Phosphine-catalyzed [5+1] annulation of δ-sulfonamido-substituted enones with: N -sulfonylimines: A facile synthesis of tetrahydropyridines

Article abstract of DOI:10.1039/c7sc04515h

Phosphine-catalyzed [5+1] annulation of δ-sulfonamido-substituted enones with N-sulfonylimines for the synthesis of 1,2,3,6-tetrahydropyridines is developed. The reaction proceeds smoothly under mild reaction conditions to give the annulation products in moderate to excellent yields. Mechanistic exploration of this new annulation shows that the δ-sulfonamido-substituted enone and the N-sulfonylimine serve as C5 and C1 synthons to furnish the annulation, respectively. Using chiral phosphine as the catalyst, an asymmetric variant of the model reaction gave the chiral product in up to 73% ee.

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DOI: 10.1039/C7SC04515H
Journal Name
ARTICLE
Phosphine‐catalyzed [5+1] annulation of δ‐sulfonamido‐
substituted enones with N‐sulfonylimines: a facile synthesis of
tetrahydropyridines
Received 00th January 20xx,
Accepted 00th January 20xx
Leijie Zhou, Chunhao Yuan, Yuan Zeng, Honglei Liu, Chang Wang, Xing Gao, Qijun Wang, Cheng
Zhang, and Hongchao Guo*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
phosphine‐catalyzed [5+1] annulation of δ‐sulfonamido‐substituted enones with N‐
sulfonylimines for synthesis of 1,2,3,6‐tetrahydropyridine is developed. The reaction proceeds
smoothly under mild reaction conditions to give the annulation products in moderate to excellent
yields. Mechanistic exploration on this new annulation shows that δ‐sulfonamido‐substituted
enone and N‐sulfonylimine serve as C5 and C1 synthon to furnish the annulation, respectively. Using
chiral phosphine as the catalyst, asymmetric variant of the model reaction gave chiral product in up
to 73%ee.
Introduction
Phosphine‐catalyzed annulation reactions are powerful
synthetic tools to construct carbo‐ and heterocycles.1 Since the
pioneer work of Lu on phosphine catalysis,2 many types of
phosphine‐promoted annulation reactions such as [1+n],3
[2+n],4 [3+n],5 [4+n]6 annulations have been developed. In these
reactions, the reactive intermediates from nucleophilic addition
of phosphine to activated allenes, Morita–Baylis–Hillman
carbonates, activated alkyne, et al, namely phosphorus ylides,
serve as one‐, two‐, three‐, or four‐membered synthons when
reacting with a variety of electrophilic coupling partners.
Despite extremely diverse annulation reactions have been
developed in the past two decades,1 development of phosphine
catalysis is seeing the ceiling since phosphine catalysis is stuck
with single activation mode. Therefore, exploration on new
activation modes and synthons, is very significant. Generally,
phosphorus ylides work as equal to or lesser than four‐
membered synthons in phosphine catalysis. The examples with
phosphorus ylides as greater than or equal to five‐membered
synthon, which could probably be used for synthesis of six‐
membered or medium‐ring cyclic compounds, has not been
reported.
Functionalized tetrahydropyridines are important structural
motifs of numerous biologically active natural products and
synthetic pharmaceuticals, and their synthesis has attracted
much attention.7 In the area of phosphine catalysis, several
Scheme 1 Typical reactions involving phosphine catalysis to construct
tetrahydropyridines.
