Silver(I)-catalyzed tandem reactions of N-activated aziridine-propargylic esters to pyrrolidin-3-one derivatives

Article abstract of DOI:10.1016/j.tetlet.2012.09.001

An interesting silver(I)-catalyzed intramolecular cyclization of N-activated aziridine-propargylic esters 1 has been described in this context. A variety of pyrrolidin-3-one derivatives were obtained through an unexpected rare 5-exo-tet mode in moderate yields under mild conditions.

Full text of DOI:10.1016/j.tetlet.2012.09.001

Tetrahedron Letters 53 (2012) 6173–6176
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Tetrahedron Letters
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Silver(I)-catalyzed tandem reactions of N-activated aziridine-propargylic esters
to pyrrolidin-3-one derivatives
Jin-Ming Yang a, Zhen Zhang a, Yin Wei b, Min Shi a,b,
⇑
a Laboratory for Advanced Materials & Institute of Fine Chemicals, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An interesting silver(I)-catalyzed intramolecular cyclization of N-activated aziridine-propargylic esters 1
has been described in this context. A variety of pyrrolidin-3-one derivatives were obtained through an
unexpected rare 5-exo-tet mode in moderate yields under mild conditions.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 19 June 2012
Revised 17 August 2012
Accepted 20 August 2012
Available online 13 September 2012
Keywords:
Silver catalysis
Propargylic ester
1,3-Acyloxy migration
Tandem reaction
5-Exo-tet cyclization
Propargylic esters have received extensive attention as a special
class of alkynes for their rich chemistry and easy availabilities.1
The field has seen rapid growth in recent years, with a number
of impressive methods for the conversion of propargylic esters to
various synthetically valuable molecules being developed, espe-
cially in transition-metal catalyzed reactions.1b In the presence of
gold, platinum, or rhodium catalysts, propargylic esters have
highly valuable reactivity to undergo 1,2- or 1,3-acyloxy migration,
leading to the formation of a metal-carbene or an allenic interme-
diate which allowed further transformation to valuable sub-
stances.2–4
As a part of our continuous interest in transition-metal cata-
lyzed or mediated reactions of propargylic esters, we have reported
the diverse transformations of molecules derived from readily
available propargylic ester derivatives.5 In the presence of gold cat-
alyst, diynyl esters could very efficiently undergo tandem Meyer–
Schuster-type rearrangement/5-endo-dig cycloaddition to afford
2,3-disubstituted 3-pyrrolines in good yields (Scheme 1a), rather
than products derived from 1,3-acyloxy migration as reported by
Toste and Malacria et al.6 For the challenge of selective coordina-
tion of the metal catalyst to the pendant functional group rather
than the allenic moiety of allene intermediate derived from 1,3-
migration, we succeeded by developing a silver-catalyzed tandem
1,3-acyloxy migration/Mannich-type addition/elimination of sulfo-
nyl group of N-sulfonylhydrazone–propargylic esters to 5,6-dihyd-
ropyridazin-4-one derivatives (Scheme 1b).7 In the light of these
findings, we continued to explore the scope of silver or gold catal-
ysis in the transformation of propargylic esters. Herein, we report
our investigation on silver-catalyzed transformation of N-activated
aziridine-propargylic esters to pyrrolidin-3-one derivatives via
previous work:
R3
R2
R2
R1
HO
TsN
O
OAc
R2
5-endo-dig Ts
(a)
(b)
R1
R3
N
O
Ts
Ts
N
N
R1
LAu+
AcO
R1
R2
R1
OAc
R2
R3
R2
6-endo-trig
R1
R1
N
Ts
N
δ+
N
H
N
+Ag
N
R3
R3
AcO
R2
R1
this work:
OAc
O
R2
5-exo-tet
R1
R3
Ts
N
(c)
N
Ts
N
Ar
R2
N
Ts
R1
N
Ag+
Ar
R3
⇑
Corresponding author. Tel.: +86 21 54925137; fax: +86 21 64166128.
E-mail address: Mshi@mail.sioc.ac.cn (M. Shi).
Scheme 1. Distinct cyclization modes for various propargylic esters: (a) via 5-endo-
dig; (b) via 6-endo-trig; (c) via 5-exo-tet.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.09.001

