Asymmetric Catalytic [2,3] Stevens and Sommelet–Hauser Rearrangements of α-Diazo Pyrazoleamides with Sulfides

Article abstract of DOI:10.1002/anie.201907164

Catalytic enantioselective [2,3] Stevens and Sommelet–Hauser rearrangements of α-diazo pyrazoleamides with sulfides were achieved by utilizing chiral N,N′-dioxide/nickel(^II) complex catalysts. These rearrangements proceeded well under mild reac

Full text of DOI:10.1002/anie.201907164

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Accepted Article
Title: Asymmetric Catalytic [2,3]-Stevens and Sommelet–Hauser
Rearrangements of α-Diazo Pyrazoleamides with Sulfides
Authors: Xiaobin Lin, Wei Yang, Wenkun Yang, Xiaohua Liu, and
Xiaoming Feng
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10.1002/anie.201907164
Angewandte Chemie International Edition
RESEARCH ARTICLE
Asymmetric Catalytic [2,3]-Stevens and Sommelet–Hauser
Rearrangements of -Diazo Pyrazoleamides with Sulfides
Xiaobin Lin, Wei Yang, Wenkun Yang, Xiaohua Liu,* and Xiaoming Feng*
Abstract: Catalytic enantioselective [2,3]-Stevens and Sommelet–
Hauser rearrangements of -diazo pyrazoleamides with sulfides were
achieved by utilizing chiral N,N′-dioxide/nickel(ӀӀ) complex catalysts.
These rearrangements proceeded well under mild conditions,
providing a rapid and facile access to a series of functionalized 1,6-
dicarbonyls or sulfane-substituted phenylacetates with high to
excellent enantioselectivity. The catalytic system showed excellent
stereo-control, discriminating between the heterotopic lone pairs of
sulfur and controlling both the 1,3-proton transfer and the [2,3]-σ
rearrangement.
Introduction
Optically active sulfur-containing organic compounds are
important in organic chemistry[1] and pharmaceutical
applications[2] (Scheme 1a). The development of novel methods
for the construction of such compounds has attracted attention in
the past decades.[3] Among them, [2,3]-Stevens rearrangement[4]
and Sommelet–Hauser reaction[5] of sulfonium ylides provide
direct and elegant routes to sulfur-containing variant.[6] Whereas
catalytic enantioselective [2,3]-Stevens rearrangement of allylic
ammonium salts has been achieved,[7] the related rearrangement
of sulfonium ylides remains elusive.[6,8] The asymmetric catalytic
Sommelet–Hauser reaction[5] is potentially more challenging
because dearomatization and rearomatization steps involved in
the process.
One difficulty in [2,3]-Stevens and Sommelet–Hauser
rearrangements lies in the generation of ylide intermediates,
which usually requires stoichiometric strong bases.[5,7] This issue
could be addressed by the use of reaction between transition-
metal-carbene and sulfides to generate highly reactive sulfonium
ylide intermediates.[9] For example, Wang and co-workers
described two examples of Rh(II)-catalyzed thia-Sommelet–
Hauser rearrangement of α-diazoesters.[9b-c] However, when the
Scheme 1. Sulfur-containing drugs and catalytic asymmetric [2,3]-sigmatropic
rearrangements.
chiral Rh(II) catalyst was used to promote the enantioselective
version, only racemic product was yielded (Scheme 1b). In
comparison with asymmetric Doyle–Kirmse reaction,[10]
stereocontrol is difficult. We propose that the related highly
enantioselective versions could be achieved if four points are
under control during the whole process. Firstly, chiral sulfonium
ylide could be readily generated through the differentiation of the
heterotopic lone pairs of the sulfur compound. Secondly, a chiral
C1-center in sulfonium ylide tautomer IV generates via
diastereoselective proton transfer from C2' of ylide III. Thirdly,
racemization or epimerization of the chiral ylide tautomers could
be minimized before the following relatively slow [2,3]-sigmatropic
rearrangement. Finally, a chiral intermediate-induced or catalyst-
controlled [2,3]-sigmatropic rearrangement occurs without steric
repulsion in an envelope transition state.
