Sequential organocatalytic stetter and michael-aldol condensation reaction: Asymmetric synthesis of fully substituted cyclopentenes via a [1 + 2 + 2] annulation strategy

Article abstract of DOI:10.1021/ol101969t

A stereoselective synthesis of fully substituted cyclopentenes has been achieved by a sequential organocatalyzed Stetter and Michael-aldol condensation of aromatic aldehydes, nitroalkenes, and α,β-unsaturated aldehydes via the [1 + 2 + 2] annulation strat

Full text of DOI:10.1021/ol101969t

ORGANIC
LETTERS
2010
Vol. 12, No. 21
4812-4815
Sequential Organocatalytic Stetter and
Michael-Aldol Condensation Reaction:
Asymmetric Synthesis of Fully
Substituted Cyclopentenes via a
[1 + 2 + 2] Annulation Strategy
Bor-Cherng Hong,* Nitin S. Dange, Che-Sheng Hsu, and Ju-Hsiou Liao
Department of Chemistry and Biochemistry, National Chung Cheng UniVersity,
Chia-Yi, 621, Taiwan, R.O.C.
chebch@ccu.edu.tw
Received August 19, 2010
ABSTRACT
A stereoselective synthesis of fully substituted cyclopentenes has been achieved by a sequential organocatalyzed Stetter and Michael-aldol
condensation of aromatic aldehydes, nitroalkenes, and r,ꢀ-unsaturated aldehydes via the [1 + 2 + 2] annulation strategy with excellent
diastereoselectivities and enantioselectivities (up to >99% ee).
Among the vast number of organocatalytic reactions reported,
the reactions catalyzed by N-heterocyclic carbenes (NHCs)1
represent a unique category, especially, the umpolung of
classical carbonyl activity, which includes benzoin condensa-
tion,2 homoenolate reactions,3 and Stetter reactions.4 The
asymmetric intramolecular Stetter reaction was first introduced
by Enders5 and later studied by Rovis,6 and many other
examples have since been demonstrated.7 However, much less
success has been reported for the organocatalytic enantioselec-
tive intermolecular Stetter reaction.8,9 Only one example of
the intermolecular Stetter reaction of aromatic heterocyclic
aldehydes and nitroolefins has been uncovered.10,11 On the
other hand, organocatalyzed [3 + 2] annulations toward
cyclopentane and cyclopentene derivatives have been ac-
complished recently via Michael-aldol,12 Michael/R-alkyla-
tion,13 double Michael,14 Michael-Henry,15 homoenolate Micha-
(5) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. HelV. Chim. Acta
1996, 79, 1899
.
(1) For reviews, see: (a) Enders, D.; Niemeier, O.; Henseler, A. Chem.
ReV. 2007, 107, 5606. (b) Marion, N.; Diez-Gonzalez, S.; Nolan, I. P. Angew.
Chem., Int. Ed. 2007, 46, 2988. (c) Nair, V.; Bindu, S.; Sreekumar, V.
Angew. Chem., Int. Ed. 2004, 43, 5130. (d) Enders, D.; Balensiefer, T. Acc.
Chem. Res. 2004, 37, 534.
(6) Kerr, M. S.; de Alaniz, J. R.; T.; Rovis, T. J. Am. Chem. Soc. 2002,
124, 10298
.
(7) (a) de Alaniz, J. R.; Kerr, M. S.; Moore, J. L.; Rovis, T. J. Org.
Chem. 2008, 73, 2033. (b) Kerr, M. S.; Rovis, T. J. Am. Chem. Soc. 2004,
126, 8876. (c) Moore, J.; Kerr, M. S.; Rovis, T. Tetrahedron 2006, 62,
11477. (d) Reynolds, N. T.; Rovis, T. Tetrahedron 2005, 61, 6368. (e) de
Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2005, 127, 6284. (f) Mennen,
S. M.; Blank, J. T.; Tran-Dube´, M. B.; Imbriglio, J. E.; Miller, S. J. Chem.
(2) (a) Shimakawa, Y.; Morikawa, T.; Sakaguchi, S. Tetrahedron Lett.
2010, 51, 1786. (b) Enders, D.; Alexander, H. AdV. Synth. Catal. 2009,
351, 1749. (c) Enders, D.; Han, J. Tetrahedron: Asymmetry 2008, 19, 1367.
(d) Ma, Y.; Wei, S.; Wu, J.; Yang, F.; Liu, B.; Lan, J.; Yang, S.; You, J.
