Phosphine-catalyzed [4 + 1] annulation between α,β-unsaturated imines and allylic carbonates: Synthesis of 2-pyrrolines

Article abstract of DOI:10.1021/jo200164v

In this report, a phosphine-catalyzed [4 + 1] annulation between α,β-unsaturated imines and allylic carbonates is described. This reaction represents the first realization of catalytic [4 + 1] cyclization of 1,3-azadienes with in situ formed phosphorus yl

Full text of DOI:10.1021/jo200164v

NOTE
pubs.acs.org/joc
Phosphine-Catalyzed [4 þ 1] Annulation between r,β-Unsaturated
Imines and Allylic Carbonates: Synthesis of 2-Pyrrolines
Junjun Tian, Rong Zhou, Haiyun Sun, Haibin Song, and Zhengjie He*
The State Key Laboratory of Elemento-Organic Chemistry and Department of Chemistry, Nankai University, Tianjin 300071,
People's Republic of China
S Supporting Information
b
ABSTRACT: In this report, a phosphine-catalyzed [4 þ 1] annulation
between R,β-unsaturated imines and allylic carbonates is described.
This reaction represents the first realization of catalytic [4 þ 1]
cyclization of 1,3-azadienes with in situ formed phosphorus ylides,
which provides highly efficient and diastereoselective synthesis of
2-pyrrolines.
ive-membered nitrogen heterocycles are important and ubi-
quitous substructures in a vast array of natural products and
circumvent the problem arising from the poor leaving group
ability of the phosphonium moiety. Even in some cases, in situ
formed phosphorus ylide intermediates are presumably involved
in such cyclizations.28 To date, many important annulations like
[3 þ 2] and [4 þ 2] annulations to generate five- and six-
membered nitrogen heterocycles have been developed under
nucleophilic phosphine catalysis.29-32 Very recently, two exam-
ples of the phosphine-catalyzed [4 þ 1] annulations to produce
five-membered oxygen heterocycles were also reported.33,34
Herein, we wish to report a PPh3-catalyzed [4 þ 1] annulation
between R,β-unsaturated imines and allylic carbonates which
represents the first synthesis of 2-pyrrolines through a phos-
phorus ylide-based [4 þ 1] cyclization of 1,3-azadienes (vide
infra).
As part of our continuous efforts on exploring phosphorus
ylide-based carbon-carbon bond forming reactions, recently we
disclosed a PBu3-catalyzed cascade [3 þ 2] cyclization-allylic
alkylation reaction of conjugated enones with allylic carbonates
(Scheme 2).35 While we attempted to extend the reaction to R,β-
unsaturated imines, to our surprise, a phosphine-catalyzed
[4 þ 1] annulation between R,β-unsaturated imines and allylic
carbonates occurred, leading to a highly efficient and diastereo-
selective synthesis of polysubstituted 2-pyrrolines (Scheme 2).
Our investigation was initiated with the model reaction of the
chalcone-derived imine 1a and allylic carbonate 2a (Table 1). In
CH2Cl2 solvent and at rt, several tertiary phosphines were
screened as catalysts (Table 1, entries 1-6). All tested phos-
phines could effectively catalyze the model reaction with PPh3
and P(4-MeO-Ph)3 giving almost quantitative yields of 3a
(entries 4 and 5). Lowering the catalyst loading of PPh3 to 10
mol % resulted in considerable reduction of the yield (entry 7).
Choosing PPh3 as the catalyst, some common solvents were also
investigated. It was found that the model reaction readily
occurred in nonpolar or polar aprotic solvents, giving the product
F
biologically interesting compounds.1-3 Among this group of
heterocycles, pyrrolines (dihydropyrroles) are not only versatile
intermediates which allow ready access to pyrrolidines and
pyrroles,4,5 but also occur in numerous natural products and
therapeutic agents.6-8 A number of synthetic approaches toward
pyrrolines therefore have been developed,9-12 but the majority
of the existing synthetic methods are centered upon 3-pyrrolines.
The synthetic methodology on 2-pyrrolines featuring an enam-
ine skeleton is pretty underdeveloped,13-22 although 2-pyrro-
lines are very important with regard to their versatility in organic
synthesis and interest in pharmaceuticals.1-8 Developing new
and efficient synthesis of 2-pyrrolines is thus highly desirable.
The formal [4 þ 1] cycloaddition of 1-aza-1,3-dienes (R,β-
unsaturated imines) with one-carbon units such as ylides pro-
vides a potential and straightforward protocol to construct
2-pyrroline ring system (Scheme 1).23 The analogous syntheses
of 2,3-dihydrofurans by the [4 þ 1] cyclization between R,β-
unsaturated carbonyl compounds and ylides have been well
documented.23,24 It is only recently that the syntheses of
2-pyrrolines via the [4 þ 1] annulations of R,β-unsaturated
imines have been realized with sulfur and nitrogen ylides
independently by Xiao13 and Tang.14 It is recognized that
phosphorus ylides have been rarely applied to ylide-based
cyclizations, primarily due to their intrinsic reactivity preference
for Wittig olefinations and the poorest leaving group ability of the
phosphonium moiety compared with sulfur and nitrogen
ylides.25,26 Consequently, the formal [4 þ 1] cycloaddition of
1-aza-1,3-dienes with phosphorus ylides has not yet been realized
prior to this study.
