Hemin Catalyzed Dealkylative Intercepted [2, 3]-Sigmatropic Rearrangement Reactions of Sulfonium Ylides with 2, 2, 2-Trifluorodiazoethane

Article abstract of DOI:10.1002/adsc.201901534

A dealkylative intercepted [2, 3]-sigmatropic rearrangement reaction of allylic sulfides with 2, 2, 2-trifluorodiazoethane (CF₃CHN₂) is reported, the commercially available and biocompatible catalyst hemin was found to efficiently catalyze this transformation across a diverse set of allylic sulfides with in situ generated CF₃CHN₂, providing excellent yields (up to 99%) under mild condition without inert gas protection. In addition, CF₃CHN₂ exhibited unique reactivity toward this process compared with other frequently used diazo reagents. This work expands the range of carbene-mediated transformations catalyzed by hemin and introduces a concise and general strategy for exploiting new possibility of reactions concerning organosulfides. (Figure presented.).

Full text of DOI:10.1002/adsc.201901534

Title: Hemin Catalyzed Dealkylative Intercepted [2, 3]-Sigmatropic
Rearrangement Reactions of Sulfonium Ylide with 2, 2, 2-
Trifluorodiazoethane
Authors: Xiaojing Yan, Chang Li, Xiaofei Xu, Xiaoyong Zhao, and
Yuan-Jiang Pan
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901534
Link to VoR: http://dx.doi.org/10.1002/adsc.201901534

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
Very Important Publication
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Hemin Catalyzed Dealkylative Intercepted [2, 3]-Sigmatropic
Rearrangement Reactions of Sulfonium Ylides with 2, 2, 2-
Trifluorodiazoethane
Xiaojing Yan,a Chang Li,b* Xiaofei Xu,a Xiaoyong Zhaoa and Yuanjiang Pana*
a
Department of Chemistry, Zhejiang University, Zheda Road 38, Hangzhou, 310027 (P. R. China)
Fax: +86571 87951629; Tel: +86571 87951629; E-mail: panyuanjiang@zju.edu.cn.
Zhejiang Chinese Medical University, Bingwen Road 548, Hangzhou, 310053 (P. R. China)
b
Fax: +86571 86613716; Tel: +86571 86613712; E-mail: lichang@zju.edu.cn.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
materials[6]. 2, 2, 2-trifluorodiazoethane (CF3CHN2),
Abstract. A dealkylative intercepted [2, 3]-sigmatropic
rearrangement reaction of allylic sulfides with 2, 2, 2-
trifluorodiazoethane (CF3CHN2) is reported, the
commercially available and biocompatible catalyst
hemin was found to efficiently catalyze this
transformation across a diverse set of allylic sulfides
with in situ generated CF3CHN2, providing excellent
yields (up to 99%) under mild condition without inert
gas protection. In addition, CF3CHN2 exhibited unique
reactivity toward this process compared with other
frequently used diazo reagents. This work expands the
range of carbene-mediated transformations catalyzed by
hemin and introduces a concise and general strategy for
exploiting new possibility of reactions concerning
organosulfides.
a highly reactive fluoroalkylating reagent, offers a
useful method to introduce trifluoromethyl group into
organic molecules. Even though gaseous CF3CHN2
was firstly discovered in 1943 by Gilman and Jones[7],
it is until after 2010, when methods for in situ
generation of this compound in solution were
developed[8], that this reagent becomes blooming in
chemistry. Up to now, various reactions have been
reported[6g, 9], providing accesses to simple, safe and
controllable preparation of this compound. And
CF3CHN2 has emerged as an attractive CF3-
containing synthon in various reactions such as
10]
cyclopropanation[9b,
,
cyclopropenation[8], X-H
insertion[11], and other reactions[6h, 12]. However, as a
widely used and highly valued diazo reagent, it’s
potential on intercepted [2, 3]-sigmatropic
rearrangement reaction has not been explored.
Keywords: Hemin; Intercepted [2, 3]-sigmatropic
rearrangement; Sulfides; Sulfonium ylide, 2, 2, 2-
Trifluorodiazoethane.
Introduction
Hemin is well known as the cofactor of many
metalloproteins, such as hemoglobin, myoglobin,
cytochrome c and P450s. Recent studies have
demonstrated the promising and synthetic value of
hemin and the corresponding metalloproteins for
promoting some important reactions, such as X-H
insertion[1], [2, 3]-sigmatropic rearrangement
(Scheme 1c)[2], sommelet-hauser rearrangement[3], C-
S
bond
cleavage[4]
(Scheme
1d)
and
biological/biomimetic oxidative reaction[5] with
excellent catalytic activity and selectivity. As an
economic, commercially available and biocompatible
catalyst, the potential catalytic values of hemin still
need to be explored.