6174
J.-M. Yang et al. / Tetrahedron Letters 53 (2012) 6173–6176
Table 1
When 1a was treated with PtCl2, no reaction occurred (Table 1, en-
Optimization of the reaction conditions
try 7). After identifying an appropriate catalyst, we optimized other
critical reaction parameters, such as solvent, the amount of water,
and the additives. In particular, the transformation was strongly
influenced by the solvent. In 1,2-dichloroethane (DCE), chloroben-
zene, and fluorobenzene, the desired product 2a was formed in low
yields (Table 1, entries 8, 13, and 14). Coordinative solvents, such
as acetonitrile (CH3CN), tetrahydrofuran (THF), and dioxane, were
not suitable for this transformation (Table 1, entries 9, 11, and
12). When using chloroform or 1,1,1-trichloroethane as the sol-
vent, no desired product was obtained (Table 1, entries 10 and
15). Increasing the amount of water and catalyst did not give better
results (Table 1, entries 16–19). We also made some other at-
tempts by adding some additives into the reaction, but the reaction
outcomes were disappointing (Table 1, entries 20–25). Thus, the
use of AgSbF6 (10 mol %) and 1.0 equiv water in dry dichlorometh-
ane at room temperature was found to be the most efficient in this
transformation and was used as the standard conditions.
Under the optimized conditions, we next investigated the toler-
ance of silver(I)-catalyzed tandem reactions of aziridines–propar-
gylic esters 1b–1p and the results are summarized in Table 2. As
can be seen from Table 2, all of the reactions proceeded smoothly
to give the corresponding products 2b–2d, 2g, and 2h in 40–62%
yields at room temperature when R1 and R2 were ethyl, isopropyl,
isobutyl, or cycloalkyl group, suggesting that the steric effect of R1
and R2 groups plays a significant role in this reaction (Table 2, en-
tries 1–3 and 6–7). When sulfonyl group was 4-bro-
mobenzenesulfonyl (Bs) or benzenesulfonyl, the corresponding
products were obtained in 35–61% yields (Table 2, entries 4–5
and 12–13). Moreover, whether Ar bears an electron-rich or -poor
group, the reactions proceeded smoothly to give the corresponding
adducts 2a, 2c, and 2e in 40–54% yields, indicating that the elec-
tronic property of Ar group did not have a significant impact on
the reaction outcome (Table 2, entries 8–11). Other substrates,
such as 1o and 1p tethered by a carbon or an oxygen atom respec-
tively, only afforded complex product mixtures under the standard
conditions (Table 2, entries 14–15).
OAc
cat. (10 mol%)
solvent, t, rt
Ts
N
Ts
N
N
Ns
O
2a
Ph
Entrya Catalyst Additive (equiv)
1a
Solvent
Time
(h)
Yieldb (%)
1
2
3
4
5
6
7
8
AgSbF6
AgOTf
AgBF4
AgNTf2
AgOAc
AuCl3
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (2.0)
H2O (3.0)
H2O (1.0)
H2O (1.0)
TBAB (1.0), H2O(1.0)
TBAB (0.1), H2O(1.0)
Ph3P (0.05), H2O (1.0)
Ph3P(0.1), H2O(1.0)
NaHCO3 (1.0), H2O(1.0) CH2Cl2
NaHCO3 (0.5), H2O(1.0) CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
CH3CN
CHCl3
THF
Dioxane 24
PhCl
PhF
10
24
6
65
50
30
21
n.r.
40
n.r.
47
n.r.
n.p.
n.p.
n.p.
41
25
Complex
54
32
58
63
n.p.
36
51
25
24
24
10
24
12
24
24
24
PtCl2
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
9
10
11
12
13
14
15
16
17
18c
19d
20
21
22
23
24
25
10
10
CH3CCl3 24
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10
10
10
10
24
24
4
1
1
2
36
57
n.r. = no reaction, n.p. = no desired product.
Reaction conditions: 10 mol % of catalyst; 0.1 mmol 1a; 1.0 equiv H2O, or other
additive; 1.0 mL of dry solvent.
a
b
Isolated yield.
15 mol % AgSbF6 used.
20 mol % AgSbF6 used.
c
d
Table 2
Substrate scope of silver-catalyzed cyclization of 1
R1
OAc
R2
R2
AgSbF6 (10 mol%)
R1
R3
X
X
H2O (1.0 eq), DCM, rt, 10 h
N
O
2
Ar
1
Entrya
1
R1/R2
X
R3
Ar
Yieldb (%)
1
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
1g
1h
1i
Et/Et
NTs
NTs
NTs
NBs
NBs
Ns Ph
Ns Ph
Ns Ph
2b, 62
2c, 51
2d, 40
2e, 36
2f, 43
2g, 53
2h, 44
2a, 40
2e, 52
Figure 1. ORTEP drawing of 2a.
iPr/iPr
iBu/iBu
Me/Me
Et/Et
Bs
Bs
Ph
Ph
–CH2(CH2)2CH2– NTs
–CH2(CH2)3CH2– NTs
Me/Me
Me/Me
Me/Me
iPr/iPr
Ns Ph
Ns Ph
tandem 1,3-acyloxy migration, 5-exo-tet cyclization, and an
unprecedented carbon–carbon bond cleavage (Scheme 1c).8
Initially, we started our investigation by using 2-methyl-5-(4-
methyl-N-((1-(4-nitrophenylsulfonyl)-3-phenylaziridin-2-
NTs
NBs
NTs
NTs
NBs
PhSO2N
Ns 4-FC6H4
Ns 4-BrC6H4
Bs
9
1j
1k
1l
10
11
12
13
14
15
4-MeC6H4 2a, 54
Ns 4-ClC6H4
Ns Ph
Ns Ph
2c, 54
2e, 35
2i,61
Complex
Complex
yl)methyl)phenylsulfonamido)pent-3-yn-2-yl acetate 1a, 10 mol %
AgSbF6 and 1.0 equiv of water in dry dichloromethane at room
temperature; the desired product 4-(propan-2-ylidene)-1-tosyl-
pyrrolidin-3-one 2a was formed in 65% yield after 10 h (Table 1,
entry 1). The structure of 2a has been unequivocally confirmed
by X-ray diffraction and its ORTEP drawing is shown in Figure 1.9
Other catalysts, such as AgOTf, AgBF4, AgNTf2, AgOAc, and AuCl3
gave no better results than that of AgSbF6 (Table 1, entries 2–6).
1m Me/Me
1n
1o
1p
Me/Me
Me/Me
Me/Me
C(CO2Me)2 Ns Ph
Ns Ph
O
Ns = 4-O2NPhSo2, Bs = 4-BrPhSo2.
a
Reaction conditions: 10 mol % of AgSbF6; 0.1 mmol of 1; 1.0 equiv of H2O;
1.0 mL of dry DCM at room temperature for 10 h.
b
Isolated yield.

