236–9239; h) J. Shen, T. T. Nguyen, Y.-P. Goh, W.
Ye, X. Fu, J. Xu, C.-H. Tan, J. Am. Chem. Soc. 2006, 128, 13692–
13693; i) E. J. Corey, S. Sarshar, D.-H. Lee, J. Am. Chem. Soc. 1994,
116, 12089–12090.
[3] a) S. Harada, N. Kumagai, T. Kinoshita, S. Matsunaga, M. Shibasaki,
J. Am. Chem. Soc. 2003, 125, 2582–2590; b) J. K. Myers, E. N. Jacob-
sen, J. Am. Chem. Soc. 1999, 121, 8959–8960.
[4] a) R. Shintani, W.-L. Duan, T. Hayashi, J. Am. Chem. Soc. 2006,
128, 5628–5629; b) R. Shintani, W.-L. Duan, T. Nagano, A. Okada,
T. Hayashi, Angew. Chem. 2005, 117, 4687–4690; Angew. Chem. Int.
Ed. 2005, 44, 4611–4614; c) R. Shintani, K. Ueyama, I. Yamada, T.
Hayashi, Org. Lett. 2004, 6, 3425–3427.
[5] For selected examples, see: a) X. Yang, C. Wang, Q. Ni, D. Enders,
Synthesis 2012, 44, 2601–2606; b) L. Li, W. Chen, W. Yang, Y. Pan,
H. Liu, C.-H. Tan, Z. Jiang, Chem. Commun. 2012, 48, 5124–5126;
c) A. Mazzanti, T. Calbet, M. Font-Bardia, A. Moyano, R. Rios,
Org. Biomol. Chem. 2012, 10, 1645–1652; d) J.-F. Bai, L.-L. Wang,
L. Peng, Y.-L. Guo, L.-N. Jia, F. Tian, G.-Y. He, X.-Y. Xu, L.-X.
Wang, J. Org. Chem. 2012, 77, 2947–2953; e) E. Gꢁmez-Torres,
D. A. Alonso, E. Gꢁmez-Bengoa, C. Nꢂjera, Org. Lett. 2011, 13,
6106–6109; f) Q.-Y. Zhao, C.-K. Pei, X.-Y. Guan, M. Shi, Adv.
Synth. Catal. 2011, 353, 1973–1979; g) Y.-H. Liao, X.-L. Liu, Z.-J.
Wu, X.-L. Du, X.-M. Zhang, W.-C. Yuan, Adv. Synth. Catal. 2011,
353, 1720–1728; h) Y. Qin, G. Yang, L. Yang, J. Li, Y. Cui, Catal.
Lett. 2011, 141, 481–488; i) J. Wang, M.-M. Zhang, S. Zhang, Z.-A.
Xu, H. Li, X.-H. Yu, W. Wang, Synlett 2011, 473–476; j) A.-N. R.
Alba, G. Valero, T. Calbet, M. Font-Bardꢃa, A. Moyano, R. Rios,
[6] J. Lu, W.-J. Zhou, F. Liu, T.-P. Loh, Adv. Synth. Catal. 2008, 350,
1796–1800.
[7] M. S. Manna, V. Kumar, S. Mukherjee, Chem. Commun. 2012, 48,
5193–5195.
[8] For selected applications of deconjugated butenolides in asymmetric
catalysis, see: a) X. Huang, J. Peng, L. Dong, Y.-C. Chen, Chem.
Commun. 2012, 48, 2439–2441; b) A. Quintard, A. Alexakis, Chem.
Commun. 2011, 47, 7212–7214; c) L. Zhou, L. Lin, J. Ji, M. Xie, X.
Liu, X. Feng, Org. Lett. 2011, 13, 3056–3059; d) A. Quintard, A. Le-
franc, A. Alexakis, Org. Lett. 2011, 13, 1540–1543; e) H.-L. Cui, J.-
R. Huang, J. Lei, Z.-F. Wang, S. Chen, L. Wu, Y.-C. Chen, Org. Lett.
2010, 12, 720–723.
[9] C. B. Tripathi, S. Kayal, S. Mukherjee, Org. Lett. 2012, 14, 3296–
3299.
[10] For selected reviews on the generation of quaternary stereocenters,
see: a) J. P. Das, I. Marek, Chem. Commun. 2011, 47, 4593–4623;
b) C. Hawner, A. Alexakis, Chem. Commun. 2010, 46, 7295–7306;
c) M. Bella, T. Gasperi, Synthesis 2009, 1583–1614; d) B. M. Trost,
C. Jiang, Synthesis 2006, 369–396; e) J. Christoffers, A. Baro, Adv.
Synth. Catal. 2005, 347, 1473–1482; f) C. J. Douglas, L. E. Overman,
Proc. Natl. Acad. Sci. USA 2004, 101, 5363–5367; g) E. J. Corey, A.