enantioselective
[2,3]-Stevens
and
Sommelet–Hauser
rearrangements are much more complicated, because there are
vicinal S- and C-stereogenic centers in the reaction intermediate
before [2,3]-rearrangement step. In addition, the [2,3]-
rearrangement step is a remote functionalization whose
[*]
X. B. Lin, W. Yang, W. K. Yang, Prof. Dr. X. H. Liu, Prof. Dr. X. M.
Feng.
Key Laboratory of Green Chemistry & Technology, Ministry of
Education, College of Chemistry, Sichuan University
Chengdu 610064 (China)
E-mail: liuxh@scu.edu.cn; xmfeng@scu.edu.cn.
Recently, our group designed -diazo pyrazoleamides as
new carbene precursors for highly enantioselective Doyle–Kirmse
reaction in the presence of chiral N,N′-dioxide/Ni(ӀӀ) complex
Supporting information for this article is given via a link at the end
of the document.((Please delete this text if not appropriate))
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10.1002/anie.201907164
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RESEARCH ARTICLE
catalysts.[10a,11] We envision that this catalytic system could be
adopted for the enantioselective [2,3]-Stevens and Sommelet–
Hauser rearrangements of sulfonium ylides by introduction of
vinyl or aryl substituent to the -diazo pyrazoleamides (Scheme
1c). The excellent chiral pocket created by chiral N,N′-dioxides
might be capable of directing the enantioselective nucleophilic
attack to Ni(II)-carbene intermediate, generating a S-stereogenic
center; and chiral Lewis acid-bounded ylides might govern the
issues in 1,3-proton shift and [2,3]-sigmatropic rearrangement. If
the hypothesis mentioned above works, it will provide an efficient
solution to such challenging reactions. Herein, we report the
results in enantioselective [2,3]-Stevens and Sommelet–Hauser
rearrangements of vinyl and aryl -diazo pyrazoleamides with
sulfides. Various functionalized 1,6-dicarbonyls and sulfane-
substituted phenylacetates are available in high to excellent
enantioselectivity.
acids, molecular sieves, and others (See Table S4 for details).
AgNTf2, in favor of the reactivity and enantioselectivity in
Doyle−Kirmse reaction,[10] resulted in quick decomposition of the
diazo substrate 1a, and no desired product was detected (entry
2). Interestingly, the addition of 3-phenylpropanoic acid was
advantageous to the overall outcomes, affording the product 3a
in 62% yield with 83:17 dr and 94.5:5.5 er (entry 3). Then other
parameters including solvent (entry 4), temperature (entry 5), as
well as the loadings of additive and catalyst (entries 6 and 7) were
carefully investigated (see SI for details), and the optimized
conditions for [2,3]-Stevens rearrangement entailed the use of L2-
PiPr2/Ni(OTf)2 complex (5 mol%) as the catalyst, and 3-
phenylpropanoic acid (20 mol%) as the additive in MeOAc (0.2 M)
at 20 C for 35 minutes. Under such conditions, the product 3a
was isolated in 76% yield with 83:17 dr and 97:3 er (entry 7).
With the optimized reaction conditions in hand, the substrate
generality in the [2,3]-Stevens rearrangement was evaluated
(Table 2). This catalytic system was applicable to a range of vinyl
substituted -diazo compounds and aryl thioacetates. In detail,
enantioselective [2,3]-Stevens rearrangement of diazo
compounds 1b-1f bearing chloride or methyl substituents at
different positions of the phenyl groups afforded the targeted
products 3b-3f in 55−83% yield with 79:21 to 84:16 dr and
92.5:7.5 to 96.5:3.5 er within 70 minutes (entries 2-6). The diazo
compounds bearing 2-naphthyl group and heterocyclic rings, also
performed well to yield the corresponding products (3g-3j) in
excellent enantio- and diastereoselectivity (entries 7-10). The low
yields of the furyl-containing products 3h and 3i were attributed to
the quick decomposition of the corresponding diazo substrates
(39% and 51% yield; entries 8 and 9). Furthermore, if the Z/E
mixture of 1a was used for the reaction, it was found that a
majority of Z-1a was recovered, and the E-isomer was consumed,
yielding the desired product 3a in 46% yield, 84:16 dr and 97:3 er.
