Nickel-Catalyzed Thiolation and Selenylation of Cycloketone Oxime Esters with Thiosulfonate or Seleniumsulfonate

Article abstract of DOI:10.1021/acs.joc.9b02431

A nickel-catalyzed ring opening and, subsequently, reductive cross-coupling of cycloketone oxime esters with thiosulfonate or seleniumsulfonate are reported, which involves C-C bond cleavage and C(sp³)-S or C(sp³)-Se bond formation. Notably, S-aryl/alkyl sulfonothioates and Se-alkyl seleniumsulfonothioates could be employed in this reaction to afford a variety of 1° and 2° alkyl sulfides, aryl sulfides, and 1° and 2° alkyl selenides in one step. This strategy features easily available substrates and mild reaction conditions.

Full text of DOI:10.1021/acs.joc.9b02431

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Article
Nickel-Catalyzed Thiolation/ and Selenylation of Cycloketone
Oxime Esters with Thiosulfonate or Selenium sulfonate
Jian Li, Shun-Yi Wang, and Shun-Jun Ji
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02431 • Publication Date (Web): 26 Nov 2019
Downloaded from pubs.acs.org on December 2, 2019
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Page 1 of 15
The Journal of Organic Chemistry
Nickel-Catalyzed Thiolation/ and Selenylation of Cycloketone Oxime Esters with
Thiosulfonate or Selenium sulfonate
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Jian Li, Shun-Yi Wang,* and Shun-Jun Ji*
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Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123,
P. R. China; E-mail: shunyi@suda.edu.cn; shunjun@suda.edu.cn
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RECEIVED DATE
*CORRESPONDING AUTHOR FAX: 86-512-65880307.
O
R1
R4
R3
O
O
N
R2 R3
X
S
R5
Y
Y
CN
Ni
+
R5
X
R4
R2
R5=aryl, 1o alkyl or 2o alkyl
Y=S or Se
R1
= p-CF3C6H5CO
X=C or N
ABSTRACT: A nickel-catalyzed ring opening and subsequently reductive cross-coupling of
cycloketone oxime esters with thiosulfonate or seleniumsulfonate is reported, which involves C-C bond
cleavage and C(sp3)-S or C(sp3)-Se bond formation. Notably, S-aryl/alkyl sulfonothioates and Se-alkyl
seleniumsulfonothioates could be employed in this reaction to afford a variety of 1º, 2º alkyl sulfides,
aryl sulfides and 1º, 2º alkyl selenides in one step. This strategy features easily available substrates and
mild reaction conditions.
KEYWORDS: Nickel catalysis, reductive coupling, ring opening, sulfides, selenides.
1. INTRODUCTION
The cleavage of C-C bonds attracts fundamental attention and plays an important role in various
unique transformations.1 In recent years, C–C bond cleavage of cycloketone oxime ester derivatives has
attracted considerable interest to construct C–C, C-O, C-X and C-N bonds.2-4 Among them, sp3C–S and
sp3C–Se bonds via C–C bond cleavage of cycloketone oxime esters has been rarely studied. In 2005,
Uemura and co-workers first reported an Ir-catalyzed reaction of cycloketone oxime esters with
diphenyl dichalcogenides to construct phenyl alkyl sulfide and phenyl alkyl sulfides with limited
substrates through the reaction of carbon radical with dichalcogenides.5 Recently, Zhou group
developed a visible light promoted reaction of cycloketone oxime esters with disulfide and diselenide at
room temperature based on a similar radical trapping strategy. However, only diphenyl disulfide,
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diphenyl diselenide and dimethyl disulfide were studied (Scheme 1, a).6 More recently, Lin group
reported a copper catalyzed reaction of cycloketone oxime esters with heteroaryl thiols through the
reaction of carbocation with sulfur nucleophile in the presence of excess DBU.7 However, the reaction
of substituted thiophenols led to the desired products in <25% yields (Scheme 1, b).
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9
Sulfur-containing and selenium-containing compounds play important roles in synthetic chemistry,
medicinal chemistry and functional materials.8 The traditional C-S and C-Se bonds.
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Scheme 1. Methods for Activation of Cyclobutanone Oximes.
O
N
LG
CN
radical traps
CN
Photocatalysis
SET
a)
XR
RXXR
X=S or Se
R= Ph or Me (58%)
O
N
LG
CN
Cu
RS
CN
b)
SR
base
R=Het, 32%-88%
R=substituted thiophenol, <25%
R1
R1
R1
SET
FG
FG
R1
FG
c)
Br
X
H
H
H
Ph
C-S or C-Se bond formation
S
O
O
S
Ni/Mn
Ligand
N
N
O
XR1
NiII
Ph
XR1
O
X = S or Se
This Work
R2
R3
R3
d)
N
SET
R1
NC
X
NC
R3
4 R5
4R5
R
R
R4 R5
R1= aryl, primary alkyl, secondary alkyl
1
up to 99% yield
formation strategy need thiols or limited dichalcogenides. It is more desirable to apply odourless and
easily prepared thiosulfonates and seleniumsulfonates to construct C-S and C-Se bonds.9 Recently, we
developed a Ni-catalyzed reductive cross-coupling of alkyl bromides with sulfonothioates or
seleniumsulfonates to synthesize sulfides and selenides (Scheme 1, c).10 The key process for the reaction
is that an alkyl radical reacts with NiII intermediate, which is in situ generated by the oxidative addition
of sulfonothioate with Ni0 . We reasoned that the carbon radical could be generated from cycloketone
oxime esters through C-C bond cleavage, which could react with NiII intermediate generated by the
oxidative addition sulfonothioate with Ni0. Herein, we report a Ni-catalyzed ring opening and
subsequently reductive cross-coupling of cycloketone oxime esters with thiosulfonate or
seleniumsulfonate to afford a variety of cyano-containing sulfides and selenides (Scheme 1, d).
2. RESULTS AND DISCUSSION
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The initial study was focused on the reaction of cyclobutanone O-(4-(trifluoromethyl)benzoyl) oxime
1a with S-phenyl benzenesulfonothioate 2a in the presence of NiBr2 (10 mol%), 2,9-dimethyl-1,10-
2
3
4
o
phenanthroline L1 (15 mol%), and Mn powder (2 equiv) in N,N-dimethylformamide (DMF) at 40 C
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6
7
8
for 24 h. To our delight, the desired product 4-(phenylthio)butanenitrile 3a was obtained in 67% yield
(Table 1, entry 1). It was found that no desired product was obtained at all in the absence of NiBr2, Mn
or ligand (Table 1, entries 2-4). These results clearly indicate that the nickel catalyst, reductant and
ligand are necessary for this reaction. Other Ni-salts such as NiF2, NiCl2, NiI2, Ni(PPh3)2Cl2, Ni(acac)2
or Ni(OAc)2 were ineffective for this reaction. (Table 1, entries 5-10) Notably, the ligand was critical for
this transformation. Other phenanthroline-based ligands L2-5, bipyridine L6, phenanthrenequinone L7
and terpyridine L8 were also applied to the reaction (Table 1, entries 11-17). L1 is the best choice to
afford the designed product. Replacing Mn by Zn as reducing reagent resulted in a lower yield (Table 1,
entry 18). When other solvents such as DMA and DMSO were used, the reaction afforded the cross-
coupled product 3a in lower yields (entries 19-20). O-Acyl oximes bearing different substituted aryl
groups including C6H5 and C6F5 led to 3a in 51% and 64% yields, respectively (entries 21-22). The
yield of 3a increased to 95% with a higher oxime ester loading (entry 23).
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Table 1. Optimization of the Reaction Conditions. a
Ni
[
] (10 mol%)
O
S
S
SO2Ph
CN
R1
Ligand (15 mol%)
N
+
Mn (2 equiv)
Solvent, 40 oC, 24h
1a
2a
3a
R1= p-CF3C6H5CO, R2= C6H5CO, R3= C6F5CO
R1
R2
1
2
L1
L2
L3
R =Me, R =Me
1
2
L4
L5
R =Me, R =Me
1
2
R =H, R =H
1
2
R =Ph, R =Ph
N
N
N
N
1
2
R =H, R =Me
R1
R2
N
N
O
O
N
N
N
N
N
L6
L7
L8
Entry
1
[Ni]
Ligand Solvent Reductant
R
yield (%)c
NiBr2
-
L1
L1
L1
-
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Mn
Mn
-
R1
R1
R1
R1
R1
R1
R1
R1
R1
R1
R1
R1
67
0
2
3
NiBr2
NiBr2
NiF2
NiCl2
NiI2
0
4
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
0
5
L1
L1
L1
L1
L1
L1
L2
L3
0
6
0
7
6
8
Ni(PPh3)2Cl2
Ni(acac)2
Ni(OAc)2
NiBr2
39
24
0
9
10
11
12
25
53
NiBr2
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23b
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
NiBr2
L4
L5
L6
L7
L8
L1
L1
L1
L1
L1
L1
DMF
DMF
DMF
DMF
DMF
DMF
DMA
DMSO
DMF
DMF
DMF
Mn
Mn
Mn
Mn
Mn
Zn
R1
R1
R1
R1
R1
R1
R1
R1
R2
R3
R1
32
24
61
16
35
25
52
58
51
64
95
1
2
3
4
5
6
7
8
Mn
Mn
Mn
Mn
Mn
9
10
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a Standard conditions: 1a (0.1 mmol), 2a (0.1 mmol), NiBr2 (10 mol%), Mn (2 equiv), liand (15 mol%), solvent (0.5 mL) at
40 oC under N2 for 24h. b 0.2 mmol 2a was used. c Yields of isolated product.
