Rh(II)-Catalyzed [2,3]-Sigmatropic Rearrangement of Sulfur Ylides Derived from Cyclopropenes and Sulfides

Article abstract of DOI:10.1021/acs.orglett.5b01542

(Chemical Equation Presented) A new type of Rh₂(OAc)₄-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides is reported. A series of cyclopropenes were successfully employed for [2,3]-sigmatropic rearrangement by a reaction with either allylic or propargylic sulfides. Under the optimized conditions, the reaction afforded the products in moderate to excellent yields. In these transformations, the vinyl metal carbenes generated in situ from the cyclopropenes were effectively trapped by sulfides, resulting in the formation of corresponding products upon [2,3]-sigmatropic rearrangements.

Full text of DOI:10.1021/acs.orglett.5b01542

Letter
pubs.acs.org/OrgLett
Rh(II)-Catalyzed [2,3]-Sigmatropic Rearrangement of Sulfur Ylides
Derived from Cyclopropenes and Sulfides
Hang Zhang,† Bo Wang,† Heng Yi,† Yan Zhang,† and Jianbo Wang*,†,‡
†Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular
Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
‡State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: A new type of Rh2(OAc)4-catalyzed [2,3]-sigmatropic rearrangement of sulfur ylides is reported. A series of
cyclopropenes were successfully employed for [2,3]-sigmatropic rearrangement by a reaction with either allylic or propargylic
sulfides. Under the optimized conditions, the reaction afforded the products in moderate to excellent yields. In these
transformations, the vinyl metal carbenes generated in situ from the cyclopropenes were effectively trapped by sulfides, resulting
in the formation of corresponding products upon [2,3]-sigmatropic rearrangements.
yclopropenes have diverse reactivity due to the high strain
of the small ring, which makes this type of unique
organic synthesis.7 The key intermediate, the sulfur ylide, can be
formed either by deprotonation of sulfonium salt8 or through the
reaction of sulfide with carbene. Diazo compounds are the
commonly used carbene precursors in the catalytic sulfur ylide
[2,3]-sigmatropic rearrangement, a transformation known as the
Doyle−Kirmse reaction.9 In 2012, we demonstrated that N-
tosylhydrazones could be utilized as the precursors of diazo
compounds in the Doyle−Kirmse reaction.10 In addition, other
carbene precursors, such as enyne carbonyl compounds11 and
terminal alkynes,12 are also demonstrated to participate in such
transformations.
C
compound an excellent three-carbon structure unit for organic
synthesis.1 Among the various transformations, the generation of
vinyl metal carbene intermediates from cyclopropenes under
transition-metal-catalyzed conditions has attracted considerable
attention in recent years. The metal carbene species generated
through ring-opening undergoes typical carbene transforma-
tions, such as cyclopropanations,2 C−H bond insertions,3 O−H
bond insertions,4 and other related rearrangement reactions
(Scheme 1).5 Recently, we have reported a Rh(III)-catalyzed
As the continuation of our interest in the exploration of
cyclopropenes as vinyl metal carbene precursors, we report
herein the Rh(II)-catalyzed [2,3]-sigmatropic rearrangement of
sulfur ylides derived from cyclopropenes and sulfides. This
reaction represents the first example of using cyclopropenes as
the carbene precursors in [2,3]-sigmatropic rearrangement of
sulfur ylides.
Scheme 1. Transformations of Vinyl Metal Carbene
Generated from Cyclopropene
At the outset of this study, we employed 3,3-diphenylcyclo-
propene 1a and allyl phenyl sulfide 2a as the model substrate with
Rh2(OAc)4 as the catalyst to optimize the reaction conditions
(Table 1). Upon examining the solvents, THF was proved to be
suitable for this transformation, which afforded the desired
product 3a in moderate yield (Table 1, entries 1−4). Reducing
the amount of solvent improved the yield (Table 1, entry 5).