It indicated that the Z-1a was unfavorable in this asymmetric [2,3]-
Stevens rearrangement.
Results and Discussion
Initially, [2,3]-Stevens rearrangement of vinyl substituted -diazo
pyrazoleamide 1a with (phenylthio)acetate 2a was selected as the
model reaction (Table 1). Ni(OTf)2 with chiral N,N′-dioxide ligands
bearing a varied amino acid backbone, amide substituent, and
carbon linker was firstly evaluated (See Table S1 for details). It
was found that L2-PiPr2/Ni(OTf)2 complex could promote the
asymmetric [2,3]-Stevens rearrangement smoothly, providing the
desired product 3a with a promising results (Table 1, entry 1; 48%
yield, 75:25 dr, and 81:19 er). Next, different types of additives
were explored, such as organic and inorganic bases, organic
Table 1: Condition optimization for asymmetric [2,3]-Stevens rearrangement
Subsequently, the scope of the phenylthioacetate derivatives
2 was also examined (Table 2, entries 11-17). The meta- or para-
substituents on the phenyl group of sulfides 2 had little influence
on the reactivity, and all the reactions finished in 15−30 min. As
shown in Table 2, electron-donating and -withdrawing substituted
arylthioacetates 2 could be transformed into the corresponding
products (4a-4f) in 69−84% yield with 78:22 to 83:17 dr and 93:7
to 96:4 er (entries 11-16). In comparison, electron-donating
substituted sulfides slightly decreased the enantioselectivity (4a
and 4b vs 4c; 4d vs 4e). It was noteworthy that the sulfides with
ortho-substituent on the phenyl group could not deliver the final
product efficiently due to the problem of steric hindrance. In
addition, a gram-scale experiment was conducted with phenyl 2-
(phenylthio)acetate to yield the product 3z (entry 17), whose
absolute configuration of the major stereoisomer was assigned to
be (2R,3S,E) based on the X-ray crystallographic analysis (See
SI for details).[12]
Entry[a]
1
Sol. / Add. / Time
Yield [%][b]
dr[c]
er[c]
EtOAc / - / 2 h
48
0
75:25
--
81:19/73:27
--
2[d]
EtOAc / AgNTf2 / 10 min
EtOAc / acid / 0.5 h
MeOAc / acid / 20 min
MeOAc / acid / 35 min
MeOAc /acid / 35 min
MeOAc / acid / 35 min
3[e]
62
69
73
76
76
83:17
84:16
83:17
83:17
83:17
94.5:5.5/87:13
94.5:5.5/87:13
97:3
4[e]
5[e,f]
6[f, g]
7[h]
97:3
97:3
[a] Unless otherwise noted, the reactions were carried out with 1a (0.1 mmol),
sulfide 2a (1.0 equiv), Ni(OTf)2/L2-PiPr2 (1:1, 10 mol%) in solvent (0.1 M) at 35
C. [b] Isolated yields of 3a. [c] Determined by HPLC on a chiral stationary
phase. [d] AgNTf2 (2 mol%) was added. [e] Ph(CH2)2CO2H (10 mol%) was
added. [f] At 20 C. [g] Ph(CH2)2CO2H (20 mol%) was added. [h] 1a (0.1 mmol),
sulfide 2a (2.5 equiv), Ni(OTf)2/L2-PiPr2 (1:1, 5 mol%), Ph(CH2)2CO2H (20
mol%) in MeOAc (0.2 M) at 20 C.