With the optimal reaction conditions in hand, we first explored the scope of various sulfonothioates in
this Nickel-catalyzed reductive cross-coupling reaction (Scheme 2).
Scheme 2. Scope of thiosulfonates. a,d
NiBr2 (10 mol%)
L1
O
R1
N
(15 mol%)
S
CN
R2 SO2Ph
+
S
R2
Mn (2 equiv)
DMF, 40 oC or 60 o
C
1a
R1 = p-CF3C6H5CO
2
3
Aryl thiosulfonates scope
S
CN
S
S
CN
CN
F
3a
3b
3c
, 95%
, 93%
, 67%
S
CN
3d
R=F
, 56%
S
CN
3e
R=Cl , 52%
3f
R=Br , 66%
R
3g
, 93%
Alkyl thiosulfonates scope
S
CN
C10H21
S
S
CN
CN
CN
b
b
3h
3i
3j
, 73%
,
42%, 99%b, 91%c
80%
S
CN
S
S
4
CN
EtOOC
3k
3l
,
40%b
,
56%b
traceb
3m
,
a Standard conditions: 1a (0.4 mmol), 2 (0.2 mmol), NiBr2 (10 mol%), L1 (15 mol%) Mn (2 equiv), DMF (1.0 mL) at 40 oC
under N2. b At 60 oC c At 100 oC d Yields of isolated product.
ortho-substituted S-aryl benzenesulfonothioates with electron-neutral (Me) groups underwent the
transformation smoothly (93% yields). Substrates containing transformable groups such as fluoro,
chloro and bromo showed good reactivity, and the corresponding thioethers (3c-3f) were obtained in 52-
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67% yields. More bulky S-(2,6-dimethylphenyl) benzenesulfonothioate 2g was also suitable, and the
desired product 3g was isolated in up to 93% yield. Thus, a variety of S-alkyl benzenesulfonothioates
were also investigated and results are summarized in Scheme 2. By contrast, these compounds showed
slightly lower reactivity than S-aryl benzenesulfonothioates. It was found that higher temperature led to
satisfactory results (4h-4j). Moreover, the cyanopropyl sulfide product is not limited to the the 1º alkyl
sulfide, secondary S-alkyl thiosulfonates were also compatible with 1a. and the 2º alkyl sulfide 3k was
successfully obtained in 40% yield under the modified reaction conditions. It is worth mentioning that
substrates bearing functionalized group such as aster gave product in 56% yield (3l). However, alkynyl
group could not tolerate this condition (3m).
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Scheme 3. Scope of cyclobutanone oximes. a b
NiBr2 (10 mol%)
O
R3
R2
X
R1
R4
R3
N
L1
(15 mol%)
S
CN
S
+
Ph SO2Ph
Ph
Mn (2 equiv)
DMF, 60 o
R4
X
R2
C
1
2a
4
R1 = p-CF3C6H5CO, X=C or N
Cyclobutanone oximes scope
Ph
S
CN
Ph
Ph
Ph
S
CN
OBn
S
S
CN
CN
Ph
OBn
N
Boc
4a
4b
4c
4d
, 98%
, 86%
, 55%
, 40%
Ph
Ph
Ph
S
N
CN
S
S
N
CN
COOEt
CN
Ph
Boc
S
CN
Ph
Ph
4e
4f
4g
4h
, 98%
, 26%
, 73%
, 82%
Ph
C8H17
Ph
Ph
Ph
S
CN
S
CN
S
CN
4i
4j
4k
, 88%
, 98%
, 98%
a Standard conditions: 1 (0.4 mmol), 2a (0.2 mmol), NiBr2 (10 mol%), L1 (15 mol%) Mn (2 equiv), DMF (1.0 mL) at 40 oC
under N2. b Yields of isolated product.
Subsequently, a range of cycloketone oxime esters were tested to react with S-phenyl
benzenesulfonothioate 2a (Scheme 3). A variety of 3-aryl, oxybenzyl and alkyl substituted oxime esters
were efficiently engaged in this nickel-catalyzed reductive cross-coupling reaction to provide the
corresponding thioethers 4a–4c in moderate to good isolated yields (40%-86%). The 3,3-disubstituted
substrates 1d also afforded the target products 4d in up to 76% yield, respectively. Unfortunately, the
reactions of 3-ester oxime esters 1e with 2a provided 4e in 26% yield. In this case, 3-heteroatom was
also explored and products 4f and 4g were obtained in 73-82% yields. The α-substituted cyclobutanone
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oxime esters with diverse functional groups, such as n-butyl (1h), n-octyl (1i) phenylpropyl (1j) and
allyl (1k), could all undergo the desired pathway to deliver the corresponding thioethers 4h-4k in 88-
98% yield under this conditions.
1
2
3
4
5
6
Scheme 4. Scope of selenosulfonates. a,b
NiBr2 (10 mol%)
L1
7
8
9
O
(15 mol%)
R1
N
Se
CN
+
R2
Se
SO2Ph
R2
Mn (2 equiv)
DMF, 60 o
C
10
11
12
13
14
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59
60
1a
R1 = p-CF3C6H5CO
5
6
Selenosulfonates scope
Se
Se
Ph
CN
CN
Se
CN
6a
6b
6c
, 49%
, 61%
, 66%
Se
CN
Se
CN
6d
6e
55%
, 75%
a Standard conditions: 1a (0.4 mmol), 2 (0.2 mmol), NiBr2 (10 mol%), L1 (15 mol%) Mn (2 equiv), DMF (1.0 mL) at 60 oC
under N2. b Yields of isolated product.
A variety of Se-primary alkyl benzenesulfonoselenoates were well tolerated under the standard
conditions and produced the corresponding 1o alkyl selenides 6a-6d in moderate to good yields (49-
75%). Additionally, Se-secondary alkyl benzenesulfonoselenoates 5e was also suitable for this
transformation under this conditions and afforded corresponding 2o alkyl selenides 6e in 55% yield
(Scheme 3).
Scheme 5. The Ni-catalyst loading could be reduced to 1 mol% without loss of catalytic activity.
1 mol%
NiBr2
OR1
1.5 mol% L1
N
S
CN
S
SO2Ph
+
Ph
Ph
Mn (2 equiv)
DMF (5 mL) , 40 o
C
1a
2a
3a
0.4032 g
, 4mmol
, 3mmol
, 76%,
R1= p-CF3C6H5CO
To illustrate the application of this reductive cross coupling reactions, the scale-up reaction of 1a (4
mmol) with 2a (3 mmol) in the presecne of only 1 mol% NiBr2 was investigated. As shown in Scheme
5, the desired product 3a was obtained in 76% isolated yield with decreased Ni- catalyst.
Scheme 6. Control experiments.
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R1= p-CF3C6H5CO
1
2
3
4
NiBr2 (10 mol%)
L1
OR1
N
(15 mol%)
S
CN
a)
+
S
Ph
SO2Ph
Ph
Mn (2 equiv)
DMF, 40 oC or 60 o
C
1a
2a
3a
, trace
TEMPO
(3 equiv)
5
6
7
8
9
10
11
12
13
NiBr2 (10 mol%)
L1
OR1
Ph
N
S
(10 mol%)
S
+
Ph SO2Ph
b)
Mn (2 equiv)
DMF, 60 o
*
*
CN
C
1l
2a
4l
, 43% dr=3:1
Several radical trapping experiments were conducted to preliminarily probe into the mechanism of
the reaction. When TEMPO as radical scavenger was added in this reaction system, no desired product
3a was observed (Scheme 6, a).
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As expected, when cyclobutanone oxime ester 1l incorporating a bishomoallyl group was used to
react with S-phenyl benzenesulfonothioate 2a, a cyclic product 4l could be afforded with a good
diastereomeric ratio (Scheme 6, b). These experiments suggested that a radical intermediate was
generated in this transformation.
Based on above experimental results and also inspired by Wang’s work11 and literature reports,12,13
we proposed the mechanism for this Ni-catalyzed reductive cross-coupling of cycloketone oxime ester
with thiosulfonate. (Scheme 7). Initially, the in situ generated active Ni0(L)2 complex A reacts with
thiosulfonate 2 to afford R1S-NiII(L)2 species (B) by oxidative addition. B recombines rapidly with C-
centered radical to form NiIII(L)2 C. The cyano-containing sulfides (3) is formed by reductive
elimination of C and a NiI (L)2 D intermediate is generated. Next, D reacts with cycloketone oxime ester
1 to generate the C-centered radical by instant C-C bond cleavage and provide NiII E, which
subsequently undergoes an reductive elimination to regenerate the Ni0(L)2 species A for the next
catalytic cycle.
Scheme 7. Proposed mechanism.
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Br
NiII
Br
1
2
Mn
3
4
5
6
O
MnX2
S
YR5
Ph
Mn(O2SPh)R1
O
N
2 (Y=S or Se)
Ph
Ni0
Mn
N
7
S
O
(A)
8
9
N
N
O
Ph
NiII
(B)
S
O
YR5
N
N
O
NiII
10
11
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14
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17
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19
20
21
22
23
24
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R4
R1
(E)
NC
X
Ph
R2 R3
S
O
O
R1
N
NiIII
YR5
R2
R3
N
N
(C)
Ph
R4
R4
X
S
O
X
1
R3
R2
CN
N
N
O
NiI
(D)
R4
R5
NC
X
Y
R3
R2
3
3. CONCLUSION
In summary, we have developed a Ni-catalyzed reductive cross-coupling of cycloketone oxime ester
with thiosulfonate or seleniumsulfonate, which involves C-C bond cleavage and C(sp3) -S or C(sp3) -Se
bond formation. Notably, all of the S-aryl/alkyl sulfonothioate and Se-alkyl seleniumsulfonothioate
could be employed in this reaction to produce a variety of 1º, 2º alkyl sulfide, aryl sulfides and 1º, 2º
alkyl Selenide through one step. This method showed a wide substrate scope, providing ready access to
various cyanopropyl sulfides and cyanopropyl selenides. A mechanism involving iminyl radical-
triggered C–C bond cleavage is described. Further studies including detailed mechanistic studies are
currently underway.
