Synthesis of 2-(α-substituted N-tosylaminomethyl)-2,5-dihydrofurans by reaction of N-sulfonylimines with arsonium or sulfonium 4-hydroxyl-cis-2- butenylides

Article abstract of DOI:10.1016/S0040-4020(00)00191-5

On treatment of N-tosylimines 1 and 4-hydroxyl-cis-butenyl arsonium salt 5 or sulfonium salt 11a with KOH in acetonitrile at room temperature, 2-(α- substituted N-tosylaminomethyl)-2,5-dihydrofurans 4 were obtained in moderate yields through a new ylide cyclization process. Ylide 2 acts formally as an equivalent of the 2,5-dihydrofuran anion. However, the reaction of 4- hydroxyl-trans-butenyl sulfonium salt 11b with N-tosylimine lb under the same conditions gave only the normal aziridination product 12. A plausible mechanism was proposed for this new 5-membered cyclization reaction, and a high yield process for the synthesis of target molecules 4 is also recommended. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00191-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2967±2974
Synthesis of 2-(a-Substituted N-Tosylaminomethyl)-2,5-
Dihydrofurans by Reaction of N-Sulfonylimines with Arsonium or
Sulfonium 4-Hydroxyl-cis-2-butenylides
*
Wei-Ping Deng, An-Hu Li, Li-Xin Dai and Xue-Long Hou
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People's Republic of China
Received 18 November 1999; revised 14 February 2000; accepted 2 March 2000
AbstractÐOn treatment of N-tosylimines 1 and 4-hydroxyl-cis-butenyl arsonium salt 5 or sulfonium salt 11a with KOH in acetonitrile at
room temperature, 2-(a-substituted N-tosylaminomethyl)-2,5-dihydrofurans 4 were obtained in moderate yields through a new ylide
cyclization process. Ylide 2 acts formally as an equivalent of the 2,5-dihydrofuran anion. However, the reaction of 4-hydroxyl-trans-butenyl
sulfonium salt 11b with N-tosylimine 1b under the same conditions gave only the normal aziridination product 12. A plausible mechanism
was proposed for this new 5-membered cyclization reaction, and a high yield process for the synthesis of target molecules 4 is also
recommended. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
that, in contrast to common N-alkyl- or N-aryl-imines,
N-sulfonylimines 1 showed unusually high reactivity
towards either semi-stabilized allylic6a±c and propargylic6e
sulfonium ylides or stabilized allylic ylides6d and even a
carboxamide stabilized ylide.6f This encouraged us to
further extend the application of ylide reagents.
The discovery of the Wittig reaction in 19531 symbolized
the formal entering of ylides into the ®eld of organic
chemistry as an important synthetic tool. Over the past
46 years, three types of ylide reactions, i.e. ole®na-
tions, cyclizations to three-membered ring compounds
(epoxidation, cyclopropanation, and aziridination), and
rearrangements, have been developed and some of them
have been successfully applied in the synthesis of complex
molecules.2 In our previous work on the reactivities of semi-
stabilized and stabilized ylides, an ef®cient asymmetric3 and
a stereocontrolled4 epoxidation, stereochemically tunable
cyclopropanations,5 and N-sulfonylimines-based aziridina-
tions,6a±d including their asymmetric version,6e,f have been
realized. In the study of ylide aziridinations, we found
We have reported in a preliminary communication that
when functionalized arsonium or sulfonium 4-hydroxyl-
cis-2-butenylides 2 were used to react with N-sulfonyl-
imines 1, instead of the expected aziridine 3, a ®ve-
membered heterocyclic ring product 4 was obtained
(Scheme 1).6g To our knowledge, this was the ®rst example
of the reaction of an imine with an ylide to form a ®ve-
membered ring compound. Herein, we report the full details
about this reaction.
Scheme 1.
Keywords: dihydrofuran; ylide; aziridination; N-tosylimines.
* Corresponding author. Tel.: 186-21-6416-3300; fax: 186-21-6416-6128; e-mail: dailx@pub.sioc.ac.cn
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00191-5

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W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
ology for preparing 2,5-dihydrofuran derivatives, the above
newly found reaction (Scheme 3) was noteworthy. Firstly,
this reaction formally looks like a direct addition of a 2,5-
dihydrofuran anion to an imine and ylide 2 acted as an
equivalent of a 2,5-dihydrofuran anion (Scheme 1).
Secondly, the present one-pot process may provide a
simpler, mild, and direct entry to dihydrofuran derivatives.10
Also, 2,5-dihydrofuran-derived amines 4 are expected to
be a type of very useful synthetic intermediate. This is not
only because they exist as a structural unit in antibiotics
such as furanomycin11 but also because they can undergo
a variety of chemical transformations,12 e.g. conversion into
g-butenolides,13 and many synthetic applications have been
reported.14
Scheme 2.
