Amine-catalyzed formal (3 + 3) annulations of 2-(acetoxymethyl)buta-2,3- dienoate with sulfur ylides: Synthesis of 4H-pyrans bearing a vinyl sulfide group

Article abstract of DOI:10.1039/c2cc30242j

A DABCO-catalyzed (3 + 3) annulation between 2-(acetoxymethyl)buta-2,3- dienoate and sulfur ylides has been developed, which provides a facile method for the synthesis of 4H-pyrans bearing a vinyl sulfide group. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2cc30242j

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COMMUNICATION
Amine-catalyzed formal (3 + 3) annulations of 2-(acetoxymethyl)buta-
2,3-dienoate with sulfur ylides: synthesis of 4H-pyrans bearing a vinyl
sulfide groupw
Kun Li, Jian Hu, Hui Liu and Xiaofeng Tong*
Received 12th January 2012, Accepted 20th January 2012
DOI: 10.1039/c2cc30242j
A DABCO-catalyzed (3 + 3) annulation between 2-(acetoxy-
methyl)buta-2,3-dienoate and sulfur ylides has been developed,
which provides a facile method for the synthesis of 4H-pyrans
bearing a vinyl sulfide group.
betaine intermediate B, containing several active functional
groups and would achieve some novel transformations.
To validate the above postulation, we conducted the reaction
of allenoate 1a and Me2S sulfonium salt 2a in benzene solvent
with the use of 20 mol% DABCO as catalyst and 1.2 equiv.
K2CO3 as base (Table 1, entry 1). To our delight, compound
3aa was obtained in 70% isolated yield. Thus, the sulfur atom
of the ylide was successfully transferred into the product. The
formation of 3aa could be rationalized by the following
sequence (Scheme 1). Contrary to expected cyclopropanation5
for betaine intermediate B, it undergoes 1,2-elimination of
DABCO catalyst to form intermediate C.6 Subsequently, the
methyl group of Me2S sulfonium would be attacked by AcOꢀ
or Brꢀ to yield intermediate D,7 which is followed by intra-
molecular oxa-Michael addition to produce 4H-pyran 3aa
(Scheme 1). Unfortunately, intermediate D was not detected
although several endeavors were made.
Sulfur ylides are an important class of reagents widely used for
synthesis of epoxide, aziridine and cyclopropane.1 In these
cases, sulfur ylide exhibits dual functions: good nucleophilicity
of ylide carbon to initiate addition to an electrophilic carbon
center and efficient leaving ability of sulfide to ensure formation
of three-membered product. However, the latter process renders
the sulfur moiety being wasted. Thus, special attention has been
paid to the development of novel transformations for sulfur atom
transfer from ylide into product, providing an alternative method
for the synthesis of organosulfur compounds.2 In addition,
organosulfur compounds have received great attention due to
their special biological and chemical properties.3 Herein, we
report an amine-catalyzed synthesis of S-containing 4H-pyran
3 from allenoate 1a and sulfur ylide which is generated in situ
through the reaction of sulfonium salt 2 and a base (eqn (1)).
With these primary results in hand, we then briefly screened
base and the reaction solvent in order to establish the optimized
conditions (Table 1). Finally, it was found that the combination
of K2CO3 as base and acetone as solvent afforded compound
3aa in as high as 96% yield (Table 1, entry 7). It should be
emphasized that no product 3aa was observed without DABCO
catalyst and 79% of 1a was recovered.
Under the optimized conditions, the substrate scope was
further investigated and the results are summarized in Table 2.
The reaction worked well for allenoate 1a with various aromatic
ketone-stabilized sulfonium salts 2a–2i; good to excellent yields
were attainable, regardless of the electronic nature and the
ð1Þ
Recently, we have developed the DABCO-catalyzed annula-
tions of allenoate 1a with bis-nucleophiles (DBCO: 1,4-
diazabicyclo[2.2.2]octane).4 The success can be attributed to the
following reasons: (1) the interaction between 1a and catalyst
readily leads to the formation of intermediate A via an addition–
elimination process (Scheme 1); (2) more importantly, the 4C of
intermediate A exhibits good electrophilicity for C-nucleophile
attack. These findings lead us to envision that sulfur ylide would
also be able to attack intermediate A, resulting in the formation of
Shanghai Key Laboratory of Functional Materials Chemistry,
East China University of Science and Technology, Shanghai 200237,
P. R. China. E-mail: tongxf@ecust.edu.cn; Fax: 86-21-64253881;
Tel: 86-21-64253881
w Electronic supplementary information (ESI) available: Experimental
procedures and copies of NMR spectra for all new products. See DOI:
10.1039/c2cc30242j
Scheme 1 Proposal for the formation of compound 3aa (NR3
=
DABCO).
c
2900 Chem. Commun., 2012, 48, 2900–2902
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Table 1 Optimization of reaction conditions
salt 2l was employed, ring-opened products 3al-1 and 3al-2
were isolated in 39 and 22% yield, respectively (eqn (4)). In
