Synthesis of: N -alkylated 2-pyridones through Pummerer type reactions of activated sulfoxides and 2-fluoropyridine derivatives

Article abstract of DOI:10.1039/c8ob00860d

N-Alkylated 2-pyridone products were obtained in good to excellent yields through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride activated sulfoxides and 2-fluoropyridine derivatives, followed by hydrolysis. This is a rare case that uses 2-fluoropyridine as a nucleophile in Pummerer type reactions.

Full text of DOI:10.1039/c8ob00860d

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: G. Hu, J. Xu and
P. Li, Org. Biomol. Chem., 2018, DOI: 10.1039/C8OB00860D.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 8
View Article Online
DOI: 10.1039/C8OB00860D
Journal Name
ARTICLE
Synthesis of N-alkylated 2-Pyridones through Pummerer
Type Reactions of Activated Sulfoxides and 2-Fluoropyridine
Derivatives
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Gang Hu, Jiaxi Xu*, and Pingfan Li*
www.rsc.org/
Abstract: N-alkylated 2-pyridone products were obtained in good to excellent yields through a one-pot procedure
involving either normal or interrupted Pummerer reactions between triflic anhydride activated sulfoxides and 2-
fluoropyridine derivatives, followed by hydrolysis. This is a rare case that uses 2-fluoropyridine as a nucleophile in
Pummerer type reactions.
Introduction
2-Pyridone, the tautomer of 2-hydroxypyridine, is the core structure
for many biologically active heterocycles.1-3 Thus, the syntheses of
2-pyridones have been a continuing research topic for decades.4,5
N-alkylation of 2-pyridone is one of the most direct method to
prepare N-alkylated 2-pyridones, but the competitive O-alkylation is
almost always a problematic side reaction (Scheme 1a).6-10 During
their total synthesis of the anti-cancer natural product
camptothecin, Bennasar and co-workers developed a methodology
for constructing the 2-pyridone ring structures.11,12 Thus, alkylation
of 2-fluoropyridine derivatives with freshly prepared highly
electrophilic benzyl triflates, followed by hydrolysis to give the
desired N-alkylated 2-pyridones (Scheme 1b). As part of our
research program13,14 on the reactivity of activated sulfoxides,15-25
we serendipitously found that 2-fluoropyridine could participate as
a nucleophile in normal or interrupted Pummerer reactions with
triflic anhydride activated sulfoxides, and the products we obtained
after hydrolysis were N-alkylated 2-pyridones (Scheme 1c). It should
be noted that 2-chloropyridine13,26-30 and 2-fluoropyridine31-36 have
been widely used as acid scavengers in reactions involving triflic
anhydride activation of sulfoxides or amides due to their low
nucleophilicity. So this is a very rare case to use them as nucleophile
in Pummerer type reactions.
Scheme 1. Synthesis of N-alkylated 2-Pyridones
Results and discussion
The optimized reaction conditions between methyl phenyl sulfoxide
(1a) and 2-fluoropyridine (2a) were shown in Scheme 2 (entry 1).
After treating the dichloromethane solution of 1a and 2a with triflic
anhydride at -43 °C, the reaction mixture was gradually warmed up
to room temperature overnight; and then quenched with saturated
sodium bicarbonate solution; after workup and flash column
purification, the Pummerer product 1-(phenylthio)methylpyridin-2-
one (3aa) was obtained in 89% yield. Changing the reaction solvent
to acetonitrile gave 72% yield (entry 2). If the amount of 2a was
reduced by half, no desired product 3aa was obtained (entry 3),
indicating the double role of 2-fluoropyridine in this reaction: both
nucleophile and acid scavenger. Additive inorganic base was not
helpful for reducing the amount of 2-fluoropyridine (entry 4). In
addition, if trifluoroacetic anhydride was used instead of Tf2O to
a.State Key Laboratory of Chemical Resource Engineering, Department of Organic
Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing
íìììîõU tꢀ}‰oꢀ[• wꢀ‰µꢁo]ꢂ }( /Z]vꢃX
Email: jxxu@mail.buct.edu.cn (J. X.), lipf@mail.buct.edu.cn (P.L.).
Electronic Supplementary Information (ESI) available: [Copies of 1H and 13C NMR
spectra of products ]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 8
View Article Online
DOI: 10.1039/C8OB00860D
ARTICLE
Journal Name
activate the sulfoxide, no desired product 3aa was obtained (entry
5).
entry
variation from standard conditions
none
yield of 3aa (%) a,b
1
2
3
4
5
89
72
0
use MeCN as solvent
use 1.2 eq 2a
use 1.2 eq 2a, 2.4 eq K2CO3
use (CF3CO)2O instead of Tf2O
0
0
a Reactions were performed with 0.4 mmol 1a
Scheme 2. Influence of Reaction Parameters
.
b Isolated yields.
Scheme 4. Further Substrate Scope for sulfoxides
but it could be deprotonated by 2-fluoropyridine to give phenyl
vinyl sulfide (B), which would then attack another molecule of
We then explored the substrate scope by using a number of
substituted aryl methyl sulfoxides and 2-fluoropyridine derivatives
(Scheme 3). The 1-(phenylthio)methylpyridin-2-one type products
were obtained in good to excellent yields. The aldehyde containing
product 3da was obtained in lower yield, while the nitro group
containing product 3la was still obtained in excellent yield.
However, if 2-chloro-6-fluoropyridine or 2-fluoro-3-nitropyridine
were used, no desired product was obtained, presumably due to
the even lower nucleophilicity of these substituted pyridines.
Pummerer-type intermediate
A to give the formally [4+2]
typeproduct 4. On the other hand, sulfoxide (1e) bearing an ester
group could successfully give the desired product 3ea in 57% yield
(Scheme 4b).
We then further explored the substrate scope by using a number of
substituted benzyl phenyl sulfoxides and 2-fluoropyridine
derivatives. Instead of the normal Pummerer reaction, interrupted
Pummerer reaction occurred, and the 1-benzylpyridin-2-one type
products were obtained in good to excellent yields (Scheme 5).
To further expand the substrate scope, we tried to use ethyl phenyl
sulfoxide. However, no desired product was obtained, and a
disulfide type product 4 was obtained instead (Scheme 4a). We
suspect the formation of 4 is resulting from the dimerization of
Pummerer-type intermediates: the initially formed Pummerer-type
intermediate (A) might be less prone to react with 2-fluoropyridine,
Two related reaction mechanisms were proposed to account for the
formation of 1-(phenylthio)methylpyridin-2-one (3aa) from methyl
a use 1.2 eq 2-fluoropyrdine
Scheme 3. Substrate Scope for 1-(phenylthio)methylpyridin-2-one type
Scheme 5. Substrate scope for 1-benzylpyridin-2-one type products
products
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 8
View Article Online
DOI: 10.1039/C8OB00860D
Journal Name
ARTICLE
intermediates (int1 and int2) from the reactions using 2-
chloropyridine as substrates. The chloro substituent is less electron-
withdrawing than fluoro substituent, so hydrolysis of the
corresponding pyridinium salts (int1 and int2) to give the N-
alkylated 2-pyridone products through nucleophilic aromatic
substitution should be more difficult.