The trifluoromethyl group can dramatically
influence the properties of organic molecules, thereby
increasing their applicability as pharmaceuticals,
agrochemicals, or building blocks for organic
Scheme 1. Recent reactions involving sulfides with
diazo reagents.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
[2, 3]-sigmatropic rearrangement of allylic
1), in which the yield of 3a increased obviously, we
guess that the solvent plays an important role in the
reaction, so solvents were screened. As shown in
Table 1 and Table S1, when DMF (N, N-
sulfides have been well studied in the past few
years[13]. Among them, the diazo compound-based
reactions were intensively investigated, in which the
key intermediate, sulfonium ylide, can be formed
through the reaction of sulfide with carbene, which is
easily generated from diazo compounds. Ethyl
diazoacetate (EDA), a model substrate for acceptor-
only substituted diazo compound, was reported to
efficiently promote this conversion in aqueous
Dimethylformamide)
Dimethylacetamide)
or
DMA
(N,
N-
was
employed,
nearly
quantitative product 3a was obtained (Table 1, entry
6 & 7); while when hexane was employed (Table 1,
entry 8), nearly quantitative product 4a was obtained;
however, when (Et)3N was employed, no result was
obtained (Table 1, entry 13); In addition, when other
commonly used solvents (such as MeCN, THF and
Methanol) were employed, low yields or mixture
products were obtained (Table 1, entry 9-12). It
seems that solvents with higher polarity have better
efficiency to the formation of dealkylative intercepted
[2, 3]-sigmatropic rearrangement product. Finally,
DMF (1.25 mL) was chosen as the optimized solvent
(details see Table S1).
solvent (scheme 1c)[2c] or by a biocatalytic strategy[2a]
Branched diazo reagents, such as phenyldiazoacetate
;
and
its
derivatives,
were
employed
for
enantioselective [2, 3]-sigmatropic rearrangement of
13c,
sulfonium ylides[6f,
14]; Diazoacetonitrile[15] and
CF3CHN2, which are representatives of the highly
explosive diazo compounds and are usually prepared
by in situ approaches, exhibited safe and scalable
application in [2, 3]-sigmatropic rearrangement
reactions (scheme 1b)[15f]
;
And other diazo
Table 1. Solvent screening a).
compounds such as (trimethylsilyl) diazomethane
(TMSD) was also reported to be applicable in this
transformation[16]. Though numerous excellent works
were focused on the novel transformation, the
interruption of sigmatropic rearrangement reactions
also received a lot of attention[17]. However, among
them, little attention has been paid to the interruption
of [2, 3]-sigmatropic rearrangement, not to mention
the use of CF3CHN2 as a carbene precursor in this
transformation. Inspired by the work described by
Koenigs (scheme 1a &1b), we speculate sulfonium
ylide generated from a metal carbene and allylic
sulfide could undergo a nucleophilic substitution
process to give the dealkylative intercepted [2, 3]-
sigmatropic rearrangement product (scheme 1e),
which is complementary to the [2, 3]-sigmatropic
rearrangement reaction.
3ab)
(%)
4ab)
(%)
Catalyst
(10 mol %)
Solvent
(1.25 mL)
Entry
1
2
hemin
hemin
FePc
/
CHCl3
CHCl3
Diethyl ester
DMSO
DMF
25
43
28
30
50
98
98
2
75
57
72
70
0
3
4
hemin
hemin
hemin
hemin
hemin
hemin
hemin
hemin
hemin
hemin
5
6
2
7
DMA
2
8
Hexane
MeCN
THF
98
51
14
0
9
32
48
53
32
0
10
11
12
13
Results and Discussion
Acetone
Methanol
(Et)3N
In the initial study, 0.2 mmol phenyl allyl sulfide
(1a) and 1.0 mmol (5 equiv.) CF3CHN2 (2a, in situ
generated from the reaction of sodium nitrite and 2, 2,
2-trifluoroethylamine hydrochloride) were employed
as substrates to optimize the reaction conditions
(Table 1 & Table 2). Upon treatment of 1a and 2a in
CHCl3 at ambient temperature for 5h with 10 mol%
hemin as the catalyst, the dealkylative intercepeted [2,
3]-sigmatropic rearrangment product 2, 2, 2-
trifluoroethyl phenyl sulfide (3a) and [2, 3]-
0
0
a)
Reaction conditions: 0.2 mmol 1a, catalyst (10 mol%),
and 2a (5 equiv.) were dissolved in 1 mL H2O and
different solvents (1.25 mL) at ambient temperature, a
solution of 6 equiv. NaNO2 in 0.25 mL H2O was added
over a period of 2.5h, after which the reaction was stirring
1
for another 10 h; b) Yields were determined by H NMR
analysis of the crude reaction mixtures.
