The marriage of organocatalysis with metal catalysis: Access to multisubstituted chiral 2,5-dihydropyrroles by cascade iminium/enamine-metal cooperative catalysis

Article abstract of DOI:10.1002/chem.201103083

Organocatalyst and metal cooperate: The integration of iminium catalysis and enamine-metal cooperative catalysis into a single process facilitates the rapid and controlled production of valuable chiral pyrrolines in excellent diastereo- and enantioselectivities (see scheme). Copyright

Full text of DOI:10.1002/chem.201103083

DOI: 10.1002/chem.201103083
The Marriage of Organocatalysis with Metal Catalysis: Access to
Multisubstituted Chiral 2,5-Dihydropyrroles by Cascade Iminium/Enamine–
Metal Cooperative Catalysis
Wangsheng Sun, Gongming Zhu, Liang Hong,* and Rui Wang*[a]
The development of efficient catalytic systems for valua-
ble organic transformations has always been one of the pur-
suits of organic chemists.[1] In the past, transition-metal cat-
alysis has dominated this fascinating field.[2] However, the
field of organocatalysis has grown with a breathtaking pace
and has emerged as one of the most powerful tools for con-
structing enantiomerically enriched compounds during the
last decade.[3] Very recently, the combination of transition
Scheme 1. Simplified depiction of cascade reactions.
metal catalysis and organocatalysis in one process under
mild conditions, which we call ꢀorgano–metal cooperative
catalysisꢁ, has caught the chemistsꢁ attention, thus, opening
up new frontiers in the field of catalysis, as unprecedented
transformations could potentially be achieved that are not
currently possible by the use of the transition metal complex
or the organocatalyst individually.[4–5] Despite its advantages,
the number of ꢀcooperative catalysisꢁ reactions that have
been developed is by far less than those in which a single
catalyst is employed. One major factor that contributes to
this disparity is the incompatibility between transition
metals and organocatalysts. Thus, the design and discovery
of novel cooperative catalytic systems to conquer this chal-
lenge is particularly pressing.
tion, providing products that are difficult or impossible to
obtain by the traditional approach (Scheme 1, path c).
Multisubstituted chiral 2,5-dihydropyrroles are encoun-
tered in significantly important pharmaceuticals, bioactive
natural products, and building blocks in organic and diversi-
ty-oriented synthesis (Scheme 2).[7] As a consequence, the
On the other hand, cascade reactions enable the construc-
tion of molecules with great structural complexity with a
minimum of manual operations, thereby saving time, effort,
and production costs. To date, many asymmetric organocata-
lytic cascade reactions, catalyzed by a single catalyst or
more than one compatible catalyst by using the combination
of iminium/enamine catalysis, have been developed
(Scheme 1, path a and b).[6] We hypothesized that the com-
bination of organocatalysis with organo–metal cooperative
catalysis could be a valuable alternative in a cascade reac-
Scheme 2. Biologically active 2,5-dihydropyrroles.
construction of dihydropyrrole rings bearing diverse substi-
tution patterns has received much attention.[8] Despite great
efforts that have been made, the asymmetric synthesis is still
limited to the phosphine-catalyzed [3+2] cycloaddition of
electron-deficient allenoates with imines.[9] In this case, both
the catalyst and the allenoate substrates are not easily pre-
pared. Another drawback is their limited substrate scope
and the difficulty of synthesizing multisubstituted pyrroles.
Given the importance of these valuable 2,5-dihydropyrroles
and their potential biological properties, as well as the lack
of efficient asymmetric methods for the preparation of these
important agents, the development of alternative methodol-
[a] W. Sun, G. Zhu, Dr. L. Hong, Prof. Dr. R. Wang
Key Laboratory of Preclinical Study for New Drugs of Gansu
Province, School of Basic Medical Science
Institute of Biochemistry and Molecular Biology
School of Life Science
Lanzhou University, Lanzhou, 730000 (P.R. China)
Fax : (+86)931-891-2567
E-mail: hong@lzu.edu.cn
wangrui@lzu.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103083.