For product derivatization, we were able to substitute the chloro
group in 3cd with PhSNa to give sulfide 5. We could also oxidize it to
corresponding sulfoxide 6 or sulfone 7 by either Oxone or mCPBA
(Scheme 7).
Conclusions
In conclusion,
a one-pot synthesis of N-alkylated 2-pyridone
products were achieved in good to excellent yields through either
normal or interrupted Pummerer reactions between triflic
anhydride activated sulfoxides and 2-fluoropyridine derivatives,
followed by hydrolysis. Unlike its conventional role as a weakly
nucleophilic amine base, 2-fluoropyridine participated in these
Pummerer type reactions as a nucleophile.
Experimental
Unless otherwise noted, all materials were purchased from
commercial suppliers. Dichloromethane was refluxed over CaH2,
and freshly distilled prior to use. Flash column chromatography was
performed using silica gel (normal phase, 200-300 mesh). Reactions
were monitored by thin-layer chromatography on silica gel 60-F254
1
coated 0.2 mm plates. H and 13C NMR spectra were recorded on a
Scheme 6. Proposed reaction mechanisms
400 MHz spectrometer, usually in CDCl3 with TMS as an internal
standard, and the chemical shifts (w) were reported in parts per
million (ppm). The IR spectra (KBr pellets, v [cm>1]) were taken on a
FTIR spectrometer. HRMS measurements were carried out on a TOF
mass spectrometer. Melting points were obtained on a melting
point apparatus and were uncorrected.
phenyl sulfoxide, and the formation of 1-benzylpyridin-2-one (3fa)
from benzyl phenyl sulfoxide (Scheme 6). The normal Pummerer
intermediate C generated from methyl phenyl sulfoxide and triflic
anhydride was attacked by 2-fluoropyridine to give a pyridinium salt
D, which could be hydrolyzed to 3aa. While in the case of benzyl
phenyl sulfoxide, since the benzyl position is very easy to
participate in nucleophilic substitution reactions, interrupted
General procedure for synthesis of oxiranes 4a-c, 4h, and 4k-m
A. Preparation of sulfoxide substrates
General Procedure 1Ö
Pummerer reaction occurred to give
a benzyl substituted
pyridinium salt E, which could be hydrolyzed to 3fa. In support of
our proposed mechanism, we isolated two pyridinium salt
A 100 mL round bottom flask was charged with 1 eq (912 mg, 6
mmol) of 4-(methylthio)benzaldehyde and 30 mL dichloromethane,
1.2 g of m-chloroperbenzoic acid in dichloromethane was added
drop by drop at 0 ºC, the reaction was stirred at 0 ºC for 2 hours.
The reaction solution was washed with saturated sodium
bicarbonate solution three times and once with brine. The organic
phase was dried over anhydrous sodium sulfate and the solvent was
removed by rotary evaporation to get white solid. The solid was
added with appropriate amount of diethylether for slurry operation
(if necessary, twice) then filtered to obtain 720 mg of white solid 1d
in 71% yield.
methyl phenyl sulfoxide (1a) was synthesized according to General
Procedure 1 from methyl phenyl sulfide .
Scheme 7. Product derivatization
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 8
View Article Online
DOI: 10.1039/C8OB00860D
ARTICLE
Journal Name
4-(methylsulfinyl)benzonitrile (1b) was synthesized according to 1-Methoxy-4-((phenylsulfinyl)methyl)benzene (1h) was synthesized
General Procedure 1 from 4-cyanophenyl methyl sulfide. 1H NMR according to General Procedure 2 benzenethiol (2.2 g, 20 mmol), to
1
(400 MHz, CDCl3• w óXôï ~ꢀU J = 8.0 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), give 2.928 g product 1h as awhite solid in 60% yield. H NMR (400
2.77 (s, 3H).
MHz, CDCl3• w óXñï-7.31 (m, 5H), 6.89 (d, J = 8.8 Hz, 2H), 6.78 (d, J =
8.4 Hz, 2H), 4.03 (d, J = 12.4 Hz, 1H), 3.95 (d, J = 12.8 Hz, 1H), 3.78
(s, 3H).
4-Bromophenyl methyl sulfoxide (1c) was synthesized according to
General Procedure 1 from 4-bromophenyl methyl sulfide. 1H NMR
(400 MHz, CDCl3• w óXòó ~ꢀU J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 1-Chloro-4-((phenylsulfinyl)methyl)benzene (1i) was synthesized
2.72 (s, 3H).
according to General Procedure 2 benzenethiol (2.2 g, 20 mmol), to
give 3.329 g product 1i as awhite solid in 67% yield.
4-(methylsulfinyl)benzaldehyde (1d) was synthesized according to
General Procedure 1 from 4-(methylthio)benzaldehyde. 1H NMR 1-Chloro-2-((phenylsulfinyl)methyl)benzene (1j) was synthesized
(400 MHz, CDCl3• w íìXìõ ~•U íI•U ôXìñ ~ꢀU J = 8.0 Hz, 2H), 7.82 (d, J = according to General Procedure 2 benzenethiol (1.1 g, 10 mmol), to
8.0 Hz, 2H), 2.78 (s, 3H).
give 1.27 g product 1j as awhite solid in 51% yield. 1H NMR (400
MHz, CDCl3• w óXñï t 7.42 (m, 5H), 7.37 (d, J = 8.0 Hz, 1H), 7.30 t
7.23 (m, 1H), 7.18 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 7.2 Hz, 1H), 4.26 (d,
J = 12.4 Hz, 1H), 4.18 (d, J = 12.4 Hz, 1H).
ethyl 2-(phenylsulfinyl)acetate (1e): The corresponding sulfide was
synthesized follow Akira[• uꢁšZ}ꢀU37 from 1eq thiophenol, 1eq
triethylamine, 1 eq methyl bromoacetate in benzene was stirred at
room temperature for 4 h. Then oxidized to sulfoxide according to 1-Methyl-4-((phenylsulfinyl)methyl)benzene (1k) was synthesized
General Procedure 1. 1H NMR (400 MHz, CDCl3• w óXóò t 7.56 (m, according to General Procedure 2 benzenethiol (1.1 g, 10 mmol), to
2H), 7.48 (d, J = 3.2 Hz, 3H), 4.09 (q, J = 7.2 Hz, 2H), 3.78 (d, J = 13.6 give 1.13 g product 1k as awhite solid in 49% yield. 1H NMR (400
Hz, 1H), 3.61 (d, J = 13.6 Hz, 1H), 1.14 (t, J = 7.2 Hz, 3H).
MHz, CDCl3• w óXñí t 7.37 (m, 5H), 7.06 (d, J = 7.6 Hz, 2H), 6.87 (d, J
= 8.0 Hz, 2H), 4.07 (d, J = 12.8 Hz, 1H), 3.96 (d, J = 12.4 Hz, 1H), 2.32
(s, 3H).