AdV. Synth. Catal. 2008, 350, 2645.
Commun. 2005, 195. (g) Cullen, S. C.; Rovis, T. Org. Lett. 2008, 10, 3141
.
(8) (a) Enders, D.; Han, J.; Henseler, A. Chem. Commun. 2008, 3989.
(b) Liu, Q.; Perreault, S.; Rovis, T. J. Am. Chem. Soc. 2008, 130, 14066.
(c) Enders, D.; Han, J. Synthesis 2008, 3864. (d) Enders, D. StereoselectiVe
Synthesis; Ottow, E., Scho¨llkopf, K., Schulz, B.-G., Eds.; Springer-Verlag:
Heidelberg, Germany, 1993; p 63. (e) Liu, Q.; Rovis, T. Org. Lett. 2009,
11, 2856.
(3) (a) Nair, V.; Babu, B. P.; Vellalath, S.; Varghese, V.; Raveendran,
A. E.; Suresh, E. Org. Lett. 2009, 11, 2507. (b) Yang, L.; Tan, B.; Wang,
F.; Zhong, G. J. Org. Chem. 2009, 74, 1744.
(4) For reviews, see: (a) Christmann, M. Angew. Chem., Int. Ed. 2005,
44, 2632. (b) Alaniz, J. R.; Rovis, T. Synlett 2009, 1189.
10.1021/ol101969t  2010 American Chemical Society
Published on Web 10/11/2010

el-aldol,16 benzoin-oxy-Cope,17 phosphane-catalyzed [3 + 2]
dipolar cycloaddition,18 and iminium-enamine metal-catalyzed
enyne cycloisomerization.19 The cyclopentanes prepared from
these methods were highly functionalized, but these compounds
still bore an unfunctionalized methylene moiety in the five-
membered ring systems. Therefore, an alternative annulation
method toward fully functionalized (fully substituted) cyclo-
pentane derivatives is certainly attractive.20 Taking into account
the above observations in the context of asymmetric synthesis,
especially for multicomponent reactions,21 we envisioned an
approach to fully substituted cyclopentenes that could be
accomplished by a sequential Stetter and Michael-aldol con-
densation reaction22 of aromatic aldehydes, nitroalkenes, and
R,ꢀ-unsaturated aldehydes via the unprecedented multicompo-
nent [1 + 2 + 2] annulation strategy (Scheme 1). Initially, a
ꢀ-nitroketone could be prepared from the intermolecular Stetter
reaction of an aldehyde with a nitroalkene followed by the
cascade organocatalytic Michael-aldol reactions of the ꢀ-ni-
troketone with an R,ꢀ-unsaturated aldehyde to provide the fully
functionalized cyclopentenes. In this paper, we explore the
feasibility of such an idea; this work culminates in the
asymmetric synthesis of fully substituted cyclopentenes with
an unusual kinetic resolution of 2-alkyl-3-nitroalkanone, a base-
Scheme 1. [1 + 2 + 2] Annulation Approach to Cyclopentenes
sensitive ꢀ-nitroketone.23 Our initial efforts focused on the
systematic evaluation of various catalysts and reaction condi-
tions to optimize the intermolecular Stetter reaction of 1 and 2
(Table 1). We began our preparation of ꢀ-nitroketones by
Table 1. Screening of Catalysts and Conditions for the Stetter
Reaction of 1 and 2a
(9) For sila-Stetter reaction, see: (a) Bharadwaj, A. R.; Scheidt, K. A.
Org. Lett. 2004, 6, 2465. (b) Nahm, M. R.; Potnick, J. R.; White, P. S.;
Johnson, J. S. J. Am. Chem. Soc. 2006, 128, 2751. (c) Nahm, M. R.; Linghu,
X.; Potnick, J. R.; Yates, C. M.; White, P. S.; Johnson, J. S. Angew. Chem.,
Int. Ed 2005, 44, 2377.
additive
cat. (20 mol %)
time
(h)
yield
(%)b
(10) DiRocco, D. A.; Oberg, K. M.; Dalton, D. M.; Rovis, T. J. Am.