Results and Discussion
To explore the substrate scope of the above new reaction
(Scheme 3), a series of imines were examined and some
results are listed in Table 1. Table 1 shows that various
aromatic (entries 1±4), heteroaromatic (entry 5), and a,b-
unsaturated (entry 6) N-tosylaldimines are suitable
substrates for this reaction. However, when aliphatic aldi-
mines (t-BuCHvNTs, c-C6H11CHvNTs) and ketimine
(Me2CvNTs) were used, only carbonyl compounds
from the hydrolysis of precursor imines were obtained.
With N-aryl- or -alkyl-imines, no 2,5-dihydrofurans were
obtained. Among several solvents and bases tried, CH3CN
and solid KOH were the most suitable solvent and base. In
addition, the use of an excess amount of base (.2.0 equiv.)
was necessary to keep ylides in high concentration, which
could ensure that the ylide cyclization is more favored and
therefore leads to high yields of 2,5-dihydrofurans, because
the hydrolysis of imines to aldehydes and TsNH2 is com-
petitive with the ylide cyclization reaction. Under the above
conditions, moderate yields were obtained in all cases but
the ratios of syn and anti isomers (vide infra) were not
satisfactory.
Reaction of N-tosylimines 1 with arsonium salt 5 in the
presence of KOH under phase-transfer conditions
In 1991, Huang et al.7 found that, similar to other semi-
stabilized allylic arsonium ylides,8 hydroxyl-substituted
ylides produced in situ from cis-butenyl arsonium salt 5
react smoothly with benzaldehyde to form a 74:26 mixture
of vinylepoxides 6 and 7 in 58% yield (Scheme 2). Besides
the expected cis/trans product 7, the trans/trans product 6
was also produced as a result of isomerization of the
cis-double bond containing arsonium salts and/or the
corresponding ylides.
Based on our previous experiences in aziridination of
N-sulfonylimines with allylic ylides,6 we attempted to use
N-tosylimines instead of benzaldehyde to perform the above
reaction since hydroxyl-functionalized propenyl-substituted
aziridines might be prepared. Therefore, we mixed imine 1
(RˆPh, 1.0 equiv.), arsonium salt 5 (1.2 equiv.), and
powdered KOH (2.4 equiv.) in CH3CN at room temperature.
After completion of the reaction (5±12 min) and work-up,
we obtained a product with complex NMR spectra, which
could hardly be assigned the expected aziridination products
but looked rather like an unexpected product, 2,5-dihydro-
furan derivative 4a, in consideration of the complex
coupling patterns of this kind of compound9 (Scheme 3).
The ratio of syn4:anti4 could be determined by the integral
of NMR peak area of Hd, Hc, or two ole®nic protons. But the
assignment of each isomer was still pending. During the
study of the mechanism of this reaction, we had compound
9a with known geometry at hand. Fortunately, we found it is
easy to deprotect the TBS group of 9a and consequently
open the aziridine ring to construct the 2,5-dihydrofurans
4. In consideration of the mechanism of this reaction
intramolecular SN2 reaction, the stereocon®guration of
aziridines ring should dictate that of the product, i.e. cis
aziridine affords syn product and trans aziridine affords
anti product (Scheme 5). When a 3:7 mixture of cis/trans
isomers were exposed to the reaction condition, a 3:7
mixture of product was obtained in quantitative yields.
The syn and anti isomers were thus assigned and the ratio
of syn/anti is equal to 3:7.
To further con®rm the structure of the product we obtained,
a simple chemical transformation was performed, i.e. the
oxidation of product 4a with PCC. As expected, N-tosyl
furyl-substituted benzylamine 8 was obtained, whose struc-
ture was unambiguously assigned based on its spectroscopic
and microanalytical data (Scheme 4). The 2,5-dihydrofuran
structure of product 4a was therefore deduced and was
also in good agreement with its characteristic spectroscopic
data.
From the standpoints of both ylide chemistry and method-
Scheme 3.

W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
2969
Reaction of N-tosylimines 1b with cis sulfonium salt 11a
and trans sulfonium salt 11b in the presence of KOH
under phase-transfer conditions
In our previous aziridination by using allylic ylides, we
found that sulfonium ylides were better than the correspond-
ing arsonium and telluronium ylides.6b Furthermore,
arsonium ylides are relatively more toxic and expensive
than sulfonium ylides. For these reasons, cis sulfonium
salt 11a and its trans analog 11b were prepared15 and
used to replace arsonium salt 5 to react with imine 1b in
the presence of KOH (Scheme 6).
Scheme 4.