13958
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 13958 – 13962

COMMUNICATION
Table 1. Reaction optimization.[a]
ogies in an enantioselective fashion is of great importance
for organic and medicinal chemistry.
As a natural extension of our continuing interest in chiral
amine catalysis and chiral dihydropyrrole synthesis,[10] we
envisaged that polyfunctional dihydropyrroles could be syn-
thesized in a cascade fashion with the combination of a
chiral secondary amine and an optimal transition-metal
complex through a cascade iminium/enamine–metal cooper-
ative-catalysis reaction, by using cheap and readily available
a,b-unsaturated aldehydes and N-tosyl propargylamines as
starting materials (Scheme 3).
Entry Amine Metal
Additive
Solvent
Conv-
ersion
ee
[b]
[%][c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22[f]
23[f]
3a
–
–
PhCO2H Tol[h]
Tol
PhCO2H Tol
–
–
12
<10
<10
–
–
16
trace
–
22
35
42
trace
trace
<10
30
–
<10
25
46
55
–
–
94
77
93
–
PdCl2
PdCl2
–
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3a
3a
3a
Pd(CN)2Cl2 PhCO2H Tol
Pd(Ac)2
Zn
Cu
PhCO2H Tol
PhCO2H Tol
PhCO2H Tol
DABCO Tol
ACHTUNGTRENNUNG
A
–
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
95
n.d.[i]
–
Et3N
DBU
Tol
Tol
Tol
Tol
pyridine
DMAP
95
96
96
n.d.
n.d.
91
99
–
n.d.
99
96
98
99
Scheme 3. Synthetic strategy.
DMAP[d] Tol
DMAP[d] CH2Cl2
DMAP[d] THF
DMAP[d] CHCl3
DMAP[d] CF3Ph
DMAP[d] CH3OH
DMAP[d] Tol
However, to promote this cascade reaction, the following
facts must be taken into account:
1) A suitable metal catalyst needs to act in a cooperative
manner with the organocatalyst.
2) The metal catalyst needs to have a reduced activity to-
wards p-activation of alkynes.
DMAP[d] Tol
A[e]
A[e]
B[g]
Tol
Tol
Tol
3) The metal catalyst needs to tolerate the presence of the
secondary amine, the a,b-unsaturated aldehyde and
water (formed during the catalytic cycle).
4) With the possibility of multiple catalysts being present si-
multaneously, the need for reaction selectivity is impor-
tant.
82
[a] Unless otherwise specified, the reaction was carried out with 1a
(0.20 mmol), 2a (0.30 mmol), 3a (0.04 mmol), additive (0.04 mmol), and
metal (0.01 mmol) in solvent (1.0 mL) at ambient temperature for 36 h.
[b] Determined by 1H NMR spectroscopy. [c] Determined by chiral
HPLC on a Chiralcel AD column. [d] DMAP (10 mol%) was used.
[e] Additive A: DMAP (10 mol%) and NaOAc (1.0 equiv) were used.
[f] The reaction was performed at 08C. [g] Additive B: DMAP
(10 mol%), NaOAc (1.0 equiv), and H2O (1.0 equiv) were used. [h] Tol=
toluene. [i] n.d.=not determined.
5) The significant challenge of asymmetric aza-Michael ad-
dition.[11]
Herein, we disclose the use of organocatalysis in combina-
tion with organo–metal cooperative catalysis in a cascade re-
action and demonstrate its utility in the highly enantioselec-
tive synthesis of multisubstituted chiral pyrrolines.
At the outset of our investigations, we studied the reac-
tion between cinnamaldehyde (1a) and N-tosyl propargyl-
salts and found that Pd salts in combination with 3a were
able to catalyze the reaction, while Zn and Cu salts did not
(Table 1, entries 3–7). To improve the conversion of the re-
action, we decided to investigate the influence of the addi-
tive and the solvent. Subsequent screening of additives
showed that the use of 10 mol% of 4-(dimethylamino)pyri-
dine (DMAP) was optimal (Table 1, entries 3 and 8–13). A
survey of solvents revealed that the reaction media had a
significant effect on the reaction (Table 1, entries 13–18),
and toluene gave the best result (Table 1, entry 13). Chang-
ing the bulk of the chiral pyrrolidine catalyst 3 in combina-
tion with PdCl2 could not improve the yield of 4aa (Table 1,
entries 13 and 19–20).