sigmatropic
rearrangement
product
1-
As shown in Table 2, when Cu (II)
protoporphyrin IX (Table 2, entry 1) or iron salt
FeCl3·6H2O (Table 2, entry 2) was employed as the
catalyst under the above mentioned reaction
condition, no product was observed. The same result
was obtained in the absence of hemin (Table 2, entry
3). The conversions from entry 1-3 and Table 1
indicate that both porphyrin structure and iron center
are crucial for the reaction. What’s more, hemin
shows higher catalytic capacity toward dealkylative
intercepeted [2, 3]-sigmatropic rearrangment reaction
than another iron porphyrin complex FeTPPCl,
(trifluoromethyl)-3-butenyl phenylsulfide (4a) were
obtained in 43% yield and 57% yield respectively,
which were determined by H NMR (Table 1, entry
1
2). Inspired by a previous report [17e], 10 mol% FePc
was employed as the catalyst, the yield of 3a and 4a
were generated in 28% and 72% respectively (Table
1, entry 3). A similar result was observed with 3a and
4a in 25% and 75% yield, when CHCl3 was not used
(Table 1, entry 1). The yields from entry 1 & 3 (Table
1) show that 4a is the main product under this
condition. Combined with the result in entry 2 (Table
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
whose catalytic efficiency to 3a is only 31% (Table 2,
entry 4), This yield could be increased up to 89%
after being assisted by surfactant Triton X-100[2c, 4] to
inhibit the aggregation of FeTPPCl (Table 2, entry
4*), because hemin could disperses well in DMF and
water system[18], so it needs no extra additives. Then
several other reaction parameters were optimized,
including the amount of hemin (Table 2, entries 5-9),
molar ratio of 2a/1a (Table 2, entries 10-14), and
reaction time (Table 2, entries 15-18). In addition,
several commercially available surfactants were also
screened for their ability in improvement of the
catalytic effect in this reaction, without obvious effect
(Table S1). Finally, the optimized reaction condition
was as follows, 2.5 mol% hemin, 5 equiv. 2a (in situ
generated), and 1.25 mL DMF stirred at rt for 3h
without inert atmosphere(Table 2, entry 15), and the
H2O (1 mL) for in situ generating CF3CHN2 is used
without degassing.
with in situ generated CF3CHN2. The results are
summarized in Table 3. It is demonstrated that the
catalytic system has good functional group tolerance
to halogenated phenylallylsulfides (1b-1g), as well as
trifluoromethyl (1h), methoxyl (1i-1k), alkyl (1l-1p),
hydroxyl (1q) and esterphenylallylsulfides (1r). The
para-, ortho- and meta-chlorophenyl allyl sulfides
also performed well, furnishing the corresponding
trifluoroethylphenylsulfides in excellent yields (92%-
95%) without obvious position effects. In general,
both electron-withdrawing groups (1b-1h) and
electron-donating groups (1i-1q) on the aryl ring of
the initial thioether substrates were well tolerated.
When acylaminophenylallylsulfide (1t) was used in
the reaction, only the desired product 3t was
generated in 95% yield without observation of N-H
insertion product. In addition, the substrate 1s with
bulkier functional group was readily converted to the
corresponding product in excellent yield (84%), with
no detectable C-N bond cleavage reaction product,
the results from reactions with 1r and 1s indicate that
the reactivity of C-S bond was superior to C-N and
C-O bond under this condition. What’s more,
aliphatic substrates such as phenethylallylsulfide (1u)
showed compatible in the reaction with good yield
(85%).
Table 2. Optimization of reaction conditions a).