1-(methylsulfinyl)-3-nitrobenzene (1l) was synthesized according to
General Procedure 1 from 3-Nitrothioanisole.1H NMR (400 MHz,
CDCl3• w ôXñì ~•U íI•U ôXïò ~ꢀU J = 8.4 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), B. Synthesis 2-pyrdinone through Pummerer reactions.
7.77 (t, J = 8.0 Hz, 1H), 2.81 (s, 3H).
General Procedure A:
General Procedure 2Ö
To a flame-dried Schlenk tube, 1 eq methyl phenyl sulfoxide (1a) (69
A 50 mL round bottom flask was charged with 1.25 eq (701 mg, 12.5 mg, 0.4 mmol) and 2.4 eq 2-fluoropyedine(2a) (70 mg, 0.96 mmol)
mmol) of potassium hydroxide and 25 mL of absolute ethanol. The were added, and then dissolved with dichloromethane (6 mL)
mixture was stirred until potassium hydroxide dissolved. 1 eq of before cooling down to -43 ºC. 1.2 eq Tf2h ~ôî …[U 0.48 mmol) was
thiophenol (1.1 g, 10 mmol), 2-fluorobenzyl chloride 1.25 eq (1.4 added dropwise, and then gradually warming up to room
mL, 12.5 mmol) was added. The system was further reacted for 2 temperature over 10 hours. The reaction was quenched with
hours. The inorganic salt was removed by filtration. The solvent was saturated sodium bicarbonate solution, stir vigorously for about 10
removed by rotary evaporation, 30 mL of dichloromethane was minutes, diluted with water, extracted with dichloromethane, dried
added, 1.725 g of m-chloroperbenzoic acid in dichloromethane was over sodium sulfate, and purified with flash column
added drop by drop at 0 ºC, the reaction was stirred at 0 ºC for 2 chromatography (petroleum ether/ethyl acetate/dichloromethane
hours. The reaction solution was washed with saturated sodium 6:3:1to 3:3:1) to give 93 mg product 3aa as a solid in 89% yield.
bicarbonate solution three times and once with brine. The organic
1-((Phenylthio)methyl)pyridin-2-one
(3aa)
was
synthesized
phase was dried over anhydrous sodium sulfate and the solvent was
removed by rotary evaporation to get white solid. The solid was
added with appropriate amount of diethylether for slurry operation
(if necessary, twice) then filtered to obtain 2.09 g of white solid 1g
in 93% yield.
according to General Procedure A from methyl phenyl sulfoxide (1a)
(69 mg, 0.49 mmol), eluted by 6:3:1 petroleum ether/ethyl
acetate/dichloromethane to 3:3:1 petroleum ether/ethyl
acetate/dichloromethane, to give 93 mg product 3aa as a white
solid in 89% yield. 3aa: Rf = 0.24 (1:1 petroleum ether/ethyl
(benzylsulfinyl)benzene (1f) was synthesized according to General acetate) mp 91-92 oC 1H NMR (400 MHz, CDCl3• w óXïõ t 7.31 (m,
Procedure 2 benzenethiol (1.1 g, 10 mmol), to give 1.31 g product 2H), 7.28 t 7.16 (m, 4H), 6.94 (d, J = 6.7 Hz, 1H), 6.46 (d, J = 9.2 Hz,
1f as aN orange solid in 61% yield.
1H), 5.95 (dd, J = 6.7 Hz, 6.7 Hz, 1H), 5.17 (s, 2H). 13C NMR (100
MHz, CDCl3• w 161.9, 139.6, 136.2, 133.0, 132.4, 129.3, 128.4, 120.9,
105.8, 53.0. Lw ~Y.Œ• † ~ꢂu>1) 2919, 2849, 1655, 1583, 1156, 1142,
744, 691. HRMS (ESI) calcd for C12H12NOS+ [M+H]+ m/z: 218.0634,
found: 218.0642.
1-Fluoro-2-((phenylsulfinyl)methyl)benzene (1g) was synthesized
according to General Procedure 2 benzenethiol (1.1 g, 10 mmol), to
give 2.09 g product 1g as awhite solid in 93% yield. 1H NMR (400
MHz, CDCl3• w óXñî t 7.40 (m, 5H), 7.31-7.27 (m, 1H), 7.12 t 7.03
(m, 2H), 6.97 (t, J = 9.2 Hz, 1H), 4.13 (d, J = 12.8 Hz, 1H), 4.08 (d, J = 4-Methyl-1-((phenylthio)methyl)pyridin-2-one (3ab) was synthesized
12.8 Hz, 1H).
according to General Procedure A from methyl phenyl sulfoxide (1a)
(57 mg, 0.40 mmol), eluted by petroleum ether to 6:3:1 petroleum
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 8
View Article Online
DOI: 10.1039/C8OB00860D
Journal Name
ARTICLE
ether/ethyl acetate/dichloromethane to 3:3:1 petroleum ether to 6:3:1 petroleum ether/ethyl acetate/dichloromethane to
ether/ethyl acetate/dichloromethane, to give 56 mg product 3ab as 3:3:1 petroleum ether/ethyl acetate/dichloromethane, to give 40
a white solid in 60% yield. 3ab: Rf = 0.24 (1:1 petroleum ether/ethyl mg product 3da as a white solid in 40% yield. 3da: Rf = 0.13 (1:1
1
acetate) mp 75-76 oC 1H NMR (400 MHz, CDCl3• w óXðì t 7.31 (m, petroleum ether/ethyl acetate) mp 107-108 oC H NMR (400 MHz,
2H), 7.27 t 7.18 (m, 3H), 6.84 (d, J = 7.0 Hz, 1H), 6.26 (s, 1H), 5.80 CDCl3• w õXõò ~•U íI•U óXôì ~ꢀU J = 8.3 Hz, 2H), 7.58 (d, J = 8.2 Hz, 2H),
(d, J = 6.9 Hz, 1H), 5.14 (s, 2H), 2.06 (s, 3H). 13C NMR (100 MHz, 7.34 t 7.26 (m, 2H), 6.55 (dd, J = 9.8, 0.9 Hz, 1H), 6.14 (ddd, J = 6.8,
CDCl3) w íñíX4, 135.0, 132.8, 132.6, 129.2, 128.2, 119.1, 108.4, 52.4, 6.8, 0.9 Hz, 1H), 5.43 (s, 2H). 13C NMR (100 MHz, CDCl3• w 191.2,
21.2. Lw ~Y.Œ• † ~ꢂu>1) 2918, 2849, 1655, 1142, 1075, 852, 750. 162.1, 141.3, 139.8, 135.7, 135.1, 130.3, 130.2, 121.1, 106.6, 50.1.
HRMS (ESI) calcd for C13H14NOS+ [M+H]+ m/z: 232.0791, found: Lw ~Y.Œ• † ~ꢂu>1) 2920, 2849, 1659, 1653, 1090, 765. HRMS (ESI)
232.0798.
calcd for C13H12NO2S+ [M+H]+ m/z: 246.0583, found: 246.0586.