Chem. Soc. 2009, 131, 10872.
entry
1
product
(11) Indirectly, for the addition of silyl-protected thiazolium carbinols
to nitroalkene, see: Mattson, A. E.; Zuhl, A. M.; Reynolds, T. E.; Scheidt,
K. A. J. Am. Chem. Soc. 2006, 128, 4932.
3a R1 ) p-BrC6H4;
R2 ) n-Pr
3a R1 ) p-BrC6H4;
R2 ) n-Pr
3a R1 ) p-BrC6H4;
R2 ) n-Pr
3a R1 ) p-BrC6H4;
R2 ) n-Pr
3a R1 ) p-BrC6H4;
R2 ) n-Pr
3a R1 ) p-BrC6H4;
R2 ) n-Pr
3b R1 ) p-BrC6H4;
R2 ) n-C6H13
3c R1 ) p-ClC6H4;
R2 ) n-C6H13
I
Cs2CO3
K2CO3
Et3N
0.25
8
55
16
12
24
16
0
(12) (a) Wang, J.; Li, H.; Xie, H.; Zu, L.; Shen, X.; Wang, W. Angew.
Chem., Int. Ed. 2007, 46, 9050. (b) Rueping, M.; Kuenkel, A.; Tato, F.;
Bats, J. W. Angew. Chem., Int. Ed. 2009, 48, 3699.
2
3
4
5
6
7
8
I
(13) Ibrahem, I.; Zhao, G. L.; Rios, R.; Vesely, J.; Sunden, H.; Dziedzic,
P.; Co´rdova, A. Chem.sEur. J. 2008, 14, 7867.
I
6
(14) (a) Zhao, G. L.; Ibrahem, I.; Dziedzic, P.; Sun, J.; Bonneau, C.;
Co´rdova, A. Chem.sEur. J. 2008, 14, 10007. (b) Zu, L.; Li, H.; Xie, H.;
Wang, J.; Tang, Y.; Wang, W. Angew. Chem., Int. Ed. 2007, 46, 3732. (c)
Tan, B.; Shi, Z.; Chua, P. J.; Zhong, G. Org. Lett. 2008, 10, 3425.
(15) Tan, B.; Chua, P. J.; Zeng, X.; Lu, M.; Zhong, G. Org. Lett. 2008,
10, 3489.
I
DIEPA
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
3
II
III
I
0.5
10
(16) (a) Nair, V.; Vellalath, S.; Poonoth, M.; Suresh, E. J. Am. Chem.
Soc. 2006, 128, 8736. (b) Nair, V.; Babu, B. P.; Vellalath, S.; Suresh, E.
Chem. Commun. 2008, 747.
0.33
52
(17) (a) Chiang, P. C.; Kaeobamrung, J.; Bode, J. W. J. Am. Chem.
Soc. 2007, 129, 3520. (b) Chiang, P. C.; Rommel, M.; Bode, J. W. J. Am.
Chem. Soc. 2009, 131, 8714.
I
0.5
48
(18) Hones, R. A.; Krische, M. J. Org. Lett. 2009, 11, 1849.
(19) (a) Zhao, G. L.; Ullah, F.; Deiana, L.; Lin, S.; Zhang, Q.; Sun, J.;
Ibrahem, I.; Dziedzic, P.; Co´rdova, A. Chem.sEur. J. 2010, 16, 1585. (b)
Jensen, K. L.; Franke, P. T.; Arro´niz, C.; Kobbelgaard, S.; Jørgensen, K. A.
Chem.sEur. J. 2010, 16, 1750.
a Unless otherwise noted, the reactions were performed in 0.13 M 1
with a ratio 1:1.2 of 1/2 at 25 °C. b Isolated yields of the adducts 3.
(20) For a recent review of fully substituted cyclopentanes, see: Heasley,
B. Eur. J. Org. Chem. 2009, 1477.
screening several thiazolium- and imidazolium-based precatal-
ysts, e.g., I-III. The initial reaction provided 3a in moderate
yield (55%) from 1a and 2a with the precatalyst I and Cs2CO3
(Table 1, entry 1). The same reaction with other base additives,
e.g., K2CO3, Et3N, and DIEPA, unfortunately gave lower yields
of 3a (Table 1, entries 2-4). The ꢀ-nitroketone compounds are
somewhat sensitive to basic conditions, and a large amount of
1-phenyl-2-methylenepentan-1-one (4) was obtained in these
reactions. The same reaction using the precatalyst II provided a
(21) For our previous efforts in exploring new organocatalytic annula-
tions, see: (a) Hong, B.-C.; Kotame, P.; Tsai, C.-W.; Liao, J.-H. Org. Lett.