2a
/1a
Catalyst
(mol %)
Additional 3ab)
Time (h) (%) (%)
4ab)
Entry
Table 3. Investigation of diverse substituted sulphides a), b)
Cu(II)protoporphy
rinIX(10)
1
5
10
0
0
2
3
4*
5
5
5
5
5
5
5
5
1
2
4
8
10
5
5
5
5
FeCl3·6H2O(10)
/
10
10
3
0
0
0
0
FeTPPCl (10)
hemin (0.5)
hemin (1)
31
34
49
98
99
99
10
20
50
99
99
76
98
99
99
69
40
20
2
5
10
10
10
10
10
10
10
10
10
10
1
6
7
hemin (2.5)
hemin (5.0)
hemin (20)
hemin (2.5)
hemin (2.5)
hemin (2.5)
hemin (2.5)
hemin (2.5)
hemin (2.5)
hemin (2.5)
hemin (2.5)
hemin (2.5)
8
1
9
1
10
11
12
13
14
15
16
17
18
20
30
25
1
1
10
2
3
6
1
9
1
a)
Reaction conditions: 0.2 mmol 1a, catalyst, and 2a (5
equiv.) were dissolved in 1 mL H2O and 1.25 mL DMF at
ambient temperature, a solution of 6 equiv. NaNO2 in 0.25
mL H2O was added over a period of 2.5h, after which the
reaction was stirring for another additional time. b) Yields
were determined by 1H NMR analysis of the crude reaction
mixtures. *The yield of 3a could be obtained in 89% yield
after adding Triton X-100 (20 mol%).
With the optimized reaction conditions in hand,
a variety of substituted phenylallylsulfides were
employed in the hemin catalyzed dealkylative
intercepted [2, 3]-sigmatropic rearrangement reactions
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
a)
Reaction conditions: 0.2 mmol 1a, 2.5 mol% catalyst,
and 5.0 eq. 2a (in situ generated) were dissolved in 1 mL
b)
H2O and 1.25 mL DMF at ambient temperature for 3h.
1
Yields were determined by H NMR analysis of the crude
reaction mixtures. Values in the parentheses are isolated
yields.
Some undesired results were obtained when
naphthyl (1v) and thienylallylsulfide (1w) were used
as reactants. For substrate 1v (Scheme 2a), the
dealkylative intercepted rearrangement product 3v
was obtained in 43% yield, accompanying with the
unexpected C-H insertion product 3v’ in 55% yield;
While for substrate 1w (Scheme 2b), only C-H
insertion product 3w was obtained in 98% yield
without observation of dealkylative intercepted [2, 3]-
sigmatropic rearrangement product. This interesting
exception was also found in Gary’s work, C-H
functionalization product at the 3-position of the
indole ring instead of the β-F elimination product
from the 3:1 adduct was obtained in the presence
CF3CHN2[19]. And a recent work from Arnold shows
that engineered cytochrome P450 enzymes can adopt
C−H fluoroalkylation activity with CF3CHN2 as
carbene precursor[20]. In addition, this result could
also arise from an electrophilic substitution reaction
a)
Reaction conditions: 0.2 mmol 1a, 2.5 mol% catalyst,
and 5.0 eq. 2a (in situ generated) were dissolved in 1 mL
H2O and 1.25 mL DMF at ambient temperature for 3h.
Yields were determined by H NMR analysis of the crude
reaction mixtures. Values in the parentheses are isolated
yields
b)
1
Furthermore, several diazo reagents which were
also generated in situ were investigated under the
optimized condition. As shown in Table 5, methyl
(2b), ethyl (2c) and tert-butyldiazoacetate (2d) can
react smoothly with sulfide, giving the [2, 3]-
sigmatropic rearrangement products in excellent
yields (95%-98%). Compared with our previous
work[2c], this method shows higher efficiency to [2,
3]-sigmatropic rearrangement reaction, especially
when 2d was employed as the carbene precursor, 4d
was obtained in 95% yield without steric issue in 3h
(in our previous work, 4d was only generated in 35%
yield after 48h). Similarly, when diazoacetonitrile
was used, an excellent yield of 2-(phenylthio) pent-4-
enenitrile (4e) was achieved. This phenomenon
indicated the distinctive reactivity of CF3CHN2 in the
similar
functionalization of indoles with diazoesters as
reported by Fasan group [21]
to
the
myoglobin-catalyzed
C-H
.
Scheme 2. Undesired C-H insertion reaction.
The high efficiency observed in the Table 3
encouraged us to test the potential of this strategy in
other carbenoid transformation. Substrates with
substitution at the allyl group were designed and their
reactivities were investigated under the optimized
conditions (Table 4). Results showed that 1-Chloro-4-
[(2-methyl-2-propen-1-yl)thio]benzene (1x) and 1-
Chloro-4-[(3-methyl-2-buten-1-yl)thio]benzene (1y)
both generate expected product (3b) with excellent
yields (99%) without any [2, 3]-sigmatropic
rearrangement product. However, the reaction of
phenylpropargylsulfide (1z) with the in situ generated
CF3CHN2 only had a moderate yield (31%).