1-(((4-Nitrilphenyl)thio)methyl)pyridin-2-one (3ba) was synthesized ethyl 2-(2-oxopyridin-1(2H)-yl)-2-(phenylthio)acetate (3ea) was
according to General Procedure A from methyl 4-nitrilphenyl synthesized according to General Procedure A from ethyl 2-
sulfoxide (1b) (47 mg, 0.28 mmol), eluted by petroleum ether to (phenylsulfinyl)acetate (1e) (84mg, 0.30 mmol), eluted by
6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1 petroleum
ether
to
6:3:1
petroleum
ether/ethyl
petroleum ether/ethyl acetate/dichloromethane, to give 61 mg acetate/dichloromethane to 3:3:1 petroleum ether/ethyl
product 3ba as a yellow solid in 84% yield. 3ba: Rf = 0.54 (10:1 acetate/dichloromethane, to give 66 mg product 3ea as an oil in
dichloromethane /methanol)) mp 106-108 oC 1H NMR (400 MHz, 57% yield. 3ea: Rf = 0.63 (1:1 petroleum ether/ethyl acetate) 1H
CDCl3• w óXòì t 7.50 (m, 4H), 7.34 t 7.26 (m, 2H), 6.54 (d, J = 9.7 Hz, NMR (400 MHz, CDCl3• w óXóñ ~ꢀꢀU J = 6.8, 1.7 Hz, 1H), 7.44 t 7.37
1H), 6.16 (dd, J = 6.5 Hz, 6.5 Hz, 1H), 5.41 (s, 2H). 13C NMR (100 (m, 2H), 7.31 t 7.26 (m, 4H), 6.44 (d, J = 9.2 Hz, 1H), 6.24 (ddd, J
MHz, CDCl3• w 139.8, 139.7, 135.6, 132.6, 130.4, 121.1, 118.3, 110.9, =6.8, 6.8, 1.0 Hz, 1H), 5.30 (s, 1H), 4.27 (q, J = 7.1 Hz, 2H), 1.31 (t, J =
106.8, 105.0, 49.9. Lw ~Y.Œ• † ~ꢂu>1) 2227, 1660, 1143, 1086. HRMS 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3• w 166.9, 162.0, 139.8, 135.5,
(ESI) calcd for C13H11N2OS+ [M+H]+ m/z: 243.0587, found: 243.0580.
132.7, 130.6, 129.4, 128.9, 120.0, 106.2, 62.9, 61.8, 14.0. Lw ~Y.Œ• †
(cm>1) 2920, 2849, 1656, 1590, 1144, 765. HRMS (ESI) calcd for
C15H16NO3S+ [M+H]+ m/z: 290.0845, found: 245.0853.
1-(((4-Bromophenyl)thio)methyl)pyridin-2-one
(3ca)
was
synthesized according to General Procedure A from 4-bromophenyl
methyl sulfoxide (1c) (65mg, 0.30 mmol), eluted by petroleum ether 1-(((4-Nitrolphenyl)thio)methyl)pyridin-2-one (3la) was synthesized
to 6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1 according to General Procedure A from methyl 4-nitrophenyl
petroleum ether/ethyl acetate/dichloromethane, to give 74 mg sulfoxide (1l) (56mg, 0.30 mmol), eluted by petroleum ether to
product 3ca as a white solid in 83% yield. 3ca: Rf = 0.69 (10:1 6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1
dichloromethane /methanol) mp 139-140 oC 1H NMR (400 MHz, petroleum ether/ethyl acetate/dichloromethane, to give 71 mg
CDCl3• w óXðò t 7.41 (m, 2H), 7.33 t 7.25 (m, 3H), 7.07 (dd, J = 6.7, product 3la as a yellow solid in 90% yield. 3la: Rf = 0.59 (10:1
1.6 Hz, 1H), 6.54 (d, J = 9.2 Hz, 1H), 6.07 (dd, J = 6.7 Hz, J = 6.7 Hz, dichloromethane /methanol) mp 106-107 oC 1H NMR (400 MHz,
1H), 5.23 (s, 2H). 13C NMR (100 MHz, CDCl3) w íòíXõU íïõX7, 136.1, CDCl3• w ôXîò ~•U íI•U ôXíð ~ꢀU J = 8.2 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H),
134.5, 132.4, 131.5, 122.9, 121.1, 106.1, 52.6. Lw ~Y.Œ• † ~ꢂu>1) 7.50 (dd, J = 8.0 Hz, 1H), 7.33 t 7.27 (m, 1H), 7.22 (dd, J = 6.8, 1.3
3018, 2964, 2921, 1659, 1587, 1537, 1143, 1066, 1008, 812, 772. Hz, 1H), 6.52 (d, J = 9.2 Hz, 1H), 6.15 (dd, J = 6.4 Hz, 6.4 Hz, 1H), 5.36
HRMS (ESI) calcd for C12H11BrNOS+ [M+H]+ m/z: 295.9739, found: (s, 2H). 13C NMR (100 MHz, CDCl3• w 162.1, 139.8, 139.7, 135.6,
295.9742.
132.6, 130.4, 121.1, 118.3, 110.9, 106.8, 105.0, 49.9. Lw ~Y.Œ• †
(cm>1) 3074, 3026, 2922, 2856, 1660, 1586, 1523, 1349, 1158, 805,
732. HRMS (ESI) calcd for C12H11N2O3S+ [M+H]+ m/z: 263.0485,
found: 263.0490.
1-((4-Bromophenylthio)methyl)-4-chloro-pyridin-2-one (3cd) was
synthesized according to General Procedure A from methyl 4-
bromophenyl sulfoxide (1c) (65 mg, 0.30 mmol), eluted by
petroleum
ether
to
6:3:1
petroleum
ether/ethyl 1-Benzylpyridin-2-one (3fa)10 was synthesized according to General
acetate/dichloromethane to 3:3:1 petroleum ether/ethyl Procedure A from benzyl phenyl sulfoxide (1f) (86mg, 0.40 mmol),
acetate/dichloromethane, to give 72 mg product 3cd as a white eluted by petroleum ether to 6:3:1 petroleum ether/ethyl
solid in 71% yield. 3cd: Rf = 0.54 (1:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1 petroleum ether/ethyl
acetate) mp 125-126 oC 1H NMR (400 MHz, CDCl3• w óXðô t 7.43 (m, acetate/dichloromethane, to give 71 mg product 3fa as a white
2H), 7.32 t 7.27 (m, 2H), 7.01 (d, J = 7.4 Hz, 1H), 6.59 (d, J = 2.2 Hz, solid in 96% yield. 3fa: Rf = 0.33 (1:1 petroleum ether/ethyl acetate)
1H), 6.11 (dd, J = 7.4, 2.3 Hz, 1H), 5.19 (s, 2H). 13C NMR (100 MHz, 1H NMR (400 MHz, CDCl3• w óXïó t 7.24 (m, 7H), 6.62 (d, J = 9.1 Hz,
CDCl3• w 160.8, 147.0, 136.1, 134.5, 132.6, 131.1, 123.2, 119.5, 1H), 6.14 (ddd, J = 6.7, 1.2 Hz, 1H), 5.15 (s, 2H). 13C NMR (100 MHz,
108.0, 52.4. IR ~Y.Œ• † ~ꢂu>1) 2920, 2849, 1660, 1589, 1521, 1384, CDCl3• w íòîXóU íïõXïU íïóXîU íïòXðU íîôXõU íîôXíU íîôXìU íîíXïU
1180, 1142, 1089, 1060, 1008, 940, 813. HRMS (ESI) calcd for 106.1, 51.8.