4. EXPERIMENTAL SECTION
1. General Information All the solvents for routine isolation of products and chromatography were reagent grade. Flash chromatography
was performed using silica gel (300−400 mesh) with the indicated solvents. Melting points were recorded on an electrothermal digital
melting point apparatus and were uncorrected. IR spectra were recorded on a spectrophotometer using KBr optics. 1H NMR and 13C NMR
spectra were recorded on a 400 MHz (1H NMR) and 100 MHz (13C NMR) spectrometer using CDCl3 or DMSO-d6 as solvent and TMS as
internal standard. The H NMR data are reported as the chemical shift in parts per million, multiplicity (s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet), coupling constant in hertz, and number of protons. High resolution mass spectra were obtained using a high
resolution ESI-TOF mass spectrometer and high resolution CI-TOF mass spectrometer.
1
2.1. General procedures for the synthesis cyclobutanone oximes.
1a-1b, 1d, 1k14, 1e, 1g15 and1h16 were prepared following the reported procedures.
2.2. General procedures for the synthesis thiosulfonate or selenium sulfonate.
2a-2k, 5a17, 5b18, 5c19, and 5d-5e20 were prepared following the reported procedures.
2.3. General Procedure for the construction of 3a. In glovebox, an oven-dried screw-capped 8 mL vial equipped with a magnetic stir bar
was charged with O-(p-CF3-benzoyl)oxime 1a (102.8 mg, 0.4 mmol) and S-phenyl benzenesulfonothioate 2a (50.0 mg 0.2 mmol) NiBr2
(4.4 mg, 0.02 mmol), 2,9-dimethyl-1,10-phenanthroline (L1, 6.2 mg, 0.03 mmol ) and Mn powder (22.0 mg, 0.4 mmol). DMF (1.0 mL)
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was added via syringe. The resulting solution was stirred for 24 h at 40 C (heat source: oil bath). After this time, the crude reaction
mixture was diluted with ethyl acetate (100 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4, filtered,
and evaporation of the solvent under reduced pressure gave a crude product which was purified by silica gel (200–300 mesh) column
chromatography by using hexane : EtOAc (20 : 1) as an eluent to afford the colorless oil product 3a (34.6mg, 95%).
2.4. General Procedure for the construction of 3h. In glovebox, an oven-dried screw-capped 8 mL vial equipped with a magnetic stir bar
was charged with O-(p-CF3-benzoyl)oxime 1a (102.8 mg, 0.4 mmol) and S-(3-phenylpropyl) benzenesulfonothioate 2h (58.4 mg 0.2
mmol) NiBr2 (4.4 mg, 0.02 mmol), 2,9-dimethyl-1,10-phenanthroline (L1, 6.2 mg, 0.03 mmol ) and Mn powder (22.0 mg, 0.4 mmol).
DMF (1.0 mL) was added via syringe. The resulting solution was stirred for 24 h at 60 oC (heat source: oil bath). After this time, the crude
reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (20 mL × 3). The organic layer was dried over Na2SO4,
filtered, and evaporation of the solvent under reduced pressure gave a crude product which was purified by silica gel (200–300 mesh)
column chromatography by using hexane : EtOAc (20 : 1) as an eluent to afford the colorless oil product 3h (34.4mg, 99%).
2.5 General Procedure for the construction of 1c and 1f
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The ketone (5.0 mmol, 1.0 eq.) and hydroxylamine hydrochloride (5.5 mmol, 1.5 eq.) were placed in a 100 mL flask equipped with stirrer.
The pH of the solution was held at 7–8 by adding saturated aq. sodium carbonate (10 mL). The resulting solution was stirred at 40°C. After
extraction with ether, the solution was dried over Na2SO4 and evaporated to provide cyclobutanone oxime which were used in the next step
without further purification; To a mixture of cyclobutanone oxime (1.0 equiv.), triethylamine (2.0 equiv.) and DCM (0.5 M) in a 50 mL
flask was added p-CF3 benzoyl chloride (1.5 equiv.) at 0 °C. After 3 h, water was added to the above solution, and the mixture was diluted
with diethyl ether. The organic layer was washed with water and dried over Na2SO4. The solvent was removed under vacuum and the
residue was subjected to column chromatography on SiO2 with pentane/EtOAc as an eluent to give cyclobutanone oxime esters.
2.6 General Procedure for the construction of 1i, 1j and 1l
The cyclobutanone (5.0 mmol, 1.0 equiv.) and hydroxylamine hydrochloride (5.5 mmol, 1.5 equiv.) were placed in a 100 mL flask
equipped with stirrer. The pH of the solution was held at 7–8 by adding saturated aq. sodium carbonate (10 mL). The resulting solution
was stirred at 80°C. After extraction with ether, the organic layer was washed with water and dried over Na2SO4. The solvent was removed
under vacuum and the residue was subjected to column chromatography to give cyclobutanone oxime as a white solid; Cyclobutanone
oxime (1.0 equiv.) in absolute dry THF (0.5 M) was added nBuLi (2.0 equiv.) slowly at 0 °C, then continuing to stir for another 15 min at
this temperature for the formation of syn dianion. Then RX (1.0 equiv.) was added dropwise at 0 °C, then the mixture was warmed to RT
for 2 h. Subsequently, the reaction was quenched by cold water, and the mixture was diluted with EtOAc. The organic layer was washed
with water and dried over Na2SO4. The solvent was removed under vacuum and the residue was subjected to column chromatography on
SiO2 with EtOAc– pentane as an eluent to give α-substituted cyclobutanone oximes; To a mixture of α-substituted cyclobutanone oxime
(1.0 equiv.), triethylamine (2.0 equiv.) and DCM (0.5 M) in a 50 mL flask was added p-CF3 benzoyl chloride (1.5 equiv.) at 0 °C. After 3 h,
water was added to the above solution, and the mixture was diluted with diethyl ether. The organic layer was washed with water and dried
over Na2SO4. The solvent was removed under vacuum and the residue was subjected to column chromatography on SiO2 with
pentane/EtOAc as an eluent to give α-substituted cyclobutanone oxime esters.
3-((Benzyloxy)methyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1c) White solid (1.36 g, 75%), Following the reported
procedures14; 1H NMR (400 MHz, Chloroform-d) δ 8.15 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.5 Hz, 2H), 7.51 – 7.19 (m, 5H), 4.56 (s, 2H),
3.57 (dq, J = 6.8, 3.3 Hz, 2H), 3.32 – 3.14 (m, 2H), 3.03 – 2.89 (m, 2H), 2.86 – 2.66 (m, 1H); 13C{1H}NMR (100 MHz, CDCl3) δ 167.8,
162.8, 138.0, 134.7 (q, JC-F = 32.5 Hz), 132.4, 132.4, 130.1, 128.6, 127.9, 127.8, 125.6 (q, JC-F = 3.6 Hz), 123.6 (q, JC-F = 271.5 Hz), 73.3,
72.4, 34.8, 28.0; 19F NMR (377 MHz, CDCl3) δ -63.2. HRMS (ESI) m/z: calcd for C20H18F3NO3Na: (M+Na)+ 400.1131, found: 400.1141.
1
1-Benzhydrylazetidin-3-one O-(4-(trifluoromethyl)benzoyl oxime (1f) White solid (1.48 g, 70%), Following the reported procedures14; H
NMR (400 MHz, Chloroform-d) δ 8.09 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.52 – 7.43 (m, 4H), 7.32 (t, J = 7.4 Hz, 4H), 7.52 –
7.20 (m, 2H), 4.59 (s, 1H), 4.22 – 4.08 (m, 4H); 13C{1H}NMR (100 MHz, CDCl3) δ 162.7, 162.6, 141.6, 135.1 (q, JC-F = 32.7 Hz),132.0,
130.2, 129.0, 128.0, 127.4, 125.7 (q, JC-F = 3.7 Hz), 123.6 (q, JC-F = 271.4 Hz), 61.0, 60.9; 19F NMR (377 MHz, CDCl3) δ -63.2. HRMS
(ESI) m/z: calcd for C24H19F3N2O2Na: (M+Na)+ 447.1291, found: 447.1289.
1
2-Octylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1i) Yellow oil (1.40 g, 76%), Following the reported procedures14; H
NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 3.64 – 3.38 (m, 1H), 3.18 – 2.87 (m, 2H), 2.34 – 2.11
(m, 1H), 2.06 – 1.88 (m, 1H), 1.87– 1.59 (m, 2H), 1.54 – 1.09 (m, 12H), 0.86 (t, J = 6.9 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ
172.1, 162.7, 134.4 (q, JC-F = 32.5 Hz), 132.4, 129.8, 125.4 (q, JC-F = 3.7 Hz), 123.4 (q, JC-F = 271.0 Hz), 46.2, 31.7, 31.2, 29.3, 29.2, 29.1,
28.8, 26.5, 22.5, 19.7, 13.8; 19F NMR (377 MHz, CDCl3) δ -63.4. HRMS (ESI) m/z: calcd for C20H26F3NONa: (M+Na)+ 392.1808, found:
392.1807.