Table 1. Preparation of 2-(a-substituted N-tosylaminomethyl)-2,5-dihydro-
furans 4 by the reaction of N-sulfonylimines 1 with arsonium salt 5 under
solid±liquid phase-transfer condition (all reactions were carried out under
solid±liquid phase-transfer conditions at 258C in a ratio of imine/arsonium
salt/KOHˆ1:1.2:2.4 at a 0.5-mmol scale in CH3CN)
As expected, under the same conditions with the reaction
using arsonium salt 5 (see Scheme 3), sulfonium ylides
produced in situ from sulfonium salt 11a reacted smoothly
with imine 1b to give 2,5-dihydrofuran 4b in 52% yield,
together with 23% of epoxide 10, which came from the
reaction of ylides with p-ClC6H4CHO (from the hydrolysis
of imine 1b). However aziridine 12 (50%), accompanied
with epoxide 13 (26%), was produced instead of 2,5-
dihydrofuran products when trans sulfonium salt 11b was
used (Scheme 7).
Entry
R (imine 1)
Product
Yield of 4 (%)a
anti/synb
1
2
3
4
5
6
Phenyl± (1a)
4a
4b
4c
4d
4e
4f
54
62
60
68
62
52
61/39
68/32
57/43
61/39
62/38
51/49
p-ClC6H4± (1b)
1-Naphthyl± (1c)
2-MeOC6H4± (1d)
2-Furyl± (1e)
Cinnamyl± (1f)
a Isolated yields based on imine (5±20%) of aldehydes from the hydro-
lysis of corresponding imine were also obtained in all cases.
b Determined by 300 MHz 1H NMR analysis and syn or anti isomers
were assigned by chemical transformation.
Although similar yields were achieved in preparing 2,5-
dihydrofuran 4b using arsonium 5 and sulfonium 11a
(comparing entry 2 in Table 1 and Scheme 6), the former
was still more preferred in consideration of the easy
work-up. In the former reaction, the main by-product was
Scheme 5.
Scheme 6.

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W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
Scheme 7.
p-ClC6H4CHO and N-TsNH2 from the hydrolysis of imine
1b, which were easily separated from the product 4b, but the
main by-product in the latter reaction was epoxide 10, which
had similar Rf value to product 4b and therefore a little
dif®culty might be encountered in the work-up process
and careful handling was necessary.
ring-opening of aziridine 14a (mechanism A) or not, vinyl-
aziridine 15 was prepared according to our previous publi-
cations6a,b and used to react with MeOH in the presence of
KOH at room temperature (the same conditions as those
reactions in Schemes 3 and 6). However, neither ring-
opening products 16 or 17 were obtained under such
conditions (Scheme 9).
Mechanistic interpretations for the reactions to produce
2,5-dihydrofuran derivatives
The failure of this model reaction demonstrated that conver-
sion of 14a into 4a under such mild conditions was, at least,
not easy. In addition, there are very few examples for
aziridine ring-openings just with KOH/CH3CN at room
temperature.17 Furthermore, an intramolecular ring-opening
reaction will be easier than that of an intermolecular one. As
shown in Scheme 5, ring opening of deprotected 9a did
afford the ®ve-membered product under the same condition
To explain the results, based on the known knowledge,16
two possible ways may be speculated upon the production
of 2,5-dihydrofuran derivatives in the reactions of N-tosyl-
imines with cis 4-hydroxyl-butenylic ylides (Scheme 8).
In order to probe if product 4a came from intramolecular
Scheme 8.

W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
2971
Scheme 9.
at last. At this moment, we are not able to discriminate
which mechanism is more possible. If mechanism A is
operative, it is possible to isolate 14a during the reaction
process. At ®rst, we were not able to see any evidence of the
presence of 14a all the time, even with very careful manipu-
lation, and mechanism B is favored by this phenomenon. On
further consideration, we think, perhaps, compound 14a is
too susceptible in the reaction conditions. Therefore, we
changed the reaction conditions by using NaOH aqueous
solution and dichloromethane. Under these conditions,
compound 14a may enter the organic phase immediately
on its formation and then is prevented from further reaction.
Actually, compound 14a was obtained as an impure
product.19 IR spectra showed a clear indication of a free
reaction to form a ®ve-membered ring product owing to the
trans con®guration of the double bond (Scheme 10).
Upon this understanding, the dihydrofuran compound could
also be synthesized in high yield. When ylide 11c was
reacted with N-tosylimines, as expected, corresponding
aziridine compounds were derived in high yields under
the same reaction condition, though the stereoselectivity is
still not satisfactory, as shown in Scheme 11. The TBS
protecting group of 9a can be removed by treating with
TBAF/THF, and the aziridine ring was opened immediately
and 2,5-dihydrofuran compound 4a was obtained in
quantitative yields at re¯uxing temperature.
1
hydroxyl group and H NMR seemed to be a spectrum of
14a and 4a. On the other hand, by the analysis of 1H NMR in
DMSO-d6, a multiple peak was found, but it disappears on
treatment with D2O. From this fact, the existence of a free
hydroxyl group was further con®rmed. Anyhow, on treat-
ment of 14a with KOH/THF, only a single product of 4a
was obtained in quantitative yield. So, mechanism A of this
reaction is a very plausible one.