C12H11ClNOS+ [M+H]+ m/z: 329.9350, found: 329.9357.
1-(2-Fluorobenzyl)pyridin-2-one (3ga) was synthesized according to
1-(((4-Formylphenyl)thio)methyl)pyridin-2-one
(3da)
was General Procedure A from 2-fluorobenzyl phenyl sulfoxide (1g)
synthesized according to General Procedure A from 4-formylphenyl (73mg, 0.31 mmol), eluted by petroleum ether to 6:3:1 petroleum
methyl sulfoxide (1d) (68mg, 0.30 mmol), eluted by petroleum ether/ethyl acetate/dichloromethane to 3:3:1 petroleum
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 8
View Article Online
DOI: 10.1039/C8OB00860D
ARTICLE
Journal Name
ether/ethyl acetate/dichloromethane, to give 53 mg product 3ga as ether/ethyl acetate/dichloromethane to 3:3:1 petroleum
a pale yellow solid in 96% yield. 3ga: Rf = 0.29 (1:1 petroleum ether/ethyl acetate/dichloromethane, to give 63 mg product 3ia in
ether/ethyl acetate) mp 70-71 oC H NMR (400 MHz, CDCl3• w óXðî 96% yield. 3ia: Rf = 0.27 (1:1 petroleum ether/ethyl acetate) 1H
1
(dd, J = 7.6 Hz, 7.6 Hz, 1H), 7.37 (d, J = 6.7 Hz, 1H), 7.33 t 7.24 (m, NMR (400 MHz, CDCl3• w óXîó t 7.13 (m, 6H), 6.51 (d, J = 9.1 Hz, 1H),
2H), 7.14 t 7.02 (m, 2H), 6.57 (d, J = 9.2 Hz, 1H), 6.14 (dd, J = 6.7 Hz, 6.07 (dd, J = 6.6 Hz, 1H), 5.01 (s, 2H). 13C NMR (100 MHz, CDCl3• w
1H), 5.17 (s, 2H). 13C NMR (100 MHz, CDCl3) w íòîXñU íòìX9 (d, JC-F
=
162.6, 139.5, 137.0, 134.8, 133.8, 129.3, 128.9, 121.2, 106.3, 51.3.
246.5 Hz), 139.4, 137.52, 137.49, 131.2, 131.1, 129.8 (d, JC-F = 8.2 Lw ~Y.Œ• † ~ꢂu>1) 2921, 2849, 1655, 1578, 1146, 1087, 766. HRMS
Hz), 124.4 (d, JC-F = 3.6 Hz), 123.1 (d, JC-F = 14.6 Hz), 121.0, 115.3 (d, (ESI) calcd for C12H11ClNO+ [M+H]+ m/z: 220.0524, found: 220.0530.
JC-F = 21.5 Hz), 106.1, 46.0 (d, JC-F = 3.7 Hz). 19F NMR (376 MHz,
1-(2-Chlorobenzyl)pyridin-2-one (3ja)10 was synthesized according
to General Procedure A from 2-chlorobenzyl phenyl sulfoxide (1j)
(70mg, 0.28 mmol), eluted by petroleum ether to 6:3:1 petroleum
ether/ethyl acetate/dichloromethane to 3:3:1 petroleum
CDCl3• w -118.42. Lw ~Y.Œ• † ~ꢂu>1) 3070, 2927, 1650, 1589, 1539,
1492, 756. HRMS (ESI) calcd for C12H11FNO+ [M+H]+ m/z: 204.0819,
found: 204.0825.
1-(4-Methoxybenzyl)pyridin-2-one
(3ha)10
was
synthesized ether/ethyl acetate/dichloromethane, to give 52 mg product 3ja in
according to General Procedure A from 4-methoxybenzyl phenyl 96% yield. 3ja: Rf = 0.29 (1:1 petroleum ether/ethyl acetate) 1H
sulfoxide (1h) (71mg, 0.29 mmol), eluted by petroleum ether to NMR (400 MHz, CDCl3• w óXðï t 7.29 (m, 3H), 7.23 (s, 3H), 6.62 (d, J
6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1 = 9.1 Hz, 1H), 6.16 (t, J = 6.7 Hz, 1H), 5.25 (s, 2H). 13C NMR (100
petroleum ether/ethyl acetate/dichloromethane, to give 59 mg MHz, CDCl3• w 162.6, 139.5, 137.4, 133.6, 133.4, 130.0, 129.6, 129.2,
product 3ha in 95% yield. 3ha: Rf = 0.17 (1:1 petroleum ether/ethyl 127.2, 121.1, 106.2, 49.5. Lw ~Y.Œ• † ~ꢂu>1) 3069, 2926, 1661, 1590,
acetate) 1H NMR (400 MHz, CDCl3• w óXïî t 7.22 (m, 4H), 6.87 (d, J = 1538, 1445, 1144, 751. HRMS (ESI) calcd for C12H11ClNO+ [M+H]+
8.5 Hz, 2H), 6.59 (d, J = 9.1 Hz, 1H), 6.12 (dd, J = 6.6 Hz, 1H), 5.07 (s, m/z: 220.0524, found: 220.0530.
2H). 13C NMR (100 MHz, CDCl3• w 159.4, 139.2, 137.0, 129.8, 128.4,
1-(4-Methylbenzyl)pyridin-2-one (3ka)10 was synthesized according
to General Procedure A from 4-methylbenzyl phenyl sulfoxide (1k)
(70mg, 0.30 mmol), eluted by petroleum ether to 6:3:1 petroleum
ether/ethyl acetate/dichloromethane to 3:3:1 petroleum
121.2, 114.2, 106.1, 55.3, 51.4. Lw ~Y.Œ• † ~ꢂu>1) 2930, 2836, 1655,
+
1581, 1512, 1248, 1178, 1030, 768. HRMS (ESI) calcd for C13H14NO2
[M+H]+ m/z: 216.1019, found: 216.1028.