In the past decade, the nucleophilic phosphine catalysis has
effected many powerful annulations of electron-deficient alkenes
or alkynes with various electrophiles to construct carbo- and
heterocycles.27,28 In principle, those phosphine-mediated
annulations proceed via an addition-elimination mechanism,
by which the intramolecularity of the ring-closure step can
Received: January 24, 2011
Published: March 09, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200164v J. Org. Chem. 2011, 76, 2374–2378
|

The Journal of Organic Chemistry
NOTE
Table 1. Preliminary Survey on Model Reaction Conditionsa
Table 2. Synthesis of 2-Pyrrolines 3a
entry
catalyst
PBu3
solvent
yield of 3a (%)b
entry
R1 in 1
R2 in 1
R3 in 2
yield of 3 (%),b drc
1
2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
THF
40
58
66
99
99
50
90
99
70
60
88
1
2
Ph
Ph (1a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
Et (2a)
3a, 99, >20:1
3b, 80, >20:1
3c, 85, >20:1
3d, 97, >20:1
3e, 99, >20:1
3f, 94, >20:1
3g, 87, >20:1
3h, 88, >20:1
3i, 84, >20:1
3j, 96, >20:1
3k, 89, >20:1
3l, 95, >20:1
3m, 91, >20:1
3n, 84, >20:1
3o, 94, >20:1
3p, 90, >20:1
PhPMe2
Ph2PMe
PPh3
4-MeO-Ph Ph (1b)
3
3
4-Cl-Ph
4-F-Ph
4-CF3-Ph
3-NO2-Ph
2-furyl
Ph (1c)
4
4
Ph (1d)
5
P(4-MeO-Ph)3
P(4-F-Ph)3
PPh3
5
Ph (1e)
6
7c
6
Ph (1f)
7
Ph (1g)
8
PPh3
8
4-Cl-Ph
4-F-Ph
Ph
4-Br-Ph (1h)
4-Br-Ph (1i)
4-Cl-Ph (1j)
9
PPh3
9
10
11
PPh3
ether
10
11
12
13
14
15
16
PPh3
CH3CN
4-CF3-Ph 4-Cl-Ph (1k)
a Typical conditions: under N2 atmosphere, a mixture of 1a (0.25
mmol), 2a (0.3 mmol), and phosphine (0.05 mmol) in solvent
(2.0 mL) was stirred at rt for 24 h. b Isolated yield based on 1a and dr
>20:1 by 1H NMR of 3a. c 10 mol % of PPh3 was employed.
Ph
4-NO2-Ph (1l)
4-Cl-Ph
4-F-Ph
Ph
4-NO2-Ph (1m) Et (2a)
4-NO2-Ph (1n)
Ph (1a)
Et (2a)
n-Bu (2b)
t-Bu (2c)
Ph
Ph (1a)
a For details, see the Experimental Section. b Isolated yield based on 1.
Scheme 1. Formal [4 þ 1] Ylide Cycloaddition of 1,3-Aza-
c Determined by 1H NMR.
dienes To Generate 2-Pyrrolines
Scheme 3. Synthesis of Fused Cyclic Product 3q
Scheme 2. Phosphine-Catalyzed Annulations of Enones or
Azadienes with Allylic Carbonates
15 and 16). In all tested cases, the product 2-pyrroline 3 was
1
isolated as a single diastereomer, as determined by H and
13C NMR.
Interestingly, cyclic unsaturated imine 1o was also an effective
substrate (Scheme 3). Under the optimized conditions, the
corresponding fused cyclic product 3q was obtained in 83%
isolated yield. However, methyl- or phenyl-substituted analogues
(2d and 2e) of the allylic carbonate 2a failed in giving the
expected [4 þ 1] annulation products with the imine 1a, when
subjected to similar conditions (Scheme 4). In the case of 2d, the
imine substrate 1a was inert, but the carbonate 2d gradually
decomposed into a complex mixture under the influence of PPh3;
for the phenyl-substituted allylic carbonate 2e, a [3 þ 2]
annulation product 4 was obtained in 65% yield under the
catalysis of more nucleophilic phosphine PhPMe2. Similar
PBu3-catalyzed [3 þ 2] annulation of the carbonate 2e with
enones was also developed in our laboratory.35
3a in good to excellent yields (entries 8-11). The results in
Table 1 show that the annulation of 1a and 2a has good tolerance
to reaction conditions.
