The Rh(II)-catalyzed formal N-S bond insertion reaction of aryldiazoacetates into: N -phenyl-sulfenyl phthalimide

Article abstract of DOI:10.1039/c6cc02641a

The Rh(ii)-catalyzed sulfur ylide [1,2]-rearrangement of carbenoids generated from aryldiazoacetates has been realized via N-S bond insertion, generating tertiary sulfides in moderate to excellent yields. This demonstrates the first use of the sulfur ylide [1,2]-rearrangement undergoing N-S bond insertion. This protocol could proceed smoothly with high regioselectivity, low catalyst loading (0.1 mol% Rh₂(OAc)₄), gram-scale reaction and broad substrate scope. And the product could be converted into glycine derivatives through simple procedures.

Full text of DOI:10.1039/c6cc02641a

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Rh(II)-Catalyzed Formal N-S Bond Insertion Reaction of
Aryldiazoacetates into N-Phenyl-Sulfenyl Phthalimide
Zhuang Song†, Yizhou Wu†, Tao Xin, Chao Jin, Xiaoan Wen, Hongbin Sun,* and Qing-Long Xu*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Rh(II)-catalyzed sulfur ylide [1,2]-rearrangement of carbenoids Scheme 1. Two main types of reactions of the ylide generated
generated from aryldiazoacetates has been realized via N-S bond from metal carbene.
insertion, generating tertiary sulfides in moderate to excellent
The key intermediate, sulfur ylide, can mainly fall into two
yields. This demonstrates the first use of the sulfur ylide [1,2]- types of reactions as shown in Scheme 1: (1) [2,3]-sigmatropic
rearrangement undergoing through N-S bond insertion. This rearrangement. (2) [1,2]-sigmatropic rearrangement. With
protocol could proceed smoothly with high regioselectivity, low regards to simple allylic or propargyl sulfides, [2,3]-sigmatropic
catalyst loading (0.1 mol% Rh2(OAc)4), gram-scale reaction and rearrangement is the major reaction pathway, providing access
broad substrate scope. And the product could be converted into to structurally diverse allylic sulfides or allene sulfides.[3,4]
glycine derivatives through simple procedures.
Amongst the reported [1,2]-sigmatropic rearrangement based
on sulfur ylide, previous studies mainly got through the [1,2]-
C-C-shift to form new C-C bond, always by means of the
expansion of the heterocycles.[5-7] To the best of our
knowledge, the reports on other types of the [1,2]-sigmatropic
rearrangements are rather limited. Herein, we describe a
catalytic [1,2]-C-N-shift reaction of sulfonium ylides, leading to
the formation of new C-N and C-S bonds.
The metal carbenoids are important and useful intermediates
that play a critical role in diverse transformations due to their
high reactivity. The catalytic insertion of metal carbenoids into
X-H (X = C, N, O, Si, S, etc.) bonds is a powerful method for
constructing versatile chemical frameworks and has received
considerable attention in the past decades.[1] On the other
hand, the reaction of sulfide with metal carbenes, which can
be easily generated in situ by the transition-metal catalyzed
decomposition of diazo compounds, is an available approach
to form sulfonium ylide.[2] This protocol has been
demonstrated as an efficient and operationally simple method
in contrast to the classic approaches with using stoichiometric
base.
ref 8b
(a) Wang's work (
)
SR2
R3
S
R3
N
CO2R4
R3
R2
thia-Sommelet-Hauser
rearrangement
N
R1
SR2
O
CO2R4
Rh(II)
S
+
N
R1
R2
N
R1
N2
R1
[2,3]-rearrangement
R3
CO2R4
(b) Our work
O
CO2Me
Ph
O
N2
Rh(II)
N
S
N
Ph
S
+
Ph
Ph
CO2Me
O
S
S
O
MLn
[S]
MLn
MLn
Ph
[S]
O
O
SPh
[S]
[2,3]-σ rearrangement
M
O
Ph
Ph
CO2Me
Ph
SPh
CO2Me
N2
N
S
N
Metal = Rh, Cu...