Conclusions
A simple and ef®cient one-pot process for the preparation of
dihydrofuran-substituted N-tosyl amines through the
reaction of N-tosylimines with arsonium or sulfonium
4-hydroxyl-cis-butenylides under very mild conditions
was developed. Ylides produced from arsonium salt 5 or
sulfonium salt 11a may be formally regarded as the
equivalents of 2,5-dihydrofuran anions. The products
dihydrofuran-substituted amines may ®nd applications in
the synthesis of many complex molecules. Based on the
results of comparative experiments, a tandem aziridination/
When trans sulfonium salt 11b is used to replace cis sul-
fonium salt 11a, the addition intermediate C is formed,
which undergoes 1,3-elimination to construct aziridine 12.
However, it cannot undergo an intramolecular ring-opening
Scheme 10.
Scheme 11.

2972
W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
intramolecular ring opening reaction mechanism was
proposed. An alternative tandem reaction is proposed for
the synthesis of dihydrofuran derivatives 4 in high yield.
(48), 133 (3.8), 117 (5.1), 91 (26), 73 (100), 69 (9.7), 57
(3.7), 44 (14); HRMS Calcd for (C14H14NO2S, M12C4H5O)
260.0745, found 260.0745. syn-4a: 1H NMR (CDCl3) d 2.36
(s, 3H), 4.37±4.41 (m, 3H), 4.90 (m, 1H), 5.38 (d,
Jˆ5.2 Hz, 1H), 5.47 (m, 1H), 5.94 (m, 1H), 7.07±7.18
(m, 7H), 7.51 (dd, Jˆ1.5, 8.3 Hz, 2H).
Experimental
2-[a-(p-Chlorophenyl) N-tosylaminomethyl]-2,5-dihydro-
furan (4b) (method A). A white solid, mp 76±778C; IR
(KBr pellet): 3250, 1600, 1495, 1440, 1325, 1160, 1090,
Materials and general procedure
All reagents and solvents, unless otherwise speci®ed, are
commercially available and used without further puri®ca-
tion. All N-sulfonylimines 1 were prepared according to
literature methods in reasonable yields.18 Arsonium salt 5
and sulfonium salts 11a and 11b were prepared by the reac-
tion of corresponding 4-hydroxyl-2-butenyl bromides with
Ph3As or dimethylsul®de, and sulfonium salt 11c was
prepared by the reaction of corresponding bromide with
dimethylsul®de in a little amount of acetone at room
temperature with excellent yields.7,15
1
1070, 1015, 890, 810,760, 690; anti-4b: H NMR (CDCl3)
d 2.36 (s, 3H), 4.44±4.54 (m, 3H), 5.00±5.04 (m, br., 1H),
5.30 (d, Jˆ7.2 Hz, 1H), 5.53±5.57 (m, 1H), 5.83±5.86 (m,
1H), 7.00±7.14 (m, 6H), 7.52±7.56 (m, 2H); MS m/z 296
(17), 294 (43.7), 281 (0.8), 262 (1.2), 223 (4.9), 193 (11.7),
165 (1), 155 (61), 138 (16), 125 (4), 111 (5.7), 91 (100), 77
(9), 69 (78.4), 65 (27), 51 (6); HRMS Cacld for
(C14H1335ClNO2S, M12C4H5O) 294.0356, found 294.0349;
Calcd for (C14H1337ClNO2S, M12C4H5O) 296.0326, found
1
296.0323. syn-4b: H NMR (CDCl3) d 2.36 (s, 3H), 4.27±
4.36 (m, 3H), 4.85±4.87 (m, br., 1H), 5.34 (d, Jˆ5.4 Hz,
1H), 5.46±5.49 (m, 1H), 5.90±5.93 (m, 1H), 7.00±7.14 (m,
6H), 7.52±7.56 (m, 2H).
General procedure for the preparation of 2,5-dihydro-
furans (method A). A 25-mL ¯ask containing a magnetic
stirring bar was charged with imine (1, 0.5 mmol), arsonium
salt 5 (0.6 mmol), and acetonitrile (4 mL, reagent grade; it
need not be dried before use). Powdered potassium
hydroxide (2.0 mmol) was subsequently added under stir-
ring. After the reaction was complete according to TLC, the
reaction mixture was ®ltered on a short silica gel column to
remove solid materials. The ®ltrate was concentrated and
puri®ed by chromatography on a preparative silica gel plate
with a mixture of light petroleum (60±908C) and ethyl
acetate (3:1) as the eluent to give a white solid product 4.