attractive strategies involving phosphine‐catalyzed annulation
reactions have been established for synthesis of functionalized
tetrahydropyridines. In 2003, Kwon described a PBu3‐catalyzed
[4+2] annulation of imines with allenes as a facile pathway to
access functionalized tetrahydropyridines(Scheme 1a).8 Two
years later, through using a bulky tert‐butyl‐substituted
Department of Applied Chemistry, China Agricultural University, Beijing 100193,
China. E‐Mail: hchguo@cau.edu.cn
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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binaphthyl‐based chiral phosphine as catalyst, Fu accomplished Table 1 Screening of reaction conditionsa
asymmetric version of the above [4+2] reaction with excellent
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DOI: 10.1039/C7SC04515H
enantioselectivities.9 After the work of Kwon and Fu, Shi,10a
Marinetti10b and Zhao10c made much contribution to the
development of this classic [4+2] annulation reaction, and the
reaction was also utilized by Kwon as a key step in the synthesis
of natural products.11 In 2012, Loh and Zhong reported a
phosphine‐catalyzed asymmetric [2+4] annulation of olefins
with conjugate imines, which provided an alternative approach
to synthesis of enantioenriched tetrahydropyridines (Scheme
1b).12 After the work, Chi,13a Shi,13b Wu13c and Zhang13d enriched
this reaction by intramolecular mode or introducing of other
types of catalysts. The [3+3] annulation mode is another typical
way to synthesize functionalized tetrahydro‐pyridines. In 2009,
Kwon developed the first phosphine‐promoted [3+3]
annulation of aziridines with allenoate to afford highly
functionalized tetrahydropyridines under mild conditions,14
broadening the synthetic strategies of tetrahydropyridines by
utilizing different type of building blocks (Scheme 1c). Herein, as
the initial attempt of our exploration on new five‐membered
linear synthon for [5+n] annulation reaction, we report a
phosphine‐catalyzed [5+1] annulation reation of δ‐sulfonamido
‐substituted enones with N‐sulfonylimines (Scheme 1d). To the
best of our knowledge, this is the first phosphine‐catalyzed
[5+1] annulation with phosphorus ylide as five‐membered
synthon.
Entry
Cat.
t (h)
Yieldb (%)
1
2
3
4
5c
6d
7
8
9
Ph3P
72
72
36
3
28
72
72
72
72
72
NRe
20
75
95
90
MePPh2
Me2PPh
Bu3P
Bu3P
Bu3P
15
Et3N
NR
NR
NR
20
DMAP
DABCO
DBU
10
a Unless otherwise stated, all reactions were carried out with 1a (0.1 mmol),
b
2a (0.15 mmol), and catalyst (0.02 mmol) in CH2Cl2 (1 mL) at rt. Isolated
yield. c 10 mol% PBu3 was used. d 5 mol% PBu3 was used. e No reaction.
Table 2 Substrate scope of N-sulfonyliminesa
Entry
R
t (h)
3
Yieldb (%)
Results and discussion
1
2
3
4
5
6
7
8
Ph (2a)
2-FC6H4 (2b)
3-FC6H4 (2c)
4-FC6H4 (2d)
3
2
6
2
12
9
1
16
6
2
28
48
10
8
6
0.75
2
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao
3ap
3aq
3ar
3as
95
96
85
93
75
82
85
68
81
84
41
79
95
90
98
95
98
72
NRc
At the outset of our experiment, the reaction between δ‐
sulfonamido‐substituted enone 1a and N‐sulfonylimine 2a was
chosen as the model reaction, and various Lewis bases such as
phosphines and amines were examined as the catalyst (Table 1).
PPh3 (20 mol%) did not show any catalytic activity, and no
annulation product was observed after the reaction mixture
was stirred at rt for 72 h (Table 1, entry 1). Under otherwise
identical conditions, the [5+1] annulation product 3aa was
obtained in 20%yield when MePPh2 was employed as the
catalyst (entry 2). It seems that more nucleophilic phosphines
were beneficial to the reaction. With the use of Me2PPh as the
catalyst, the reaction worked at rt for 36 h to give the product
3aa in 75% yield (entry 3). Compared with Me2PPh, more
nucleophilic Bu3P displayed much better catalytic activity,
greatly shortening the reaction time to 3 h to afford the product
3aa in 95% yield (entry 4). Lowering catalyst loading to 10 mol%
still resulted in the product in 90% yield, albeit requiring 28 h of
reaction time (entry 5). However, when the catalyst loading was
lowered to 5 mol%, the yield of 3aa was greatly decreased to
15% (entry 6). With the use of organic amines such as Et3N,
DMAP and DABCO instead of phosphines as the catalyst, no
annulation product was observed even the reaction time was
prolonged to 72 h under otherwise identical conditions (entries
7–9). A stronger Lewis base DBU displayed certain catalytic
activity, promoting the reaction to afford the annulation
product 3aa in 20% yield (entry 10).