Phenylcinnamysulfide and its derivatives were also
investigated. As shown in Table 4, good to excellent
conversion (75%-98%) were observed for electron-
withdrawing groups (1ab-1ag) and electron-donating
groups (1ah-1ap) as R4. Similar results were
dealkylative
intercepted
[2,
3]-sigmatropic
rearrangement reactions for allylic sulfides. Overall,
this method is more efficient than the previously
reported works[2c,
about [2, 3]-sigmatropic
15f]
rearrangement, in terms of reaction time, reaction
conversion and reaction operation.
Table 5. Investigation of various diazo esters a)
a)
Reaction conditions: 0.2 mmol 1a, 2.5 mol% catalyst,
observed
for
aliphatic
substrate
and 5.0 eq. 2b-e (in situ generated) were dissolved in 1 mL
H2O and 1.25 mL DMF at ambient temperature for 3h.
Yields were determined by H NMR analysis of the crude
phenethylcinnamysulfide (1aq).
1
Table 4. Investigation of diverse substituted sulfides a).
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
reaction mixtures. Values in the parentheses are isolated
yields.
To gain insight of the reaction mechanism, the
reaction of cinnamyl (4-trifluromethylphenyl) sulfide
1ag with CF3CHN2 was detected carefully under the
standard reaction conditions. As shown in Scheme 3,
cinnamic alcohol (5a) and cinnamyl formate (6a)
were confirmed as the byproducts with 5a and 6a in
15% and 45% isolated yield respectively (scheme 3a).
the 18O-labeled experiment confirmed that the O atom
in 5a origins from H2O. According to koenigs’s work,
benzyl chloride was obtained through nucleophilic
attack of the sulfonium salt by chloride ion (from the
hydrochloride salt), which is the key step for
intercepted arrangement[17e]. So we suspect the
original source of 5a and 6a is probably cinnamyl
chloride. Control experiments show that cinnamyl
chloride can react with H2O and DMF to give 5a and
6a (Scheme 3b & Scheme S1). In addition, the
conversion of intercepted [2, 3]-sigmatropic
rearrangement product 3n was increased after adding
extra NaCl in the reaction of 1am with in situ
generated 2a (Scheme S2). Which gives further
support on the proposed mechanism.
Scheme 4. The proposed reaction mechanism.
Conclusion
In summary ， we developed a hemin-catalyzed
dealkylative
intercepted
[2,
3]-sigmatropic
rearrangement transformation between CF3CHN2 and
allylic sulfides, which involved the sulfonium ylide
formation and intercepted [2, 3]-sigmatropic
rearrangement. This study shows an unexpected
example of dealkylative intercepted [2, 3]-
sigmatropic rearrangement for allylic sulfides
catalyzed by hemin. In addition, this novel and
concise method exhibited broad substrates tolerance
with excellent yield (up to 99%) in the presence of in
situ generated CF3CHN2, which displayed a distinct
reactivity for this conversion. What’s more, the
mechanism was preliminarily proposed.
Experimental Section
Scheme 3. Reaction mechanism study
General procedures of Dealkylative Intercepted [2, 3]-
sigmatropic Rearrangement Reaction: A solution of
sodium nitrite (c = 4.8 mol/L, 0.25 mL, 6.0 eq., 82.8 mg)
was added via syringe pump in 2.5 h into the reaction
vessel, in which the 2, 2, 2-trifluoroethylamine
hydrochloride (138 mg, 5.0 eq.), hemin (3.3 mg, 2.5
mol%), H2O (1.0 mL), DMF (1.25 mL) and the
corresponding substrate (0.2 mmol, 1.0 eq.) were placed
before. After stirring another 3h , the mixture was
extracted twice with EtOAc (2 mL×2). The organic layer
was further washed with brine and then dried with Na2SO4.
Then the organic solvent was removed in vacuum and
hemin was removed by a short silica gel column, and
eluted by petroleum ether/hexane to give the corresponding
product.
Based on experimental results and reported
literatures,
a plausible reaction mechanism is
depicted in Scheme 4 in which CF3CHN2 is generated
in situ, and then reacts with the hemin to form
carbenoid intermediate 1[22]. Which is trapped by the
substrate (2) to form the sulfonium ylide 3[2c, 14, 23]
,
following attack of chloride ion (from hydrochloride
salt) to sulfonium salt (4) led to the formation of the
dealkylative
intercepted
[2,
3]-sigmatropic
rearrangement product 5 and allyl chloride (6) as
byproduct.[4] Subsequently, 6 was consumed by H2O
and DMF, generating corresponding alcohol and ester.