2-(3-Phenylpropyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1j) Yellow oil (1.44 g, 77%), Following the reported
procedures14; 1H NMR (400 MHz, Chloroform-d) δ 8.01 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.32 – 6.85 (m, 5H), 3.66 – 3.33 (m,
1H), 3.23 – 2.86 (m, 2H), 2.64 (t, J = 7.0 Hz, 2H), 2.29 – 2.12 (m, 1H), 2.09 – 1.88 (m, 1H), 1.88 – 1.60 (m, 4H); 13C{1H}NMR (100 MHz,
CDCl3) δ 172.1, 1631, 141.7, 134.7 (q, JC-F = 32.7 Hz), 132.5, 130.0, 128.5, 128.5, 126.1, 125.7 (q, JC-F = 3.7 Hz), 123.7 (q, JC-F = 271.3
Hz), 46.3, 35.6, 30.9, 29.1, 28.4, 19.9; 19F NMR (377 MHz, CDCl3) δ -63.2. HRMS (ESI) m/z: calcd for C21H20F3NO2Na: (M+Na)+
398.1338, found: 398.1330.
2-(Pent-4-en-1-yl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1l) Yellow oil (0.89 g, 55%), Following the reported
procedures14; 1H NMR (400 MHz, Chloroform-d) δ 8.04 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 6.00 – 5.58 (m, 1H), 5.04 – 4.73 (m,
2H), 3.58 – 3.35 (m, 1H), 3.13 – 2.77 (m, 2H), 3.18 – 2.04 (m, 1H), 2.03 – 1.82 (m, 3H), 1.76 – 1.51 (m, 2H), 1.51 – 1.16 (m, 2H);
13C{1H}NMR (100 MHz, CDCl3) δ 171.99, 162.76, 137.94, 134.5 (q, JC-F = 32.6 Hz), 132.29, 129.83, 125.0 (q, JC-F = 3.7 Hz), 123.4 (q,
JC-F = 271.1 Hz), 114.82, 45.99, 33.17, 30.53, 28.77, 25.61, 19.64; 19F NMR (377 MHz, CDCl3) δ -63.3. HRMS (ESI) m/z: calcd for
C17H18F3NO2Na: (M+Na)+ 348.1182, found: 348.1192.
1
Ethyl 6-((phenylsulfonyl)thio)hexanoate (2l) Colourless oil (1.30 g, 82%), Following the reported procedures10; H NMR (400 MHz,
Chloroform-d) δ 7.93 (d, J = 8.0 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.7 Hz, 2H), 4.11 (q, J = 6.8 Hz, 2H), 3.00 (t, J = 7.3 Hz,
2H), 2.24 (t, J = 7.4 Hz, 2H), 1.59 (dp, J = 22.8, 7.4 Hz, 4H), 1.33 (p, J = 7.8 Hz, 2H), 1.28 – 1.17 (m, 3H); 13C{1H}NMR (101 MHz,
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CDCl3) δ 173.3, 144.8, 133.7, 129.3, 126.9, 60.3, 35.8, 33.9, 28.3, 27.9, 24.2, 14.2. HRMS (ESI) m/z: calcd for C14H20NO4S2Na: (M+Na)+
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399.0695, found: 399.0695.
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S-(but-3-yn-1-yl) benzenesulfonothioate (2m) Colourless oil (0.81 g, 72%), Following the reported procedures10; H NMR (400 MHz,
Chloroform-d) δ 8.06 – 7.89 (m, 2H), 7.73 – 7.63 (m, 1H), 7.61 – 7.48 (m, 2H), 3.14 (td, J = 7.2, 1.3 Hz, 2H), 2.60 – 2.49 (m, 2H), 2.02 (t,
J = 2.6 Hz, 1H); 13C{1H}NMR (101 MHz, CDCl3) δ 144.6, 134.0, 129.5, 127.09, 80.8, 70.7, 34.6, 19.3. HRMS (ESI) m/z: calcd for
C10H10O2S2Na: (M+Na)+ 249.0014, found: 249.0019.
4-(Phenylthio)butanenitrile (3a) Yellow oil (34.6 mg, 95%), IR (neat, ν, cm-1): 3059, 2929, 1733, 1583, 1480, 1439, 1242, 1025, 738 cm-1.
1H NMR (400 MHz, Chloroform-d) δ 7.40 – 7.24 (m, 4H), 7.24 – 7.18 (m, 1H), 3.02 (t, J = 6.9 Hz, 2H), 2.49 (t, J = 7.1 Hz, 2H), 1.94 (m,
2H); 13C{1H}NMR (100 MHz, CDCl3) δ 134.8, 130.1, 129.2, 126.8, 119.1, 32.6, 24.9, 16.0 ppm. HRMS (ESI) m/z: calcd for C10H11NSNa:
(M+Na)+ 200.0504, found: 200.0503.
4-(O-tolylthio)butanenitrile (3b) Yellow oil (35.5 mg, 93%), IR (neat, ν, cm-1): 2925, 2246, 1589, 1469, 1424, 1065, 1048, 743 cm-1. H
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NMR (400 MHz, Chloroform-d) δ 7.31 – 7.26 (m, 1H), 7.22 – 7.09 (m, 3H), 3.00 (t, J = 6.9 Hz, 2H), 2.51 (t, J = 7.1 Hz, 2H), 2.39 (s, 3H),
1.96 (p, J = 7.0 Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 138.4, 134.1, 130.5, 129.1, 126.7, 126.6, 119.1, 31.8, 24.9, 20.5, 16.2 ppm.
HRMS (CI) m/z: calcd for C11H14NS: (M+H)+ 192.0841, found: 192.0853.
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4-((2-Fluorophenyl)thio)butanenitrile (3c) Yellow oil (26.1 mg, 67%), IR (neat, ν, cm-1): 2928, 2247, 1570, 1446, 1219, 1072, 819, 750
cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.38 – 7.23 (m, 1H), 7.22-7.16 (m, 1H), 7.09 – 6.92 (m, 2H), 2.93 (t, J = 6.9 Hz, 2H), 2.45 (t, J
= 7.1 Hz, 2H), 1.85 (q, J = 7.0 Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 162.0 (d, JC-F= 244.2 Hz), 133.4 (d, JC-F= 1.2 Hz), 129.5 (d, JC-
F= 7.9 Hz),124.8 (d, JC-F=3.7 Hz), 121.3 (d, JC-F= 17.6 Hz), 119.0, 116.0 (d, JC-F= 225.0 Hz), 32.4, 25.0, 15.9 ppm. 19F NMR (376 MHz,
CDCl3) δ -108.7. HRMS (CI) m/z: calcd for C10H11FNS: (M+H)+ 196.0591, found: 196.0598.
4-((4-Fluorophenyl)thio)butanenitrile (3d) Yellow oil (21.8 mg, 56%), IR (neat, ν, cm-1): 2927, 2247, 1589, 1489, 1220, 1157, 1090, 824
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cm-1. H NMR (400 MHz, Chloroform-d) δ 7.54 – 7.29 (m, 2H), 7.12 – 6.86 (m, 2H), 2.98 (t, J = 6.9 Hz, 2H), 2.51 (t, J = 7.1 Hz, 2H),
1.92 (p, J = 7.0 Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 162.2 (d, JC-F= 246.0 Hz), 133.3 (d, JC-F= 8.0 Hz), 129.6 (d, JC-F= 3.1 Hz),
119.0, 116.3 (d, JC-F= 21.7 Hz), 33.9, 24.8, 15.9 ppm. 19F NMR (376 MHz, CDCl3) δ -114.3. HRMS (CI) m/z: calcd for C10H11FNS:
(M+H)+ 196.0591, found: 196.0596.
4-((4-Chlorophenyl)thio)butanenitrile (3e) Yellow (21.9 mg, 52%), IR (neat, ν, cm-1): 2927, 2247, 1668, 1475, 1389, 1093, 1010, 811 cm-
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1. H NMR (400 MHz, Chloroform-d) δ 7.28 (s, 4H), 3.01 (t, J = 6.9 Hz, 2H), 2.50 (t, J = 7.0 Hz, 2H), 1.94 (p, J = 7.0 Hz, 2H);
13C{1H}NMR (100 MHz, CDCl3) δ 133.4, 132.9, 131.5, 119.0, 32.9, 24.8, 16.0 ppm. HRMS (ESI) m/z: calcd for C10H11ClNS: (M+H)+
212.0295, found: 212.0285.
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4-((4-Bromophenyl)thio)butanenitrile (3f) Yellow (33.7 mg, 66%), IR (neat, ν, cm-1): 2925, 2246, 1472, 1090, 1005, 806 cm-1. H NMR
(400 MHz, Chloroform-d) δ 7.46 – 7.38 (m, 2H), 7.25 – 7.18 (m, 2H), 3.02 (t, J = 6.9 Hz, 2H), 2.51 (t, J = 7.0 Hz, 2H), 1.95 (p, J = 7.0 Hz,
2H); 13C{1H}NMR (100 MHz, CDCl3) δ 134.1, 132.3, 131.6, 120.8, 119.0, 32.7, 24.8, 16.1 ppm. HRMS (CI) m/z: calcd for C10H11BrNS:
(M+H)+ 255.9790, found: 255.9796.
4-((2,4-Dimethylphenyl)thio)butanenitrile (3g) Yellow oil (38.1 mg, 93%), IR (neat, ν, cm-1): 2921, 2246, 2246, 1477, 1444, 1057, 807 cm-
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1. H NMR (400 MHz, Chloroform-d) δ 7.22 (d, J = 7.9 Hz, 1H), 7.06 – 6.93 (m, 2H), 2.94 (t, J = 6.9 Hz, 2H), 2.50 (t, J = 7.1 Hz, 2H),
2.37 (s, 3H), 2.29 (s, 3H), 1.92 (p, J = 7.0 Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 139.1, 137.0, 131.5, 130.7, 130.2, 127.4, 119.2,
32.5, 24.9, 21.0, 20.6, 16.1 ppm. HRMS (CI) m/z: calcd for C12H16NS: (M+H)+ 206.0998, found: 206.1008.