2010, 12, 776. (b) Hong, B.-C.; Jan, R.-H.; Tsai, C.-W.; Nimje, R. Y.;
Liao, J.-H.; Lee, G.-H. Org. Lett. 2009, 11, 5246. (c) Hong, B.-C.; Nimje,
R. Y.; Liao, J.-H. Org. Biomol. Chem. 2009, 7, 3095. (d) Kotame, P.; Hong,
B.-C.; Liao, J.-H. Tetrahedron Lett. 2009, 50, 704. (e) Hong, B.-C.; Nimje,
R. Y.; Sadani, A. A.; Liao, J.-H. Org. Lett. 2008, 10, 2345. (f) Hong, B.-
C.; Nimje, R. Y.; Wu, M.-F.; Sadani, A. A. Eur. J. Org. Chem. 2008, 1449.
(22) For other selected examples of domino Micheal reactions in the
synthesis of cyclohexenes, see: (a) Enders, D.; Hu¨ttl, M. R. M.; Grondal,
C.; Raabe, G. Nature 2006, 441, 861. (b) Ishikawa, H.; Suzuki, T.; Hayashi,
Y. Angew. Chem., Int. Ed. 2009, 48, 1304. (c) Zhu, S.; Yu, S.; Wang, Y.;
Ma, D. Angew. Chem., Int. Ed. 2010, 49, 4656. (d) Tan, B.; Chua, P. J.; Li,
Y.; Zhong, G. Org. Lett. 2008, 10, 2437. (e) Tan, B.; Shi, Z.; Chua, P. J.;
Li, Y.; Zhong, G. Angew. Chem., Int. Ed. 2009, 48, 758.
(23) For recent synthesis of ꢀ-nitroketones, see: Enders, D.; Fo¨rster,
D.; Raabe, G.; Bats, J. W. J. Org. Chem. 2008, 73, 9641.
Org. Lett., Vol. 12, No. 21, 2010
4813

lower yield, and attempts with precatalyst III afforded no product
3 (Table 1, entries 5-6). Several ꢀ-nitroketones (3b, 3c) were
prepared via the I-Cs2CO3 conditions (Table 1, entries 7 and 8).
With the ꢀ-nitroketone 3a in hand, several catalysts and reaction
conditions were screened to explore the feasibility of the domino
Michael-aldol condensation (Table 2). At the outset of this study,
Table 3. Scope of the Domino Michael-Aldol Condensationa
c
time yieldb
%
ee
entry
1
product
(h)
(%)d
(%)d
Table 2. Screening of Catalysts and Optimization for the
6a R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 4-OMeC6H4
Domino Michael-Aldol Reactiona
170
168
162
157
165
168
163
173
148
172
169
54 (36) >99e
60 (24) 97f
62 (31) 96f
56 (24) >99f
63 (21) 98f
72 (30) 99f (77)g
55 (25) 99f
65 (22) 97f
48 (19) >99f
68 (25) 96f
58 (23) 92e
2
6b R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 3,4-(OMe)2C6H4
3
6c R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 3,4,5-(OMe)3C6H4
4
6d R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) pyridin-3-yl
5
6e R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 3-OMe-4-OAcC6H4
6f R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 3-OMe-4-OEt-C6H4
6g R1 ) p-BrC6H4; R2 ) n-hexyl;
R3 ) 4-OMeC6H4
6
7
8
6h R1 ) p-BrC6H4; R2 ) n-hexyl;
R3 ) 3-OMe-4-OEt-C6H4
6i R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 3-NO2-C6H4
6j R1 ) p-ClC6H4; R2 ) n- hexyl;
R3 ) 3-OMe-4-OEt-C6H4
6k R1 ) p-BrC6H4; R2 ) n-Pr;
R3 ) 4-NMe2-C6H4
entry cat. (mol %) additiveb solvent time (h) yieldc (%)
9
1
2
3
4
5
6
7
8
IV (30)
V (30)
V (30)
V (30)
V (30)
V (30)
V (30)
V (30)
V (30)
V (30)
V (30)
VI (30)
VII (30)
VIII (30)
IX (30)
CH3CN
CH3CO2H EtOH
CH3CO2H DMF
CH3CO2H CH2Cl2
CH3CO2H CH3CN
CH3CO2H CHCl3
CH3CO2H Et2O
CH3CO2H toluene
160
160
164
165
171
96
∼0
10
11
∼0
∼0
trace
trace
18
a Unless otherwise noted, the reactions were performed in 0.25 M of 5
with a ratio 2.4:1 of 3/5 at 25 °C. b Isolated yields of the adducts 6. c Isolated
yields by Method B: catalyst V was added in seven portions (a total
accumulated quantity of 30 mol %) in 24 h intervals. d Isolated yields by
Method A in parentheses (30 mol % V was added at once in the beginning).
e Determined by HPLC with a chiral column (Chiracel OD-H). f Determined
by HPLC with a chiral column (Chiralpak IA). g Values in parentheses
indicate the enantiomeric excess of the recovered 3a after 168 h reaction,
analyzed by Chiracel OD-H.