N
CO2Me
S
S
O
O
O
B
[1,2]-rearrangement
N-S bond insertion
C
[1,2]-rearrangement
C-S bond insertion
Ar
A
[2,3]-rearrangement
Ar
[1,2]-σ rearrangement
Scheme 2. Different reaction pathway of N-S bonds via sulfur
ylide.
According to Wang’s work, Rh(II)-catalyzed thia-Sommelet-
Hauser rearrangement of sulfonium ylides afforded a series of
3-arylthio-1,3-disubstituted-oxindoles (Scheme 2a).[8] We
proposed that N-phenyl-sulfenyl phthalimide, a good sulfur(II)
electrophile, could form sulfoium ylide intermediate by the
reaction of the metal carbene, which could be easily generated
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from the metal-catalyzed reaction of α-diazocarbonyl
compounds (Scheme 2b). The initially formed sulfur ylide may
subsequently undergoes [2,3]-sigmatropic rearrangement,
entry
1
cat. (5 mol%)
Rh2(OAc)4
Rh2(OAc)4
FeCl2
solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
CHCl3
yield (%) b
72
2 c
3
64
leading to compound
A. Meanwhile, compounds B and C
14
would be formed via N-S bond and C-S bond insertion,
respectively.[9]
4
Pd(PPh3)4
CuI
24
5
27
Initially, when a 2:1 mixture of methyl phenyldiazoacetate
2a and N-phenyl-sulfenyl phthalimide 1a in toluene was
catalyzed by 5 mol% of Rh2(OAc)4, N-S bond insertion product
3aa was isolated as the sole product in 72% yield (entry 1,
Table 1), the structure of 3aa was further confirmed by X-ray
crystallography (Figure 1).[10] It is worth noting that no
6
CoCl2
28
7
NiCl2·6H2O
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
-
21
8
72
28
9
10
11
12
13
14 d
15
16 e
17 f
DCE
59
THF
trace
85
products
A
and
C
were detected in this reaction. This indicates
) is a favored reaction
Hexane
MeCN
that [1,2]-C-N-shift (N-S bond insertion,
B
22
pathway. We surmised that the N-S bond insertion was
obtained as the major product, probably, because N-S bond
was weaker than C-S bond. Then we found when 1.5 equiv. of
2a was used in the reaction, the yield of the product was
decreased to 64% (entry 2, Table 1). Further investigation by
altering the catalyst and solvents revealed some interesting
aspects about this reaction (Table 1). First, the reaction
catalyzed by Rh2(OAc)4 gave the insertion product in good
yield. By contrast, other transition metals, including Fe, Pd, Cu,
Co, Ni were evaluated under the standard reaction conditions
and all produced the desired product in lower yields than the
corresponding Rh catalyst (entries 3-7, Table 1), because the
reactions were not converted completely for other metals as
the catalysts. Meanwhile, other Rh(II) catalysts (e.g. Rh2(O2n-
Oct)4, (Rh2(R-DOSP)4)) were evaluated, giving the products in
lower yield, probably because of the steric hindrance of the
catalysts. Second, solvents play a significant effect on the yield
of the product. Through the solvents screening, n-hexane was
determined as the best solvent, affording the product in 85%
yield (entry 12, Table 1). We surmised that both the poor
solubility of the substrate 1a in hexane and the stability of Rh-
carbenoid in hexane are important to this transformation. The
reaction was permitted with reducing the catalyst loading to 1
mol% without compromising yield (entry 14, Table 1).
However, in the absence of Rh catalyst, no reaction took place
(entry 15, Table 1). Furthermore, the temperature was found
as an important parameter for this transformation. When the
Hexane
Hexane
Hexane
Hexane
84
N.R.