4-((3-Phenylpropyl)thio)butanenitrile (3h) Yellow oil (43.4 mg, 99%), IR (neat, ν, cm-1): 2925, 2246, 1496, 1453, 744, 699 cm-1. 1H NMR
(400 MHz, Chloroform-d) δ 7.28 (t, J = 7.3 Hz, 2H), 7.18 (t, J = 7.6 Hz, 3H), 2.71 (t, J = 7.5 Hz, 2H), 2.62 (t, J = 6.9 Hz, 2H), 2.52 - 2.45
(m, 4H), 1.89 (m, 4H); 13C{1H}NMR (100 MHz, CDCl3) δ 141.3, 128.5, 128.5, 126.0, 119.2, 34.7, 31.3, 31.0, 30.5, 25.2, 16.0 ppm.
HRMS (ESI) m/z: calcd for C13H17NSNa: (M+Na)+ 242.0974, found: 242.0963.
4-(Decylthio)butanenitrile (3i) Yellow oil (38.6 mg, 80%), IR (neat, ν, cm-1): 2922, 2853, 2247, 2656, 1457, 1365, 1260, 1099, 721 cm-1.
1H NMR (400 MHz, Chloroform-d) δ 2.64 (t, J = 6.9 Hz, 2H), 2.53 - 2.49 (m, 4H), 1.94 (p, J = 7.0 Hz, 2H), 1.57 (q, J = 7.7 Hz, 2H), 1.27
(s, 14H), 0.88 (t, J = 6.7 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 119.3, 32.2, 32.0, 30.7, 29.7, 29.6, 29.6, 29.4, 29.3, 29.0, 25.4, 22.8,
16.1, 14.2 ppm. HRMS (ESI) m/z: calcd for C14H27NSNa: (M+Na)+ 264.1756, found: 264.1740.
4-(Benzylthio)butanenitrile (3j) Yellow oil (27.9 mg, 73%), IR (neat, ν, cm-1): 2921, 2246, 1494, 1453, 1421, 1241, 1071, 1027, 700 cm-1.
1H NMR (400 MHz, Chloroform-d) δ 7.37 – 7.22 (m, 5H), 3.71 (s, 2H), 2.53 (t, J = 6.9 Hz, 2H), 2.42 (t, J = 7.1 Hz, 2H), 1.85 (p, J = 7.0
Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 138.0, 129.0, 128.7, 127.3, 119.3, 36.3, 29.9, 25.0, 16.1 ppm. HRMS (CI) m/z: calcd for
C11H14NS: (M+H)+ 192.0841, found: 192.0850.
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4-(Cyclopentylthio)butanenitrile (3k) Yellow oil (13.5 mg, 40%), IR (neat, ν, cm-1): 2952, 2867, 2246, 1651, 1448, 1243, 935 cm-1. H
NMR (400 MHz, Chloroform-d) δ 3.08 (p, J = 7.0 Hz, 1H), 2.67 (t, J = 6.9 Hz, 2H), 2.52 (t, J = 7.1 Hz, 2H), 1.97 (dp, J = 21.0, 7.0, 6.3
Hz, 4H), 1.81 – 1.68 (m, 2H), 1.63 – 1.42 (m, 4H); 13C{1H}NMR (100 MHz, CDCl3) δ 119.4, 43.9, 33.9, 30.5, 25.5, 24.8, 16.2 ppm.
HRMS (CI) m/z: calcd for C9H16NS: (M+H)+ 170.0998, found: 170.1008.
Ethyl 6-((3-cyanopropyl)thio)hexanoate (3l) Yellow oil (27 mg, 56%), IR (neat, ν, cm-1): 2933, 2859, 2246, 1728, 1655, 1447, 1422, 1371,
1257, 1178, 1126, 1098, 858, 736 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 4.13 (q, J = 7.1 Hz, 2H), 2.64 (t, J = 6.9 Hz, 2H), 2.52 (t, J =
7.2 Hz, 4H), 2.30 (t, J = 7.5 Hz, 2H), 1.93 (p, J = 7.0 Hz, 2H), 1.71 – 1.54 (m, 4H), 1.48 – 1.37 (m, 2H), 1.26 (t, J = 7.1 Hz, 3H);
13C{1H}NMR (101 MHz, CDCl3) δ 173.6, 119.3, 60.3, 34.2, 31.9, 30.7, 29.3, 28.3, 25.3, 24.6, 16.1, 14.3. HRMS (ESI) m/z: calcd for
C12H21NO2SNa: (M+Na)+ 266.1185 , found: 266.1196.
3-Phenyl-4-(phenylthio)butanenitrile (4a) Yellow oil (43.5 mg, 86%), IR (neat, ν, cm-1): 3060, 3029, 2921, 2246, 1783, 1582, 1480, 1025,
738, 690 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.41 – 7.26 (m, 7H), 7.26 – 7.17 (m, 3H), 3.33 (dd, J = 13.4, 5.8 Hz, 1H), 3.24 - 3.19
(m, 1H), 3.16-3.09 (m, 1H), 2.94 – 2.70 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 140.3, 134.9, 130.2, 129.3, 129.1, 128.1, 127.2,
127.0, 118.2, 41.5, 39.0, 23.3 ppm. HRMS (CI) m/z: calcd for C16H16NS: (M+H)+ 254.0998, found: 254.1013.
3-(Benzyloxy)-4-(phenylthio)butanenitrile (4b) Yellow oil (31.1 mg, 55%), IR (neat, ν, cm-1): 3061, 3031, 2927, 2869, 2250, 1583, 1439,
1415, 1088, 1066, 1025, 736 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.43 – 7.11 (m, 10H), 4.59 (s, 2H), 3.80 - 3.74 (m, 1H), 3.25 (dd,
J = 14.1, 4.8 Hz, 1H), 3.01 (dd, J = 14.1, 7.7 Hz, 1H), 2.81 – 2.61 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 137.1, 134.8, 130.0, 129.4,
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128.7, 128.3, 128.1, 127.0, 117.3, 73.6, 72.3, 37.3, 22.5 ppm. HRMS (ESI) m/z: calcd for C17H17NOSNa: (M+Na)+ 306.0923, found:
306.0922.
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4-(Benzyloxy)-3-((phenylthio)methyl)butanenitrile (4c) Yellow oil. (23.8 mg, 40%), IR (neat, ν, cm-1): 2923, 2860, 2246, 1583, 1480, 1439,
1364, 1099, 1025, 736 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.44 – 7.16 (m, 10H), 4.48 (s, 2H), 3.57 (qd, J = 9.5, 5.4 Hz, 2H), 3.11
(dd, J = 13.8, 6.4 Hz, 1H), 2.94 (dd, J = 13.8, 7.6 Hz, 1H), 2.63 (d, J = 6.9 Hz, 2H), 2.23 - 2.17 (m, 1H); 13C{1H}NMR (101 MHz, CDCl3)
δ 137.8, 135.1, 130.0, 129.3, 128.6, 128.0, 127.8, 126.8, 118.3, 73.5, 70.2, 36.3, 34.9, 18.9 ppm. HRMS (ESI) m/z: calcd for
C18H19NOSNa: (M+Na)+ 320.1080, found: 320.1077.
Tert-butyl 4-(cyanomethyl)-4-((phenylthio)methyl)piperidine-1-carboxylate (4d) Yellow oil (67.8 mg, 98%), IR (neat, ν, cm-1): 2975, 2929,
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2861, 1783, 1683, 1478, 1418, 1365, 1245, 1148, 972, 741, 690 cm-1. H NMR (400 MHz, Chloroform-d) δ 7.49 – 7.37 (m, 2H), 7.36 –
7.07 (m, 3H), 3.42 (m, 2H), 3.34 (m, 2H), 3.15 (s, 2H), 2.59 (s, 2H), 1.64 (tt, J = 13.8, 9.2 Hz, 4H), 1.47 (s, 9H); 13C{1H}NMR (100 MHz,
CDCl3) δ 154.7, 135.8, 130.8, 129.3, 127.2, 117.2, 80.0, 56.5, 42.3, 36.6, 33.8, 28.5, 26.0 ppm. HRMS (ESI) m/z: calcd for
C19H26N2O2SNa: (M+Na)+ 369.1607, found: 369.1607.
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Methyl 3-cyano-2-((phenylthio)methyl)propanoate (4e) Yellow oil (12.9 mg, 26%), IR (neat, ν, cm-1): 2954, 2250, 1734, 1438, 1198, 1025,
829, 741, 691 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.49 – 7.13 (m, 5H), 3.68 (s, 3H), 3.42 (dd, J = 14.1, 5.2 Hz, 1H), 3.14 (dd, J =
14.1, 7.8 Hz, 1H), 3.02 – 2.86 (m, 1H), 2.86 – 2.75 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 171.3, 133.8, 131.0, 129.4, 127.6, 117.4,
52.8, 41.5, 35.2, 18.3 ppm. HRMS (CI) m/z: calcd for C12H14NO2S: (M+H)+ 236.0740, found: 236.0736.
2-(Benzhydryl((phenylthio)methyl)amino)acetonitrile (4f) Yellow oil (50.2 mg, 73%), IR (neat, ν, cm-1): 3061, 3028, 2935, 2836, 2251,
1809, 1584, 1492, 1454, 1273, 1132, 1075, 908, 730, 693 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.44 – 7.36 (m, 2H), 7.34 – 7.16 (m,
13H), 4.78 (s, 1H), 4.25 (s, 2H), 3.77 (s, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 140.5, 134.6, 133.0, 129.2, 129.1, 128.0, 127.8, 127.9,
115.8, 71.3, 59.5, 38.8 ppm. HRMS (CI) m/z: calcd for C22H21N2S: (M+H)+ 345.1420, found: 345.1438.