Under the preferred conditions (PPh3 used as the catalyst in
CH2Cl2 at rt for 24 h), the substrate scope and limitations for the
[4 þ 1] annulation of unsaturated imines 1 and allylic carbonates
2 were studied (Table 2). For a wide range of aryl-substituted
imines 1 (R1, R2 = aryl) with either relatively electron-poor or -
rich aryl groups, their corresponding [4 þ 1] annulations with
the allylic carbonate 2a readily proceeded, giving 2-pyrrolines 3
in good to excellent yields (entries 1-14). Bulky alkyl-substi-
tuted allylic carbonates 2b (R3 = n-Bu) and 2c (R3 = t-Bu) were
also examined in the reactions with the imine 1a, readily affording
the corresponding 2-pyrrolines 3o and 3p in high yields (entries
The structures of compounds 3 and 4 were identified by 1H,
13C NMR, and HRMS-ESI measurements. X-ray crystallographic
analysis for representative compound 3a provided unequivocal
evidence for structural assignments of 3 (for details, also see the
Supporting Information).
Possible mechanisms to account for the formation of 3 are
depicted in Scheme 5. Presumably, the catalytic cycle is initiated
with the in situ formation of the allylic phosphorus ylide 5
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NOTE
Scheme 4. Investigations on Methyl- or Phenyl-Substituted
Allylic Carbonates 2d and 2e
and to exploit the use of this reaction in organic synthesis are
ongoing.
’ EXPERIMENTAL SECTION
Unless otherwise noted, all reactions were carried out in a nitrogen
atmosphere under anhydrous conditions. Column chromatography was
performed on silica gel (200-300 mesh). The unsaturated imines 1
were readily prepared from the corresponding ketones according to the
reported procedure.39 Allylic carbonates 2 were prepared by the known
method.36
Preparation of N-(2-benzylidene-3,4-dihydro-2H-naphtha-
len-1-ylidene)-4-methylbenzenesulfonamide (1o): To a solu-
tion of 4-methylbenzenesulfonamide (0.86 g, 5.0 mmol) and (E)-2-
benzylidene-3,4-dihydronaphthalen-1(2H)-one (1.17 g, 5.0 mmol) in
CH2Cl2 (15 mL) were successively added Et3N (1.01 g, 10 mmol) and
TiCl4 (0.95 g, 5.0 mmol) at 0 °C with stirring. The resulting mixture was
heated at reflux overnight. After being cooled to room temperature and
quenched with water (100 mL), the organic layer was separated and the
aqueous layer was extracted with CH2Cl2 (3 ꢀ 50 mL). The combined
organic phase was washed with water (3 ꢀ 20 mL) and dried over
Na2SO4. After filtration and evaporation of solvent, the crude product
was further purified by recrystallization from petroleum ether/ethyl
acetate (5:1) to afford pure imine 1o (1.26 g) in 65% yield. Yellow solid;
mp 132-133 °C; 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 7.7 Hz,
1H), 7.94 (d, J = 8.2 Hz, 2H), 7.84 (s, 1H), 7.47-7.37 (m, 5H), 7.36-
7.29 (m, 3H), 7.25 (t, J = 3.8 Hz, 1H), 7.19 (d, J = 7.7 Hz, 1H), 2.97
(s, 4H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.6, 142.8,
142.7, 139.7, 138.6, 135.4, 135.3, 133.4, 132.9, 129.4, 129.3, 128.6, 128.4,
128.2, 126.8, 126.7, 30.0, 27.2, 21.4; HRMS-ESI calcd for C24H21NO2S
[M þ Na]þ 410.1185, found 410.1180.
Scheme 5. Possible Mechanisms for Formation of 3
General procedure for PPh3-catalyzed [4 þ 1] annulation
of 1 and 2: A mixture consisting of the imine 1 (0.25 mmol), allylic
carbonate 2 (0.3 mmol), and PPh3 (13 mg, 0.05 mmol) in CH2Cl2
(2 mL) was stirred at room temperature for 24 h. The reaction mixture
was then concentrated on a rotary evaporator under reduced pressure
and the residue was subjected to purification by column chromatography
(gradient elution with petroleum ether-ethyl acetate from 20:1 to 10:1)
to afford the product 3. Following the above procedure, 2-pyrrolines
3a-q were readily prepared from corresponding 1,3-azadienes 1 and
allylic carbonates 2 (Table 2 and Scheme 3).