1-(4-Methoxybenzyl)-4-methypyridin-2-one (3hb) was synthesized ether/ethyl acetate/dichloromethane, to give 59 mg product 3ka in
according to General Procedure A from 4-methoxybenzyl phenyl 97% yield. 3ka: Rf = 0.33 (1:1 petroleum ether/ethyl acetate) 1H
sulfoxide (1h) (72mg, 0.29 mmol), eluted by petroleum ether to NMR (400 MHz, CDCl3• w óXïï t 7.28 (m, 1H), 7.26 (dd, J = 6.7, 1.6
6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.62 (d, J =
petroleum ether/ethyl acetate/dichloromethane, to give 58 mg 9.0 Hz, 1H), 6.14 (ddd, J = 6.7, 6.7, 0.9 Hz, 1H), 5.11 (s, 2H), 2.33 (s,
product 3hb as a white solid in 92% yield. 3hb: Rf = 0.17 (1:1 3H). 13C NMR (100 MHz, CDCl3• w 162.6, 139.3, 137.7, 137.1, 133.2,
petroleum ether/ethyl acetate) mp 86-87 oC 1H NMR (400 MHz, 129.4, 128.1, 121.0, 106.2, 51.5, 21.0. Lw ~Y.Œ• † ~ꢂu>1) 3026, 2923,
CDCl3• w óXîð ~ꢀU J = 8.4 Hz, 2H), 7.13 (d, J = 6.9 Hz, 1H), 6.86 (d, J = 1655, 1586, 1539, 1151, 767. HRMS (ESI) calcd for C13H14NO+
8.4 Hz, 2H), 6.40 (s, 1H), 5.97 (d, J = 6.8 Hz, 1H), 5.04 (s, 2H), 3.78 (s, [M+H]+ m/z: 200.1070Èfound: 200.1079.
3H), 2.15 (s, 3H). 13C NMR (100 MHz, CDCl3• w 159.3, 150.9, 135.9,
129.6, 128.6, 119.4, 114.2, 108.7, 55.2, 50.9, 21.1. Lw ~Y.Œ• † ~ꢂu>1)
1-(4-Methylbenzyl)-4-methylpyridin-2-one (3kb) was synthesized
according to General Procedure A from 4-methylbenzyl phenyl
sulfoxide (1k) (70mg, 0.30 mmol), eluted by petroleum ether to
6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1
2920, 2849, 1656, 1583, 1512, 1247, 1178, 1032, 782. HRMS (ESI)
calcd for C14H16NO2+ [M+H]+ m/z: 230.1176, found: 230.1184.
1-(4-Methoxybenzyl)-2-methypyridin-2-one (3hd) was synthesized petroleum ether/ethyl acetate/dichloromethane, to give 41 mg
according to General Procedure A from 4-methoxybenzyl phenyl product 3kb as a viscosity oil in 64% yield. 3kb: Rf = 0.33 (1:1
sulfoxide (1h) (72mg, 0.29 mmol), eluted by petroleum ether to petroleum ether/ethyl acetate) 1H NMR (400 MHz, CDCl3• w óXíô ~ꢀU
6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1 J = 7.9 Hz, 2H), 7.13 (d, J = 5.0 Hz, 2H), 7.11 (d, J = 4.0 Hz, 1H), 6.40
petroleum ether/ethyl acetate/dichloromethane, to give 33 mg (s, 1H), 5.96 (d, J = 6.8 Hz, 1H), 5.06 (s, 2H), 2.32 (s, 3H), 2.15 (s, 3H).
product 3hd as a viscosity oil in 52% yield. 3hd: Rf = 0.17 (1:1 13C NMR (100 MHz, CDCl3• w í62.6, 150.8, 137.6, 136.0, 133.5,
petroleum ether/ethyl acetate) 1H NMR (400 MHz, CDCl3• w óXîï 129.4, 128.1, 119.4, 108.7, 51.0, 21.1, 21.0. Lw ~Y.Œ• † ~ꢂu>1) 2922,
(dd, J = 6.7 Hz, 9.0Hz, 1H), 7.12 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.4 Hz, 1668, 1660, 1538, 773, 604. HRMS (ESI) calcd for C14H16NO+ [M+H]+
2H), 6.53 (d, J = 9.0 Hz, 1H), 6.01 (d, J = 6.7 Hz, 1H), 5.28 (s, 2H). 13C m/z: 214.1226, found: 214.1236.
NMR (100 MHz, CDCl3• w 158.8, 146.6, 139.0, 128.5, 127.9, 117.9,
114.1, 106.9, 55.3, 46.7, 20.6. Lw ~Y.Œ• † ~ꢂu>1) 2924, 2849, 1655,
1-(4-Methylbenzyl) -6-methyl pyridin-2-one (3kd) was synthesized
1571, 1550, 1248, 1178, 1031, 792. HRMS (ESI) calcd for C14H16NO2+
[M+H]+ m/z: 230.1176, found: 230.1182.
according to General Procedure A from 4-methylbenzyl phenyl
sulfoxide (1k) (74mg, 0.32 mmol), eluted by petroleum ether to
6:3:1 petroleum ether/ethyl acetate/dichloromethane to 3:3:1
1-(4-Chlorobenzyl)pyridin-2-one (3ia)10 was synthesized according petroleum ether/ethyl acetate/dichloromethane, to give 46 mg
to General Procedure A from 4-chlorobenzyl phenyl sulfoxide (1i) product 3kd as a viscosity oil in 67% yield. 3kd: Rf = 0.33 (1:1
(75mg, 0.30 mmol), eluted by petroleum ether to 6:3:1 petroleum petroleum ether/ethyl acetate).1H NMR (400 MHz, CDCl3• w óXîô t
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 7 of 8
View Article Online
DOI: 10.1039/C8OB00860D
Journal Name
ARTICLE
7.20 (dd, J = 9.0 Hz, 6.6 Hz, 1H), 7.10 (d, J = 7.8 Hz, 2H), 7.05 (d, J = t 7.38 (m, 1H), 7.37 t 7.31 (m, 4H), 6.00 (s, 2H). 13C NMR (100 MHz,
7.8 Hz, 2H), 6.54 (d, J = 9.0 Hz, 1H), 6.01 (d, J = 6.6 Hz, 1H), 5.30 (s, CDCl3• w 148.2, 146.7, 146.3, 134.6, 130.6, 130.2, 128.0, 126.0,
2H), 2.30 (s, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3• w 163.9, 120.3 (q, JCF = 319.8 Hz)È65.5. Lw ~Y.Œ• † ~ꢂu>1) 3077, 2922, 1259,
146.6, 139.0, 136.8, 133.3, 129.3, 126.4, 117.7, 106.8, 46.8, 20.9, 1157, 1030, 638. HRMS (ESI) calcd for C12H11ClN+: 204.0575, found:
20.5. Lw ~Y.Œ• † ~ꢂu>1) 2920, 2849, 1655, 1571, 1142, 1074, 793. 204.0589.
HRMS (ESI) calcd for C14H16NO+ [M+H]+ m/z: 214.1226, found:
D. Derivatization of the products
214.1236.