2-ClOC6H4 (2e)
3-ClC6H4 (2f)
4-ClC6H4 (2g)
2-BrC6H4 (2h)
3-BrC6H4 (2i)
4-BrC6H4 (2j)
2-MeC6H4 (2k)
3-MeC6H4 (2l)
4-MeC6H4 (2m)
3-MeOC6H4 (2n)
4-MeOC6H4 (2o)
2-thiophenyl (2p)
2-naphthyl (2q)
N-Boc-3-indole (2r)
Et (2s)
9
10
11
12
13
14
15
16
17
18
19
24
72
a Unless otherwise stated, all reactions were carried out with 1a (0.2 mmol),
2 (0.3 mmol), and PBu3 (0.04 mmol) in CH2Cl2 (2 mL) at rt. b Isolated yield. c
No reaction.
investigated (Table 2). The results indicated that imines with
either electron‐deficient or rich substituents on benzene ring
are suitable substrates, and the corresponding 1,2,3,6‐
tetrahydropyridine derivatives were obtained with usually good
to high yields. However, the position of the substituent on
benzene ring have remarkable influence on the reaction. For
example, the 2‐Cl, 2‐Br, and 2‐Me substituted aryl imines led to
lower yields of the products, compared with their 3‐ or 4‐
substituted counterparts (entry 5 vs entries 6–7, entry 8 vs
entries 9–10, entry 11 vs entries 12–13). The 2‐thiophenyl and
After the optimal conditions were determined, various N‐
sulfonylimines with different substituents were carefully
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2‐naphthyl imines were also compatible substrates with the enones did not undergo the annulation in theVipewreAsrteicnlecOenlionef
DOI: 10.1039/C7SC04515H
optimal reaction conditions and the corresponding products phosphine. Meanwhile, when benzoyl group was replaced by
were obtained in excellent yields (entries 16–17). A N‐Boc‐3‐ ester group, the reaction didn’t work either. Therefore, the
indole derived imine 2r also underwent the reaction, providing acidity of substituted amine group at δ‐position of ketone
the product 3ar in 72% yield (entry 18). Unfortunately, alkyl N‐ probably has remarkable impact on the reaction process, and so
sulfonylimine 2s did not perform the reaction and no desired does the benzoyl group. Replacement of the imine substrate
product was observed (entry 19). The structure of the [5+1] with benzaldehyde did not yield the desired annulation product
annulation product was unambiguously determined through X‐ (Scheme 2). These results demonstrated that the amino‐group
ray crystallographic analysis of the product 3aq 15
.
in the annulation product comes from the enone substrate.
a
Table 3 Substrate scope of δ-sulfonamido-substituted ketones
Entry
R
t (h)
3
Yieldb (%)
1
2
3
4
5
6
7
8
2-FC6H4 (1b)
4-FC6H4 (1c)
4
3
2
3
3
5
5
1.5
5
12
12
36
12
3
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
3ja
3ka
3la
3ma
3na
3oa
3sa
97
90
90
91
84
98
87
90
91
98
98
75
93
88
73
2-ClC6H4 (1d)
3-ClC6H4 (1e)
4-ClC6H4 (1f)
3-BrC6H4 (1g)
4-BrC6H4 (1h)
3,4-Cl2C6H3 (1i)
4-MeC6H4 (1j)
2-MeOC6H4 (1k)
3-MeOC6H4 (1l)
4-NO2C6H4 (1m)
2-thiophenyl (1n)
2-naphthyl (1o)
Me (1s)
9
10
11
12
13
14
15
Scheme 2 Control experiments.