J.-M. Yang et al. / Tetrahedron Letters 53 (2012) 6173–6176
6175
On the basis of a GC–MS and recycling preparative HPLC
study,11 4-nitrobenzenesulfonamide was observed to serve as an-
other byproduct along with the desired product 2a in the silver-
catalyzed tandem reaction of 1a.
Based on the above investigations, we proposed a plausible
reaction mechanism for this silver(I)-catalyzed tandem reaction
in Scheme 3. The cationic silver(I) first coordinates to the alkyne
moiety, affording intermediate A, which undergoes a 3,3-sigma-
tropic rearrangement to give carboxyallene 3.12 Then the cationic
silver(I) coordinates to the nitrogen atom of aziridine moiety and
results in the formation of intermediate B, which undergoes a 5-
exo-tet cyclization13 to form intermediate C and regenerates Ag(I)
specie. Meanwhile it releases an aziridine moiety, which decom-
poses to complex product mixtures including 4-nitrobenzenesulf-
onamide or 4-bromobenzenesulfonamide. Finally, in the presence
of water, intermediate C undergoes hydrolysis to afford the desired
product 2.
In conclusion, we have developed an interesting silver(I)-cata-
lyzed intramolecular cyclization of N-activated aziridine–propar-
gylic esters for the construction of a variety of pyrrolidin-3-one
derivatives through an unexpected rare 5-exo-tet mode under mild
conditions. Further investigation on the mechanistic insights and
the extension of this procedure to the synthesis of other heterocy-
cles are under way in our laboratory.
Figure 2. ORTEP drawing of 3e.
OAc
OAc
AgSbF6 (10 mol%)
Bs
N
Bs
N
dry toluene, rt, 30 min
no water
N
Bs
N
Bs
Bs
Ph
Ph
1e
OAc
3e, 50% yield
AgSbF6 (10 mol%)
N
Bs
Bs N
Acknowledgments
H2O (1.0 eq), DCM, rt, 10 h
N
O
We thank the Shanghai Municipal Committee of Science and
Technology (11JC1402600), the National Basic Research Program
of China (973)-2009CB825300, the Fundamental Research Funds
for the Central Universities, and the National Natural Science Foun-
dation of China for financial support (21072206, 20472096,
20872162, 20672127, 21121062 and 20732008) and Mr. Jie Sun
for performing X-ray diffraction.
2e, 58% yield
Ph
3e
Scheme 2. The control experiment of 1e.
To verify the reaction pathway, the control experiment has been
performed by treating 1e with the best silver catalyst AgSbF6 in dry
toluene (without water) and it was found that the 1,3-acyloxy
migration product 3e could be obtained in 50% yield after
30 min. Compound 3e was characterized by NMR, ESI-MS, and IR
spectroscopic data and its structure has been further confirmed
by a X-ray diffraction study of the single crystals. Its ORTEP draw-
ing is shown in Figure 2 and the related CIF data are presented in
Supporting Information.10 When using 3e as the starting material
and subjected to the standard conditions, 2e was formed in 58%
yield, indicating that compound 3e was the intermediate of this
reaction (Scheme 2).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
09.001.
References and notes
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O
O
OAc
R2
AcO
Ts
R2
R1
Ag+
Ag+
R2
R1
R3
Ag+
N
R1
Ts
N
Ts
N
Ar
N
R3
N
N
3
Ar
A
Ar
1
R3
Ag+
H2O
R2
O
Ag+
AcO
R2
R1
O
O
Ts
N
Ts
N
R2
N
Ar
R1
R1 aziridine moiety
HOAc
Ts
2
C
N
Ag+
R3
B
Scheme 3. A plausible reaction mechanism.