98
19
36
26
27
144
105
153
90
100
100
120
120
9
PhCO2H
PNBA
DABCO
toluene
toluene
toluene
10
11
12
13
14
15
∼0
CH3CO2H toluene
CH3CO2H toluene
CF3CO2H toluene
trace
∼0
trace
∼0
-
toluene
applied in the reactions. The high enantiomeric excess of 6 obtained
under these conditions provided evidence for the kinetic asymmetric
transformation in the domino Michael-aldol condensation of
racemic 3 with 5.24 This transformation contributes to the few
examples of organocatalytic aldol condensation of aromatic ketones
with aldehydes.25 On the other hand, the observation of an
intermediate 726 in these reactions implied that the moderate
isolated yields (19-36%) probably arose because formation of the
stable 7 by consumption of the catalyst V resulted in early termi-
nation of the catalytic cycle during the domino reaction process.27
Unfortunately, the parasitical dead-end product 7 of the cascade
reaction was quite stable with respect to a variety of acid and moi-
sture conditions, and several attempts to modify the reaction condi-
tions to regenerate the active catalyst V from 7 in the reaction
sequence were in vain. To sustain sufficient quantities of catalyst
during the reaction progress, catalyst V was added in seven portions
(a total accumulated quantity of 30 mol %, the same amount of
catalyst used previously) in 24 h intervals (Method B). The reaction
series was repeated using the new method, and the resulting yields
a Unless otherwise noted, the reactions were performed in 0.25 M 5a
with a ratio 2.4:1 of 3a/5a at 25 °C. b Additive/catalyst ) 1:1. c Isolated
yields of the adducts 6a.
reaction of 3a and 5a with L-Pro (IV) in CH3CN gave the
disappointing outcome of no expected product 6a (Table 2, entry
1). The same reaction with the Jørgensen-Hayashi catalyst (V)
and acetic acid in EtOH, DMF, CH2Cl2, and CH3CN also provided
no or only trace amounts of 6a (Table 2, entries 2-5). Satisfyingly,
the same reaction conditions in CHCl3, Et2O, or toluene provided
6a, although in moderate yields (Table 2, entries 6-8). Replace-
ment of acetic acid with benzoic acid or p-nitrobenzoic acid did
not improve the yields (Table 2, entries 9 and 10). When DABCO
was substituted for the acid, no product 6a was observed (Table
2, entry 11). Moreover, the reactions with other catalysts, e.g.,
VI-IX, were fruitless (Table 2, entries 12-14).
Having established the optimal reaction conditions for 6a,
although moderate yields only were obtained, we investigated the
use of the ꢀ-nitroketone 3 and R,ꢀ-unsaturated aldehydes 5 for
synthesizing a variety of fully substituted cyclopentene derivatives
6. The all-trans isomers (6a-k) were, in all cases, the only
observable diastereoisomers with high enantioselectivities (92%
to >99% ee, entries 1-11, Table 3). Because ꢀ-nitroketones 3 was
somewhat unstable and a certain amount of material tended to be
diverted to the production of 4, a ratio 2.4:1 of racemic 3 to 5 was
(24) An enantiomeric excess of 77% for the recovered 3a was observed
after 168 h of reaction.
(25) For other examples, see: (a) Brandau, S.; Maerten, E.; Jørgensen,
K. A. J. Am. Chem. Soc. 2006, 128, 14986. (b) Hara, N.; Nakamura, S.;
Shibata, N.; Toru, T. Chem.sEur. J. 2009, 15, 6790. (c) Chen, W.-B.; Cun,
L.-F.; Zhang, X.-M.; Yuan, W.-C.; Du, X.-L. Tetrahedron 2010, 66, 1441.