Ethyl trans-2-(3,5-diphenyl-1-tosyl-2,3-dihydro-1H-pyr-
rol-2-yl)acrylate (3a): yield 99%; white solid; mp 153-155 °C; 1H
NMR (400 MHz, CDCl3) δ 7.68 (dd, J = 6.6, 2.9 Hz, 2H), 7.42 (m, 3H),
7.30 (d, J = 8.2 Hz, 2H), 7.03 (m, 5H), 6.72 (d, J = 7.3 Hz, 2H), 6.50
(s, 1H), 6.26 (s, 1H), 5.27 (d, J = 3.4 Hz, 1H), 5.01 (d, J = 3.0 Hz, 1H),
4.28 (q, J = 7.2 Hz, 2H), 3.61 (t, J = 3.4 Hz, 1H), 2.40 (s, 3H), 1.30 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.8, 144.8, 143.6, 142.2,
140.9, 133.6, 132.6, 129.5, 129.1, 128.4, 128.1, 128.0, 127.9, 127.4, 126.2,
125.5, 116.0, 69.7, 61.1, 53.4, 21.5, 14.1; HRMS-ESI calcd for
C28H27NO4S [M þ Na]þ 496.1553, found 496.1550.
through an addition-elimination-deprotonation process.36
Ylide 5 most likely undergoes the sterically favored γ-carbanion
addition to 1,3-azadiene 1 (path A) leading to intermediate 6,
which interconverts with intermediate 7 through a hydrogen
transfer process.37 Intermediate 7 furnishes 2-pyrroline 3 and
regenerates the PPh3 catalyst via an intramolecular Michael
addition followed by elimination of PPh3. The failure of methyl-
and phenyl-substituted allylic carbonates 2d and 2e to undergo
the [4 þ 1] annulations and the formation of the [3 þ 2]
annulation product 4 (Scheme 4) are in favor of the path A
mechanism. Another possibility that could not be completely
ruled out is the formation of the 2-pyrroline 3 through R-
carbanion addition of the allylic phosphorus ylide 5 to the imine
1 (path B). The resulting intermediate 8 subsequently under-
takes an intramolecular SN2 cyclization to afford 3 and release the
PPh3 catalyst (Scheme 5). Similar mechanisms were also pro-
posed to rationalize the [4 þ 1] annulations of 1,3-azadienes with
sulfur and nitrogen ylides.13,14 Recently, our group reported a
PPh3-catalyzed [2 þ 2 þ 2] annulation between two different
alkenes, in which an intramolecular SN2 cyclization step invol-
ving PPh3 moiety as a leaving group was also proposed.38
In summary, the [4 þ 1] annulation between R,β-unsaturated
imines and allylic carbonates has been realized under the catalysis
of PPh3, which provides highly efficient and diastereoselective
synthesis of polysubstituted 2-pyrrolines. This annulation repre-
sents the first example of the formal [4 þ 1] cycloaddition of 1,3-
azadienes and phosphorus ylides, although it is very likely that the
annulation proceeds through a typical nucleophilic phosphine-
catalyzed mechanism. Efforts to clarify the accurate mechanism
Ethyl trans-2-(3-(4-methoxyphenyl)-5-phenyl-1-tosyl-2,3-
dihydro-1H-pyrrol-2-yl)acrylate (3b): yield 80%; white solid; mp
154-155 °C; 1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J = 6.5, 2.9 Hz,
2H), 7.42 (m, 3H), 7.31 (d, J = 8.2 Hz, 2H), 7.09 (d, J = 8.2 Hz, 2H), 6.64
(d, J = 8.7 Hz, 2H), 6.56 (d, J = 8.7 Hz, 2H), 6.48 (s, 1H), 6.25 (s, 1H),
5.25 (d, J = 3.5 Hz, 1H), 4.97 (d, J = 2.7 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H),
3.77 (s, 3H), 3.57 (t, J = 3.2 Hz, 1H), 2.42 (s, 3H), 1.31 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 165.8, 158.1, 144.6, 143.7, 140.9,
134.6, 133.9, 132.7, 129.5, 129.0, 128.4, 128.0, 127.9, 125.3, 116.3, 113.5,
70.0, 61.0, 55.2, 52.7, 21.5, 14.2; HRMS-ESI calcd for C29H29NO5S
[M þ Na]þ 526.1659, found 526.1663.
Ethyl trans-2-(3-(4-chlorophenyl)-5-phenyl-1-tosyl-2,3-
dihydro-1H-pyrrol-2-yl)acrylate (3c): yield 85%; white solid; mp
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NOTE
195-197 °C; 1H NMR (400 MHz, CDCl3) δ 7.69 (dd, J = 6.3,
2.6 Hz, 2H), 7.45 (m, 3H), 7.26 (d, J = 3.4 Hz, 1H), 7.03 (d, J = 8.1
Hz, 2H), 6.98 (d, J = 8.3 Hz, 2H), 6.79 (d, J = 8.3 Hz, 2H), 6.51 (s, 1H),
6.30 (s, 1H), 5.29 (d, J = 3.5 Hz, 1H), 5.02 (s, 1H), 4.30 (q, J =
7.1 Hz, 2H), 3.57 (t, J = 2.8 Hz, 1H), 2.42 (s, 3H), 1.34 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 165.9, 145.4, 144.2, 141.0, 140.3,
133.7, 132.4, 132.1, 129.4, 129.3, 128.7, 128.4, 128.2, 128.0, 127.8, 125.6,
115.3, 69.6, 61.2, 52.1, 21.5, 14.2; HRMS-ESI calcd for C28H26ClNO4S
[M þ Na]þ 530.1163, found 530.1157.
Ethyl trans-2-(5-(4-bromophenyl)-3-(4-fluorophenyl)-1-
tosyl-2,3-dihydro-1H-pyrrol-2-yl)acrylate (3i): yield 84%; white
solid; mp 233-234 °C; 1H NMR (400 MHz, CDCl3) δ 7.56 (m, 4H),
7.28 (m, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.72 (m, 4H), 6.49 (s, 1H), 6.21
(s, 1H), 5.29 (d, J = 3.6 Hz, 1H), 4.96 (d, J = 2.7 Hz, 1H), 4.29 (q, J = 7.1
Hz, 2H), 3.59 (t, J = 3.2 Hz, 1H), 2.41 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 165.7, 161.5 (d, J = 245.4 Hz), 144.2,
144.1, 140.5, 137.9 (d, J = 2.8 Hz), 133.6, 131.4, 131.2, 129.9, 129.7,
128.9 (d, J = 7.8 Hz), 127.9, 125.5, 123.3, 116.2, 114.9 (d, J = 21.2 Hz),
69.9, 61.2, 52.4, 21.5, 14.2; HRMS-ESI calcd for C28H25BrFNO4S [M þ
Na]þ 592.0564, found 592.0560.
Ethyl trans-2-(3-(4-fluorophenyl)-5-phenyl-1-tosyl-2,3-di-
hydro-1H-pyrrol-2-yl)acrylate (3d): yield 97%; white solid; mp
183-185 °C; 1H NMR (400 MHz, CDCl3) δ 7.69 (dd, J = 6.1, 2.5 Hz,
2H), 7.44 (m, 3H), 7.29 (d, J = 8.1 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H),
6.79-6.68 (m, 4H), 6.50 (s, 1H), 6.29 (s, 1H), 5.28 (d, J = 3.5 Hz, 1H),
4.99 (br s, 1H), 4.30 (q, J = 7.1 Hz, 2H), 3.59 (t, J = 2.9 Hz, 1H), 2.41
(s, 3H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.9,
161.4 (d, J = 245.0 Hz), 145.1, 144.0, 140.6, 138.2 (d, J = 2.7 Hz), 133.8,
132.5, 129.5, 129.3, 129.0 (d, J = 7.9 Hz), 128.4, 127.93, 127.90, 125.5,
115.6, 114.8 (d, J = 21.1 Hz), 69.8, 61.1, 52.3, 21.5, 14.2; HRMS-ESI
calcd for C28H26FNO4S [M þ Na]þ 514.1459, found 514.1450.
Ethyl trans-2-(5-phenyl-1-tosyl-3-(4-(trifluoromethyl)phenyl)-
2,3-dihydro-1H-pyrrol-2-yl)acrylate (3e): yield 99%; white solid;
mp 177-178 °C; 1H NMR (400 MHz, CDCl3) δ 7.71 (m, 2H), 7.45
(m, 3H), 7.28 (s, 1H), 7.23 (s, 1H), 6.99 (d, J = 8.1 Hz, 4H), 6.53
(s, 1H), 6.34 (s, 1H), 5.32 (d, J = 3.6 Hz, 1H), 5.06 (s, 1H), 4.31 (q, J =
7.1 Hz, 2H), 3.65 (t, J = 2.8 Hz, 1H), 2.37 (s, 3H), 1.34 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 165.9, 146.3, 145.8, 144.1, 140.3,
133.8, 132.3, 129.4, 128.40, 128.43 (q, J = 32.1 Hz), 128.3, 128.0, 127.8,
127.7, 125.7, 124.9 (q, J = 3.7 Hz), 124.2 (q, J = 272.0 Hz), 114.8, 69.4,
61.2, 52.4, 21.3, 14.2; HRMS-ESI calcd for C29H26F3NO4S [M þ Na]þ
564.1427, found 564.1422.
Ethyl trans-2-(3-(3-nitrophenyl)-5-phenyl-1-tosyl-2,3-di-
hydro-1H-pyrrol-2-yl)acrylate (3f): yield 94%; white solid; mp
197-199 °C; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 6.6 Hz, 1H),
7.75 (dd, J = 6.6, 2.8 Hz, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.59 (s, 1H), 7.48
(m, 3H), 7.32 (t, J = 7.9 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H), 6.93 (d, J = 8.1
Hz, 2H), 6.56 (s, 1H), 6.38 (s, 1H), 5.38 (d, J = 3.6 Hz, 1H), 5.10 (s, 1H),
4.33 (m, 2H), 3.70 (t, J = 2.8 Hz, 1H), 2.26 (s, 3H), 1.37 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 165.9, 147.9, 146.6, 144.7, 144.1,
139.9, 134.3, 133.6, 132.1, 129.6, 129.4, 129.2, 128.5, 128.1, 127.6, 126.0,
122.1, 121.4, 113.8, 69.4, 61.4, 51.8, 21.3, 14.2; HRMS-ESI calcd for
C28H26N2O6S [M þ Na]þ 541.1404, found 541.1408.
Ethyl trans-2-(5-(4-chlorophenyl)-3-phenyl-1-tosyl-2,3-
dihydro-1H-pyrrol-2-yl)acrylate (3j): yield 96%; white solid; mp
209-210 °C; 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.4 Hz, 2H),
7.40 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 7.14-7.00 (m, 5H),
6.68 (d, J = 7.4 Hz, 2H), 6.49 (s, 1H), 6.19 (s, 1H), 5.28 (d, J = 3.5 Hz,
1H), 4.98 (d, J = 3.0 Hz, 1H), 4.28 (m, 2H), 3.63 (t, J = 3.3 Hz, 1H), 2.41
(s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.7,
144.0, 143.8, 142.0, 140.8, 134.9, 133.4, 131.1, 129.6, 129.4, 129.1, 128.2,
128.0, 127.3, 126.4, 125.6, 116.6, 69.9, 61.1, 53.4, 21.6, 14.2; HRMS-ESI
calcd for C28H26ClNO4S [M þ Na]þ 530.1163, found 530.1159.
Ethyl trans-2-(5-(4-chlorophenyl)-1-tosyl-3-(4-(trifluoro-
methyl)phenyl)-2,3-dihydro-1H-pyrrol-2-yl)acrylate (3k):
yield 89%; white solid; mp 211-212 °C; 1H NMR (400 MHz, CDCl3)
δ 7.65 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.30-7.20 (m, 4H),
7.00 (d, J = 8.1 Hz, 2H), 6.95 (d, J = 8.1 Hz, 2H), 6.52 (s, 1H), 6.27
(s, 1H), 5.33 (d, J = 3.5 Hz, 1H), 5.04 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H),
3.66 (s, 1H), 2.37 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 165.7, 146.1, 144.7, 144.3, 140.2, 135.3, 133.5, 130.7, 129.6,
129.5, 128.4 (q, J = 32.2 Hz), 128.3, 127.7, 127.6, 125.7, 125.0 (q, J = 3.6
Hz), 124.1 (q, J = 272.0 Hz), 115.3, 69.5, 61.2, 52.4, 21.3, 14.2; HRMS-
ESI calcd for C29H25ClF3NO4S [M þ Na]þ 598.1037, found 598.1036.
Ethyl trans-2-(5-(4-nitrophenyl)-3-phenyl-1-tosyl-2,3-di-
hydro-1H-pyrrol-2-yl)acrylate (3l): yield 95%; white solid; mp
224-225 °C; 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.7 Hz, 2H),
7.85 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.13 (m, 3H), 7.03
(m, 2H), 6.64(d, J= 7.4 Hz, 2H), 6.50(s, 1H), 6.16 (s, 1H), 5.48 (d, J =3.5
Hz, 1H), 4.93 (d, J = 3.4 Hz, 1H), 4.29 (m, 2H), 3.71 (t, J = 3.5 Hz, 1H),
2.43 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 165.5, 147.9, 144.4, 143.1, 141.5, 140.6, 139.2, 132.9, 129.8, 128.9, 128.3,
128.0, 127.3, 126.6, 125.9, 123.3, 119.7, 70.2, 61.2, 53.8, 21.6, 14.1; HRMS-
ESI calcd for C28H26N2O6S [M þ Na]þ 541.1404, found 541.1403.
Ethyl trans-2-(3-(4-chlorophenyl)-5-(4-nitrophenyl)-1-to-
syl-2,3-dihydro-1H-pyrrol-2-yl)acrylate (3m): 91% yield; white
solid; mp 231-232 °C; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.7
Hz, 2H), 7.86 (d, J = 8.7 Hz, 2H), 7.27 (d, J = 7.0 Hz, 2H), 7.09 (d, J = 8.0
Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 6.71 (d, J = 8.4 Hz, 2H), 6.51 (s, 1H),
6.21 (s, 1H), 5.50 (d, J = 3.5 Hz, 1H), 4.97 (d, J = 2.3 Hz, 1H), 4.30 (q, J =
7.1 Hz, 2H), 3.66 (t, J = 3.0 Hz, 1H), 2.44 (s, 3H), 1.34 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 165.6, 148.1, 144.8, 143.6, 140.2,
140.1, 138.9, 133.0, 132.5, 129.7, 128.9, 128.6, 128.4, 127.8, 125.8, 123.4,
118.9, 69.9, 61.3, 52.6, 21.6, 14.2; HRMS-ESI calcd for C28H25ClN2O6S
[M þ Na]þ 575.1014, found 575.1012.