2-[a-(o-Methoxyphenyl) N-tosylaminomethyl]-2,5-dihydro-
furan (4c) (method A). A colorless oil; IR (KBr pellet):
3250, 1600, 1490, 1460, 1320, 1240, 1150, 1070, 1020, 820;
1
anti-4c: H NMR (CDCl3) d 2.27 (s, 3H), 3.72 (s, 3H),
4.32±4.49 (m, 3H), 4.60±4.72 (m, 1H), 4.93±4.96 (m,
1H), 5.49±5.52 (m, 1H), 5.62 (d, Jˆ8.6 Hz, 1H), 5.86±
5.89 (m, 1H), 6.63±6.72 (m, 2H), 6.92±7.10 (m, 4H), 7.50
(dd, Jˆ1.3, 8.2 Hz, 2H); MS m/z 360 (M111, 0.4), 359
(M1, 0.1), 342 (3.4), 290 (100), 274 (0.9), 262 (3), 223
(7.7), 203 (2.7), 189 (38), 187 (11.7), 175 (0.7), 155
(25.9), 134 (8.3), 121 (17.4), 104 (9), 91 (77.3), 77 (8.6),
69 (55), 65 (22), 51 (5.1); HRMS Calcd for (C15H16NO3S,
Oxidation of 2-(a-phenyl N-tosylaminomethyl)-2,5-di-
hydrofuran (4a). Compound 4a (99 mg, 0.3 mmol) and
PCC (65 mg, 0.3 mmol) were dissolved in anhydrous
ClCH2CH2Cl (3 mL) and stirred under re¯ux for 1 h. Two
other portions of PCC (130 mg, 0.6 mmol) were then added
to the reaction mixture at an interval of 1 h. After the reac-
tion was complete according to TLC, the reaction mixture
was ®ltered on a short silica gel column to remove solid
materials. The ®ltrate was concentrated and chromato-
graphed on a preparative silica gel plate with a mixture of
light petroleum (60±908C) and ethyl acetate (3:1) as the
eluent to give a white solid product 8, 60 mg, yield, 60%.
Mp 160±1618C; IR (KBr pellet): 3269, 1599, 1458, 1444,
1322, 1161, 1095, 1057, 929, 811, 704, 666, 566; 1H NMR
(CDCl3) d 2.30 (s, 3H), 5.27 (d, Jˆ7.7 Hz, 1H), 5.54 (d,
Jˆ7.7 Hz, 1H), 5.92 (d, Jˆ2.9 Hz, 1H), 6.11 (dd, Jˆ2.0,
3.2 Hz, 1H), 7.06±7.19 (m, 8H), 7.51 (dd, Jˆ2.0, 8.3, 2H);
MS m/z 250 (2.2), 172 (100), 157 (25.4), 143 (31.3), 128
(17.1), 91 (21), 77 (8.1), 43 (5.0); FAB-MS m/z 327 (M1);
Anal. Calcd for C18H17NO3S: C, 66.05; H, 5.18; N, 4.25.
Found: C, 66.01; H, 5.10; N, 3.98.
1
M12C4H5O) 290.0851, found 290.0844. syn-4c: H NMR
(CDCl3) d 2.27 (s, 3H), 3.74 (s, 3H), 4.20 (m, 1H), 4.32±
4.49 (m, 1H), 4.60±4.72 (m, 1H), 4.98±5.02 (m, 1H), 5.58
(d, Jˆ 8.6 Hz, 1H), 5.70±5.76 (m, 1H), 5.86±5.89 (m, 1H),
6.63±6.72 (m, 2H), 6.92±7.10 (m, 4H), 7.22 (m, 2H).
2-[a-(1-Naphthyl) N-tosylaminomethyl]-2,5-dihydrofuran
(4d) (method A). A colorless oil; IR (KBr pellet): 3300,
3040, 1600, 1520, 1420, 1335, 1165, 1100, 1080, 915;
1
anti-4d: H NMR (CDCl3) d 2.25 (s, 3H), 4.45±4.70 (m,
2H), 5.05±5.27 (m, 2H), 5.44±5.61 (m, 2H), 5.88±5.93 (m,
1H), 6.86±7.97 (m, 11H); MS m/z 360 362 (1.8), 310 (41.8),
262 (1.9), 223 (4.4), 209 (18.5), 191 (1.9), 178 (2.2), 165
(3.2), 154 (46), 141 (4.8), 139 (5), 127 (26.3), 115 (2.6), 102
(2.7), 91 (46), 89 (9), 77 (5.2), 69 (100), 65 (20.5), 51 (4.3);
HRMS Calcd for (C18H16NO2S, M12C4H5O) 310.0902,
1
found 310.0917. syn-4d: H NMR (CDCl3) d 2.27 (s, 3H),
4.45±4.70 (m, 2H), 5.05±5.27 (m, 2H), 5.44±5.61 (m, 2H),
5.82±5.85 (m, 1H), 6.86±7.97 (m, 11H).