16
a Unless otherwise stated, all reactions were carried out with 1 (0.2 mmol), 2a (0.3
mmol), and PBu3 (0.04 mmol) in CH2Cl2 (2 mL) at rt. b Isolated yield.
As shown in Table 3, a series of functionalized ketones with
variations of the R group were examined under the optimal
reaction conditions. The results showed that no matter what
the electronic properties or the substitution positions of
substituents are, such as F‐, Cl‐, Br‐, Me‐, MeO‐, and ‐NO2
substituted enones at the benzene ring, the reactions
proceeded smoothly to afford the desired 1,2,3,6‐
tetrahydropyridine derivatives with good to excellent yields
(entries 1–12). However, the MeO and NO2 substituted
substrates required longer time to finish the reactions (entries
10–12). In addition, the 2‐thiophenyl and 2‐naphthyl modified
enones underwent the [5+1] annulation reaction to produce the
corresponding products in excellent yields (entries 13–14). To
our delight, aliphatic enone 1s underwent this reaction to afford
the desired product 3sa in 73% yield (entry 15).
Following the substrate scope evaluation, we attempted to
figure out how the reaction works. As a result, several control
experiments were carried out under the optimal reaction
conditions (Scheme 2). In the presence of PBu3, treatment of
enone 1a with N‐sulfonylimine 2t afforded the annulation
product 3aa in 96% yield together with benzenesulfonamide. In
contrast, treatment of enone 1p with imine 2a afforded the
annulation product 3pa in 94% yield together with p‐
toluenesulfonamide. By comparison, δ‐Boc‐amido‐substituted
Scheme 3 A plausible mechanism.
On the basis of the results obtained, a plausible mechanism
was proposed (Scheme 3).1 Nucleophilic addition of phosphine
catalyst to enone 1a produces a zwitterionic intermediate I,
which then performs another nucleophilic addition to imine 2a
to afford the intermediate II. The intermediate III generated
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from the intermediate II via an intramolecular proton transfer the reaction worked at rt to give the product in 29% yield and
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eliminates 4‐methylbenzenesulfonamide anion to produce the 71% ee, which is similar to results from DthOeI: 1r0e.1a0c3t9io/Cn7SuCs0in4g5125H0
intermediate IV. Through the abstraction of a proton, the mol% of catalyst at low temperature. With the use of chiral
intermediate IV is transformed into the intermediate
V
.
phosphines P2 or P3 as the catalyst, moderate enantiomer
Subsequent intramolecular nucleophilic addition furnishes excesses were obtained. Unfortunately, a variety of attempts to
annulation to form the intermediate VI, which regenerates improve enantioselectivity failed.
phosphine catalyst to give the final annulation product 3aa
.
As indicated in Scheme 4, a gram‐scale preparation of the
product 3aa was carried out. 1.02 g of the enone 1a (3.1 mmol)
reacted with the N‐sulfonylimine 2a (1.22 g, 4.7 mmol) under
the optimal reaction conditions to give 1,2,3,6‐
tetrahydropyridine derivative 3aa in 85% yield. Treatment of
3aa with 4‐methylbenzenethiol and K2CO3 in air provided good
Conclusions
In summary, we have developed a phosphine‐catalyzed [5+1]
annulation of δ‐sulfonamido‐substituted enones with N‐
sulfonimines to prepare tetrahydropyridines with good to
excellent yields. The reaction has broad substrate scope for
both enones and N‐sulfonimines. A plausible mechanism was
proposed according to the results of control experiments. In
addition, the reaction on the gram‐scale worked well and
further transformation of the product provided pyridine
derivative. Asymmetric version of the model [5+1] annulation
reaction was also investigated, and up to 73% ee was achieved.
yield of the pyridine derivative
aromatization. Further exploration on the variety of
sulfonamido‐substituted enone indicated that the enone
4 via dehydrogenation
5,
which is a homologue of the enone 1a, could work as C4 synthon
to perform the [4+1] annulation reation to give 2,5‐dihydro‐1H‐
pyrrole derivative 6 in 23% yield (Scheme 4).