Encouraged by the outcomes in the asymmetric [2,3]-
Stevens rearrangement, we turned our attention to the
enantioselective Sommelet−Hauser rearrangement of aryl
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10.1002/anie.201907164
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Table 2: Substrate scope for the asymmetric [2,3]-Stevens rearrangement.
Table 3: Optimization of the reaction conditions of asymmetric
Sommelet−Hauser rearrangement
Entry[a]
1
R1
R2
Yield [%][b]
76 (3a)
66 (3b)
55 (3c)
83 (3d)
62 (3e)
75 (3f)
61 (3g)
39 (3h)
51 (3i)
dr[c]
er[d]
C6H5
C6H5
83:17
84:16
83:17
82:18
79:21
80:20
84:16
85:15
84:16
88:12
78:22
81:19
80:20
81:19
83:17
81:19
19:1
97:3
Entry[a]
Sulfide
2a
T (C)
Time
3 h
Yield (%)[b]
57 (6a)
62 (6a)
49 (8a)
64 (8b)
88 (8b)
84 (8b)
80 (8b)
er[c]
2
4-MeC6H4
4-ClC6H4
3-MeC6H4
3-ClC6H4
2-MeC6H4
2-naphthyl
2-furyl
3-furyl
3-thienyl
C6H5
C6H5
96:4
1
35
0
80.5:19.5
85:15
88.5:11.5
92.5:7.5
93:7
3[e]
4
C6H5
94.5:5.5
96.5:3.5
92.5:7.5
96:4
2
2a
3 d
C6H5
3
7a
0
3 d
5
C6H5
4
7b
0
3 d
6
C6H5
5[d]
6[d,e]
7[d,f]
7b
0
2 d
7
C6H5
96:4
7b
0
1.5 d
1.5 d
93:7
8
C6H5
96:4
7b
0
93:7
9
C6H5
96.5:3.5
96.5:3.5
93:7
[a] Unless otherwise noted, the reactions were carried out with 5a (0.1 mmol),
2a or 7 (1.0 equiv), Ni(OTf)2/L2-PiPr2 (1:1, 10 mol%), and CH3CN (0.1 M) until
the diazo compound 5a was consumed. [b] Isolated yields. [c] Determined by
HPLC on a chiral stationary phase. [d] 7b (2.5 equiv) under N2 atmosphere. [e]
MeOAc (0.1 M) instead of CH3CN (0.1 M). [f] Ph(CH2)2CO2H (10 mol%) was
added.
10
11
12
13
14
15
16
17[f]
C6H5
48 (3j)
4-MeC6H4
4-iPrC6H4
4-BrC6H4
3-MeC6H4
3-BrC6H4
2-naphthyl
C6H5
84 (4a)
84 (4b)
79 (4c)
83 (4d)
69 (4e)
79 (4f)
25 (3z)
C6H5
93.5:6.5
94.5:5.5
94.5:5.5
96:4
C6H5
sulfide 7b bearing a trifluoromethoxy group was chosen as the
best substrate due to its good solubility in CH3CN and potential
medicinal value of fluorine-containing compounds[13], thus the
rearranged product 8b was generated in 64% yield and 92.5:7.5
er (entry 4). When N2 atmosphere, and 2.5 equivalents of sulfide
7b were employed, a yield of 88% with high enantiometric ratio
(93:7 er) was obtained (entry 5). The use of CH3CO2Me instead
of CH3CN as the reaction solvent enabled the transformation with
maintained enantioselectivity and a slightly reduced yield (entry
6). In this case, the additive of 3-phenylpropanoic acid did not play
a positive role on enantioselectivity (entry 7). It is noteworthy that
the related oxidation byproduct from the diazo compound 5a was
isolated under air atmosphere, but no [1,2]-Stevens
rearrangement product was observed.[9a,14]
C6H5
C6H5
C6H5
93.5:6.5
99:1
C6H5
[a] The condition is as the same as in footnote [h] in Table 1. [b] Isolated yield.
[c] Determined by 1H NMR analysis. [d] Determined by HPLC on a chiral
stationary phase. [e] Ni(OTf)2/L2-PiPr2 (1:1, 10 mol%) in CH3CO2Me (0.1 M). [f]
1a (4.0 mmol), phenyl 2-(phenylthio)acetate (2.5 equiv). The result was
obtained after recrystallization.
substituted α-diazo pyrazoleamides 5 with sulfides. Initially, the -
diazo(phenyl) pyrazoleamide 5a and ethyl 2-(phenylthio)acetate
2a were employed as the model substrates to optimize the
reaction conditions (Table 3). Similarly, Ni(OTf)2 was applied to
recognize various ligands derived from chiral amino acids, and
the same ligand as L2-PiPr2 was confirmed to be optimal one in
CH2Cl2 at 35 C, giving the desired product 6a in 51% yield with
74:26 er after 3 hours (See Table S8 for details). After careful
screening of the solvents, CH3CN proved to be best choice, and
the product 6a was isolated in 57% yield with 80.5:19.5 er (entry
1). No better results were observed when different ester groups
of sulfides 2 were examined (See Table S9 for details).
Decreasing the temperature to 0 C was favorable to the
enantioselectivity (entry 2). Next, the survey of the electron-
withdrawing group of the sulfides indicated that the
The substrate scope for Sommelet−Hauser rearrangement
was investigated (Scheme 2). CH3CO2Me was used instead of
CH3CN in some occasions due to the low solubility of some
substrates in CH3CN at 0 C. As for -diazo(aryl) pyrazoleamides
5, either electron-donating or electron-withdrawing substituent at
para- or meta-position of the phenyl group showed a negative
effect on the reactivity and enantioselectivity. The desired
products 8c-8h could be isolated in 51-78% yield with 80:20 to
90.5:9.5 er. For meta-substituted diazo substrates, the reaction
occurred at the less sterically hindered ortho-position and
afforded only one product in moderate to good results (8e-8h).[15]
Additionally,
when
2-chlorophenyl
substituted
-diazo
pyrazoleamide was subjected to the ligand L2-PiPr2-based
catalyst system, only trace amount of the product 8i was detected;
and a 52% yield with 65:35 er was given in the presence of N,N'-
dioxide L2-PiCy instead. -Diazo(2-naphthyl) pyrazoleamide
could undergo the reaction smoothly, to afford the product 8j in
phenylcarbamothioates
7
could elevate the er of the
Sommelet−Hauser rearrangement, affording the product 8a in
49% yield with 88.5:11.5 er (entry 3). Further examination of the
substituents on the phenyl group of the amides concluded that the
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10.1002/anie.201907164
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RESEARCH ARTICLE
79% yield with 70:30 er.[15] Subsequently, various
phenylcarbamothioates 7 were investigated by reacting with -
diazo(phenyl) pyrazoleamide 5a, giving readily the rearrangement
products (9b-9e) in 58-78% yield with 87.5:12.5 to 92.5:7.5 er.
Phenylthioates containing electron-rich aryl groups gave the
desired products in slightly higher enantioselectivities than these
with electron-deficient aryl groups. Similarly, when the sulfide 7f
with an ortho-chloride substituent was used, the Ni(OTf)2/L2-PiEt2
complex catalyst proved more efficient. Meanwhile, 2-naphthyl
substituted sulfide exhibited high reactivity and enantioselectivity
(9g; 86% yield, and 93:7 er). Moreover, 2- thienyl or ethyl
substituted sulfides transformed into the corresponding products
9h and 9i in good yields (64% and 83% yields, respectively) with
less stereocontrol (80:20 er for 9h; 73.5:26.5 er for 9i).
Additionally, the product 9q with an ester group and 9u with a
nitro-group at the phenylacetamide unit of sulfides were obtained
in 81% and 53% yields with 92.5:7.5 er and 92:8 er, respectively.
The absolute configuration of 9u was determined to be R by using
single-crystal X-ray diffraction analysis.[16]
Scheme 3. Control experiments with other diazo compound and sulfide.
In order to determine the mechanism of these two types of
[2,3]-sigmatropic rearrangement reactions, a series of explored
experiments were conducted. Firstly, methyl (E)-2-diazo-4-
phenylbut-3-enoate 10a was subjected to the reaction system
instead of -diazo pyrazoleamide 1a under the standard reaction
conditions of the asymmetric [2,3]-Stevens rearrangement
(Scheme 3a). But the desired product was formed in only a trace
amount as determined by HRMS analysis. The result confirms the
necessity of pyrazole group for the reaction reactivity and stereo-
control. Moreover, when diethyl 2,2'-thiodiacetate was used for
the asymmetric [2,3]-rearrangement reactions, the corresponding
products were obtained as racemates (Schemes 3b and 3c). The
result was different from the findings in our previous Doyle–
Kirmse reaction of diallylsulfane which yield the corresponding
product in high enantioselectivity.[10a] This enantioselective
Doyle–Kirmse reaction was mainly controlled by the nickel-
bounded, less stereo-centered envelope-transition state, and the
formation of carbon-carbon bond occurs at the vicinal position of
the pyrazoleamide which could by readily controlled by the nearby
chiral catalyst. In contrast, when diethyl 2,2'-thiodiacetate was
subjected to the asymmetric [2,3]-Stevens and Sommelet–
Hauser reactions, the proton in the 1,3-H transfer process could
come from two methylene groups of the sulfide 12a. The
formation of ylide IV is less enantioselective. Additionally, carbon-
carbon bond occurs at the γ-position of the pyrazoleamides, which
is a remote functionalization process and the enantio-control is
much more difficult. This might imply that the S-stereogenic center
generated via discrimination of the heterotopic lone pairs of the
sulfur reagent in [2,3]-Stevens and Sommelet–Hauser reactions
are important, which will affect the stereochemistry of the
sequential proton shift and rearrangement.
Subsequently, deuterium-labelled experiments were carried
out to clarify the 1,3-proton transfer process. We synthesized
deuterium-labelled sulfide methyl 2-(p-tolylthio)acetate-d2 15-d2
(94% D) for control experiments. All the reactions were purified
Scheme 2. Substrate scope for catalytic asymmetric Sommelet−Hauser
rearrangement.
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10.1002/anie.201907164
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until complete conversion (Scheme 4). As shown in Scheme 4a,
when 15-d2 was employed for the asymmetric [2,3]-Stevens
reaction of diazo compound 1j, deuterium-labelled product 16-d2
was detected after longer reaction time, in which the
sulfanylacetate unit (D1) has around 88% deuterated ratio, and
the deuterated ratio of the α-D in the double bond for the major
diastereoisomer (D2) is 44%. It indicates that intermolecular 1,3-
proton shift exist in the reaction. The hydrogen atoms (H2/H1) in
the product might come from the trace amount of water in the
catalytic system. The deuterated ratio has discrepancy in multiple
experiments due to moisture-sensitivity. Nevertheless, the
reaction slows down after strict dehydration. When 3-
phenylpropanoic acid was added into the reaction of 15-d2, less
deuterium (D2, 0%) is found in the product, and the reactivity and
enantioselectivity of the reaction increases obviously (Scheme
4b). It indicates that intermolecular 1,3-proton shift outweighs the
direct intramolecular process. Furthermore, if non-deuterium
sulfide 15 and deuterated additives (D2O or PhCH2CH2CO2D)
were used in the reaction, double-deuterium-labelled product 16-
d2 were detected (Schemes 4c and 4d). Thus, a reversible
transformation might exist between the sulfonium ylide tautomers
III and IV, which impacts the stereo-outcome of the reaction
(Scheme 1c). The different deuterated ratio and reactivity in these
cases shows that water is a faster proton-shuttle than acid, but
the isolated yield of the target product is low due to the formation
of byproducts. We think that acid could act as a mild proton-
shuttle, enabling slower tautomerization process and higher
enantioselectivity. Because if reversal tautomerization is
dominated, the chiral S-center and C1 might undergo a higher
racemization risk.[17]
Scheme 5. Deuterium-labelled experiments for Sommelet−Hauser
rearrangements.
The deuterium-labelled phenylcarbamothioate 7b-d2 (92% D)
was examined in the asymmetric Sommelet–Hauser
rearrangement reactions (Scheme 5). We carried out the
experiments without moisture as much as possible, and found that
the reactions slow down dramatically, and low yields were
obtained. When 7b-d2 was used for the reaction in the absence or
presence of the acid additive, the product 8b-d1 was found nearly
non-deuterium at the methene position (Schemes 5a and 5b). It
manifests that the proton (H2 or H3) comes from outside rather
than sulfide and the tautomerization process became sluggish.
When non-deuterium 7b with deuterated additives (D2O or
PhCH2CH2CO2D) were used in the reaction, it is interesting that
double-deuterium product 8b-d2 was detected (Scheme 5c and
5d). It demonstrates that proton can easily step from outside both
in 1,3-H shift step and in the rearomatization step. Water has
better proton-transfer ability than acid. Nevertheless, we could not
rationalize the reduced deuterium ratio (D1) shown in Scheme 5b.
Neither the sulfide substrates (7b and 15) nor the products (8b
and 16) themselves could be deuterium in the catalyst system,
but H/D exchange of ylide III or the carbene-insertion intermediate
during the reaction process could not be ruled out, because the
methylene position is enolisable.
According to our previous work,[10a] the absolute configuration
of the major products,[12,17] controlled experiments and deuterium-
Scheme 4. Deuterium-labelled experiments for [2,3]-Stevens rearrangement
reaction.
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labelled experiments, as well as the general mechanism of [2,3]-
sigmatropic rearrangement,[18] the catalytic models for the
in Figure 1a, due to the steric hindrance of ester group and aryl
group of sulfide reagent with the ligand, the discrimination of the
heterotopic lone pairs is available. Thus, (R)-configured sulfonium
ylide species B1 and B2 are favorable (Figure 1a, left). Next,
carbonic acid additive might act as a proton shuttle to assist the
carbanion translocation to yield a tautomeric ylide (Scheme 4).[19]
As shown in transition state B1, due to the chiral induction raised
from sulfur center and chiral catalyst, diastereoselective
intermolecular proton transfer occurs to generate (R,R)-
intermediate C1. Fortunately, the strong Lewis acid-bounded ylide
intermediate by introducing a pyrazoleamide group and the
perfect chiral environment in concert benefit the enantioselective
1,3-proton transfer. Next, as shown in D1, [2,3]- rearrangement
process occurs for the -Si face of (E)-type C=C double bond via
an envelope transition state, in which all the larger substituents
(Ph, CO2Ph, and pyrazoleamide) locate at the opposite sites to
exclude the steric hindrance. The chiral catalyst benefits the
match of multiple stereogenic centers, and the desired (2R,3S,E)-
configured product 3z was generated as the major isomer.
Similarly, the formation of sulfonium ylide intermediate B2 for
Sommelet–Hauser rearrangement occurs readily (Figure 1b,
bottom), but it undergoes an enantioselective intermolecular 1,3-
proton shift from trace amount of water in the system. The
tautomeric ylide C2 with uniform stereo-selection performs the
[2,3]-σ rearrangement process at the ortho-position of the aryl
group, which is proposed to be slower than 1,3-proton transfer
step due to the high activation energy of the dearomatization step.
As shown in D2, the amide substituent is opposite to the phenyl
group at sulfur atom in the envelope transition state to release the
steric hindrance. The attack of prochiral C'-2-atom with its Re-face
to the aryl substituent, following another 1,3-proton shift to
generate rearomatization product (R)-9u as the major product.