1-(((4-bromophenyl)thio)methyl)-4-(phenylthio)pyridin-2-one (5)To a
5 mL flame dried flask, 1.5 eq sodium hydride 60 %(6 mg, 0.15
mmol), 1.5 eq thiophenol (16 mg, 0.15 mmol), and THF (2.0 mL)
were added, and the mixture was stirred at room tempreture for 15
minutes, then added 1eq pyrdin-2-one 3cd (34mg, 0.1 mmol), the
mixture was heated to 60oC and reacted at 60oC for 6 hours. The
mixture was cooled to room temperature, and then extracted by
dichloromethane (8 mL × 3). After drying with anhydrous sodium
sulfate, it was concentrated and purified with flash column
chromatography, eluted by petroleum ether/ethyl acetate (5/1), to
give 41 mg product as a viscosity oil in 99% yield. 1H NMR (400 MHz,
CDCl3• w óXñî ~uU îI•U óXðï ~uU U ñI•U óXîõ ~ꢀU J = 8.4 Hz, 2H), 6.91 (m,
1H), 5.95 (d, J = 1.8 Hz, 1H), 5.90 (dd, J = 7.3, 2.0 Hz, 1H), 5.16 (s, 2H).
13C NMR (100 MHz, CDCl3• w íòìXòU íñðXôU íïñXñU íïðXôU íïðXîU íïîXðU
2-methyl-4-(phenylthio)thiochroman (disulfide 4). The reaction of
ethyl phenyl sulfoxide according to General Procedure A from ethyl
phenyl sulfoxide (61 mg, 0.4 mmol), eluted by 50:1 petroleum
ether/dichloromethane to 10:1 petroleum ether/dichloromethane,
to give 21 mg sulfide as an orange oil in 39% yield (based on 2
molecules of ethyl phenyl sulfoxide). 1H NMR (400 MHz, CDCl3• w
7.39 (d, J = 7.0 Hz, 2H), 7.31 t 7.21 (m, 3H), 7.10 (d, J = 7.7 Hz, 1H),
7.01 (d, J = 3.8 Hz, 2H), 6.93 t 6.85 (m, 1H), 4.51 (dd, J = 3.0 Hz, 3.0
Hz, 1H), 3.92 (ddd, J = 11.4, 6.8, 2.5 Hz, 1H), 2.19 (ddd, J = 14.1, 2.9
Hz, 2.9 Hz, 1H), 1.84 (ddd, J = 14.5, 11.7, 3.3 Hz, 1H), 1.26 (d, J = 6.7
Hz, 3H).13C NMR (100 MHz, CDCl3• w íïðXñU íïðXðU íïïXíU íïíXðU
131.0, 129.1, 127.7, 127.7, 126.1, 123.7, 48.9, 35.7, 30.9, 21.2.LRMS
+
(EI) calcd for C16H16S2 : 272, found: 272.
C. Isolation of the pyridinium salts
131.6, 130.1, 129.9, 128.1, 122.7, 113.6, 105.2, 52.0. Lw ~Y.Œ• † ~ꢂu>1
2930, 2856, 1644, 1574, 1347, 1244, 1151, 1068, 1010, 946. HRMS
(ESI) calcd for C18H15BrNOS2+ [M+H]+ m/z 403.9773, found 403.9779.
)
2-Chloro-1-((phenylthio)methyl)pyridin-1-ium
trifluoromethanesulfonate (int1). To a flame-dried Schlenk tube, 1
eq methyl phenyl sulfoxide (1a) (42 mg, 0.30 mmol), and then 2.4 1-(((4-bromophenyl)sulfinyl)methyl)-4-chloropyridin-2-one (6) To a 5
eq 2-chloropyridine (82 mg, 0.72 mmol) and dichloromethane (6 mL flask, pyridine-2-one 3cd (22 mg, 0.067 mmol), 1.5 eq Oxone (42
mL) were added under nitrogen atmosphere, after cooling down to mg, 0.1 mmol), and ethanol (2.0 mL) were added, and the mixture
-43 ºC. 1.2 eq Tf2h ~òí …[U ìXòì uu}o• Áꢃ• ꢃꢀꢀꢁꢀ ꢀŒ}‰Á]•ꢁX !(šꢁŒ was stirred at 60 °C for 6 hours. The mixture was cooled to room
gradually warming up to room temperature overnight,, the reaction temperature, added with brine (5 mL), and then extracted by
was quenched with saturated sodium bicarbonate solution, dichloromethane. The organic phase was drying with anhydrous
extracted with dichloromethane, dried over sodium sulfate, and sodium sulfate, then it was concentrated and purified with flash
purified with flash column chromatography (1:1 petroleum column chromatography, eluted by petroleum ether/ethyl
ether/ethyl acetate to 10:1 dichloromethane /methanol) to give 90 acetate/dichloromethane (20/10/1) to petroleum ether/ethyl
mg product int1 in 77% yield. Int1: Rf = 0.27 (10:1 dichloromethane acetate/dichloromethane (10/10/1), to give 20 mg product as a
/methanol). 1H NMR (400 MHz, CDCl3• w õXíð ~ꢀU J = 6.0 Hz, 1H), 8.50 white solid in 86% yield. mp 196-197 oC 1H NMR (400 MHz, CDCl3• w
(dd, J = 7.9 Hz, 1H), 8.08 t 8.00 (m, 2H), 7.42 t 7.30 (m, 5H), 5.94 (s, 7.70 (d, J = 8.5 Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.36 (d, J = 7.4 Hz,
2H).13C NMR (100 MHz, CDCl3• w 148.2, 146.7, 146.3, 134.6, 130.6, 1H), 6.59 (d, J = 2.1 Hz, 1H), 6.26 (dd, J = 7.3, 2.2 Hz, 1H), 5.19 (d, J =
130.5, 130.2, 128.0, 126.0, 120.4 (q, JCF = 319.9 Hz), 65.5. Lw ~Y.Œ• † 12.3 Hz, 1H), 4.67 (d, J = 12.3 Hz, 1H). 13C NMR (100 MHz, CDCl3• w
(cm>1) 3077, 2922, 1259, 1157, 1030, 638.HRMS (ESI) calcd for 160.5, 148.2, 139.2, 137.6, 132.8, 126.7, 125.8, 119.0, 108.4, 70.2.
C12H11ClNS+: 236.0295, found: 236.0301.
Lw ~Y.Œ• † ~ꢂu>1) 2961, 2921, 2849, 1660, 1593, 1348, 1082, 1047.
HRMS (ESI) calcd for C12H10BrClNO2S+ [M+H]+ m/z 345.9299, found
345.9306.