Guzman-Perez, Angew. Chem. 1998, 110, 2092–2118; Angew. Chem.
Int. Ed. 1998, 37, 388–401.
[11] For selected reviews on vinylogous reactions, see: a) S. V. Pansare,
E. K. Paul, Chem. Eur. J. 2011, 17, 8770–8779; b) G. Casiraghi, L.
Battistini, C. Curti, G. Rassu, F. Zanardi, Chem. Rev. 2011, 111,
3076–3154; c) S. E. Denmark, J. R. Heemstra Jr., G. L. Beutner,
Angew. Chem. 2005, 117, 4760–4777; Angew. Chem. Int. Ed. 2005,
44, 4682–4698; d) R. C. Fuson, Chem. Rev. 1935, 16, 1–27.
[12] For selected reviews on bifunctional catalysis, see: a) L.-Q. Lu, X.-L.
An, J.-R. Chen, W.-J. Xiao, Synlett 2012, 490–508; b) W.-Y. Siau, J.
Wang, Catal. Sci. Technol. 2011, 1, 1298–1310; c) Y. Takemoto,
Chem. Pharm. Bull. 2010, 58, 593–601; d) S. J. Connon, Chem.
Commun. 2008, 2499–2510.
[13] For selected examples, see: a) S. Sakamoto, T. Inokuma, Y. Takemo-
to, Org. Lett. 2011, 13, 6374–6377; b) T. Okino, Y. Hoashi, Y. Take-
moto, J. Am. Chem. Soc. 2003, 125, 12672–12673.
[14] For seminal works on bifunctional cinchona alkaloid-derived thio-
AHCTUNGERTGuNNUN rea derivatives, see: a) L. Bernardi, F. Fini, R. P. Herrera, A. Ricci,
V. Sgarzani, Tetrahedron 2006, 62, 375–380; b) S. H. McCooey, S. J.
Connon, Angew. Chem. 2005, 117, 6525–6528; Angew. Chem. Int.
Ed. 2005, 44, 6367–6370; c) J. Ye, D. J. Dixon, P. S. Hynes, Chem.
Commun. 2005, 4481–4483; d) B. Vakulya, S. Varga, A. Csꢂmpai, T.
Soꢁs, Org. Lett. 2005, 7, 1967–1969; e) B.-J. Li, L. Jiang, M. Liu, Y.-
C. Chen, L.-S. Ding, Y. Wu, Synlett 2005, 603–606.
[15] a) Y. Zhu, J. P. Malerich, V. H. Rawal, Angew. Chem. 2010, 122,
157–160; Angew. Chem. Int. Ed. 2010, 49, 153–156; b) J. P. Male-
rich, K. Hagihara, V. H. Rawal, J. Am. Chem. Soc. 2008, 130, 14416–
Chem. Eur. J. 2012, 18, 15277 – 15282
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
15281

S. Mukherjee and M. S. Manna
14417; for a review on squaramides, see: J. Alemꢂn, A. Parra, H.
Jiang, K. A. Jørgensen, Chem. Eur. J. 2011, 17, 6890–6899.
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[16] For selected examples on tert-leucine-based bifunctional thiourea–
tertiary amine catalysts, see: a) J. A. Birrell, J.-N. Desrosiers, E. N.
Jacobsen, J. Am. Chem. Soc. 2011, 133, 13872–13875; b) D. E.
Fuerst, E. N. Jacobsen, J. Am. Chem. Soc. 2005, 127, 8964–8965;
c) A. Berkessel, S. Mukherjee, F. Cleemann, T. N. Mꢅller, J. Lex,
Chem. Commun. 2005, 1898–1900.
[18] a) S. J. Zuend, E. N. Jacobsen, J. Am. Chem. Soc. 2009, 131, 15358–
15374; b) S. J. Zuend, E. N. Jacobsen, J. Am. Chem. Soc. 2007, 129,
15872–15883.
Received: September 7, 2012
Revised: October 11, 2012
Published online: November 6, 2012
[17] CCDC-900197 (3ac), and 900198 (V) contain the supplementary
crystallographic data for this paper. These data can be obtained free
15282
www.chemeurj.org
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Chem. Eur. J. 2012, 18, 15277 – 15282