Then, a higher yield of 90% could be obtained by increasing the
amount of 2a (Table 1, entry 6). To our delight, reducing the
synthesis of 2H-chromenes from cyclopropenes and N-
phenoxyacetamides that involves C−H bond activation and the
migratory insertion of the vinyl rhodium carbene generated from
cyclopropene.6
On the other hand, the [2,3]-sigmatropic rearrangement of
sulfur ylide is an efficient method to build C−C and C−S bonds
simultaneously, which represents a unique transformation in
Received: May 26, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01542
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Organic Letters
Letter
a
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Scope of Allylic Sulfides
b
solvent
(mL)
Rh2(OAc)4
(mol %)
temp
(°C)
time
(h)
yield
entry
1
1a/2a
(%)
toluene
(0.2)
1:1.5
2.0
70
12
54
2
3
4
DCE (0.5)
THF (0.5)
1:1.5
1:1.5
1:1.5
2.0
2.0
2.0
70
70
70
12
12
12
56
68
53
hexane
(0.5)
5
THF (0.2)
THF (0.2)
THF (0.2)
THF (0.2)
THF (0.2)
THF (0.2)
1:1.5
1:3.0
1:3.0
1:3.0
1:3.0
1:3.0
2.0
2.0
0.5
0
70
70
70
70
50
30
12
12
12
12
18
36
75
90
91
13
99
99
6
7
8
9
0.5
0.5
10
a
Reaction conditions are as follows if not otherwise noted: 1a (0.30
mmol), 2a, and Rh2(OAc)4 were stirred at the indicated temperature.
b
All of the yields refer to the isolated yields by column
chromatography. DCE = 1,2-dichloroethane.
amount of Rh catalyst to 0.5 mol % did not affect the outcome of
the reaction (Table 1, entry 7). Interestingly, 13% yield of the
desired product 3a could be obtained in the absence of the Rh
catalyst (Table 1, entry 8). This should be attributed to the
formation of free carbene through thermal rearrangement under
the heating conditions (70 °C). Finally, lowering the reaction
temperature could further improve the yield, although the
reaction needed longer time under such conditions (Table 1,
entries 9 and 10).
With the optimized conditions, the scope of allylic sulfides was
then examined. As shown in Scheme 2, aryl allyl sulfides were
reacted smoothly with cyclopropene 1a, affording the corre-
sponding products in excellent yields (3b−f). In these reactions,
the electronic nature of the substituents (3b−d) and steric effects
at ortho positions (3e, f) have no significant impact on the
outcome. It is noteworthy that naphthyl and heteroaryl
substrates 2g−i were also tolerated, giving the corresponding
products 3g−i in good to excellent yields. Next, a series of alkyl
substituted allyl sulfides were subjected to the reaction. To our
delight, the desired products 3j−l were also obtained in
moderate to good yields when the benzyl, methyl and allyl
substituted sulfides were used as the substrates. Additionally,
substituted allyl phenyl sulfides were also the suitable substrates
for this reaction. 2-Methyl-substituted allyl phenyl sulfide 2m
afforded the corresponding products 3m in 88% yield. The
structure of 3m was unambiguously confirmed by X-ray
diffraction. We assume that all of the products have the same
constitution based on the comparison of their NMR spectra. It is
worth mentioning that the desired products 3n and 3o were
obtained in 93% and 95% yields as 1.7:1 and 2.1:1 mixtures of
diastereomers.
a
Reaction conditions: 1a (0.30 mmol), 2b−o (0.90 mmol), and
Rh2(OAc)4 (0.5 mol %) in THF (0.2 mL) at 50 °C for 18 h. All the
yields refer to the isolated yields by column chromatography.
a
Scheme 3. Scope of Cyclopropenes
Next, we examined the scope of cyclopropenes. A series of 3,3-
disubstituted cyclopropenes 1b−i were examined (Scheme 3).
For cyclopropenes 1b−e the reaction all gave the corresponding
products in good yields, but prolonging the reaction time was
necessary in these cases. However, phenyl-substituted spiro
cyclopropene 1f produced a 1.7:1 mixture of diastereomers in
73% yield. On the other hand, the reaction of cyclopropenes 1g−
i, which bears two different substituents, afforded the mixture of
a
Reaction conditions: 1b−i (0.30 mmol), 2a (0.90 mmol), and
Rh2(OAc)4 (0.5 mol %) in THF (0.2 mL) at 50 °C. All of the yields
refer to the isolated yields by column chromatography. The reaction
time is 18 h.
b
B
DOI: 10.1021/acs.orglett.5b01542
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Organic Letters
Letter
E- and Z-isomeric products 3u−w in an essentially nonselective
manner.
Scheme 5. Reactions of Cyclopropene 1a with Aryl
Propargylic Sulfides 4h and 4i
Encouraged by these results, we further turned our attention to
explore the reaction of cyclopropenes with propargylic sulfides.