Tert-butyl (cyanomethyl)((phenylthio)methyl)carbamate (4g) White solid (45.6 mg, 82%), mp: 66.2-69.0 oC. IR (neat, ν, cm-1): 2977, 2913,
1686, 1472, 1441, 1392, 1242, 1184, 926, 873, 750, 678 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.65 – 7.39 (m, 2H), 7.29 (d, J = 13.3
Hz, 3H), 4.81 (d, J = 19.6 Hz, 2H), 4.24 (d, J = 69.5 Hz, 2H), 1.30 (d, J = 67.4 Hz, 9H); 13C{1H}NMR (100 MHz, CDCl3) δ 153.3, 134.1,
132.5, 132.3, 129.3, 128.6, 127.9, 115.8, 82.6, 82.2, 53.5, 52.2, 34.04, 33.1, 28.0, 27.8 ppm. HRMS (ESI) m/z: calcd for C14H18N2O2SNa:
(M+Na)+ 301.0981, found: 301.0969.
4-(Phenylthio)octanenitrile (4h) Yellow oil (45.7 mg, 98%), IR (neat, ν, cm-1): 2956, 2929, 2859, 2246, 1583, 1477, 1438, 1091, 1068,
1024, 744, 692 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.52 – 6.99 (m, 5H), 3.04 (p, J = 7.3, 6.8 Hz, 1H), 2.60 – 2.39 (m, 2H), 1.92 -
1.83 (m, 1H), 1.80 – 1.64 (m, 1H), 1.59 – 1.31 (m, 4H), 1.23 (dp, J = 13.3, 6.8, 6.4 Hz, 2H), 0.82 (t, J = 7.3 Hz, 3H); 13C{1H}NMR (100
MHz, CDCl3) δ 133.8, 132.9, 129.2, 127.6, 119.6, 48.4, 34.3, 30.3, 29.1, 22.5, 14.8, 14.0. HRMS (ESI) m/z: calcd for C14H19NSNa:
(M+Na)+ 256.11130, found: 256.1129.
4-(Phenylthio)dodecanenitrile (4i) Yellow oil (56.6 mg, 98%), IR (neat, ν, cm-1): 2924, 2854, 2247, 1584, 1466, 1366, 1090, 1025, 745,
692 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.43 – 7.36 (m, 2H), 7.34 – 7.24 (m, 3H), 3.15 - 3.08 (m, 1H), 2.70 – 2.46 (m, 2H), 2.03 –
1.89 (m, 1H), 1.84 - 1.75 (m, 1H), 1.61 – 1.44 (m, 4H), 1.26 (s, 10H), 0.88 (t, J = 6.9 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 133.9,
132.9, 129.2, 127.6, 119.6, 48.4, 34.6, 31.9, 30.3, 29.5, 29.4, 29.3, 26.9, 22.8, 14.8, 14.2 ppm. HRMS (ESI) m/z: calcd for C18H27NSNa:
(M+Na)+ 312.1756, found: 312.1746.
7-Phenyl-4-(phenylthio)heptanenitrile (4j) Yellow oil (57.8 mg, 98%), IR (neat, ν, cm-1): 2931, 2857, 2245, 2583, 1495, 1452, 1483, 1088,
1025, 744, 693 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.41 – 7.01 (m, 10H), 3.20 – 2.98 (m, 1H), 2.77 – 2.33 (m, 4H), 1.98 – 1.66 (m,
4H), 1.65 – 1.46 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 141.8, 133.5, 133.1, 129.2, 128.5, 127.7, 126.0, 119.5, 48.3, 35.5, 33.9, 30.3,
28.5, 14.8 ppm. HRMS (CI) m/z: calcd for C19H22NS: (M+H)+ 296.1467, found: 296.1472.
4-(Phenylthio)hept-6-enenitrile (4k) Yellow oil (42.6 mg, 88%), IR (neat, ν, cm-1): 3075, 2926, 2247, 2640, 1583, 1475, 1438, 1421, 1024,
993, 918, 744, 691 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.44 - 7.41 (m, 2H), 7.37 – 7.20 (m, 3H), 5.89 - 5.79 (m, 1H), 5.22 – 4.98
(m, 2H), 3.28 – 3.08 (m, 1H), 2.75 – 2.50 (m, 2H), 2.46 - 2.39 (m, 1H), 2.33 - 2.26 (m, 1H), 2.09 – 1.88 (m, 1H), 1.88 – 1.67 (m, 1H);
13C{1H}NMR (100 MHz, CDCl3) δ 134.4, 133.4, 133.0, 129.2, 127.8, 119.4, 118.2, 47.5, 39.0, 29.4, 14.9 ppm. HRMS (CI) m/z: calcd for
C13H16NS: (M+H)+ 218.0998, found: 218.1008.
3-(2-((Phenylthio)methyl)cyclopentyl)propanenitrile (4l) Yellow oil (21.1 mg, 43%), IR (neat, ν, cm-1): 2945, 2868, 2245, 1583, 1479,
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1438, 1089, 1025, 737 cm-1. H NMR (400 MHz, Chloroform-d) δ 7.37 – 7.26 (m, 4H), 7.24 – 7.13 (m, 1H), 3.06 - 2.91 (m, 1H), 2.89 –
2,73 (m, 1H), 2.45 – 2.23 (m, 2H), 2.22 – 1.51 (m, 9H), 1.37 – 1.29 (m, 1H); 13C{1H}NMR (100 MHz, CDCl3) δ 136.7, 129.2, 128.9,
126.0, 119.7, 44.7, 44.5, 41.7, 41.5, 39.0, 34.7, 32.2, 31.8, 30.8, 30.5, 29.5, 25.5, 23.9, 22.3, 16.2 ppm. HRMS (CI) m/z: calcd for C15H20:
(M+H)+ 246.1311, found: 246.1311.
4-(Hexylselanyl)butanenitrile (6a) Yellow oil (28.4 mg, 61%), IR (neat, ν, cm-1): 2924, 2854, 2246, 1451, 1423, 1233, 1189, 724 cm-1. 1H
NMR (400 MHz, Chloroform-d) δ 2.67 (t, J = 7.1 Hz, 2H), 2.59 - 2.50 (m, 4H), 2.00 (p, J = 7.1 Hz, 2H), 1.66 (p, J = 7.3 Hz, 2H), 1.46 –
1.15 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 119.3, 31.4, 30.6, 29.7, 26.3, 24.6, 22.7, 22.0, 17.3, 14.2 ppm.
HRMS (CI) m/z: calcd for C10H20NSe: (M+H)+ 234.0755, found: 234.0768.
4-((3-Phenylpropyl)selanyl)butanenitrile (6b) Yellow oil (35.2 mg, 66%), IR (neat, ν, cm-1): 2926, 2854, 2245, 1495, 1452, 1421, 1234,
1029, 743, 699 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.28 (q, J = 6.7, 6.2 Hz, 2H), 7.19 (t, J = 8.4 Hz, 3H), 2.72 (t, J = 7.5 Hz, 2H),
2.66 (t, J = 7.1 Hz, 2H), 2.57 (t, J = 7.4 Hz, 2H), 2.49 (t, J = 7.1 Hz, 2H), 1.98 (h, J = 7.4 Hz, 4H); 13C{1H}NMR (100 MHz, CDCl3) δ
141.3, 128.6, 128.6, 126.1, 119.3, 35.9, 32.1, 26.2, 23.7 22.1, 17.3 ppm. HRMS (ESI) m/z: calcd for C13H17NSeNa: (M+Na)+ 290.0418,
found: 290.0420.
4-(Benzylselanyl)butanenitrile (6c) Yellow oil (23.4 mg, 49%), IR (neat, ν, cm-1): 2926, 2245, 1603, 1495, 1452, 1421, 1234, 1029, 743,
699 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.41 – 7.10 (m, 5H), 3.79 (s, 2H), 2.58 (t, J = 7.1 Hz, 2H), 2.41 (t, J = 7.1 Hz, 2H), 1.88 (p,
J = 7.1 Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 138.9, 128.9, 128.8, 127.1, 119.2, 27.4, 26.0, 22.1, 17.2 ppm. HRMS (CI) m/z: calcd
for C11H14NSe: (M+H)+ 240.0286, found: 240.0299.
4-((Cyclopropylmethyl)selanyl)butanenitrile (6d) Yellow oil (30.5 mg, 75%), IR (neat, ν, cm-1): 3077, 3002, 2860, 2245, 1422, 1208, 1016,
958, 824, 772 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 2.74 (t, J = 7.1 Hz, 2H), 2.60 – 2.46 (m, 4H), 2.02 (p, J = 7.1 Hz, 2H), 1.04 (pt, J
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= 7.5, 4.9 Hz, 1H), 0.72 – 0.55 (m, 2H), 0.24 - 0.20 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 119.3, 29.7, 26.4, 21.8, 17.3, 12.1, 6.8
ppm. HRMS (CI) m/z: calcd for C8H14NSe: (M+H)+ 204.0286, found: 204.0300.
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4-(Sec-butylselanyl)butanenitrile (6e) Yellow oil (22.6 mg, 55%), IR (neat, ν, cm-1): 2962, 2924, 2872, 2246, 1450, 1187, 956, 748 cm-1.