49
Rh2(OAc)4
Rh2(OAc)4
38
a
Reaction condition: 1a (0.2 mmol), 2a (0.4 mmol), cat. (5
o
mol%), solvent (4.0 mL), 80 C, 12 h. b Isolated yield. c Using 2a
(0.3 mmol). Rh2(OAc)4 (1 mol%). e Reacted at 50 C. f Reacted
at room temperature. N.R. = no reaction.
d
o
o
reaction was conducted under lower temperature (50 C and
Figure 1. X-ray crystallography of product 3aa (Thermal ellipsoids
are set at 30% probability).
room temperature), the desired product was obtained in 49%
and 38% yield, respectively (entries 16, 17, Table 1). Finally, we
determined the optimal reaction conditions as follows: 2.0
equiv. of 2a, 1 mol% Rh2(OAc)4 as a catalyst, hexane as a
solvent, 80 oC.
With the optimal reaction conditions in hand, we then
explored the scope of the N-aryl-sulfenyl phthalimides
1 in the
reaction (Table 2). The electronic effect of the substituents on
the aromatic ring of S-Ar group was investigated. To our
delight, the substrates bearing either electron-donating (p-Me,
p-MeO, m-MeO) or electron-withdrawing (p-F, p-Cl, p-Br)
substituents on the aromatic ring of S-Ar underwent the
reaction smoothly, affording the corresponding N-S bond
Table 1. Rh-Catalyzed formal N-S bond insertion reaction of
methyl phenyldiazoacetate into N-phenyl-sulfenyl phthalimide.
a
O
O
O
N2
OMe
Ph
OMe
cat.
(5 mol%)
solvent, 80 o
Ar, seal tube
+
N
N
SPh
insertion products 3aa-3ga in good yields (entries 1-7, Table 2),
C
O
SPh
and we found the stronger electron-withdrawing substituent
of S-Ar decreased the yields of the desired products. When N-
(2-naphthyl)-sulfenyl phthalimide 1h was employed in the
O
O
1a
2a
3aa
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reaction, the desired product 3ha was obtained in 68% yield condition in the parenthesis: 1 (0.3 mmol), 2 (0.6 mmol),
Rh2(OAc)4 (0.1 mol%), hexane (6.0 mL), 80 oC, 12 h.
(entry 8, Table 1). Next, the scope of the diazo compounds
2
was evaluated (Table 2). First, the electronic and steric effect
of the substituents on the benzene ring was investigated. For
Then, to further extend the substrate scope, other N-
para-substituted diazo compounds, the reaction either with substituted-sulfenyl imides were examined for this
electron-riched (Me, MeO) or electron-poor (F, Cl, Br) transformation (Scheme 3). When N-benzyl-sulfenyl
substituents could proceed smoothly, affording the phthalimide 1i was employed as the substrate, the reaction
corresponding products in good to excellent yields. However, proceeded smoothly under the optimal reaction conditions,
for the ortho-substituted diazo compounds, such as 2-Me, the providing the desired product 3ia in 96% yield. However, when
reaction worked, but gave the desired products in lower yields the substrate 1j derived from succinimide, the corresponding
(entries 10, Table 2). This result indicates that this [1,2]-C-N- product 3ja was obtained in only 21% yield.[11] Meanwhile, to
shift (N-S bond insertion) reaction is sensitive to the steric demonstrate the practical utility of this transformation, a
effect of the aromatic substituents. Meanwhile, we found that gram-scale reaction (1.0 gram) was carried out to furnish the
the stronger electron-withdrawing (e.g. p-F) substituent on the desired product 3aa in 83% yield (Scheme 3), comparable with
benzene ring of diazo compounds gave the product in high that obtained in 0.2 mmol scale reaction.
yield (94%). Second, various ester groups of the diazo
substrates were examined (entries 16-19, Table 2). It was
found that increasing the bulk of the ester groups had little
effect on the reaction activity, giving the product yields
comparable to other substrates. Comparing the 12 examples in
Table 2, 9 of them gave higher yields when 0.1 mol% catalyst
used instead of 1 mol%, while 2 of them gave almost identical
yields and only one gave slighter lower yield. Clearly, lowering
the catalyst loading helps the reaction.
Table 2. Reaction of N-aryl-sulfenyl phthalimides
a
1 with diazo
compounds
2.