view of ready availability of allenoate 1a and sulfonium salts,
the transformation provides convenient access to organosulfur
compounds under mild conditions.
Entry
Base
Solvent
Yieldb (%)
ð3Þ
1
2
3
4
5
6
7
8
K2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Benzene
Benzene
PhMe
CH2Cl2
MeCN
DMF
70
59
27
88
62
47
96
88
Acetone
Acetone
a
Reaction conditions: to a solution of 2a (0.12 mmol, 1.2 equiv.), base
(0.12 mmol, 1.2 equiv.), DABCO (0.02 mmol, 20 mol%) in the
specified solvent (1.3 mL), was slowly added the solution of 1
(0.10 mmol, 1.0 equiv.) in the same solvent (1.3 mL) over 20 min.
ð4Þ
b
Surprisingly, the behavior of ester-stabilized sulfur ylides
was found to be quite different from that of ketone-stabilized
ylides. Indeed, the reaction of 1a and 2m under the same
conditions delivered cyclopropane derivative 4 in 24% yield
(Scheme 2). In 2009, Lee and co-workers found that allenoate
1a can be readily converted into compound 5 in the presence of
DABCO and base (Scheme 2).8 Thus, 4 might be formed
via normal cyclopropanation between 5 and the corresponding
ylide derived from 2m (Scheme 2).9
Isolated yield.
Table 2 Reaction scope
Entry
2 (R)
3
Yieldb (%)
Indeed, compound 5, which was independently prepared,
reacted well with sulfonium salt 2m with the assistance of
K2CO3, affording 4 in 53% yield (Scheme 3). The reaction of
5 and 2a also underwent smoothly to give cyclopropane
6 in 68% yield (Scheme 3). Sulfonium 2a has a more acidic
a-proton than 2m although the corresponding ester-stabilized
ylide is more reactive than the ketone-stabilized one.10 Thus,
deprotonation of 2a is believed to be easier, to generate
ketone-stabilized ylide which would readily intercept inter-
mediate A to form intermediate B (Scheme 1). However,
similar interception might not be achieved by 2m due to its
slower deprotonation. Therefore, intermediate A would follow
a second pathway to form compound 5 in the case of 2m
(Scheme 2).
1
2
3
4
5
6
7
8
2a (Ph)
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
96
86
75
84
84
83
88
80
91
17
2b (4-BrC6H4)
2c (4-NO2C6H4)
2d (4-ClC6H4)
2e (4-MeC6H4)
2f (3-NO2C6H4)
2g (2-furyl)
2h (2,4-Me2C6H3)
2i (3,4-Me2C6H3)
2j (Me)
9
10c
3aj
a
Reaction conditions: to a solution of 2 (0.12 mmol, 1.2 equiv.),
K2CO3 (0.12 mmol, 1.2 equiv.), DABCO (0.02 mmol, 20 mol%)
in acetone (1.3 mL), was slowly added a solution of 1 (0.10 mmol,
b
c
1.0 equiv.) in acetone (1.3 mL) over 20 min. Isolated yield. Reaction
time: 24 h.
Interestingly, when Baylis–Hillmann adduct 1c,11 instead of
1a, was subjected to otherwise identical conditions, organosulfur
compound 3ca was obtained, albeit in only 20% yield (eqn (5)).12
This result led us to conclude that the allenic moiety of D
(Scheme 1) might be beneficial for cyclization in a 6-endo-dig
fashion, which is a favorable process according to Baldwin’s rule.13
substitution pattern of the aryl groups (Table 2, entries 1–9).
However, the reaction of methyl ketone-stabilized sulfonium
salt 2j was found to be very sluggish and only 17% isolated
yield of 3aj was obtained even with a prolonged reaction time
(Table 1, entry 10).
ð2Þ
The transformation could be extended to b0-substituted sub-
strate 1b, which afforded the corresponding 4-substituted 4H-pyran
3ba in 29% yield (eqn (2)). The low yield was likely due to the steric
hindrance imposed by phenyl substituent. On the other hand,
PhSMe sulfonium 2k also reacted well with 1a to give product
3ak in 42% yield (eqn (3)). When tetrahydrothiophene sulfonium
Scheme 2 Proposal for the formation of compound 4 (NR3
=
DABCO).
c
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Scheme 3 The reaction of 5 with ylide.
In the case of 1c, further cyclization might be interrupted likely
due to the less active acrylate moiety, resulting in the isolation
of acyclic compound 3ca.
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ð5Þ
In summary, we have developed amine-catalyzed (3 + 3)
annulations of allenoate 1a and ketone-stabilized ylides under
mild reaction conditions, in which the sulfur atom of the ylide
was transferred into the product 4H-pyran. Furthermore, the
allenic moiety of 1a might provide an advantage for further
cyclization in the 6-endo-dig fashion. We believe that these
mechanistic insights would be helpful for the development of
both allenoate 1a and S-ylide related reactions.
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The financial support from NSFC (No. 21002025), the
Fundamental Research Funds for the Central Universities,
Shanghai Rising-Star Program (11QA1401700), Science and
Technology Commission of Shanghai Municipality (STCSM,
contract No. 10dz2220500), and Specialized Research Fund
for the Doctoral Program of Higher Education
(20100074120014) is highly appreciated.
Notes and references
10 R. Appel, N. Hartmann and H. Mayr, J. Am. Chem. Soc., 2010,
132, 17894.
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c
2902 Chem. Commun., 2012, 48, 2900–2902
This journal is The Royal Society of Chemistry 2012