Conclusion
In summary, we have developed the unique examples of
asymmetric catalytic [2,3]-Stevens and Sommelet–Hauser
rearrangements of sulfonium ylides generated in situ from -diazo
carbonyl compounds and sulfides. The introducing vinyl or aryl
substituted -diazo pyrazoleamides, and the use of chiral N,N'-
dioxide-Ni(II) complex, as well as additives are critical to the
outcome of the two kinds of rearrangements. A series of -diazo
pyrazoleamides and sulfides could undergo the reaction smoothly,
affording functionalized 1,6-dicarbonyls and sulfane-substituted
phenylacetates with good outcomes. Beside of high reactivity, the
catalytic system showed an excellent stereo-control performance
for fine discrimination of the heterotopic long pairs of sulfur,
enantioselective 1,3-proton transfer, and [2,3]-σ rearrangement
as well. Intermolecular 1,3-proton transfer was confirmed by
deuterium-labelled experiments. Further application of the
functional group-direct-strategy with chiral N,N'-dioxide-metal
complex catalysts to other enantioselective synthesis are ongoing
in our laboratory.
Figure 1. Proposed catalytic models for stereoinduction.
enantiocontrol in [2,3]-Stevens and Sommelet−Hauser
rearrangements were proposed (Figure 1). When -diazo
pyrazoleamide 1a is mixed with the chiral nickel(II) complex
catalyst (Figure 1b, top), decomposition via loss of nitrogen
proceeds readily to form chiral nickel carbene intermediate A1.
The (phenylthio)acetate prefers to attack from the Re-face of
nickel carbene because the opposite Si-face is blocked by the left
amide unit of the ligand (Figure 1a). As shown in the right model
Experimental Section
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10.1002/anie.201907164
Angewandte Chemie International Edition
RESEARCH ARTICLE
General procedure for enantioselective [2,3]-Stevens rearrangement
of vinyl substituted -diazo pyrazoleamides 1: A dry reaction tube was
charged with L2-PiPr2 (0.005 mmol), Ni(OTf)2 (0.005 mmol) and
Ph(CH2)2CO2H (0.02 mmol) under an N2 atmosphere. Then CH3CO2Me
(0.5 mL) was added and the mixture was stirred at 35 C for 40 minutes.
Subsequently, sulfide 2 (0.25 mmol) and diazo compound 1 (0.1 mmol)
were added successively at 20 C. The reaction was detected by TLC.
After the diazo compound 1 was consumed (detected by TLC), the residue
was purified by column chromatography on silica gel to afford the product
(Pet/EtOAc = 25/1 as eluent).
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by column chromatography on silica gel to afford the product (Pet/EtOAc
= 15/1 to 10/1 as eluent).
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Acknowledgements
We acknowledgement financial support from the National Natural
Science Foundation of China (grant no. 21625205), and the
Graduate Student's Research and Innovation Foundation of
Sichuan University (2018YJSY050).
Keywords: [2,3]-σ rearrangement • sulfonium ylides • -diazo
compound • sulfide • chiral nickel(II) complex
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10.1002/anie.201907164
Angewandte Chemie International Edition
RESEARCH ARTICLE
RESEARCH ARTICLE
Xiaobin Lin, Wei Yang, Wenkun Yang,
Xiaohua Liu,* and Xiaoming Feng*
Page No. – Page No.
Asymmetric Catalytic [2,3]-Stevens
and Sommelet–Hauser
Rearrangements of -Diazo
Pyrazoleamides with Sulfides
Chiral N,N'-dioxide-Ni(II) complex catalysts were found to work efficiently in the
asymmetric catalytic [2,3]-Stevens and Sommelet–Hauser rearrangements of -
diazo pyrazoleamides with sulfides. The catalytic system showed excellent stereo-
control, discriminating between the heterotopic lone pairs of sulfur and controlling
both the 1,3-proton transfer and the [2,3]-σ rearrangement.
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