Which probably promote the dealkylative intercepted
[2, 3]-sigmatropic rearrangement reaction to move
forward. For works about the reaction of 2 with other
diazoreagents, such as catalyzed by hemin, product 7
was obtained after [2, 3]-sigmatropic rearrangement.
Acknowledgements
Financial support from the National Natural Science Foundation
of China (21532005, 21502168) and the National Key R&D
Program of China (2016YFF0200503) are gratefully
acknowledged.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
References
Koenigs, Chem. Eur. J., 2018, 24, 10571-10583; d) J.
Britton, T. F. Jamison, Angew. Chem. Int. Ed., 2017, 56,
8823-8827. e) B. Pieber, C. O. Kappe, Org. Lett., 2016,
18, 1076-1079.
[1] a) Z. J. Wang, N. E. Peck, H. Renata, F. H. Arnold,
Chem. Sci., 2014, 5, 598-601; b) V. Tyagi, R. B. Bonn,
R. Fasan, Chem. Sci., 2015, 6, 2488-2494; c) X. Xu, C.
Li, Z. Tao, Y. Pan, Adv. Synth. Catal., 2015, 357,
3341–3345; d) G. Sreenilayam, R. Fasan, Chem.
Commun., 2015, 51, 1532-1534; e) S. B. J. Kan, R. D.
Lewis, K. Chen, F. H. Arnold, Science 2016, 354,
1048-1051; f) R. D. Lewis, M. Garcia-Borràs, M. J.
Chalkley, A. R. Buller, K. N. Houk, S. B. J. Kan, F. H.
Arnold, Proc. Natl Acad. Sci., 2018, 115, 7308-7313;
g) X. Huang, M. Garcia-Borràs, K. Miao, S. B. J. Kan,
A. Zutshi, K. N. Houk, F. H. Arnold, ACS Cent. Sci.,
2019, 5, 270-276; h) V. Steck, G. Sreenilayam, R.
Fasan, Synlett, 2019, DOI: 10.1055/s-0039-1690007 .
[10] a) M. A. J. Duncton, L. Ayala, C. Kaub, S. Janagani,
W. T. Edwards, N. Orike, K. Ramamoorthy, J. Kincaid,
M. G. Kelly, Tetrahedron Lett., 2010, 51, 1009-1011;
b) M. A. J. Duncton, R. Singh, Org. Lett., 2013, 15,
4284-4287; c) P. Le Maux, S. Juillard, G. Simonneaux,
Synthesis, 2006, 2006, 1701-1704.
[11] a) H. Luo, G. Wu, Y. Zhang, J. Wang, Angew. Chem.
Int. Ed., 2015, 54, 14503-14507; b) S. Hyde, J. Veliks,
B. Liégault, D. Grassi, M. Taillefer, V. Gouverneur,
Angew. Chem. Int. Ed., 2016, 55, 3785-3789.
[12] a) B. Morandi, E. M. Carreira, Angew. Chem. Int. Ed.,
2011, 50, 9085-9088; b) O. A. Argintaru, D. Ryu, I.
Aron, G. A. Molander, Angew. Chem. Int. Ed., 2013,
52, 13656-13660; c) A. V. Arkhipov, V. V. Arkhipov, J.
Cossy, V. O. Kovtunenko, P. K. Mykhailiuk, Org. Lett.,
2016, 18, 3406-3409; d) M.-Y. Rong, L. Yang, J. Nie,
F.-G. Zhang, J.-A. Ma, Org. Lett., 2019, 21, 4280-
4283; e) Z. Chen, N. Ren, X. Ma, J. Nie, F.-G. Zhang,
J.-A. Ma, ACS Catal., 2019, 9, 4600-4608.
[2] a) V. Tyagi, G. Sreenilayam, P. Bajaj, A. Tinoco, R.
Fasan, Angew. Chem. Int. Ed., 2016, 55, 13562-13566;
b) C. K. Prier, T. K. Hyster, C. C. Farwell, A. Huang, F.
H. Arnold, Angew. Chem. Int. Ed., 2016, 55, 4711-
4715; c) X. Xu, C. Li, Z. Tao, Y. Pan, Green Chem.,
2017, 19, 1245-1249.
[3] X. Xu, C. Li, M. Xiong, Z. Tao, Y. Pan, Chem.
Commun., 2017, 53, 6219-6222.