Ethyl trans-2-(3-(furan-2-yl)-5-phenyl-1-tosyl-2,3-dihydro-
1H-pyrrol-2-yl)acrylate (3g): yield 87%; white solid; mp 122-
124 °C; 1H NMR (400 MHz, CDCl3) δ 7.64 (m, 2H), 7.42 (m, 3H),
7.35 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 7.09 (s, 1H), 6.51
(s, 1H), 6.29 (s, 1H), 6.03 (m, 1H), 5.39 (d, J = 3.0 Hz, 1H), 5.25 (d, J =
3.6 Hz, 1H), 5.14 (br s, 1H), 4.30 (m, 2H), 3.64 (t, J = 3.0 Hz, 1H), 2.40
(s, 3H), 1.32 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.5,
154.2, 145.3, 143.6, 141.4, 140.1, 133.5, 132.3, 129.4, 129.2, 128.3, 128.0,
127.9, 125.7, 113.4, 109.9, 105.8, 67.2, 61.1, 47.2, 21.5, 14.1; HRMS-ESI
calcd for C26H25NO5S [M þ Na]þ 486.1346, found 486.1345.
Ethyl trans-2-(5-(4-bromophenyl)-3-(4-chlorophenyl)-1-
tosyl-2,3-dihydro-1H-pyrrol-2-yl)acrylate (3h): yield 88%;
Ethyl trans-2-(3-(4-fluorophenyl)-5-(4-nitrophenyl)-1-to-
syl-2,3-dihydro-1H-pyrrol-2-yl)acrylate (3n): yield 84%; white
solid; mp 203-205 °C; 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.8
Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.0
Hz, 2H), 6.71 (m, 4H), 6.50 (s, 1H), 6.19 (s, 1H), 5.48 (d, J = 3.6 Hz, 1H),
4.93 (d, J = 3.0 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 3.68 (t, J = 3.3 Hz, 1H),
2.43 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 165.6, 161.6 (d, J = 245.7 Hz) 148.0, 144.6, 143.3, 140.3, 139.0, 137.4
(d, J = 3.3 Hz), 133.1, 129.7, 128.94, 128.86 (d, J = 7.8 Hz), 127.9, 125.8,
123.3, 119.3, 115.0 (d, J = 21.3 Hz), 70.1, 61.2, 52.7, 21.5, 14.2; HRMS-ESI
calcd for C28H25FN2O6S [M þ Na]þ 559.1310, found 559.1313.
1
white solid; mp 231-232 °C; H NMR (400 MHz, CDCl3) δ 7.57
(m, 4H), 7.25 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.4
Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H), 6.50 (s, 1H), 6.24 (s, 1H), 5.31 (d, J =
3.6 Hz, 1H), 4.99 (br s, 1H), 4.30 (q, J = 7.1 Hz, 2H), 3.57 (t, J = 2.9 Hz,
1H), 2.43 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 165.7, 144.4, 144.6, 140.7, 140.2, 133.4, 132.2, 131.3, 131.2,
129.8, 129.5, 128.6, 128.2, 127.7, 125.6, 123.4, 115.9, 69.7, 61.2, 52.1,
21.5, 14.2; HRMS-ESI calcd for C28H25BrClNO4S [M þ Na]þ
608.0268, found 608.0261.
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dx.doi.org/10.1021/jo200164v |J. Org. Chem. 2011, 76, 2374–2378

The Journal of Organic Chemistry
NOTE
Butyl trans-2-(3,5-diphenyl-1-tosyl-2,3-dihydro-1H-pyr-
rol-2-yl)acrylate (3o): yield 94%; white solid; mp 131-132 °C; 1H
NMR (400 MHz, CDCl3) δ 7.68 (m, 2H), 7.43 (m, 3H), 7.31 (d, J = 7.9
Hz, 2H), 7.06 (m, 5H), 6.71 (d, J = 7.6 Hz, 2H), 6.49 (s, 1H), 6.26
(s, 1H), 5.27 (d, J = 3.4 Hz, 1H), 5.00 (s, 1H), 4.30-4.05 (m, 2H), 3.61
(s, 1H), 2.40 (s, 3H), 1.68-1.59 (m, 2H), 1.38 (m, 2H), 0.93 (t, J =
7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.8, 144.8, 143.8, 142.3,
141.0, 133.6, 132.6, 129.5, 129.1, 128.4, 128.1, 128.0, 127.9, 127.4, 126.2,
125.4, 116.0, 69.7, 64.9, 53.5, 30.5, 21.6, 19.2; 13.7; HRMS-ESI calcd for
C30H31NO4S [M þ Na]þ 524.1866, found 524.1860.
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tert-Butyl trans-2-(3,5-diphenyl-1-tosyl-2,3-dihydro-1H-
pyrrol-2-yl)acrylate (3p): yield 90%; white solid; mp 93-95 °C;
1H NMR (400 MHz, CDCl3) δ 7.67 (m, 2H), 7.41 (m, 3H), 7.33
(m, 2H), 7.10 (m, 3H), 7.02 (m, 2H), 6.68 (d, J = 7.5 Hz, 2H), 6.38
(s, 1H), 6.16 (s, 1H), 5.24 (s, 1H), 4.98 (s, 1H), 3.60 (s, 1H), 2.41
(s, 3H), 1.49 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.9, 144.8,
143.7, 142.5, 142.4, 133.6, 132.7, 129.5, 129.0, 128.4, 128.1, 128.1, 127.8,
127.4, 126.3, 124.4, 116.2, 81.5, 69. 7, 53.8, 28.0, 21.6; HRMS-ESI calcd
for C30H31NO4S [M þ Na]þ 524.1866, found 524.1869.
Ethyl
trans-2-(3-phenyl-1-tosyl-2,3,4,5-tetrahydro-1H-
benzo[g]indol-2-yl)acrylate (3q): yield 83%; white solid; mp
1
142-144 °C; H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.7 Hz,
1H), 7.37 (m, 4H), 7.23 (m, 1H), 7.13-7.06 (m, 3H), 6.99 (m, 2H),
6.54 (d, J = 7.4 Hz, 2H), 6.39 (s, 1H), 6.07 (s, 1H), 4.90 (d, J = 3.3 Hz,
1H), 4.21 (m, 2H), 3.42 (s, 1H), 2.91-2.70 (m, 2H), 2.44 (s, 3H),
2.12-1.89 (m, 2H), 1.21 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 165.7, 143.8, 141.1, 141.0, 138.0, 135.8, 132.9, 131.1, 129.6,
129.4, 129.1, 128.4, 128.2, 127.7, 127.6, 127.2, 126.3, 126.0, 125.4, 70.2,
61.00, 56.6, 29.3, 23.2, 21.6, 14.0; HRMS-ESI calcd for C30H29NO4S
[M þ Na]þ 522.1709, found 522.1706.
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Ethyl 4,5-diphenyl-3-(phenyl(tosylimino)methyl)cyclopent-
1-enecarboxylate (4): A mixture of imine 1a (90 mg, 0.25 mmol),
allylic carbonate 2e (93 mg, 0.3 mmol), and PhPMe2 (8 μL, 0.05 mmol) in
CH2Cl2 (2 mL) was stirred at room temperature for 24 h. Then the
reaction mixture was concentrated on a rotary evaporator under reduced
pressure and the residue was purified by column chromatography (eluted
with petroleum ether-ethyl acetate 10:1) to afford the product 4 (90 mg)
in 65% yield: colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.1
Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.27 (m, 1H), 7.19-7.09 (m, 7H), 7.08
(m, 3H), 6.92 (m, 2H), 6.85 (m, 2H), 6.79 (s, 1H), 4.46 (d, J= 8.0 Hz, 2H),
4.10-3.88 (m, 2H), 3.66 (m, 1H), 2.46 (s, 3H), 1.01 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 184.6, 163.9, 143.9, 143.5, 142.9, 141.9,
138.2, 137.5, 136.9, 130.9, 129.4, 128.6, 128.3, 127.8, 127.5, 127.4, 127.3,
127.2, 127.0, 126.4, 70.0, 60.2, 54.8, 53.9, 21.5, 13.8; HRMS-ESI calcd for
C34H31NO4S [M þ H]þ 550.2047, found 550.2050.
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’ ASSOCIATED CONTENT
1
Supporting Information. Copies of H and 13C NMR
S
b
spectra for 1o, 3, and 4, X-ray crystallographic data (CIF file),
and an ORTEP drawing for 3a. This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: zhengjiehe@nankai.edu.cn.
(37) Similar hydrogen transfer processes were also proposed in the
phosphine-catalyzed annulation reactions. See refs 32 and 33.
(38) Cai, L.; Zhang, B.; Wu, G.; Song, H.; He, Z. Chem. Commun.
2011, 47, 1045.
’ ACKNOWLEDGMENT
(39) Esquivias, J.; Arrayas, R. G.; Carretero, J. C. J. Am. Chem. Soc.
2007, 129, 1480.
Financial support from the National Natural Science Foundation
of China (Grant Nos. 20872063 and 21072100) is gratefully acknowl-
edged. The authors also thank Professor Qilin Zhou of Nankai
University for his valuable advice in the preparation of this manuscript.
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dx.doi.org/10.1021/jo200164v |J. Org. Chem. 2011, 76, 2374–2378