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work is supported by the NSFC (21372256 and 21572264)
and the opening foundation of the Key Laboratory of Green
Pesticide and Agricultural Bioengineering, Ministry of Education,
Guizhou University (No. 2014GDGP0103).
Notes and references
1
Scheme 4 The reaction on the gram-scale and further transformations.
For selected reviews, see: (a) A. Marinetti and A. Voituriez,
Synlett, 2010, 174; (b) S. Wang, X. Han, F. Zhong, Y. Wang and
Y. Lu, Synlett, 2011, 2766; (c) Q. Zhao, Z. Lian, Y. Wei and M.
Shi, Chem. Commun., 2012, 48, 1724; (d) Y. C. Fan and O.
Kwon, Chem. Commun., 2013, 49, 11588; (e) Y. Wei and M.
Shi, Chem. Rev., 2013, 113, 6659; (f) Z. Wang, X. Xu and O.
Kwon, Chem. Soc. Rev., 2014, 43, 2927; (g) Y. Xiao, Z. Sun, H.
Guo and O. Kwon, Beilstein J. Org. Chem., 2014, 10, 2089; (h)
P. Xie and Y. Huang, Org. Biomol. Chem., 2015, 13, 8578; (i)
Y. Xiao, H. Guo and O. Kwon, Aldrichim. Acta., 2016, 49, 3; (j)
T. Wang, X. Han, F. Zhong, W. Yao and Y. Lu, Acc. Chem. Res.,
2016, 49, 1369; (k) W. Li and J. Zhang, Chem. Soc. Rev., 2016,
45, 1657; (l) Y. Wei and M. Shi, Org. Chem. Front., 2017, 4,
1876; (m) H. Li and Y. Lu, Asian J. Org. Chem., 2017,
C. Zhang and X. Lu, J. Org. Chem., 1995, 60, 2906.
6, 1130.
2
3
For selected examples, see: (a) J. Szeto, V. Sriramurthy and
O. Kwon, Org. Lett., 2011, 13, 5420; (b) X. Han, W. Yao, T.
Wang, Y. R. Tan, Z. Yan, J. Kwiatkowski and Y. Lu, Angew.
Chem. Int. Ed., 2014, 53, 5643; (c) Z. Gao, C. Wang, C. Yuan,
L. Zhou, Y. Xiao and H. Guo, Chem. Comm., 2015, 51, 12653.
For selected examples, see: (a) X. Meng, Y. Huang, H. Zhao,
P. Xie, J. Ma and R. Chen, Org. Lett., 2009, 11, 991; (b) R. Na,
C. Jing, Q. Xu, H. Jiang, X. Wu, J. Shi, J. Zhong, M. Wang, D.
Benitez, E. Tkatchouk, W. A. Goddard, H. Guo and O. Kwon,
J. Am. Chem. Soc., 2011, 133, 13337; (c) J. Zheng, Y. Huang
and Z. Li, Org. Lett., 2013, 15, 5064; (d) W. Yao, X. Dou and Y.
Lu, J. Am. Chem. Soc., 2015, 137, 54; (e) H. Ni, W. Yao, A.
Waheed, N. Ullah and Y. Lu, Org. Lett., 2016, 18, 2138.
Scheme 5 Investigation on asymmetric [5+1] annulation.
4
As shown in Scheme 5, asymmetric version of the reaction
was also investigated. To our delight, with the use of chiral
phosphine P1 as the catalyst and CF3Ph as the solvent, the [5+1]
annulation of the enone 1a with the N‐sulfonylimine 2a worked
at −10 C for 65 h to give chiral product 3aa in 28% yield with up
to 73% ee. When we decrease the amount of P1 to 10 mol%,
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5
For selected examples, see: (a) A. Voituriez, A. Panossian, N.
Fleury‐Brégeot, P. Retailleau and A. Marinetti, J. Am. Chem.
Soc., 2008, 130, 14030; (b) H. Xiao, Z. Chai, C. Zheng, Y. Yang,
71, 4255; (d) H. Wang, W. Zhou, M. Tao, A. HuVaienwdArJt.icZlehOannlinge,
Org. Lett., 2017, 19, 1710.
DOI: 10.1039/C7SC04515H
14 H. Guo, Q. Xu and O. Kwon, J. Am. Chem. Soc., 2009, 131
,
W. Liu, J. Zhang and G. Zhao, Angew. Chem. Int. Ed., 2010, 49
,
6318.
4467; (c) Y. Fujiwara and G. C. Fu, J. Am. Chem. Soc., 2011,
133, 12293; (d) X. Han, Y. Wang, F. Zhong and Y. Lu, J. Am.
Chem. Soc., 2011, 133, 1726; (e) F. Zhong, X. Han, Y. Wang
and Y. Lu, Angew. Chem., Int. Ed., 2011, 50, 7837; (f) X. Han,
15 Crystallographic data for 3aq have been deposited with the
Cambridge Crystallographic Data Centre as deposition number
CCDC 1575011.
F. Zhong, Y. Wang and Y. Lu, Angew. Chem., Int. Ed, 2012, 51
,
767; (g) X. Zhang and M. Shi, ACS Catal., 2013, , 507; (h) C.
3
E. Henry, Q. Xu, Y. C. Fan, T. J. Martin, L. Belding, T. Dudding
and O. Kwon, J. Am. Chem. Soc., 2014, 136, 11890; (i) L.
Zhang, H. Liu, G. Qiao, Z. Hou, Y. Liu, Y. Xiao and H. Guo, J.
Am. Chem. Soc., 2015, 137, 4316; (j) S. Y. Lee, Y. Fujiwara, A.
Nishiguchi, M. Kalek and G. C. Fu, J. Am. Chem. Soc., 2015,
137, 4587; (k) M. Gicquel, Y. Zhang, P. Aillard, P. Retailleau,
A. Voituriez and A. Marinetti, Angew. Chem. Int. Ed, 2015, 54
,
5470; (l) Y. Gu, P. Hu, C. Ni and X. Tong, J. Am. Chem. Soc.,
2015, 137, 6400; (m) D. Wang, G.‐P. Wang, Y.‐L. Sun, S.‐F.
Zhu, Y. Wei, Q.‐L. Zhou and M. Shi, Chem. Sci., 2015, 6, 7319;
(n) X. Han, W.‐L. Chan, W. Yao, Y. Wang and Y. Lu, Angew.
Chem. Int. Ed., 2016, 55, 6492; (o) M. G. Sankar, M. Garcia‐
Castro, C. Golz, C. Strohmann and K. Kumar, Angew. Chem.
Int. Ed., 2016, 55, 9709; (p) E. Li, H. Jin, P. Jia, X. Dong and Y.
Huang, Angew. Chem. Int. Ed., 2016, 55, 11591; (q) G. Zhan,
M. L. Shi, Q. He, W.‐J. Lin, Q. Ouyang, W. Du and Y.‐C. Chen,
Angew. Chem. Int. Ed., 2016, 55, 2147; (r) W. Zhou, H. Wang,
M. Tao, C. Zhu, T. Lin and J. Zhang, Chem. Sci., 2017,
(s) W. Yao, Z. Yu, S. Wen, H. Ni, N. Ullah, Y. Lan and Y. Lu,
Chem. Sci., 2017, , 5196; (t) H. Ni, Z. Yu, W. Yao, Y. Lan, N.
Ullah and Y. Lu, Chem. Sci., 2017, , 5699.
8, 4660;
8
8
6
For selected examples, see: (a) Y. S. Tran and O. Kwon, J. Am.
Chem. Soc., 2007, 129, 12632; (b) S. Castellano, H. D. G. Fiji,
S. S. Kinderman, M. Watanabe, P. de Leon, F. Tamanoi and O.
Kwon, J. Am. Chem. Soc., 2007, 129, 5843; (c) Q. Zhang, L.
Yang and X. Tong, J. Am. Chem. Soc., 2010, 132, 2550; (d) F.
Zhong, X. Han, Y. Wang and Y. Lu, Chem. Sci., 2012, 3, 1231;
(e) S. Kramer and G. C. Fu, J. Am. Chem. Soc., 2015, 137, 3803;
(f) Y. Gu, P. Hu, C. Ni and X. Tong, J. Am. Chem. Soc., 2015,
137, 6400; (g) H. Liu, Y. Liu, C. Yuan, G.‐P. Wang, S. F. Zhu, Y.
Wu, B. Wang, Z. Sun, Y. Xiao, Q.‐L. Zhou and H. Guo, Org.
Lett., 2016, 18, 1302; (h) H. Ni, X. Tang, W. Zheng, W. Yao, N.
Ullah and Y. Lu, Angew.Chem.Int. Ed., 2017, 56, 14222.
(a) D. O'Hagan, Nat. Prod. Rep., 2000, 17, 435; (b) J. P.
Michael, Nat. Prod. Rep., 2004, 21, 625; (c) W. Maison, in
Highlights in Bioorganic Chemistry: Pipecolic acid derivatives,
Wiley‐VCH, Weinheim, 2004, 18.
7
8
9
X. F. Zhu, J. Lan and O. Kwon, J. Am. Chem. Soc., 2003, 125,
4716.
R. P. Wurz and G. C. Fu, J. Am. Chem. Soc., 2005, 127, 12234.
10 (a) G. Zhao and M. Shi, Org. Biomol. Chem., 2005, 3, 3686; (b)
A. Panossian, N. Fleury‐Brégeot and A. Marinetti, Eur. J. Org.
Chem., 2008, 3826; (c) H. Xiao, Z. Chai, H. Wang, X. Wang, D.
Cao, W. Liu, Y. Lu, Y. Yang and G. Zhao, Chem. Eur. J., 2011,
17, 10562.
11 (a) Y. S. Tran and O. Kwon, Org. Lett., 2005, 7, 4289; (b) D.
Cruz, Z. Wang, J. Kibbie, R. Modlin and O. Kwon, Proc. Natl.
Acad. Sci. USA 2011, 108, 6769; (c) R. A. Villa, Q. Xu and O.
Kwon, Org. Lett., 2012, 14, 4634; (d) G. A. Barcan, A. Patel, K.
N. Houk and O. Kwon, Org. Lett., 2012, 14, 5388.
12 (a) Z. Shi, Q. Tong, W. W. D. Leong and G. Zhong, Chem. Eur.
J., 2012, 18, 9802; (b) Z. Shi, P. Yu, T.P. Loh and G. Zhong,
Angew. Chem. Int. Ed., 2012, 51, 7825.
13 (a) Z. Jin, R. Yang, Y. Du, B. Tiwari, R. Ganguly and Y. R. Chi,
Org. Lett., 2012, 14, 3226; (b) X. N. Zhang, G. Q. Chen, X.
Dong, Y. Wei and M. Shi, Adv. Synth. Catal., 2013, 355, 3351;
(c) G. Wang, R. Rexiti, F. Sha and X. Y. Wu, Tetrahedron 2015,
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Chemical Science
Page 6 of 6
View Article Online
DOI: 10.1039/C7SC04515H
Phosphine-catalyzed [5+1] annulation of δ-sulfonamido-substituted enones
with N-sulfonylimines: a facile synthesis of tetrahydropyridines
Leijie Zhou, Chunhao Yuan, Yuan Zeng, Honglei Liu, Chang Wang, Xing Gao, Qijun Wang, Cheng Zhang
and Hongchao Guo
One sentence of highlight: The first phosphine-catalyzed [5+1] annulation of δ-sulfonamido-substituted
enones with N-sulfonylimines works efficiently under mild conditions to give tetrahydropyridines.