ACHTUNGTRENNUNGamine (2a) catalyzed by chiral amine 3a. However, the re-
action did not afford any pyrroline product 4aa nor the aza-
Michael product 5, probably owing to the retro-aza-Michael
reaction (Table 1, entry 1). The reaction with only a palladi-
um salt did not render any product either (Table 1, entry 2).
Thus, we decided to investigate the ability of a chiral amine
in combination with a metal to catalyze this reaction.
To our delight, the common diarylprolinol catalytic
system combined with the metal salt PdCl2 catalyzed the
proposed reaction to form the corresponding pyrroline 4aa
in high enantioselectivity, albeit with low yield (Table 1,
entry 3). Encouraged by this, we examined several metal
We also found that the addition of NaOAc (1.0 equiv) to
the catalytic system slightly improved the reactivity without
a loss in enantioselectivity (Table 1, entry 21).[12] Further-
Chem. Eur. J. 2011, 17, 13958 – 13962
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13959

R. Wang et al.
more, one equivalent of water was also crucial for the yield
of 4aa (Table 1, entry 23). Apparently, water is beneficial
for the hydrolysis of intermediate 6 to release the catalyst
3a and thus enable catalytic turnover.[13] Lowering the reac-
tion temperature to 08C had a positive effect on both the
yield and the enantioselectivity, probably owing to the turn-
over of the catalyst (Table 1, entries 22 and 23).
With the optimized conditions in hand, we turned our at-
tention to the substrate scope. To our delight, various a,b-
unsaturated aldehydes could participate in the developed
cascade cooperative-catalysis sequence (Table 2). It ap-
Figure 1. X-ray structure of (S)-4ca and NOE experiment of (2S,5S)-4bc.
Table 3. Scope of N-tosyl propargylamines.[a]
Table 2. Scope of a,b-unsaturated aldehydes.[a]
Entry 2, R2, R3
Product Yield [%][b] d.r.[c]
ee [%][d]
1
2
3
4
2b, Ph, H
2c, 4-ClC6H4, H
2d, 4-MeC6H4, H 4bd
2e, H, Me 4be
4bb
4bc
48
64
52
16:1
> 20:1
19:1
98
>99
96
Entry
1, R1
Product 4
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a, Ph
4aa
4ba
4ca
4da
4ea
4 fa
4ga
4ha
4ia
4ja
4ka
4la
4ma
4na
4oa
4pa
4qa
52
78
80
68
64
63
83
81
53
87
65
67
65
52
44
41
50
99
>99
>99
>99
99
97
>99
96
>99
98
>99
96
99
96
1b, 2-FC6H4
1c, 2-ClC6H4
1d, 2-BrC6H4
1e, 2-MeC6H4
1 f, 2-MeOC6H4
1g, 3-ClC6H4
1h, 3-BrC6H4
1i, 3-MeC6H4
1j, 3-MeOC6H4
1k, 3-NO2C6H4
1l, 4-ClC6H4
1m, 4-BrC6H4
1n, 4-MeC6H4
1o, Pr
n.r.
–
–
[a] The reaction was carried out with 1b (0.20 mmol), 2 (0.40 mmol), 3a
(0.04 mmol), H2O (1.0 equiv), NaOAc (1.0 equiv), DMAP (0.02 mmol),
and PdCl2 (0.01 mmol) in toluene (1.0 mL) at 08C for 36 h. [b] Isolated
yield. [c] Determined by H NMR spectroscopy. [d] For analysis of the ee
values of the products, see the Supporting Information.
1
substituted pyrroline derivatives as the predominant diaste-
reoisomer in moderate yields and excellent enantioselectivi-
ties. The absolute configuration of C5 was determined with
NOESY experiments. H1 has strong interaction with H2,
which confirmed the relative configuration of C2 and C5
(Figure 1).
87
77
73
1p, Et
1q, Me
Control experiments (Table 1, entries 1 and 2) confirmed
that both the amine catalyst and the PdCl2 were required
for catalytic activity; no reaction was observed with either
of them independently. When 3a was employed as the orga-
nocatalyst, no conversion to the aza-Michael product 5 was
observed, indicating that this is a reversible reaction and the
retro-aza-Michael reaction is favored, giving back the start-
ing materials. However, a dynamic kinetic asymmetric trans-
formation (DYKAT)[15] involving enamine–metal coopera-
[a] The reaction was carried out with 1 (0.20 mmol), 2a (0.30 mmol), 3a
(0.04 mmol), H2O (1.0 equiv), NaOAc (1.0 equiv), DMAP (0.02 mmol),
and PdCl2 (0.01 mmol) in toluene (1.0 mL) at 08C for 36 h. [b] Isolated
yield. [c] For analysis of the ee values of the products, see the Supporting
Information.
peared that the position and electronic properties of the
substituents on the aromatic ring of the a,b-unsaturated al-
dehydes had a limited effect on the efficiency of this pro-
cess. The products were obtained in moderate to high yields
with constantly remarkable enantioselectivity (Table 2, en-
tries 1–14). In the case of less reactive aliphatic enals, good
enantioselectivities were also obtained, albeit with lower
yields (Table 2, entries 15–17). The absolute configuration of
the products was determined by X-ray analysis.[14] Suitable
crystals of compound 4ca, which enabled assignment of the
absolute configuration, were obtained, and a single-crystal
analysis revealed the configuration to be S (Figure 1).
Tetrasubstituted pyrrolines are important building blocks
widely featured in many natural products and drug mole-
cules. With this in mind, we next turned our attention to
using substituted N-tosyl propargylamines for the construc-
tion of tetrasubstituted pyrrolines (Table 3). The cascade co-
operative-catalysis reactions gave the corresponding tetra-
À
tive catalysis would shift the equilibrium towards the C N
bond formation by making the reaction irreversible.
The beneficial effect of NaOAc, H2O, and DMAP on the
acceleration of the reaction was accompanied by negligible
effects on the enantioselectivity, suggesting that these addi-
tives were not involved in the ee-determining steps. The role
of NaOAc is most likely to activate the N-nucleophilic re-
agent by deprotonation. It is likely that H2O facilitates the
hydrolysis of intermediate 6 to release the catalyst 3a and
thus enable catalytic turnover. DMAP may act as a ligand
for the palladium catalyst and an external base.[16]
Based on these observations and former studies by other
groups,[5b,c,f] we proposed the following mechanistic pathway
to account for the chemoselectivity and stereochemistry of
the cascade cooperative catalytic reaction (Scheme 4).
13960
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 13958 – 13962

2,5-Dihydropyrroles through Organo–Metal Cooperative Catalysis
COMMUNICATION
[1] a) J. F. Hartwig, Organotransition Metal Chemistry: From Bonding
to Catalysis, University Science Books, Mill Valley, 2010; b) M. T.
Reetz, B. List, S. Jaroch, H. Weinmann, Organocatalysis, Springer,
Berlin, 2008.
[2] M. Beller, C. Bolm, Transition Metals for Organic Synthesis: Build-
ing Blocks and Fine Chemicals, 2nd ed, Wiley-VCH, Weinheim,
2004.
[3] a) P. I. Dalko, Enantioselective Organocatalysis: Reactions and Ex-
perimental Procedures, Wiley-VCH, Weinheim, 2007; b) A. Berkes-
sel, H. Grçger, Asymmetric Organocatalysis: From Biomimetic Con-
cepts to Application in Asymmetric Synthesis, Wiley-VCH, Wein-
heim, 2005; c) J. Seayad, B. List, Org. Biomol. Chem. 2005, 3, 719;
d) D. W. C. MacMillan, Nature 2008, 455, 304; e) P. I. Dalko, L.
Moisan, Angew. Chem. 2004, 116, 5248; Angew. Chem. Int. Ed. 2004,
43, 5138; f) M. J. Gaunt, C. C. C. Johansson, A. McNally, N. T. Vo,
Drug Discovery Today 2007, 12, 8; g) H. Pellissier, Tetrahedron
2007, 63, 9267; h) A. Dondoni, A. Massi, Angew. Chem. 2008, 120,
4716; Angew. Chem. Int. Ed. 2008, 47, 4638.
[4] For recent reviews, see: a) Z. Shao, H. Zhang, Chem. Soc. Rev. 2009,
38, 2745; b) C. Zhong, X. Shi, Eur. J. Org. Chem. 2010, 2999.
[5] For examples of combination of catalytic enamine activation and
transition-metal catalysis, see: Pd: a) I. Ibrahem, A. Cꢃrdova,
Angew. Chem. 2006, 118, 1986; Angew. Chem. Int. Ed. 2006, 45,
1952; b) G.-L. Zhao, F. Ullah, L. Deiana, S. Lin, Q. Zhang, J. Sun, I.
Ibrahem, P. Dziedzic, A. Cꢃrdova, Chem. Eur. J. 2010, 16, 1585; c) S.
Lin, G. L. Zhao, L. Deiana, Q. Zhang, J. Sun, H. Leijonmarck, A.
Cꢃrdova, Chem. Eur. J. 2010, 16, 13930; d) F. Bihelovic, R. Matovic,
B. Vulovic, R. N. Saicic, Org. Lett. 2007, 9, 5063; e) S. Mukherjee, B.
List, J. Am. Chem. Soc. 2007, 129, 11336; Au: f) D. Monge, K. L.
Jensen, P. T. Franke, L. Lykke, K. A. Jørgensen, Chem. Eur. J. 2010,
16, 9478; g) J. Binder, B. Crone, T. T. Haug, H. Menz, S. F. Kirsch,
Org. Lett. 2008, 10, 1025; Ag: h) Q. Ding, J. Wu, Org. Lett. 2007, 9,
4959; Cu: i) T. Yang, A. Ferrali, L. Campbell, D. J. Dixon, Chem.
Commun. 2008, 2923; Ru: j) D. A. Nicewicz, D. W. C. MacMillan,
Science 2008, 322, 77; k) M. Ikeda, Y. Miyake, Y. Nishibayashi,
Angew. Chem. 2010, 122, 7447; Angew. Chem. Int. Ed. 2010, 49,
7289; l) I. Ibrahem, J. S. M. Samec, J. E. Bꢄckvall, A. Cꢃrdova, Tet-
rahedron Lett. 2005, 46, 3965; Fe: m) S. Zhou, S. Fleischer, K. Junge,
M. Beller, Angew. Chem. 2011, 123, 5226; Angew. Chem. Int. Ed.
2011, 50, 5120; n) J. F. Van Humbeck, S. P. Simonovich, R. R.
Knowles, D. W. C. MacMillan, J. Am. Chem. Soc. 2010, 132, 10012;
Ir: o) H.-W. Shih, M. N. Vander Wal, R. L. Grange, D. W. C. Mac-
Millan, J. Am. Chem. Soc. 2010, 132, 13600; In: p) R. Sinisi, M. V.
Vita, A. Gualandi, E. Emer, P. G. Cozzi, Chem. Eur. J. 2011, 17,
7404.
Scheme 4. Proposed catalytic cycle for the cascade iminium/enamine–
metal catalysis.
In summary, an unprecedented aza-Michael/carbocycliza-
tion reaction combining cheap and readily available a,b-un-
saturated aldehydes and N-tosyl propargylamines has been
discovered, using the novel ꢀogano–metal cooperative catal-
ysisꢁ concept. The integration of the two distinct catalytic
cycles into a single process facilitates the rapid and con-
trolled production of valuable chiral pyrrolines in excellent
diastereo- and enantioselectivities. Further application and
exploration of this methodology and biological evaluation of
chiral pyrroline containing compounds are ongoing in our
laboratory.
[6] For reviews, see: a) D. Enders, C. Grondal, M. R. M. Hꢅttl, Angew.
Chem. 2007, 119, 1590; Angew. Chem. Int. Ed. 2007, 46, 1570; b) G.
Guillena, D. J. Ramon, M. Yus, Tetrahedron: Asymmetry 2007, 18,
693; c) C. Grondal, M. Jeanty, D. Enders, Nat. Chem. 2010, 2, 167;
for pioneering contributions, see: d) Y. Huang, A. M. Walji, C. H.
Larsen, D. W. C. MacMillan, J. Am. Chem. Soc. 2005, 127, 15051;
e) M. Marigo, T. Schulte, J. Franzen, K. A. Jørgensen, J. Am. Chem.
Soc. 2005, 127, 15710; f) J. W. Yang, M. T. Hechavarria Fonseca, B.
List, J. Am. Chem. Soc. 2005, 127, 15036.
Experimental Section
In a vial, N-tosyl propargylamine 2a (0.3 mmol) was added to a stirred
mixture of cinnamaldehyde (1a, 0.2 mmol), catalyst 3a (0.04 mmol),
PdCl2 (0.01 mmol), DMAP (0.02 mmol), H2O (0.2 mmol), and NaOAc
(0.2 mmol) in toluene (1.0 mL) at 08C. The mixture was stirred at 08C
for 36 h. The reaction mixture was directly purified by silica gel chroma-
tography (petroleum ether/AcOEt 4:1) without work-up to give the pure
desired products 4aa.
[7] a) U. T. T. Nguyen, Z. Guo, C. Delon, Y. Wu, C. Deraeve, B. Fran-
zel, R. S. Bon, W. Blankenfeldt, R. S. Goody, H. Waldmann, D. Wol-
ters, K. Alexandrov, Nat. Chem. Biol. 2009, 5, 227; b) S. Castellano,
H. D. G. Fiji, S. S. Kinderman, M. Watanabe, P. de Leon, F. Tamanoi,
O. Kwon, J. Am. Chem. Soc. 2007, 129, 5843; c) R. J. Valentekovich,
S. L. Schreiber, J. Am. Chem. Soc. 1995, 117, 9069; d) H. Mack, D.
Baucke, W. Hornberger, U. E. W. Lange, W. Seitz, H. W. Hçffken,
Bioorg. Med. Chem. Lett. 2006, 16, 2641; e) U. E. W. Lange, D.
Baucke, W. Hornberger, H. Mack, W. Seitz, H. W. Hçffken, Bioorg.
Med. Chem. Lett. 2006, 16, 2648; f) B. E. Segelstein, T. T. Wager,
W. M. Welch (Pfizer Inc.), US Patent Appl. 2005/272800, 2005;
g) T. T. Wager, W. M. Welch, B. T. OꢁNeill (Pfizer Prod. Inc.), WO
2004/110996, 2004; h) J. M. Humphrey, T. A. Chappie (Pfizer Prod.
Inc.), WO 2005/115976, 2005; i) Z. Wang, S. Castellano, S. S. Kinder-
Acknowledgements
We gratefully acknowledge the financial support from NSFC (20932003,
90813012) and the National S&T Major Project of China
(2012ZX09504001–003).
Keywords: aldehydes
· cascade reaction · cooperative
catalysis · organocatalysis · propargylamines · pyrrolines
Chem. Eur. J. 2011, 17, 13958 – 13962
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13961

R. Wang et al.
man, C. E. Argueta, A. B. Beshir, G. Fenteany, O. Kwon, Chem.
Eur. J. 2011, 17, 649; j) M. Sampath, P.-Y. B. Lee, T.-P. Loh, Chem.
Sci. 2011, 2, 1988.
6881; i) L. Hong, L. Wang, C. Chen, B. Zhang, R. Wang, Adv. Synth.
Catal. 2009, 351, 772.
[11] D. Enders, C. Wang, J. X. Liebich, Chem. Eur. J. 2009, 15, 11058.
[12] a) H. Li, J. Wang, H. Xie, L. Zu, W. Jiang, E. N. Duesler, W. Wang,
Org. Lett. 2007, 9, 965; b) J. Wang, H. Li, H. Xie, L. Zu, X. Shen, W.
Wang, Angew. Chem. 2007, 119, 9208; Angew. Chem. Int. Ed. 2007,
46, 9050.
[13] a) B. Han, J.-L. Li, C. Ma, S.-J. Zhang, Y.-C. Chen, Angew. Chem.
2008, 120, 10119; Angew. Chem. Int. Ed. 2008, 47, 9971; b) Y. Haya-
shi, Angew. Chem. 2006, 118, 8281; Angew. Chem. Int. Ed. 2006, 45,
8103; c) A. P. Brogan, T. J. Dickerson, K. D. Janda, Angew. Chem.
2006, 118, 8278; Angew. Chem. Int. Ed. 2006, 45, 8100; d) D. G.
Blackmond, A. Armstrong, V. Coombe, A. Wells, Angew. Chem.
2007, 119, 3872; Angew. Chem. Int. Ed. 2007, 46, 3798.
[14] CCDC-813918 (4ca) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.a-
c.uk/data_request/cif.
[15] J. Steinreiber, K. Faber, H. Griengl, Chem. Eur. J. 2008, 14, 8060.
[16] a) M. H. Emmert, A. K. Cook, Y. J. Xie, M. S. Sanford, Angew.
Chem. 2011, 123, 9581; Angew. Chem. Int. Ed. 2011, 50, 9409;
b) T. W. Lyons, M. S. Sanford, Tetrahedron 2009, 65, 3211.
[8] For racemic examples, see: a) T. Xu, X. Mu, H. Peng, G. Liu,
Angew. Chem. 2011, 123, 8326; Angew. Chem. Int. Ed. 2011, 50,
8176; b) S. R. K. Minkler, B. H. Lipshutz, N. Krause, Angew. Chem.
2011, 123, 7966; Angew. Chem. Int. Ed. 2011, 50, 7820; c) L.-G.
Meng, P. Cai, Q. Guo, S. Xue, J. Org. Chem. 2008, 73, 8491; d) G.-L.
Zhao, M. Shi, J. Org. Chem. 2005, 70, 9975; e) X.-F. Zhu, C. E.
Henry, O. Kwon, Tetrahedron 2005, 61, 6276; f) Z. Xu, X. Lu, Tetra-
hedron Lett. 1997, 38, 3461; g) Z. Xu, X. Lu, J. Org. Chem. 1998, 63,
5031; h) S. Suresh, M. Periasamy, Tetrahedron Letters 2004, 45, 6291;
i) B. Zhang, Z. He, S. Xu, G. Wu, Z. He, Tetrahedron 2008, 64, 9471;
j) X.-F. Zhu, J. Lan, O. Kwon, J. Am. Chem. Soc. 2003, 125, 4716.
[9] For limited asymmetric examples, see: a) Y.-Q. Fang, E. N. Jacobsen,
J. Am. Chem. Soc. 2008, 130, 5660; b) N. Pinto, N. Fleury-Brꢆgeot,
A. Marinetti, Eur. J. Org. Chem. 2009, 146.
[10] a) X. Jiang, D. Fu, X. Shi, S. Wang, R. Wang, Chem. Commun. 2011,
47, 8289; b) G. Zhang, Y. Zhang, X. Jiang, W. Yan, R. Wang, Org.
Lett. 2011, 13, 3806; c) W. Sun, X. Ma, L. Hong, R. Wang, J. Org.
Chem. 2011, 76, 7826; d) W. Sun, L. Hong, R. Wang, Chem. Eur. J.
2011, 17, 6030; e) L. Hong, W. Sun, C. Liu, L. Wang, R. Wang,
Chem. Eur. J. 2010, 16, 440; f) L. Hong, W. Sun, C. Liu, L. Wang, K.
Wong, R. Wang, Chem. Eur. J. 2009, 15, 11105; g) L. Hong, C. Liu,
W. Sun, L. Wang, K. Wong, R. Wang, Org. Lett. 2009, 11, 2177; h) L.
Hong, L. Wang, W. Sun, K. Wong, R. Wang, J. Org. Chem. 2009, 74,
Received: October 2, 2011
Published online: November 17, 2011
13962
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 13958 – 13962