Benzyl-2-chloropyridin-1-ium trifluoromethanesulfonate (int2). To a
flame-dried Schlenk tube, 1 eq benzyl phenyl sulfoxide (1f) (65 mg,
0.30 mmol), and then 2.4 eq 2-chloropyridine (82 mg, 0.72 mmol) 1-(((4-bromophenyl)sulfonyl)methyl)-4-chloropyridin-2-one (7) To a
and dichloromethane (6 mL) were added under nitrogen 50 mL flask, pyridine-2-one 3cd (16 mg, 0.048 mmol), 10 eq mCPBA
atmosphere, after cooling down to -43 ºC. 1.2 eq Tf2h ~òí …[U ìXïò (109 mg, 0.5 mmol), and dichloromethane (15.0 mL) were added,
mmol) was added dropwise. After gradually warming up to room and the mixture was stirred at 0 °C for 4 hours. The mixture was
temperature overnight, the reaction was quenched with saturated warmed up to room temperature, washed with sat. NaS2O3 (5
sodium bicarbonate solution, extracted with dichloromethane, mL)sat, NaHCO3 (5 mL), and then combined the water phase and
dried over sodium sulfate, and purified with flash column extracted by dichloromethane. The organic phase was drying with
chromatography (1:1 petroleum ether/ethyl acetate to 10:1 anhydrous sodium sulfate, then it was concentrated and purified
dichloromethane /methanol) to give 61 mg product int2 in 57% with flash column chromatography, eluted by petroleum
yield. int2: Rf = 0.27 (10:1 dichloromethane /methanol). 1H NMR ether/ethyl acetate/dichloromethane (5/1/1), to give 16 mg
o
1
(400 MHz, CDCl3• w ôXðõ ~ꢀꢀU J = 7.8 Hz, 7.8 Hz, 1H), 8.36 (d, J = 5.9 product as a white solid in 91% yield. mp 208-210 C H NMR (400
Hz, 1H), 8.07 (d, J = 7.8 Hz, 1H), 7.73 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 7.44 MHz, CDCl3• w óXòó ~ꢀU J = 8.6 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H), 7.47
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 8
View Article Online
DOI: 10.1039/C8OB00860D
ARTICLE
Journal Name
28 M. Movassaghi, M. D. Hill, O. K. Ahmad, J. Am. Chem.
Soc. 2007, 129, 10096.
29 T. Wezeman, S. Zhong, M. Nieger, S. Bräse, Angew.
Chem. Int. Ed. 2016, 55, 3823.
(d, J = 7.4 Hz, 1H), 6.40 (d, J = 2.0 Hz, 1H), 6.30 (dd, J = 7.4, 2.2 Hz,
1H), 5.27 (s, 2H). 13C NMR (100 MHz, CDCl3• w íñõXòU íðôXíU íïóXìU
135.2, 132.7, 130.6, 130.4, 119.1, 109.1, 65.1. Lw ~Y.Œ• † ~ꢂu>1)
2954, 2926, 2853, 1663, 1598, 1340, 1325, 1288, 1245, 1151,
1068,1011, 946, 774. HRMS (ESI) calcd for C12H10BrClNO3S+ [M+H]+
m/z 361.9248, found 361.9254.
30 M. Movassaghi, M. D. Hill, J. Am. Chem. Soc. 2006, 128
14254.
,
31 J. W. Medley, M. Movassaghi, J. Org. Chem. 2009, 74
1341.
,
32 G. Pelletier, W. S. Bechara, A. B. Charette, J. Am. Chem.
Soc. 2010, 132, 12817.
33 P. Q. Huang, Y. H. Huang, K. J. Xiao, J. Org. Chem. 2016,
81, 9020.
34 D. Kaiser, A. de la Torre, S. Shaaban, N. Maulide,
Angew. Chem. Int. Ed. 2017, 56, 5921.
Acknowledgements
This research was supported in part by National Natural Science
Foundation of China (21402005, 21572017).
35 V. Tona, B. Maryasin, A. de la Torre, J. Sprachmann, L.
González, N. Maulide, Org. Lett. 2017, 19, 2662.
36 J. -L. Ye, Y. -N. Zhu, H. Geng, P. -Q. Huang, Sci. China
Chem. 2017.
37 M. Katsukiyo, F. Naoki, S. Hiroshi, W. Di, H. Akira, Org.
Lett. 2001, 3, 2591.
Notes and references
1
Q. Li, L. A. Mitscher, L. L. Shen, Med. Res. Rev. 2000, 20
231.
H. J. Jessen, K. Nat. Prod. Rep. 2010, 27, 1168.
,
2
3
Vite-Caritino, H. Gademann, O. Mendez-Lucio, H.Reyes,
A. Cabrera, D. Chavez, J. L. Medina-Franco, RSC Adv.
2016,
T. Mercedes, G. Salvador, P. Margarita, Curr. Org.
Chem. 2005, , 1757.
K. Hirano, M. Miura, Chem. Sci. 2018,
G. Hopkins, J. Jonak, H. Minnemeyer, H.Tieckelmann, J.
Org. Chem. 1967, 32, 4040.
6, 2119.
4
9
5
6
9, 22.
7
8
9
D. L. Comins, G. Jianhua, Tetrahedron Lett. 1994, 35
2819.
M. Breugst, H. Mayr, J. Am. Chem. Soc. 2010, 132
15380.
,
,
M. C. Torhan, N. P. Peet, , J. D. Williams, Tetrahedron
Lett. 2013, 54, 3926.
10 E. L. Lanni, M. A. Bosscher, B. D. Ooms, C. A. Shandro,
B. A. Ellsworth, C. E. Anderson, J. Org. Chem. 2008, 73
6425.
,
11 M. L. Bennasar, E. Zulaica, C. Juan, Y. Alonso, J. Bosch, J.
Org. Chem. 2002, 67, 7465.
12 M. L. Bennasar, C. Juan, J. Bosch, Chem. Commun.
2000, 2459.
13 G. Hu, J. Xu, P. Li, Org. Lett. 2014, 16, 6036.
14 Z. Zhang, H. Du, J. Xu, P. Li, Chem. Commun. 2016, 52
11547.
,
15 A. Padwa, Jr, D. E. Gunn, M. H. Osterhout, Synthesis,
1997, 1353.
16 S. K. Bur, A. Padwa, Chem. Rev. 2004, 104, 2401.
17 S. Akai, Y. Kita, In Sulfur-Mediated Rearrangements I;
Schaumann, E., Ed.; Springer Berlin Heidelberg: Berlin,
Heidelberg, 2007, p 35.
18 K. S. Feldman, Tetrahedron 2006, 62, 5003.
19 L. H. S. Smith, S. C. Coote, H. F. Sneddon, D. J. Procter,
Angew. Chem. Int. Ed. 2010, 49, 5832.
20 X. Huang, S. Klimczyk, N. Maulide, Synthesis 2012, 44
175.
,
21 A. P. Pulis, Procter, D. J. Angew. Chem. Int. Ed. 2016,
55, 9842.
22 A.Shafir, Tetrahedron Lett. 2016, 57, 2673.
23 H. Yorimitsu, Chem. Rec. 2017, 17, 1556.
24 L. Meng, J. Zeng, Q. Wan, Synlett 2018, 29, 148.
25 Z. Y.Tian, Y. T. Hu, H.B. Teng, C.P. Zhang, Tetrahedron
Lett. 2018, 59, 299.
26 B. A. Garcia, J. L. Poole, D. Y. Gin, J. Am. Chem. Soc.
1997, 119, 7597.
27 A. G. Myers, N. J. Tom, M. E. Fraley, S. B. Cohen, D. J.
Madar, J. Am. Chem. Soc. 1997, 119, 6072.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins