TBAI/TBHP catalyzed direct N-acylation of sulfoximines with aldehydes

Article abstract of DOI:10.1016/j.tet.2015.01.013

A direct N-acylation of NH-sulfoximines and aldehydes has been developed under metal-free TBAI/TBHP oxidation system, affording N-acylsulfoximines in moderate to good yields.

Full text of DOI:10.1016/j.tet.2015.01.013

Accepted Manuscript
TBAI/TBHP catalyzed direct N-acylation of sulfoximines with aldehydes
Wen-Jing Qin, Yi Li, Xingxin Yu, Wei-Ping Deng
PII:
S0040-4020(15)00044-7
10.1016/j.tet.2015.01.013
TET 26336
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 December 2014
Revised Date: 31 December 2014
Accepted Date: 9 January 2015
Please cite this article as: Qin W-J, Li Y, Yu X, Deng W-P, TBAI/TBHP catalyzed direct N-acylation of
sulfoximines with aldehydes, Tetrahedron (2015), doi: 10.1016/j.tet.2015.01.013.
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TBAI/TBHP catalyzed direct N-acylation of
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sulfoximines with aldehydes
Wen-Jing Qin, Yi Li, Xingxin Yu*, Wei-Ping Deng*
Shanghai Key Laboratory of New Drug Design & School of Pharmacy, East China University of Science and
Technology, 130 Meilong Road, Shanghai 200237, China