O
O
O
N2
OR2
Ar'
SAr
OR2
Rh2(OAc)4 (0.1-1 mol%)
Hexane, 80 oC, 12 h
Ar, seal tube
+
N
N
SAr
O
O
R1
O
1
2 (2.0 equiv.)
3
yield
(%) b
Scheme 3. N-S bond insertion with other substrates and gram-scale
reaction.
entry
1
, Ar
2
, R1, R2
3
1
2
1a, C6H5
2a, H, Me
3aa 85 (91)c
As shown in Scheme 4, to demonstrate the utility of the N-S bond
insertion products. The glycine derivative 9 could be obtained in
good yield over 2 steps, cleavage of the phenyl-sulfenyl group
under radical conditions and deprotecton of phthalyl group using
N2H4-H2O.
1b, p-MeC6H4
1c, p-MeOC6H4
1d, m-MeOC6H4
1e, p-FC6H4
1f, p-ClC6H4
1g, p-BrC6H4
1h, 2-naphthyl
1a, C6H5
2a, H, Me
3ba 82 (87)
3
2a, H, Me
3ca
3da
83 (89)
93
4
2a, H, Me
5
2a, H, Me
3ea 77 (87)
6
2a, H, Me
3fa
88 (87)
95
7
2a, H, Me
3ga
8
2a, H, Me
3ha 68 (63)
3ab 96 (95)
9
2b, 4-Me, Me
2c, 2-Me, Me
2d, 4-MeO, Me
10
11
12
1a, C6H5
3ac
3ad
44
83
1a, C6H5
1a, C6H5
2e
,
3,4-(MeO)2, 3ae 81 (85)
Scheme 4. Transformation of the N-S bond insertion product 3aa.
Me
13
14
15
16
17
18
19
1a, C6H5
1a, C6H5
1a, C6H5
1a, C6H5
1a, C6H5
1a, C6H5
1a, C6H5
2f, 4-F, Me
2g, 4-Cl, Me
2h, 4-Br, Me
2i, H, Et
3af
94
To gain insights into the reaction mechanism, a crossover
experiment was conducted by subjecting an equivalent
amount of 1a and 1j with 2a under the optimal reaction
conditions (Scheme 5). As expected, only the target products
3aa and 3ja were isolated in 83% and 37% yield, respectively.
The crossover products 3aa’ and 3ja’ were not detected. From
this crossover experiment, we could confirm that the
rearrangement of this transformation went through an
intramolecular process.
3ag 79 (83)
3ah 77 (85)
3ai
3aj
3ak
3al
90
2j, H, tBu
85 (89)
96
2k, H, Bn
2l, 4-Me, iPent
81 (83)
a
Reaction condition: 1 (0.2 mmol), 2 (0.4 mmol), Rh2(OAc)4 (1
mol%), hexane (4.0 mL), 80 oC, 12 h. b Isolated yield. c Reaction
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Scheme 5. Crossover experiment of 1a and 1j with 2a.
7
In conclusion, we have developed a highly regioselective
Rh(II)-catalyzed sulfur ylide [1,2]-rearrangement of carbenoids
generated from aryldiazoacetates, providing access to tertiary
sulfides in moderate to excellent yields. And the product could
be easily converted to glycine derivative. This rearrangement
went through N-S bond insertion, proceeding with low catalyst
loading and broad substrate scope. The metal-catalyzed
carbene insertion into other σ bonds are being studied in our
laboratory.
C. K. Eidell and K. J. Worsencroft, J. Org. Chem., 2001, 66
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8
9
Financial support from National Natural Science
Foundation of China (grants 81373303, 81473080, 81573299
and 21502230) is gratefully acknowledged. This project was
also supported by the Jiangsu Province Natural Science
Foundation (BK20150688), and program for Changjiang
Scholars and Innovative Research Team in University
(IRT1193).
10 CCDC-1416587 contains the supplementary crystallographic
data for the product 3aa. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
11 For the low yielding of 3ja, we found that this reaction could
not converted completely. Meanwhile, in contrast to the
products derivated from phthalimide, the product 3ja was
not stable under the standard reaction conditions.
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