1H NMR (400 MHz, Chloroform-d) δ 2.91 (q, J = 6.8 Hz, 1H), 2.68 (t, J = 7.1 Hz, 2H), 2.52 (t, J = 7.0 Hz, 2H), 2.00 (p, J = 7.1 Hz, 2H),
1.72 - 1.59 (m, 2H), 1.43 (t, J = 6.1 Hz, 3H), 0.99 (t, J = 7.4 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 119.2, 37.4, 30.8, 26.4, 22.0,
20.6, 17.3, 12.3 ppm. HRMS (CI) m/z: calcd for C8H16NSe: (M+H)+ 206.0442, found: 206.0455.
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Supporting Information Available.
The copies of 1H and 13C NMR spectra of the products. This material is available free of charge via the
Internet at http://pubs.acs.org.
ACKNOWLEDGMENT
We gratefully acknowledge the National Natural Science Foundation of China (21971174, 21772137,
21542015 and 21672157), PAPD, the project of scientific and technologic infrastructure of Suzhou
(SZS201708), the Major Basic Research Project of the Natural Science Foundation of the Jiangsu
Higher Education Institutions (No.16KJA150002), Soochow University.
REFERENCES
(1) (a) Gozin, M.; Weisman, A.; Ben-David, Y.; Milstein, D. Activation of A Carbon–Carbon Bond in Solution by
Transition-Metal Insertion. Nature 1993, 364, 699-701. (b) Jones, W. D. The Fall of The C-C Bond. Nature 1993, 364, 676-
677. (c) Murakami, M.; Amii, H.; Ito, Y. Selective Activation of Carbon–Carbon Bonds Next to A Carbonyl Group. Nature
1994, 370, 540-541. (d) Rybtchinski, B.; Milstein, D. Metal Insertion into C−C Bonds in Solution. Angew. Chem. Int. Ed.
1999, 38, 870-883. (e) Murakami, M.; Ito, Y. Top. Organomet. Chem. 1999, 3, 97. (f) Jun, C.-H. Transition Metal-Catalyzed
Carbon–Carbon Bond Activation. Chem. Soc. Rev. 2004, 33, 610. (g) Dermenci, A.; Coe, J. W.; Dong, G. Direct Activation
of Relatively Unstrained Carbon–Carbon Bonds in Homogeneous Systems. Org. Chem. Front. 2014, 1, 567-518. (h) Kim,
D.-S.; Park, W.-J.; Jun, C.-H. Metal–Organic Cooperative Catalysis in C–H and C–C Bond Activation. Chem. Rev. 2017,
117, 8977-9015.
(2) (a) Boivin, J.; Fouquet, E.; Zard, S. Z. Ring Opening Induced by Iminyl Radicals Derived from Cyclobutanones: New
Aspects of Tin Hydride Cleavage of S-Phenyl Sulfenylimines. J. Am. Chem. Soc. 1991, 113, 1055-1057. (b) Boivin, J.;
Fouquet, E.; Zard, S. Z. Iminyl Radicals: Part II. Ring Opening of Cyclobutyl- and Cyclopentyliminyl Radicals. Tetrahedron
1994, 50, 1757−1768. (c) Callier-Dublanchet, A.-C.; Quiclet-Sire, B.; Zard, S. Z. Iminyl Radical Generation via
Iminodithiocarbonate Group Transfer. Tetrahedron Lett. 1997, 38, 2463-2466. (d) Nishimura, T.; Uemura, S. Palladium(0)-
Catalyzed Ring Cleavage of Cyclobutanone Oximes Leading to Nitriles via β-Carbon Elimination. J. Am. Chem. Soc. 2000,
122, 12049. (e) Nishimura, T.; Nishiguchi, Y.; Maeda, Y.; Uemura, S. Palladium-Catalyzed Transformation of
Cyclobutanone O-Benzoyloximes to Nitriles via C−C Bond Cleavage. J. Org. Chem. 2004, 69, 5342-5347.
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(3) (a) Yang, H.-B.; Selander, N. Divergent Iron‐Catalyzed Coupling of O‐Acyloximes with Silyl Enol Ethers Chem.–Eur. J.
2017, 23, 1779-1783. (b) Zhao, B.; Shi, Z. Copper‐Catalyzed Intermolecular Heck‐Like Coupling of Cyclobutanone Oximes
Initiated by Selective C−C Bond Cleavage. Angew. Chem. Int. Ed. 2017, 56, 12727. (c) Ai, W.; Liu, Y.; Wang, Q.; Lu, Z.;
Liu, Q. Cu-Catalyzed Redox-Neutral Ring Cleavage of Cycloketone O-Acyl Oximes: Chemodivergent Access to Distal
Oxygenated Nitriles. Org. Lett. 2018, 20, 409. (d) Li, L.; Chen, H.; Mei, M.; Zhou, L. Visible-light promoted γ-cyanoalkyl
radical generation: three-component cyanopropylation/etherification of unactivated alkenes. Chem. Commun. 2017, 53,
11544-11547. (e) Jiang ， H.; Studer, A. Iminyl‐Radicals by Oxidation of α‐Imino‐oxy Acids: Photoredox‐Neutral Alkene
Carboimination for the Synthesis of Pyrrolines. Angew. Chem. Int. Ed. 2017, 56, 12273-12276. (f) Davies, J.; Sheikh, N. S.;
Leonori, D. Photoredox Imino Functionalizations of Olefins. Angew. Chem. Int. Ed. 2017, 56, 13361-13365. (g) Yu, X.;
Chen, J.; Wang, P.; Yang, M.; Liang, D.; Xiao, W. A Visible‐Light‐Driven Iminyl Radical‐Mediated C−C Single Bond
Cleavage/Radical Addition Cascade of Oxime Esters Angew. Chem. Int. Ed. 2018, 57, 738. (h) Dauncey, E. M.; Marcillo, S.
P.; Douglas, J. J.; Sheikh, N. S.; Leonori, D. Photoinduced Remote Functionalisations by Iminyl Radical Promoted C−C and
C−H Bond Cleavage Cascades. Angew. Chem. Int. Ed. 2018, 57, 744.
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10
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16
17
18
19
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(4) (a) Gu, Y.-R.; Duan, X.-H.; Yang, L.; Guo, L.-N. Direct C–H Cyanoalkylation of Heteroaromatic N-Oxides and
Quinones via C–C Bond Cleavage of Cyclobutanone Oximes. Org. Lett. 2017, 19, 5908. (b) Yang, L.; Gao, P.; Duan, X.-H.;
Gu, Y.-R.; Guo, L.-N. Direct C−H Cyanoalkylation of Quinoxalin-2(1H)‑ones via Radical C−C Bond Cleavage. Org. Lett.
2018, 20, 1034-1037. (c) Wu, J.; Zhang, J.-Y.; Gao, P.; Xu, S.-L.; Guo, L.-N.; Copper-Catalyzed Redox-Neutral
Cyanoalkylarylation of Activated Alkenes with Cyclobutanone Oxime Esters. J. Org. Chem. 2018, 83, 1046-1055. (d)
Zhang, J.-Y.; Duan, X.-H.; Yang, J.-C.; Guo, L.-N. Redox-Neutral Cyanoalkylation/Cyclization of Olefinic 1,3‑Dicarbonyls
with Cycloketone Oxime Esters: Access to Cyanoalkylated Dihydrofurans. J. Org. Chem. 2018, 83, 4239-4249. (e) Zhao, J.;
Gao, P.; Duan, X.; Guo, L. Iron‐Catalyzed Ring‐Opening/Allylation of Cyclobutanone Oxime Esters with Allylic Sulfones.
Adv. Synth. Catal. 2018, 360, 1775-1779. (f) Zhao, J.-F.; Duan, X.-H.; Gu, Y.-R.; Gao, P. ； Guo, L.-N. Iron-Catalyzed
Decarboxylative Olefination of Cycloketone Oxime Esters with α,β-Unsaturated Carboxylic Acids via C–C Bond Cleavage.
Org. Lett. 2018, 20, 4614-4617. (g) Zhang, J.-J.; Duan, X.- H.; Wu, Y.; Yang, J.-C.; Guo, L. N. Transition-metal Free C–C
Bond Cleavage/Borylation of Cycloketone Oxime Esters Chem. Sci. 2019, 10, 161-166. (h) Zheng, M.; Li, G.; Lu, H.
Photoredox- or Metal-Catalyzed in Situ SO2-Capture Reactions: Synthesis of β-Ketosulfones and Allylsulfones. Org. Lett.
2019, 21, 1216-1220.
(5) Nishimura, T.; Yoshinaka, T.; Nishiguchi, Y.; Maeda, Y.; Uemura, S. Iridium-Catalyzed Ring Cleavage Reaction of
Cyclobutanone O-Benzoyloximes Providing Nitriles. Org. Lett. 2005, 7, 2425-2427.
(6) Anand, D.; He, Y.; Li, L.; Zhou, Lei. A Photocatalytic Sp3 C–S, C–Se and C–B Bond Formation Through C–C Bond
Cleavage of Cycloketone Oxime Esters. Org. Biomol. Chem. 2019, 17, 533–540.
(7) He, M.; Yan, Z.; Zhu, F.; Lin. S. Copper-Catalyzed Coupling Reactions of Cyclobutanone Oxime Esters with Sulfur
Nucleophiles at Room Temperature. J. Org. Chem. 2018, 83, 15438−15448.
(8) (a) Liu, H.; Jiang, X. F. Transfer of Sulfur: from Simple to Diverse. Chem. Asian J. 2013, 8, 2546–2563. (b) Dénès, F.;
Pichowica, M.; Povie, G.; Renaud, P.; Thiyl Radicals in Organic Synthesis. Chem. Rev. 2014, 114, 2587–2693. (c) Kondo,
T.; Mitsudo, T. A. Metal-Catalyzed Carbon–Sulfur Bond Formation. Chem. Rev. 100, 2000, 3205–3220. (d) Correa, A.;
Macheño, O. G.; Bolm, C. Iron-Catalysed Carbon–Heteroatom and Heteroatom–Heteroatom Bond Forming Processes.