6176
J.-M. Yang et al. / Tetrahedron Letters 53 (2012) 6173–6176
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System: Monoclinic; Lattice Type: Primitive; Lattice Parameters:
a = 5.2624(2) Å, alpha = 90°; b = 11.5073(5) Å, beta = 92.5620(10) deg.;
c = 22.9797(9) Å, gamma = 90°; V = 1390.17(10) Å3; Space group: P2(1)/n;
Z = 18; Dcalc = 1.335 g/cm3; F000 = 592; Diffractometer: Rigaku AFC7R;
Residuals: R; Rw: 0.0422, 0.1240.
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10. The crystal data of 3e have been deposited in CCDC with number 802906.
Empirical Formula: C29H28Br2N2O6S2; Formula Weight: 724.47; Crystal Color,
Habit: colorless; Crystal Dimensions: 0.369 Â 0.345 Â 0.311 mm; Crystal
System: Monoclinic; Lattice Type: Primitive; Lattice Parameters:
a = 14.6715(16) Å, alpha = 90°; b = 11.4067(13) Å, beta = 98.450(2) deg.;
c = 18.823(2) Å, gamma = 90°; V = 3115.9(6) Å3; Space group: P2(1)/n; Z = 4;
Dcalc = 1.544 g/cm3; F000 = 1464; Diffractometer: Rigaku AFC7R; Residuals: R;
Rw: 0.0622, 0.1622.
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11. See Supporting Information.
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1502; (c) Uenishi, J.; Fujikura, Y.; Kawai, N. Org. Lett. 2011, 13, 2350–2353.
9. The crystal data of 2a have been deposited in CCDC with number 776038. Empirical
Formula: C3.11H3.78N0.22O0.67S0.22; Formula Weight: 62.08; Crystal Color, Habit:
colorless, prismatic; Crystal Dimensions: 0.45 Â 0.33 Â 0.26 mm; Crystal
12. (a) Fukuyama, T.; Ohta, Y.; Brancour, C.; Miyagawa, K.; Ryu, I.; Dhimane, A.;
Fensterbank, L.; Malacria, M. Chem. Eur. J. 2012, 18, 7243–7247; (b) Kikuchi, S.;
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