2-(a-Phenyl N-tosylaminomethyl)-2,5-dihydrofuran (4a)
(method A). A white solid, mp 107±1088C; IR (KBr pellet):
3280, 2840, 1600, 1500, 1440, 1320, 1165, 1080, 940, 815,
2-[a-(2-Furyl) N-tosylaminomethyl]-2,5-dihydrofuran (4e)
(method A). A white solid, mp 98±998C; IR (KBr pellet):
3250, 3000, 1600, 1500, 1440, 1330, 1160, 1080, 1010, 815;
1
700, 680; anti-4a: H NMR (CDCl3) d 2.34 (s, 3H), 4.46±
1
anti-4e: H NMR (CDCl3) d 2.41 (s, 3H), 4.46±4.61 (m,
4.58 (m, 3H), 5.03±5.06 (m, br., 1H), 5.27 (d, Jˆ7.6 Hz,
1H), 5.56±5.59 (m, 1H), 5.86±5.89 (m, 1H), 7.07±7.18 (m,
7H), 7.56 (m, 2H); MS m/z 329 (M1, 5.8), 281 (62.6), 260
(22), 249 (3), 221 (11.7), 207 (11), 178 (5), 155 (18.4), 147
3H), 5.04±5.11 (m, 2H), 5.68±5.73 (m, 1H), 5.92±6.00 (m,
1H), 6.13±6.17 (m, 1H), 6.24±6.25 (m, 1H), 7.15±7.30 (m,
3H), 7.60±7.66 (m, 2H); MS m/z 250 (59.2), 238 (1.1), 223

W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
2973
(22.3), 180 (8.3), 171 (13), 155 (56.3), 139 (3.5), 107 (9.7),
95 (7.9), 91 (100), 77 (4.6), 69 (23.5), 65 (20), 51 (3.7);
HRMS Calcd for (C12H12NO3S, M12C4H5O) 250.0498,
(C11H11O2Cl) 210.0445, found 210.0439. trans-10: 1H
NMR (CDCl3) d 2.75 (br., 1H), 4.60±4.86 (m, 2H), 4.98
(m, 1H), 5.55±5.62 (m, 1H), 5.95±6.03 (m, 1H), 7.24±7.45
(m, 4H).
1
found 250.0488. syn-4e: H NMR (CDCl3) d 2.39 (s, 3H),
3.99±4.18 (m, 3H), 5.04±5.11 (m, 2H), 5.57±5.60 (m, 1H),
5.80±5.86 (m, 1H), 6.07 (m, 1H), 6.24±6.25 (m, 1H), 7.15±
7.30 (m, 3H), 7.60±7.66 (m, 2H).
The reaction of imine 1b with sulfonium salt 11b. A 25-
mL ¯ask containing a magnetic stirring bar was charged
with imine (1b, 0.5 mmol), sulfonium salt 11b
(0.6 mmol), and acetonitrile (4 mL, reagent grade; it need
not be dried before use). Powdered potassium hydroxide
(2.0 mmol) was subsequently added under stirring. After
the reaction was complete according to TLC, the reaction
mixture was ®ltered on a short silica gel column to remove
solid materials. The ®ltrate was concentrated and chromato-
graphed on a preparative silica gel plate with a mixture of
light petroleum (60±908C) and ethyl acetate (3:1) as the
eluent to afford an aziridine 12 (50%), and an epoxide 13
(26%). For compound 12: a colorless oil; trans/cisˆ1:1; IR
(KBr pellet): 3360, 1598, 1494, 1326, 1160, 1091, 1014,
2-[a-(trans-Phenylvinyl) N-tosylaminomethyl]-2,5-dihydro-
furan (4f) (method A). A white solid, mp 42±438C; IR
(KBr pellet): 3250, 2980, 1600, 1500, 1430, 1325, 1150,
1
1080, 960, 820; anti-4f: H NMR (CDCl3) d 2.33 (s, 3H),
3.73±3.77 (m, 1H), 3.86±3.93 (m, 1H), 4.15±4.20 (m, 2H),
4.57±4.61 (m, 1H), 4.74 (d, Jˆ9.2 Hz, 1H), 5.65±5.70 (m,
1H), 5.79±6.01 (m, 2H), 6.58 (d, Jˆ16.1 Hz, 1H), 7.10±
7.31 (m, 7H), 7.69±7.75 (m, 2H); MS m/z 286 (66.6), 277
(3.8), 260 (1.6), 223 (54.8), 207 (2.9), 184 (1.7), 171 (3.6),
155 (60.8), 130 (35.2), 115 (23.3), 103 (8.2), 91 (100), 77
(10.5), 69 (18.7), 51 (4); HRMS Calcd for (C16H16NO2S,
1
1
M12C4H5O) 286.0876, found 286.0881. syn-4f: H NMR
815, 687; trans-12: H NMR (CDCl3) d 1.8 (br., OH) 2.41
(CDCl3) d 2.31 (s, 3H), 3.95±4.02 (m, 1H), 4.10±4.23 (m,
2H), 4.79±4.83 (m, 1H), 4.95 (d, Jˆ7.1 Hz, 1H), 5.65±5.70
(m, 1H), 5.79±6.01 (m, 2H), 6.30 (d, Jˆ16.0 Hz, 1H), 7.10±
7.31 (m, 7H), 7.69±7.75 (m, 2H).
(s, 3H), 3.34 (dd, Jˆ7.6, 1.8 Hz, 1H), 3.75 (d, Jˆ1.8 Hz,
1H), 3.96±4.04 (m, 2H), 5.62 (ddt, Jˆ15.7, 7.6, 1.6 Hz, 1H),
6.05 (dt, Jˆ15.7, 5.0 Hz, 1H), 7.00±7.41 (m, 6H), 7.82 (d,
Jˆ8.3 Hz, 2H); MS m/z 364 (M111, 6.51), 346 (14.6), 294
(29.7), 190 (22.4), 155 (70.5), 139 (27.4), 91 (100.0);
HRMS Calcd for (C18H18NO3SCl) 363.0692, found
The preparation of compound 4a from method B. A 25-
mL ¯ask containing a magnetic stirring bar was charged
with imine (1a, 0.5 mmol), arsonium salt 5 (0.6 mmol),
dichloromethane (4 mL) and potassium hydroxide aqueous
(1 M, 1 mL) was subsequently added under stirring at 08C.
After the reaction was complete according to TLC, organic
phase was extracted by dichloromethane (10 mL), then was
concentrated and chromatographed on a preparative silica
gel plate with a mixture of light petroleum (60±908C) and
ethyl acetate (2:1) as the eluent to give product 14a as a
colorless oil (yield: 52%), then 14a was treated with KOH in
THF at room temperature. After the reaction was complete
according to TLC, the reaction mixture was ®ltered on a
short silica gel column to remove KOH. The ®ltrate was
concentrated and gave a solid product 4a in quantitative
yield. The analytical data are the same as before.
1
363.0730. cis-12: H NMR (CDCl3) d 1.8 (br., OH) 2.44
(s, 3H), 3.66 (t, Jˆ7.7 Hz, 1H), 3.96±4.04 (m, 1H), 4.22 (m,
2H), 5.15 (ddt, Jˆ15.5, 7.7, 1.7 Hz, 1H), 6.10 (dt, Jˆ15.5,
5.0 Hz, 1H), 7.00±7.41 (m, 6H), 7.88 (d, Jˆ8.2 Hz, 2H);
For compound 13: a colorless oil; trans/cisˆ1:1; IR (KBr
1
pellet): 3412, 1698, 1218, 1024, 1014, 969; trans-13: H
NMR (CDCl3) d 2.5±2.9(br., 1H) 3.35 (dd, Jˆ8.1, 1.8 Hz,
1H), 3.75 (d, Jˆ1.8 Hz, 1H), 4.15 (d, Jˆ4.6 Hz, 2H), 5.58
(ddt, Jˆ15.7, 7.8, 1.5 Hz, 1H), 6.00±6.18 (m, 1H), 7.15±
7.41 (m, 4H); MS m/z 210 (M1, 2.43), 193 (100.0), 141
(28.3), 125 (35.1), 77 (19.5), 69 (48.1); HRMS Calcd for
1
(C11H11O2Cl) 210.0445, found 210.0451. cis-13: H NMR
(CDCl3) d 2.5±2.9(br., 1H) 3.70 (dd, Jˆ8.6, 4.2 Hz, 1H),
4.00 (dd, Jˆ5.2, 1.3 Hz, 2H), 4.20 (d, Jˆ4.2 Hz, 1 H), 5.20
(ddt, Jˆ15.7, 8.6, 1.5 Hz, 1 H), 6.00±6.18 (m, 1 H), 7.15±
7.41 (m, 4H).
The reaction of imine 1b with sulfonium salt 11a. A 25-
mL ¯ask containing a magnetic stirring bar was charged
with imine (1b, 0.5 mmol), sulfonium salt 11a (0.6 mmol),
and acetonitrile (4 mL, reagent grade). Powdered potassium
hydroxide (2.0 mmol) was subsequently added under stir-
ring. After the reaction was complete according to TLC, the
reaction mixture was ®ltered on a short silica gel column to
remove solid materials. The ®ltrate was concentrated and
chromatographed on a preparative silica gel plate with a
mixture of light petroleum (60±908C) and ethyl acetate
(3:1) as the eluent to give a white solid 4b (52%) containing
a little amount of unknown compound, which can not be
separated by chromatography on a preparative silica gel
plate and an epoxide 10 (23%). The analytical data of 4b
are the same as before, anti/synˆ2:1. Epoxide 10 was
isolated as a colorless oil, cis/transˆ2:1; IR (KBr pellet):
The preparation of aziridines 9a. A 25-mL ¯ask contain-
ing a magnetic stirring bar was charged with imine (1a,
0.5 mmol), sulfonium salt 11c (0.6 mmol), and acetonitrile
(4 mL, reagent grade; it need not be dried before use).