[13] a) R. Hoffmann, R. B. Woodward, Acc. Chem. Res.,
1968, 1, 17-22; b) A.-H. Li, L.-X. Dai, V. K. Aggarwal,
Chem. Rev., 1997, 97, 2341-2372; c) Y. Zhang, J.
Wang, Coord. Chem. Rev., 2010, 254, 941-953; d) A. C.
Jones, J. A. May, R. Sarpong, B. M. Stoltz, Angew.
Chem. Int. Ed., 2014, 53, 2556-2591; e) T. H. West, S.
S. M. Spoehrle, K. Kasten, J. E. Taylor, A. D. Smith,
ACS Catal., 2015, 5, 7446-7479.
[4] X. Yan, C. Li, X. Xu, Q. He, X. Zhao, Y. Pan,
Tetrahedron, 2019, 75, 3081-3087.
[5] a) I. G. Denisov, T. M. Makris, S. G. Sligar, I.
Schlichting, Chem. Rev., 2005, 105, 2253-2278; b) T. L.
Poulos, Chem., Rev.,2014, 114, 3919-3962; c)Y. Fu, Q.
Yu, Y. Zhang, Z. Gao, Y. Wu, F. Zhong, Org. Biomol.
Chem., 2019, 17, 9994-9998.
[6] a) M. L. Quan, P. Y. S. Lam, Q. Han, D. J. P. Pinto, M.
Y. He, R. Li, C. D. Ellis, C. G. Clark, C. A. Teleha, J.-
H. Sun, R. S. Alexander, S. Bai, J. M. Luettgen, R. M.
Knabb, P. C. Wong, R. R. Wexler, J. Med. Chem.,
2005, 48, 1729-1744; b) K. Müller, C. Faeh, F.
Diederich, Science, 2007, 317, 1881-1886; c) E. J. Cho,
T. D. Senecal, T. Kinzel, Y. Zhang, D. A. Watson, S. L.
Buchwald, Science, 2010, 328, 1679-1681; d) D.
Gillingham, N. Fei, Chem. Soc. Rev., 2013, 42, 4918-
4931; e) X. Liu, C. Xu, M. Wang, Q. Liu, Chem. Rev.,
2015, 115, 683-730; f) Z. Zhang, Z. Sheng, W. Yu, G.
Wu, R. Zhang, W.-D. Chu, Y. Zhang, J. Wang, Nature
Chem., 2017, 9, 970-976; g) X. Zhang, Z. Liu, X. Yang,
Y. Dong, M. Virelli, G. Zanoni, E. A. Anderson, X. Bi,
Nature Commun., 2019, 10, DOI:10.1038/s41467-018-
08253-z; h) X. Wang, X. Wang, J. Wang, Tetrahedron,
2019, 75, 949-964. i) P. J. Foth, F. Gu, T. G. Bolduc, S.
S. Kanani, G. M. Sammis, Chem. Sci., 2019, 10,
10331-10335.
[14] M. Y. Liao, J. B. Wang, Green Chem., 2007, 9, 184-
188.
[15] a) J. Hooz, S. Linke, J. Am. Chem. Soc., 1968, 90,
6891-6892; b) T. Curtius, Ber. Dtsch. Chem. Ges.,
1898, 31, 2489-2492; c) Y. Ferrand, P. Le Maux, G.
Simonneaux, Tetrahedron: Asymmetry, 2005, 16, 3829-
3836; d) Z. Yang, K.-I. Son, S. Li, B. Zhou, J. Xu, Eur.
J. Org. Chem., 2014, 2014, 6380-6384; e) P. K.
Mykhailiuk, Eur. J. Org. Chem., 2015, 2015, 7235-
7239; f) K. J. Hock, L. Mertens, R. Hommelsheim, R.
Spitzner, R. M. Koenigs, Chem. Commun., 2017, 53,
6577-6580; g) C. Empel, K. J. Hock, R. M. Koenigs,
Org. Biomol. Chem., 2018, 16, 7129-7133; h) A. L.
Chandgude, R. Fasan, Angew. Chem. Int. Ed., 2018, 57,
15852-15856; i) P. K. Mykhailiuk, R. M. Koenigs,
Chem. Eur. J., 2020, 26, 89-101.
[16] a) V. K. Aggarwal, M. Ferrara, R. Hainz, S. E. Spey,
Tetrahedron Lett., 1999, 40, 8923-8927; b) D. S. Carter,
D. L. Van Vranken, Org. Lett., 2000, 2, 1303-1305; c) J.
B. Perales, N. F. Makino, D. L. Van Vranken, J. Org.
Chem., 2002, 67, 6711-6717.