Gratifyingly, various allenyl-substituted sulfides 5a−m were
obtained as the anticipated products (Scheme 4). Aryl propargyl
Scheme 4. Reactions of Cyclopropenes and Aryl Propargylic
a
Sulfides
Table 2. Asymmetric [2,3]-Sigmatropic Rearrangement of
a
Sulfur Ylides
b
c
entry
cat. [Rh]*
temp (°C) time (h) yield (%) ee (%)
1
2
3
4
5
6
7
Rh2(S-TBSP)4
50
50
50
50
50
50
30
18
18
18
18
18
18
36
96
94
89
94
98
82
93
15
16
33
48
29
16
53
Rh2(S-DOSP)4
Rh2(4S-MEAZ)4
Rh2(5S-MEPY)4
Rh2(4S-MEOX)4
Rh2(4S-MPPIM)4
Rh2(5S-MEPY)4
a
Reaction conditions: 1a,b,d,e,g−i (0.30 mmol), 4a−g (0.90 mmol),
and Rh2(OAc)4 (0.5 mol %) in THF (0.2 mL) at 50 °C. All of the
yields refer to the isolated yields by column chromatography. The
reaction time is 36 h.
b
a
Reaction conditions: 1a (0.30 mmol), 2a (0.90 mmol), and catalyst
(0.5 mol %) in THF (0.2 mL). All of the yields refer to the isolated
yields by column chromatography. Enantiomeric excess values were
b
c
determined by chiral HPLC; Chiracel OD; hexane.
sulfides were reacted smoothly with cyclopropene 1a, affording
the corresponding products in good yields (5a−d). Benzyl
propargyl sulfide was also the suitable substrate for the reaction
(5e). It is worth mentioning that the desired disubstituted allene
products 5f and 5g were also obtained in 80% and 71% yields.
Next, the scope of the cyclopropenes was examined by using
phenyl propargyl sulfide 4a as the substrate. Allene products 5h−
j were obtained as single stereoisomers in moderate to good
yields, and cyclopropene 1g−i afforded the mixture of E- and Z-
isomeric products 5k−m.
1−6). Lowering the reaction temperature did not significantly
improve the result (Table 2, entry 7).
A plausible mechanism is proposed in Scheme 6. Cyclo-
propene 1 is activated by rhodium catalyst, which generates
intermediate A through ring-opening of the cyclopropene
Scheme 6. Proposed Reaction Mechanism
Unexpectedly, the reaction of cyclopropene 1a with 2-thienyl
propargyl sulfide 4h failed to give the desired allene product 5n;
instead, a cyclic product 6a was isolated in 54% yield (Scheme 5,
eq 1). This product is likely to be formed by ring closure of
intermediate allene product 5n under Lewis acid conditions. 2-
Naphthyl propargyl sulfide 4i also afforded the similar ring-
closure product 6b in 64% yield (Scheme 5, eq 2).
Finally, we attempted the asymmetric catalysis of this [2,3]-
sigmatropic rearrangement of sulfur ylides with chiral Rh(II)
catalysts. Cyclopropene 1a and phenyl allyl sulfide 2a were
chosen as the substrates, and a series of commercially available
chiral Rh(II) catalysts were screened (Table 2). All of the
catalysts afforded the products in excellent yields. However, the
enantioselectivities were only low to moderate (Table 2, entries
C
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Organic Letters
Letter
Vranken, D. L. J. Am. Chem. Soc. 1998, 120, 841. (d) Padwa, A.;
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cyclopropenes is trapped by sulfide 4, resulting in the formation
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typical [2,3]-sigmatropic rearrangement of sulfur ylide. In the
case when the R3 group is electron-rich aromatic or heteroaryl
ring, subsequent ring closure of C occurs to lead to the final ring-
closure product 6, as shown in Scheme 5, eqs 1 and 2.
In summary, a new type of Rh2(OAc)4-catalyzed [2,3]-
sigmatropic rearrangement of sulfur ylides has been developed. A
series of cyclopropenes have been successfully used for the [2,3]-
sigmatropic rearrangement by reaction with either allylic or
propargylic sulfides, and the corresponding sulfide products can
be obtained in good to excellent yields. The results significantly
extend the chemistry of vinyl metal carbenes that are generated in
situ from the cyclopropenes.
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ASSOCIATED CONTENT
* Supporting Information
Experiment details, characterization data, X-ray crystallographic
data for 3m, and 1H and 13C NMR spectra for all products. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.orglett.5b01542.
■
S
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: wangjb@pku.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This project was supported by the 973 program
(2012CB821600) and the NSFC (Grant Nos. 21272010 and
21332002).
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D
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