Powdered potassium hydroxide (2.0 mmol) was subse-
quently added under stirring. After the reaction was
complete according to TLC, the reaction mixture was
®ltered on a short silica gel column to remove inorganic
salts. The ®ltrate was concentrated and chromatographed
on a silica gel column with a mixture of light petroleum
(60±908C) and ethyl acetate (10:1) as the eluent to give
pure product. A colorless oil, yield 92%. trans/cisˆ7/3. IR
(KBr pellet): 3244, 2966, 1759, 1461, 1337, 1328, 1168,
1090, 938, 920, 820, 811, 705, 677, 657; 1H NMR
(CDCl3/TMS): trans: d 20.01 (s, 6H), 0.08 (s, 9H), 2.29
(s, 3H), 3.35 (m, 1H), 3.96 (d, Jˆ4.1 Hz, 1H), 4.1±4.4 (m,
2H), 5.93 (m, 2H), 7.0±7.3 (m, 7H), 7.74 (d, Jˆ8.1 Hz, 2H).
cis: d 0.00 (s, 6H), 0.09 (s, 9H), 2.32 (s, 3H), 3.80 (t,
Jˆ7.6 Hz, 1H), 3.97 (d, Jˆ7.4 Hz, 1H), 4.1±4.4 (m, 2H),
4.78 (td, Jˆ9.6, 1.5 Hz, 1H), 5.59 (m, 1H), 7.0±7.3 (m, 7H),
1
3417, 1598, 1492, 1086, 1014, 840, 689; cis-10: H NMR
(CDCl3) d 3.06 (br., 1H), 4.52 (d, Jˆ6.8 Hz, 1H), 4.60±4.86
(m, 2H), 5.50±5.55 (m, 1H), 5.95±6.03 (m, 1H), 7.24±7.45
(m, 4H); MS m/z 210 (M1, 0.67), 193 (100.0), 141 (18.3),
125 (29.1), 77 (17.3), 69 (53.1); HRMS Calcd for

2974
W.-P. Deng et al. / Tetrahedron 56 (2000) 2967±2974
S.-W. Wang, W.-B. In Heteroatom Chemistry; Block, E., Ed.,
VCH: New York, 1990; pp 189±206. (c) Huang, Y.-Z.; Shi,
L.-L.; Yang, J.-H.; Xiao, W.-J. Youji Huaxue 1988, 8, 10.
9. A review on the structure of 2,5-dihydrofurans: (a) Dean, F. M.,
Sargent, M. V. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Charles, W. R., Eds., Pergamon Press: Oxford,
1984; Vol. 4, pp 531±597. A leading paper on the NMR study of
2,5-dihydrofurans: (b) Bar®eld, M.; Spear, R. J.; Sternhell, S. J. Am.
Chem. Soc. 1975, 97, 5160.
7.79 (d, Jˆ8.2 Hz, 2H). MS m/z 386 (6.3), 288 (14.2), 228
(11.3), 156 (69.2), 115 (22.4), 89 (77.8), 73 (100). Anal.
Cacld for C18H17NO3Si: C, 64.97; H, 7.50; N, 3.16.
Found: C, 65.13; H, 7.81; N, 3.12.
The preparation of 2,5-dihydrofuran 4a from 9a. Aziri-
dine compound 9a (0.5 mmol) was dissolved in THF(4 mL),
then a THF solution of TBAF (1 M, 0.5 mL) was added and
heated to re¯uxing temperature. After the reaction was
complete according to TLC, the reaction mixture was
®ltered on a short silica gel column. The ®ltrate was concen-
trated and chromatographed on a preparative silica gel plate
with a mixture of light petroleum (60±908C) and ethyl
acetate (2:1) as the eluent to give a solid product 4a in
quantitative yield. The ratio of anti to syn is equal to 7:3.
The analytical data are the same as before.
10. Other than typical methods for preparing 2,5-dihydrofurans,
the reaction of a,b-unsaturated ketones with dimethylsulfonium
methylide (Bravo, P.; Ticozzi, C. J. Chem. Soc., Chem. Commun.
1979, 438) or the intramolecular cyclization of allenic alcohols
(Olsson, L.-I.; Claesson, A. Synthesis 1979, 743) are also available.
Â
11. (a) Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joullie, M. M.
J. Am. Chem. Soc. 1980, 102, 7505. (b) Masamune, T.; Ono, M.
Chem. Lett. 1975, 625.
12. A discussion on the reactivities of 2,5-dihydrofurans: Sargent,
M. V.; Dean, F. M. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Charles, W. R., Eds., Pergamon Press: Oxford,
1984; Vol. 4, pp 599±656.
Acknowledgements
Financial support from the National Natural Science
Foundation of China and Chinese Academy of Sciences is
gratefully acknowledged.
13. (a) Bloch, R.; Seck, M. Tetrahedron Lett. 1987, 28, 5819.
(b) Bonadies, F.; Fabio, R. D. J. Org. Chem. 1984, 49, 1647.
14. Recent publications on the synthetic applications of 2,5-
dihydrofurans: (a) Kang, S. H.; Lee, S. B. J. Chem. Soc., Chem.
Commun. 1995, 1017. (b) McDonald, F. E.; Gleason, M. M.
Angew. Chem., Int. Ed. Engl. 1995, 34, 350. (c) Paolucci, C.;
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