Chem. Soc. Rev. 2008, 37, 1108–1117. (e) Lee, C.; Liu, Y.; Badsara, S. S. Transition‐Metal‐Catalyzed C–S Bond Coupling
13
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Page 14 of 15
Reaction. Chem. Asian J. 2014, 9, 706–722. (f) Beletskaya, I. P.; Anikov, V. P. Transition-Metal-Catalyzed C–S, C–Se, and
C–Te Bond Formation via Cross-Coupling and Atom-Economic Addition Reactions. Chem. Rev. 2011, 111, 1596–1636.
(9) For selected examples, see：(a) Mampuys, P.; Zhu, Y.; Vlaar, T.; Ruijter, E.; Orru, R. V. A.; Maes, B. U. W. Sustainable
1
2
3
4
Three-Component Synthesis of Isothioureas from Isocyanides, Thiosulfonates, and Amines. Angew. Chem. Int. Ed. 2014, 53,
12849-12854. (b) Zhu, Y.-P.; Sergeyev, S.; Franck, P.; Orru, R. V. A.; Maes, B. U. W. Amine Activation: Synthesis of N-
(hetero)arylamides from Isothioureas and Carboxylic Acids. Org. Lett. 2016, 18, 4602-4605. (c) Wang, W.; Peng, X.; Wei,
F.; Tung, C.-H.; Xu, Z. Copper(I)-Catalyzed Interrupted Click Reaction: Synthesis of Diverse 5-Hetero-Functionalized
Triazoles. Angew. Chem. Int. Ed. 2016, 55, 649-653. (d) Peng, X.; Ma, C.; Tung, C.-H.; Xu, Z. Cu-catalyzed Three-
Component Coupling of Aryne, Alkyne, and Benzenesulfonothioate: Modular Synthesis of O-Alkynyl Arylsulfides. Org.
Lett. 2016, 18, 4154-4157. (e) Baetena, M.; Maes, B. U. W. Use of Amidines as Quanylating Agents. Adv. Synth. Catal.
2017, 358, 826-833. (f) Li, J.; Zhu, D.; Lv, L.; Li, C.-J. Radical Difluoromethylthiolation of Aromatics Enabled by Visible
Light. Chem. Sci. 2018, 9, 5781-5786.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) Fang, Y.; Rogge, T.; Ackermann, L.; Wang, S.-Y.; Ji, S.-J. Nickel-Catalyzed Reductive Thiolation and Selenylation of
Unactivated Alkyl Bromides. Nat. Commun. 2018, 9, 2240-2249.
(11) (a) Ding, D.; Wang, C. Nickel-Catalyzed Reductive Electrophilic Ring Opening of Cycloketone Oxime Esters with
Aroyl Chlorides. ACS Catal. 2018, 8, 11324-11329. (b) Ding, D.; Lan, Y.; Lin, Z.; Wang, C. Synthesis of gem-
Difluoroalkenes by Merging Ni-Catalyzed C-F and C-C Bond Activation in Cross-Electrophile Coupling. Org. Lett. 2019,
21, 2723-2730
(12) (a) Lu, X.; Wang, X.-X.; Gong, T.-J.; Pi, J.-J.; He, S.-J.; Fu, Y. Nickel-Catalyzed Allylic Defluorinative Alkylation of
Trifluoromethyl Alkenes with Reductive Decarboxylation of Redox-Active Esters. Chem. Sci. 2019, 10, 809-814. (b) Yan, X.-
B.; Li, C.-L.; Jin, W.-J.; Guo, P.; Shu, X.-Z. Reductive Coupling of Benzyl Oxalates with Highly Functionalized Alkyl
Bromides by Nickel Catalysis. Chem. Sci. 2018, 9, 4529-4534. (c) Sheng, J.; Ni, H.-Q.; Zhang, H.-R.; Zhang, K.-F.; Wang, Y.-
N.; Wang, X.-S. Nickel-Catalyzed Reductive Cross-Coupling of Aryl Halides with Monofluoroalkyl Halides for Late-Stage
Monofluoroalkylation. Angew. Chem., Int. Ed. 2018, 57, 7634-7639. (d) Wang, W.; Ding, C.; Li, Y.; Li, Z.; Li, Y.; Peng, L.;
Yin, G. Migratory Arylboration of Unactivated Alkenes Enabled by Nickel Catalysis. Angew. Chem., Int. Ed. 2019, 58,
4612-4616. (e) Xia, A.; Xie, X.; Chen, H.; Zhao, J.; Zhang, C.; Liu, Y. Nickel-Catalyzed Cyanation of Unactivated Alkyl
Chlorides or Bromides with Zn(CN)2. Org. Lett. 2018, 20, 7735-7739. (f) Lan, Y.; Yang, F.; Wang, C. Synthesis of gem-
Difluoroalkenes via Nickel-Catalyzed Allylic Defluorinative Reductive Cross-Coupling. ACS Catal. 2018, 8, 9245-9251. (g)
Jin, Y.; Wang, C. Ni-Catalysed Reductive Arylalkylation of Unactivated Alkenes. Chem. Sci. 2019, 10, 1780-1785.
(13) (a) Zhao, C.; Jia, X.; Wang, X.; Gong, H. Ni-Catalyzed Reductive Coupling of Alkyl Acids with Unactivated Tertiary
Alkyl and Glycosyl Halides. J. Am. Chem. Soc. 2014, 136, 17645-17651. (b) Wang, X.; Wang, S.; Xue, W.; Gong, H.
Nickel-Catalyzed Reductive Coupling of Aryl Bromides with Tertiary Alkyl Halides. J. Am. Chem. Soc. 2015, 137, 11562-
11565. (c) Liu, J.; Ren, Q.; Zhang, X.; Gong, H. Preparation of Vinyl Arenes by Nickel‐Catalyzed Reductive Coupling of
Aryl Halides with Vinyl Bromides. Angew. Chem., Int. Ed. 2016, 55, 15544-15548. (d) Chen, H.; Jia, X.; Yu, Y.; Qian, Q.;
Gong, H. Nickel‐Catalyzed Reductive Allylation of Tertiary Alkyl Halides with Allylic Carbonates. Angew. Chem., Int. Ed.
2017, 56, 13103-13106. (e) Wang, J.; Zhao, J. H.; Gong, H. Nickel-Catalyzed Methylation of Aryl Halides/Tosylates with
Methyl Tosylate. Chem. Commun. 2017, 53, 10180-10183. (f) Wang, X.; Ma, G.; Peng, Y.; Pitsch, C. E.; Moll, B. J.; Ly, T.
D.; Wang, X.; Gong, H. Ni-Catalyzed Reductive Coupling of Electron-Rich Aryl Iodides with Tertiary Alkyl Halides. J. Am.
Chem. Soc. 2018, 140, 14490-14497. (g) Ye, Y.; Chen, H.; Sessler, J. L.; Gong, H. Zn-Mediated Fragmentation of Tertiary
14
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The Journal of Organic Chemistry
Alkyl Oxalates Enabling Formation of Alkylated and Arylated Quaternary Carbon Centers. J. Am. Chem. Soc. 2019, 141,
820-824. (h) Panja, S.; Maity, P.; Kundu, D.; Ranu, B. C. Iron(0) Nanoparticles Mediated Direct Conversion of
Aryl/Heteroaryl Amines to Chalcogenides via In Situ Diazotization. Tetrahedron Lett. 2017, 58, 3441–3445.
(14) Min, Q.-Q.; Li, N.; Chen, G.-L.; Liu, F. Copper-Catalysed C(sp3)–N Coupling Initiated by Selective C–C Bond
Cleavage of Cyclobutanone Oxime Esters. Org. Chem. Front. 2019, 6, 1200-1204.
1
2
3
4
5
6
7
8
9
(15) Shen, X.; Zhao, J.-J.; Yu, S. Photoredox-Catalyzed Intermolecular Remote C−H and C−C Vinylation via Iminyl
Radicals. Org. Lett. 2018, 20, 5523-5527.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(16) Yin, Z.; Rabeah, J.; Brückner, A.; Wu X.-F. Gallic Acid-Promoted SET Process for Cyclobutanone Oximes Activation
and (Carbonylative-)Alkylation of Olefins. ACS Catal. 2018, 8, 10926-10930.
(17) Li, J.; Rao, W.; Wang, S.-Y.; Ji, S.-J. Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reaction of gem-
Difluoroalkenes with Thiosulfonate or Selenium Sulfonate. J. Org. Chem. 2019, 84, 11542-11552.
(18) Fang, Y.; Liu, C.; Wang, F.; Ding, R.; Wang, S.-Y.; Ji, S.-J. A Radical-Chain Reaction of Isocyanides with
Selenosulfonates and Water: Facile Synthesis of Selenocarbamates under Metal-Free Conditions. Org. Chem. Front., 2019,
6, 660–663.
(19) Jiang, N.; Fang, Y.; Fang, Y.; Wang, S.-Y.; Ji, S.-J. Iodine-Promoted One Pot Reaction of Pyridin-2-Amine with
Arylmethyl Ketone and Selenosulfonate: Synthesis of 3-(Alkylselanyl)- 2-arylimidazo[1,2-a]pyridine under Transitionmetal
Free Conditions. Org. Chem. Front., 2019, 6, 654–659.
(20) Zhang, R.; Xu, P.; Wang, S.-Y.; Ji, S.-J. Visible Light-Induced Co- or Cu-Catalyzed Selenosulfonylation of Alkynes:
Synthesis of β-(Seleno)vinyl Sulfones. J. Org. Chem. 2019, DOI: 10.1021/acs.joc.9b01626.
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