[7] H. Gilman, R. G. Jones, J. Am. Chem. Soc., 1943, 65,
1458-1460.
[8] B. Morandi, E. M. Carreira, Angew. Chem. Int. Ed.,
2010, 49, 938-941.
[17] a) C. J. Moody, R. J. Taylor, Tetrahedron Lett., 1988,
29, 6005-6008; b) T. Tomakinian, R. Guillot, C.
Kouklovsky, G. Vincent, Chem. Commun., 2016, 52,
5443-5446; c) D. Kaiser, L. F. Veiros, N. Maulide, Adv.
Synth. Catal., 2017, 359, 64-77; d) V. A. Vil, G. dos
Passos Gomes, O. V. Bityukov, K. A. Lyssenko, G. I.
[9]a) C.-B. Liu, W. Meng, F. Li, S. Wang, J. Nie, J.-A. Ma,
Angew. Chem. Int. Ed., 2012, 51, 6227-6230; b) A.
Tinoco, V. Steck, V. Tyagi, R. Fasan, J. Am. Chem.
Soc., 2017, 139, 5293-5296; c) K. J. Hock, R. M.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
Nikishin, I. V. Alabugin, A. O. Terent'ev, Angew.
Hess, Z. J. Wang, F. H. Arnold, J. Am. Chem. Soc.,
2016, 138, 12527-12533.
Chem. Int. Ed., 2018, 57, 3372-3376; e) C. Empel, K. J.
Hock, R. M. Koenigs, Chem. Commun., 2019, 55, 338-
341.
[23] a) E. J. Corey, M. Chaykovsky, J. Am. Chem. Soc.,
1965, 87, 1353-1364; b) Melvin, S. Lawrence, Sulfur
ylides: emerging synthetic intermediates, Academic
Press, 1975; c) O. Illa, M. Namutebi, C. Saha, M.
Ostovar, C. C. Chen, M. F. Haddow, S. Nocquet-
Thibault, M. Lusi, E. M. McGarrigle, V. K. Aggarwal,
J. Am. Chem. Soc., 2013, 135, 11951-11966; d) Q.
Wang, T.-R. Li, L.-Q. Lu, M.-M. Li, K. Zhang, W.-J.
Xiao, J. Am. Chem. Soc., 2016, 138, 8360-8363; e) O.
Zhurakovskyi, Y. E. Turkmen, L. E. Loffler, V. A.
Moorthie, C. C. Chen, M. A. Shaw, M. R. Crimmin, M.
Ferrara, M. Ahmad, M. Ostovar, J. V. Matlock, V. K.
Aggarwal, Angew. Chem. Int. Ed., 2018, 57, 1346-1350.
[18] a) J. W. Owens, J. Robinson, C. J. O'Connor, Inorg.
Chim. Acta, 1993, 206, 141-153; b) L. Sabbatini, E.
Desimoni, F. Palmisano, P. G. Zambonin,
Bioelectrochem. Bioenerg., 1978, 5, 25-36; c) F. A.
Walker, U. Simonis, Iron Porphyrin Chemistry. In
Encyclopedia of Inorganic Chemistry, 2nd ed.; Wiley:
Chichester, U.K., 2006.
[19] G. A. Molander, D. Ryu, Angew. Chem. Int. Ed.,
2014, 53, 14181-14185.
[20] J. Zhang, X. Huang, R. K. Zhang, F. H. Arnold, J. Am.
Chem. Soc., 2019, 141, 9798-9802.
[21] a) D. A. Vargas, R. L. Khade, Y. Zhang, R. Fasan,
Angew. Chem. Int. Ed., 2019, 58, 10148-10152; b) D.
A. Vargas, A. Tinoco, V. Tyagi, R. Fasan, Angew.
Chem. Int. Ed., 2018, 57, 9911-9915.
[22] a) Y. Li, J.-S. Huang, Z.-Y. Zhou, C.-M. Che, X.-Z.
You, J. Am. Chem. Soc., 2002, 124, 13185-13193; b) H.
Renata, R. D. Lewis, M. J. Sweredoski, A. Moradian, S.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901534
Advanced Synthesis & Catalysis
FULL PAPER
Hemin Catalyzed Dealkylative Intercepted [2, 3]-
Sigmatropic Rearrangement Reactions of
Sulfonium Ylide with 2, 2, 2-Trifluorodiazoethane
Adv. Synth. Catal. Year, Volume, Page – Page
Xiaojing Yan, Chang Li, Xiaofei Xu, Xiaoyong
Zhao and Yuanjiang Pan*
8
This article is protected by copyright. All rights reserved.