Highly enantioselective organocatalytic α-sulfenylation of azlactones

Article abstract of DOI:10.1021/ol403303k

The first asymmetric α-sulfenylation of azlactones with N-(sulfanyl)succinimides has been developed by using cinchona alkaloid-derived squaramide as a catalyst and 4 A molecular sieves as an additive. The reaction conditions were suitable to 4-alkyl and benzyl-substituted azlactones as well as N-(benzyl/alkyl/arylthio)succinimides, affording adducts with high enantioselectivities (81-94% ee).

Full text of DOI:10.1021/ol403303k

Letter
pubs.acs.org/OrgLett
Highly Enantioselective Organocatalytic α‑Sulfenylation of
Azlactones
Baokun Qiao,†,§ Xinfei Liu,‡,§ Shaobo Duan,‡ Lin Yan,† and Zhiyong Jiang*,†,‡
‡
†Institute of Chemical Biology and Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan
University, Kaifeng, Henan, China, 475004
S
* Supporting Information
ABSTRACT: The first asymmetric α-sulfenylation of azlactones
with N-(sulfanyl)succinimides has been developed by using
cinchona alkaloid-derived squaramide as a catalyst and 4 Å
molecular sieves as an additive. The reaction conditions were
suitable to 4-alkyl and benzyl-substituted azlactones as well as N-
(benzyl/alkyl/arylthio)succinimides, affording adducts with high
enantioselectivities (81−94% ee).
ue to their extensive applications in numerous areas,
Dchiral sulfur-containing compounds have attracted
increasing interest from chemists.1 Various protocols on their
asymmetric synthesis have been well established in recent
decades.2,3 In particular, asymmetric α-sulfenylation has been
demonstrated as a direct method to introduce a sulfur-
substituted heteroquaternary stereogenic center to the α-
position of carbonyl compounds, which are main frameworks in
many bioactive compounds.3 To date, several asymmetric α-
sulfenylations have been established; the reported nucleophiles
included cyclic β-keto esters, lactams and phosphonates, 1,3-
dicarbonyl compounds, aldehydes, diketopiperazines, and 3-
substituted oxindoles.3 Nevertheless, the extension of α-
Figure 1. Selected natural and non-natural products.
sulfenylation to unprecedented nucleophiles to afford more
types of valuable synthetic building blocks is still highly
desirable.
In recent years, azlactones have been recognized as the most
were chosen as model substrates (Table 1). Cinchona alkaloid-
derived thiourea I (from quinine, Figure 2) was attempted as
the catalyst for its well-established versatility in many
reactions.8 It was found that, in the presence of 10 mol %
catalyst I in THF at 30 °C, the desired adduct 3aa could be
obtained in 53% yield with 20% ee after 14 h (entry 1). The
results indicated that the framework of the cinchona alkaloid
should benefit the enantioselectivity; modification of the acid
moiety of the catalyst becomes feasible. Therefore, a series of
cinchona alkaloid-derived squaramides9 were prepared and
examined (II−V, Figure 2). We delighted that the enantiose-
lectivity increased remarkably (entries 2−5), and an 88% ee for
3aa was obtained when catalyst II was utilized (entry 2).
Further optimization of the reaction conditions was carried out
by examining different solvents in the presence of 10 mol % II
(entries 6−9); the ideal solvent was still determined to be THF
from regarding the yield and enantioselectivity (entry 2). 4 Å
Molecular sieves as an additive were subsequently investigated
to improve the reactivity and enantioselectivity (entries 10−
common nucleophilic reagents to introduce a heteroquaternary
carbon stereocenter on the α-position of α-amino acid
derivatives.4 A variety of catalytic asymmetric transformations
of azlactones have been established, such as Steglich rearrange-
ment, Michael reaction, oxyamination, allylation, benzylation,
thiolysis, Mannich reaction, and cycloaddition.4 To the best of
our knowledge, asymmetric α-sulfenylation of azlactones has
not been reported yet. In our recent research programs, we are
focusing on organocatalytic asymmetric reactions to assemble
chiral quaternary and heteroquaternary centers.3l,5 Especially,
the enantioselective α-sulfenylation of oxindoles has been
successfully addressed with excellent enantioselectivity.3l As an
extension of these works, we herein report an unprecedented
asymmetric α-sulfenylation of azlactones to furnish the first
highly enantioselective synthesis of α-sulfur-substituted α-
amino acid derivatives,6 which are important frameworks in
many natural and non-natural products with crucial biological
and medicinal properties (Figure 1).7
In our initial investigation on reaction conditions for α-
sulfenylation, azlactone 1a and N-(benzylthio)succinimide 2a
Received: November 15, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ol403303k | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
b
c
entry
1
catalyst
solvent
t (h)
3
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
I
THF
THF
THF
THF
THF
toluene
CH2Cl2
EtOAc
Et2O
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
14
14
14
14
14
14
14
14
14
14
14
14
14
16
14
16
12
16
16
20
20
20
11
14
20
20
12
14
14
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3ba
3ca
3da
3ea
3fa
53
67
59
63
48
trace
trace
40
43
65
73
78
86
71
64
68
82
61
67
85
97
32
70
75
78
70
91
80
64
20
II
III
IV
V
88
−87
−86
83
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
II
N.D.
N.D.
86
85
d
10
88
e
11
88
f
12
89
g
13
89
g
14
88
g
15
89
g
16
89
g
17
89
g
18
90
g
19
1g
1h
1i
3ga
3ha
3ia
91
g
20
92
g
Figure 2. Structures of catalysts I−V and azlactones 1a−s.
21
90
g
22
1j
3ja
91
g
23
1k
1l
3ka
3la
89
standpoint of economizing the catalyst (entry 28). A slightly
compromising ee was detected when 2.5 mol % of II were
utilized (entry 29).
g
24
90
gh
,
25
26
27
28
29
1h
1h
1h
1h
1h
3ha
3ha
3ha
3ha
3ha
91
gi
,
91
With the optimal conditions established, the scope of the
reaction was investigated with a variety of azlactones 1 and N-
(sulfanyl)succinimides 2 in the presence of 5 mol % II as the
catalyst and using 4 Å molecular sieves as the additive (Table
2). The reactions of azlactone 1f and N-(benzylthio)succin-
imides (2a−j) afforded the adducts 3ha−hj in 72−86% yield
with 86−93% ee within 14−45 h (entries 1−10). The results
revealed that the introduction of substituent groups on the
ortho-position of the aromatic ring of N-(benzylthio)succini-
mides should decrease the reactivity and enantioselectivity
slightly; 10 mol % of II were necessary and 86−88% ee for the
adducts (3hh−hj) were obtained (entries 8−10). Furthermore,
we found that the reaction conditions were also applicable to
N-(alkylthio)succinimides (2k−o, entries 11−15), giving
adducts in 75−94% yield with 90−93% ee as well as similarly
good reactivity except for 2o due to the steric effect (entry 15).
The use of N-(2-naphthylthio)succinimide 2p resulted in an
excellent yield and good enantioselectivity (entry 16). Other
azlatones (1m−q), containing different alkyl groups on the 4-
position, also provided the corresponding adducts 3ma−qa
with good to excellent enantioselectivities (entries 17−21); the
best enantioselectivity was obtained when 1q with the bulkiest
tert-butyl group was used, but the reaction was sluggish (entry
21). When the benzyl group was embedded on the 4-position
of azlatone (1r) under the established conditions, the adduct
3ra could be obtained in good yield and enantioselectivity
(entry 22). Furthermore, under the established conditions, the
α-sufenylation of 4-phenyl-substituted azlatone 1s and N-
(benzylthio)succinimide 2a could be finished within 18 h but in
moderate yield and ee, which remains a challenging task (entry
23).
gj
,
92
gk
,
92
gl
,
90
a
Reactions were performed with 0.05 mmol of 1a, 0.055 mmol of 2a,
b
and 0.005 mmol of catalyst in 1.0 mL of solvent. Yield of isolated
product. Determined by HPLC on a chiral stationary phase. 5 mg of
4 Å molecular sieves were used. 25 mg of 4 Å molecular sieves were
used. 50 mg of 4 Å molecular sieves were used. 100 mg of 4 Å
molecular sieves were used. T = 20 °C. T = 10 °C. 20 mol % of II
were used. 5 mol % of II were used. 2.5 mol % of II were used.
c
d
e
f
g
h
i
j
k
l
13).10 It was found that the molecular sieves could accelerate
the reaction rate without compromising the ee value. When 100
mg of molecular sieves were used, the adduct 3aa was obtained
in 86% yield with 89% ee (entry 13).
We next examined the influence of the aryl group of
azlactones (1b−l) on the 2-position in affecting stereo-
selectivity (entries 14−24). We found that azlactones 1b−c
with substituent groups at the para position of the phenyl ring
gave similar enantioselectivities (entries 14−15). When
substituent groups were introduced at the meta position of
the phenyl ring (1d−e), ee values were maintained (entries
16−17). A series of azlactones with different substituent groups
at the ortho position of the phenyl ring (1f−j) were then
prepared and investigated (entries 18−22). It was observed that
the enantioselectivity was improved slightly and adduct 3ha
with an o-chlorophenyl group was obtained with the best results
(85% yield, 92% ee, entry 20). A lower temperature could not
promote the enantioselectivity and made the reaction sluggish
(entries 25−26). The influence of number of equivalents of
catalyst II was also evaluated (entries 27−29). When 20 mol %
of II were used, the reaction was finished in 91% yield with 92%
ee within 12 h (entry 27). 5 mol % of II gave the same
enantioselectivity and a slightly decreased reaction rate, which
could be addressed with more suitable conditions from the
To demonstrate the utility of this methodology, the synthetic
transformations of α-sulfenylation adducts were subsequently
processed (Scheme 1). When the hydrolysis of 3ha was
conducted in the presence of 5.0 equiv of hydrochloric acid
B
dx.doi.org/10.1021/ol403303k | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
representing the first example of their synthesis with excellent
enantioselectivity. Further investigations into organocatalytic
asymmetric α-sulfenylation with other novel nucleophiles to
access various compounds with significant biological activity are
still in progress.
Table 2. Sulfenylation of Azlactones 1 to N-
(Sulfanyl)succinimide 2 Catalyzed by II
a
b
c
entry
1
R2 (2)
Bn (2a)
t (h)
3
yield (%)
ee (%)
1
2
3
4
5
6
7
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1h
1m
1n
1o
1p
1q
1r
14
15
20
22
25
18
20
35
18
45
13
25
50
20
65
14
8
3ha
3hb
3hc
3hd
3he
3hf
84
79
74
78
79
78
86
83
72
78
83
91
94
89
75
96
93
90
84
80
43
82
68
92
90
90
91
93
93
91
86
88
87
90
90
92
93
92
82
87
90
85
87
94
81
40
4-FPhCH2 (2b)
4-ClPhCH2 (2c)
4-BrPhCH2 (2d)
4-MePhCH2 (2e)
4-tBuPhCH2 (2f)
3-MePhCH2 (2g)
2-ClPhCH2 (2h)
2-BrPhCH2 (2i)
2-MePhCH2 (2j)
Et (2k)
ASSOCIATED CONTENT
* Supporting Information
■
S
General information, typical experimental procedures, charac-
terization, HPLC and NMR spectra of the compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
3hg
3hh
3hi
d
8
d
9
d
10
3hj
AUTHOR INFORMATION
Corresponding Author
11
12
13
14
15
16
17
18
19
20
21
22
23
3hk
3hl
■
nPr (2l)
1-dodecane (2m)
nBu (2n)
3hm
3hn
3ho
3hp
3ma
3na
3oa
3pa
3qa
3ra
*E-mail: chmjzy@henu.edu.cn.
Author Contributions
§B.Q. and X.L. contributed equally.
Notes
iPr (2o)
2-naphthyl (2p)
Bn (2a)
Bn (2a)
8
The authors declare no competing financial interest.
Bn (2a)
6
Bn (2a)
8
ACKNOWLEDGMENTS
■
Bn (2a)
78
12
18
This work was supported by the NSFC (Nos. 21072044,
21202034), NCET-11-0938, and Excellent Youth Foundation
of Henan Scientific Committee (114100510003).
Bn (2a)
1s
Bn (2a)
3sa
a
All reactions were performed with 0.10 mmol of 1, 0.11 mmol of 2,
200 mg of 4 Å molecular sieves, and 0.005 mmol of II in 2.0 mL of
b
c
REFERENCES
THF. Yield of isolated product. Determined by HPLC on a chiral
■
d
stationary phase. 10 mol % of II were used.
(1) (a) Shi, Y.-L.; Shi, M. Org. Biomol. Chem. 2007, 5, 1499.
(b) Mellah, M.; Voituriez, A.; Schulz, E. Chem. Rev. 2007, 107, 5133.
(c) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.;
Aggarwal, V. K. Chem. Rev. 2007, 107, 5841. (d) Organosulfur
Chemistry in Asymmetric Synthesis; Toru, T., Bolm, C., Eds.; Wiley-
VCH: Weinheim, Germany, 2008. (e) Chiral Sulfur Ligands:
Asymmetric Catalysis; Pellissier, H., Ed.; Cambridge, U.K., 2009.
(f) Clayden, J.; MacLellan, P. Beilstein J. Org. Chem. 2011, 7, 582.
(2) For a selected review on an asymmetric sulfa-Michael reaction,
Scheme 1. Synthetic Transformation of Adduct 3ha
see: (a) Enders, D.; Luttgen, K.; Narine, A. A. Synthesis 2007, 959. For
̈
selected examples of asymmetric sulfa-Michael reactions, see:
(b) Ricci, P.; Carlone, A.; Bartoli, G.; Bosco, M.; Sambri, L.;
Melchiorre, P. Adv. Synth. Catal. 2008, 350, 49. (c) Leow, D.; Lin, S.;
Chittimalla, S. K.; Fu, X.; Tan, C.-H. Angew. Chem., Int. Ed. 2008, 47,
5641. (d) Liu, Y.; Sun, B.; Wang, B.; Wakem, M.; Deng, L. J. Am.
Chem. Soc. 2009, 131, 418. (e) Kimmel, K. L.; Robak, M. T.; Ellman, J.
A. J. Am. Chem. Soc. 2009, 131, 8754. (f) Lin, S.; Leow, D.; Huang, K.-
W.; Tan, C.-H. Chem.Asian J. 2009, 4, 1741. (g) Lu, H.-H.; Zhang,
F.-G.; Meng, X.-G.; Duan, S.-W.; Xiao, W.-J. Org. Lett. 2009, 11, 3946.
(h) Dai, L.; Wang, S.-X.; Chen, F.-E. Adv. Synth. Catal. 2010, 352,
2137. (i) Rana, N. K.; Selvakumar, S.; Singh, V. K. J. Org. Chem. 2010,
75, 2089. (j) Zhao, F.; Zhang, W.; Yang, Y.; Pan, Y.; Chen, W.; Liu, H.;
Yan, L.; Tan, C.-H.; Jiang, Z. Adv. Synth. Catal. 2011, 353, 2624.
(k) Dai, L.; Yang, H.; Chen, F. Eur. J. Org. Chem. 2011, 5071. (l) Tian,
X.; Cassani, C.; Liu, Y.; Moran, A.; Urakawa, A.; Galzerano, P.; Arceo,
E.; Melchiorre, P. J. Am. Chem. Soc. 2011, 133, 17934. (m) Rana, N.
K.; Singh, V. K. Org. Lett. 2011, 13, 6520. (n) Duan, S.-W.; Li, Y.; Liu,
Y.-L.; Zou, Y.-Q.; Shi, D.-Q.; Xiao, W.-J. Chem. Commun. 2012, 48,
5160. (o) Yang, W.; Du, D.-M. Org. Biomol. Chem. 2012, 10, 6876.
(3) For selected examples of asymmetric α-sulfenylation, see:
(a) Marigo, M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A.
(conc.) in acetonitrile as solvent at room temperature after 0.5
h, an α-sulfur-substituted α-amino acid 4 was obtained in 95%
yield with 92% ee. Alternatively, an α-sulfur-substituted α-
amino methyl ester 5 could be achieved when 3ha is treated
with 1.5 equiv of TMSCl using methanol as the solvent at room
temperature. The results indicated the reaction finished
smoothly after 10 h, affording 5 in 72% yield without
compromising the ee value.
In conclusion, we have developed the first example of an
asymmetric α-sulfenylation of azlactones. Cinchona alkaloid-
derived squaramide was demonstrated as an efficient catalyst to
promote the reaction using 4 Å molecular sieves as the additive,
affording adducts with excellent enantioselectivities (81−94%
ee). The reaction conditions were most suitable to 4-alkyl and
benzyl-substituted azlactones as well as N-(benzyl/alkyl/
arylthio)succinimides. From the obtained adducts, the
important α-sulfur-substituted α-amino acid derivatives, con-
taining a chiral α-heteroquaternary center, could be readily
prepared with satisfactory results after a simple process,
́
Angew. Chem., Int. Ed. 2005, 44, 794. (b) Franzen, J.; Marigo, M.;
Fielenbach, D.; Wabnitz, T. C.; Kjærsgaard, A.; Jørgensen, K. A. J. Am.
Chem. Soc. 2005, 127, 18296. (c) Sobhani, S.; Fielenbach, D.; Marigo,
M.; Wabnitz, T. C.; Jørgensen, K. A. Chem.Eur. J. 2005, 11, 5689.
(d) Jereb, M.; Togni, A. Org. Lett. 2005, 7, 4041. (e) Jereb, M.; Togni,
A. Chem.Eur. J. 2007, 13, 9384. (f) Polaske, N. W.; Dubey, R.;
C
dx.doi.org/10.1021/ol403303k | Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Nichol, G. S.; Olenyuk, B. Tetrahedron: Asymmetry 2009, 20, 2742.
(g) Fang, L.; Lin, A.; Hu, H.; Zhu, C. Chem.Eur. J. 2009, 15, 7039.
(h) Lin, A.; Fang, L.; Zhu, X.; Zhu, C.; Cheng, Y. Adv. Synth. Catal.
2011, 353, 545. (i) Cai, Y.; Li, J.; Chen, W.; Xie, M.; Liu, X.; Lin, L.;
Feng, X. Org. Lett. 2012, 14, 2726. (j) Wang, C.; Yang, X.; Loh, C. C.
J.; Raabe, G.; Enders, D. Chem.Eur. J. 2012, 18, 11531. (k) Li, X.;
Liu, C.; Xue, X.-S.; Cheng, J.-P. Org. Lett. 2012, 14, 4374. (l) Han, Z.;
Chen, W.; Dong, S.; Yang, C.; Liu, H.; Pan, Y.; Yan, L.; Jiang, Z. Org.
Lett. 2012, 14, 4670. For the first example of an organocatalytic α-
sulfenylation, see: (m) Wang, W.; Li, H.; Wang, J.; Liao, L.-X.
Tetrahedron Lett. 2004, 45, 8229.
(10) For selected recent examples, see: (a) Li, X.-J.; Zhang, G.-W.;
Wang, L.; Hua, M.-Q.; Ma, J.-A. Synlett 2008, 1255. (b) Kim, H. Y.;
Kim, S.; Oh, K. Angew. Chem., Int. Ed. 2010, 49, 4476. (c) Yang, H.;
Carter, R. G. Org. Lett. 2010, 12, 3108. (d) Zhang, G.; Ma, Y.; Wang,
S.; Zhang, Y.; Wang, R. J. Am. Chem. Soc. 2012, 134, 12334. (e) Chang,
M.; Liu, S.; Huang, K.; Zhang, X. Org. Lett. 2013, 15, 4354.
(4) For a selected review, see: (a) Alba, A.-N. R.; Rios, R. Chem.
Asian J. 2011, 6, 720. For selected recent examples, see: (b) Uraguchi,
D.; Yoshioka, K.; Ueki, Y.; Ooi, T. J. Am. Chem. Soc. 2012, 134, 19370.
(c) Weber, M.; Jautze, S.; Frey, W.; Peters, R. Chem.Eur. J. 2012, 18,
14792. (d) Weber, M.; Frey, W.; Peters, R. Adv. Synth. Catal. 2012,
354, 1443. (f) Weber, M.; Peters, R. J. Org. Chem. 2012, 77, 10846.
(g) Dong, S.; Liu, X.; Zhu, Y.; He, P.; Lin, L.; Feng, X. J. Am. Chem.
Soc. 2013, 135, 10026. (h) Chen, W.; Hartwig, J. F. J. Am. Chem. Soc.
2013, 135, 2068. (i) Trost, B. M.; Czabaniuk, L. C. J. Am. Chem. Soc.
2012, 134, 5778. (j) Rodríguez-Docampo, Z.; Quigley, C.; Tallon, S.;
Connon, S. J. J. Org. Chem. 2012, 77, 2407. (k) Terada, M.; Moriya,
K.; Kanomata, K.; Sorimachi, K. Angew. Chem., Int. Ed. 2011, 50,
12586. (l) Zhang, W.-Q.; Cheng, L.-F.; Yu, J.; Gong, L.-Z. Angew.
Chem., Int. Ed. 2012, 51, 4085. (m) Shi, S.-H.; Huang, F.-P.; Zhu, P.;
Dong, Z.-W.; Hui, X.-P. Org. Lett. 2012, 14, 2010. (n) Melhado, A. D.;
Amarante, G. W.; Wang, Z. J.; Luparia, M.; Toste, F. D. J. Am. Chem.
Soc. 2011, 133, 3517. (o) Terada, M.; Nii, H. Chem.Eur. J. 2011, 17,
1760. (p) Trost, B. M.; Morris, P. J. Angew. Chem., Int. Ed. 2011, 50,
6167. (q) Sun, W.; Zhu, G.; Wu, C.; Li, G.; Hong, L.; Wang, R. Angew.
Chem., Int. Ed. 2013, 52, 8633.
(5) (a) Li, L.; Chen, W.; Yang, W.; Pan, Y.; Liu, H.; Tan, C.-H.; Jiang,
Z. Chem. Commun. 2012, 48, 5124. (b) Yang, Y.; Moinodeen, F.; Chin,
W.; Ma, T.; Jiang, Z.; Tan, C.-H. Org. Lett. 2012, 14, 4762. (c) Zhang,
W.; Tan, D.; Lee, R.; Tong, G.; Chen, W.; Qi, B.; Huang, K.-W.; Tan,
C.-H.; Jiang, Z. Angew. Chem., Int. Ed. 2012, 51, 10069. (d) Zhu, B.;
Zhang, W.; Lee, R.; Han, Z.; Yang, W.; Tan, D.; Huang, K.-W.; Jiang,
Z. Angew. Chem., Int. Ed. 2013, 52, 6666. (e) Han, Z.; Yang, W.; Tan,
C.-H.; Jiang, Z. Adv. Synth. Catal. 2013, 355, 1505. (f) Yan, L.; Han,
Z.; Zhu, B.; Yang, C.; Tan, C.-H.; Jiang, Z. Beilstein J. Org. Chem. 2013,
9, 1853. (g) Qiao, B.; An, Y.; Liu, Q.; Yang, W.; Liu, H.; Shen, J.; Yan,
L.; Jiang, Z. Org. Lett. 2013, 15, 2358. (h) Chen, W.; Yang, W.; Yan, L.;
Tan, C.-H.; Jiang, Z. Chem. Commun. 2013, 49, 9854. (i) Yang, C.;
Chen, W.; Yang, W.; Zhu, B.; Yan, L.; Tan, C.-H.; Jiang, Z. Chem.
Asian J. 2013, 8, 2960.
(6) As the only example of the synthesis of α-sulfur-substituted α-
amino acid derivatives with moderate ee values, see ref 3f.
(7) For selected examples, see: (a) Nyitrai, J.; Fetter, J.; Hornyak, G.;
́
Lempert, K. Tetrahedron 1978, 34, 1031. (b) Trapani, G.; Franco, M.;
Latrofa, A.; Genchi, G.; Brigiani, G. S.; Mazzoccoli, M.; Persichella, M.;
Serra, M.; Biggio, G.; Liso, G. Eur. J. Med. Chem. 1994, 29, 197.
(c) Isaka, M.; Palasarn, S.; Rachtawee, P.; Vimuttipong, S.;
Kongsaeree, P. Org. Lett. 2005, 7, 2257. (d) Nagasawa, H. T.; Goon,
D. J. W.; Crankshaw, D. L.; Vince, R.; Patterson, S. E. J. Med. Chem.
2007, 50, 6462. (e) Forseth, R. R.; Fox, E. M.; Chung, D.; Howlett, B.
J.; Keller, N. P.; Schroeder, F. C. J. Am. Chem. Soc. 2011, 133, 9678.
(f) Song, Y.; Dou, H.; Gong, W.; Liu, X.; Yu, Z.; Li, E.; Tan, R.; Hou,
Y. Eur. J. Pharmacol. 2013, 705, 49. (g) Zhao, W. Y.; Zhu, T. J.; Han,
X. X.; Fan, G. T.; Liu, H. B.; Zhu, W. M.; Gu, Q. Q. Nat. Prod. Res.
2013, 23, 203.
(8) For reviews, see: (a) Schreiner, P. R. Chem. Soc. Rev. 2003, 32,
289. (b) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348,
999. (c) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45,
1520. (d) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713.
(e) Connon, S. J. Chem. Commun. 2008, 2499. (f) Yu, X.; Wang, W.
Chem.Asian J. 2008, 3, 516.
(9) For selected reviews, see: (a) Storer, R. I.; Aciro, C.; Jones, L. H.
Chem. Soc. Rev. 2011, 40, 2330. (b) Aleman
Jørgensen, K. A. Chem.Eur. J. 2011, 17, 6890.
́
, J.; Parra, A.; Jiang, H.;
D
dx.doi.org/10.1021/ol403303k | Org. Lett. XXXX, XXX, XXX−XXX