(d) Chen, Y.; Zhong, C.; Sun, X.; Akhmedov, N. G.; Petersen, J. L.; Shi,
X. Chem. Commun. 2009, 34, 5150.
4814
Org. Lett., Vol. 12, No. 21, 2010

Scheme 2. Plausible Reaction Mechanism
doubled or even tripled in all cases with good yields and with the
same high enantioselectivities (Table 3, entries 1-11, 48-72%
yields).
The structure and relative stereochemistry of the reaction adduct
was revealed by single-crystal X-ray analysis of the racemic (()-
6a, prepared by pyrrolidine-HOAc catalysis (Figure 1). In
of the R,ꢀ-unsaturated aldehyde by catalyst V followed by the nitro-
Michael addition of the nitroalkane nucleophile from the re face
under the control of the catalyst to give an intermediate with a 4-S
configuration. It is interesting to note that the stereochemistry of
the 3,4-syn alkanal adduct was consistent with the relative topicity
previously observed for other organocatalytic nitro-Michael addi-
tions.28 Nevertheless, the formation of the (2R,3S,4S)-alkanal with
2,3-anti stereoselectivity in these reactions is unprecedented. The
resulting intermediate subsequently underwent intramolecular aldol
condensation of the aldehyde and ketone to give the cyclopent-1-
enecarbaldehyde 6.29
In conclusion, we have discovered an unprecedented sequential
organocatalytic Stetter and Michael-aldol condensation reaction
with evidence of a kinetic asymmetric transformation. Remarkably,
this methodology constitutes the first organocatalytic formal [1 +
2 + 2] annulation and provides a simple and direct protocol for
the stereoselective construction of fully functionalized cyclopentene
derivatives in a multicomponent operation. The presence of three
contiguous chiral centers with high enantioselectivity is especially
noteworthy. An increase in the yields of the organocatalytic
Michael-aldol condensation was achieved by the portionwise
addition of the organocatalysts. This methodology is the first of
its kind reported for organocatalysis reactions and may constitute
a useful technique for overcoming those organocatalytic reactions
that are limited by early terminated catalytic cycles. Further
exploration of its synthetic applications is underway.
Figure 1. Stereoplots of the X-ray crystal structures of (()-6a and
(+)-6c: C, gray; N, blue; O, red; Br, purple.
addition, the absolute configuration of the product was assigned
unambiguously on the basis of an X-ray analysis of (+)-6c (Figure
1). Thus, the origin of the stereoselectivity in this nitro-Michael
reaction by catalyst V was similar to that observed in other
examples of organocatalysis.28 To explain the stereochemistry of
this transformation, a plausible mechanism was proposed, as shown
in Scheme 2. The reaction was initiated from the iminium activation
(26) For example, the possible structure of 7c (E/Z mixtures) is
Acknowledgment. We acknowledge financial support for
this study from the National Science Council, ROC. Thanks
to the National Center for High-Performance Computing
(NCHC) for their assistance in literature searching.
(27) For the study of reactive intermediates in organocatalysis with
diarylprolinol ethers, see: (a) Groselj, U.; Seebach, D.; Badine, D. M.;
Schweizer, W. B.; Beck, A. K.; Krossing, I.; Klose, P.; Hayashi, Y.;
Uchimaru, T. HelV. Chim. Acta 2009, 92, 1225. (b) Seebach, D.; Groselj,
U.; Badine, D. M.; Schweizer, W. B.; Beck, A. K. HelV. Chim. Acta 2008,
91, 1999. (c) Lakhdar, S.; Tokuyasu, T.; Mayr, H. Angew. Chem., Int. Ed.
2008, 47, 8723.
Supporting Information Available: Experimental pro-
cedures, characterization data, and X-ray crystallographic
data. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL101969T
(28) (a) Han, B.; Xiao, Y.-C.; He, Z.-Q.; Chen, Y.-C. Org. Lett. 2009,
11, 4660. (b) Zu, L.; Xie, H.; Li, H.; Wang, J.; Wang, W. AdV. Synth.
Catal. 2007, 349, 2660. (c) Enders, D.; Wang, C.; Bats, J. W. Synlett 2009,
1777. (d) Gotoh, H.; Okamura, D.; Ishikawa, H.; Hayashi, Y. Org. Lett.
2009, 11, 4056.
(29) The possibility remained that the less stable cis adduct 6, if formed
from the 2,3-syn adduct, could epimerize to the more stable trans-adduct 6
during the reaction condition.
Org. Lett., Vol. 12, No. 21, 2010
4815