1
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Tetrahedron
journal homepage: www.elsevier.com
TBAI/TBHP catalyzed direct N-acylation of sulfoximines with aldehydes
Wen-Jing Qin, Yi Li, Xingxin Yu and Wei-Ping Deng
Shanghai Key Laboratory of New Drug Design & School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237,
China
ARTICLE INFO
ABSTRACT
Article history:
Received
A direct N-acylation of NH-sulfoximines and aldehydes has been developed under metal-free
TBAI/TBHP oxidation system, affording N-acylsulfoximines in moderate to good yields.
Received in revised form
Accepted
2014 Elsevier Ltd. All rights reserved
.
Available online
Keywords:
N-acylation
C(sp2)-H activation
metal-free catalyst
TBAI/TBHP catalyzed
1. Introduction
Recently, sulfoximines have been of great interest since the
use of sulfoximine group as a pharmacophore for drug discovery
(Figure 1).1 For instance, aminopyrimidine BAY1000394 is a
balanced pan-CDK inhibitor with potent, broad-spectrum
antiproliferative activity against human cancer cell lines, and is
currently being investigated in the phase I clinical trial for
patients with advanced solid tumors.1c,1d Sulfoxaflor is another
example that represents a novel insecticide targeting sap-feeding
pests with unique resistance and mode of action characteristics.1a
In addition, sulfoximine groups could act as the reusable
directing groups in ortho C-H functionalizations.2
As one of the important classes of sulfoximine derivatives, the
traditional approaches for the generation of N-acylsulfoximines
were primarily relied on the acylations of NH-sulfoximines with
acyl chlorides.3 N-acylation can also be achieved via boric acid
mediated cross-coupling of NH-sulfoximines with carboxylic
acids.4 Notably, Bolm's group5 has had a great interest in N-
acylsulfoximines. In 2013, they developed the copper-catalyzed
oxidative N-acylations of sulfoximines with aldehydes5a and
alkynes5b. More recently, they reported the MnO2-mediated N-
aroylation of N-chlorosulfoximines with methyl arenes.5c Though
these synthetic strategies are efficient, the usage of pre-activated
coupling partners or metal catalysts shows shortages in both
industrial and green chemistry view.
Figure 1. Selected examples of bioactive sulfoximines
On the other hand, the use of n-Bu4NI (TBAI) as the catalyst
in combination with tert-butyl hydroperoxide (TBHP) as a
powerful metal-free oxidation system6 has been the focus of
recent interest, and widely used in various oxidative coupling
reactions. It has been applied to the C-C7, C-N8, C-O9, C-S10
bonds formation. Therefore, our interest was focused on the C-N
———
Corresponding author. Tel.: +86-21-64252431; fax: +86-21-64252431; e-mail: xxyu@ecust.edu.cn; weiping_deng@ecust.edu.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
bonds formation for the generation of N-acylsulfoximines
solution of TBHP (2.0 equiv.), n-hexane, reflux, 12h, under N2
catalyzed by metal-free oxidation system.
atmosphere.
Herein, we describe the first example of TBAI-catalyzed
direct N-acylation of NH-sulfoximines with aldehydes as
coupling partners, utilizing TBHP as the green terminal oxidant.
Table 2. Screening of the ratio of reactants and catalysta
2. Results and discussion
Initially, 4-nitrobenzaldehyde 2a was chosen as the coupling
partner of the N-acylation. NH-sulfoximine 1a was readily
prepared via Bolm’s method5a and added to a sealed tube with 4-
nitrobenzaldehyde 2a in the presence of TBAI (20 mol%) and
TBHP (3.0 equiv., 70% aqueous solution) in CH3CN at reflux in
the air. To our delight, the acylation occurred, affording the N-
acylsulfoximine 3a in 16% yield (Table 1, entry 1). The reaction
provided a slightly higher yield under anaerobic conditions
(Table 1, entry 2). Solvents screening revealed that n-hexane was
superior, delivering the N-acylsulfoximine 3a in 49% yield
(Table 1, entry 4). Gratifyingly, decreasing the amount of oxidant
TBHP to 2.0 equivalents improved the yield to 56% (Table 1,
entry 6). Lowering the reaction temperature reduced the yield
significantly (Table 1, entries 8-9). In addition, only 7% yield of
3a was obtained when TBPB was used as the oxidant instead of
TBHP (Table 1, entry 10).
Sulfoximine 1a
(equiv.)
Aldehyde 2a
(equiv.)
TBAI
(mol%)
Entry
Yield(%) b
1c
2
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
3.0
4.0
5.0
4.0
4.0
4.0
20
20
20
20
20
15
10
56
72
90
86
44
79
64
3
4
5d
6
7
a
Reaction conditions: Reactions were carried out with 1a (0.3 mmol), 2a
(1.0-5.0 eq.), TBAI (20 mol%), TBHP (70% aqueous solution) in 1 mL
solvent reflux for 12h under N2 atmosphere. b Isolated yield based on NH-
sulfoximine 1a. c Isolated yield based on 4-nitrobenzaldehyde 2a. d In 10 mL
solvent.
Table 1. Optimization of reaction conditionsa
Table 3. Substrate scope of the TBAI/TBHP mediated direct
N-acylation of sulfoximine 1 with aldehyde 2a
TBAI (20 mol%)
TBHP (2 eq.)
O
S
O
S
N
R2
NH
R2CHO
+
R1
R1
Me
Me
O
n-hexane, N2
Entry
Oxidant
Solvent
CH3CN
CH3CN
DCE
Temp. (ºC)
reflux
reflux
reflux
reflux
reflux
reflux
reflux
60
Yield(%)b
reflux, 12 h
1
2
3
1c
2
TBHP (3 eq.)
TBHP (3 eq.)
TBHP (3 eq.)
TBHP (3 eq.)
TBHP (4 eq.)
TBHP (2 eq.)
TBHP (1 eq.)
TBHP (2 eq.)
TBHP (2 eq.)
TBPB (2 eq.)
16
25
37
49
46
56
29
38
trace
7
Entry
R1
R2
Yield (%)b
90 (3a)
66 (3b)
67 (3c)
35 (3d)
49 (3e)
59 (3f)
56 (3g)
60 (3h)
70 (3i)
1
2
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
4-NO2C6H4 (2a)
3-NO2C6H4 (2b)
3-CF3C6H4 (2c)
4-FC6H4 (2d)
4-ClC6H4 (2e)
4-BrC6H4 (2f)
4-MeC6H4 (2g)
4-OMeC6H4 (2h)
3
4
n-hexane
n-hexane
n-hexane
n-hexane
n-hexane
n-hexane
n-hexane
3
5
4
6
5
7
6
8
7
9
25
8
10
reflux
9
3-NO2,4-OMeC6H3 (2i)
Ph (2j)
a Reaction conditions: All reactions were carried out with 1a (0.45 mmol), 2a
(0.3 mmol), TBAI (20 mol%), TBHP (70% aqueous solution) in 1 mL solvent
10
11
12
13
14
15
16
46 (3j)
39 (3k)
74 (3l)
b
for 12h under N2 atmosphere. Isolated yield based on 4-nitrobenzaldehyde
1-naphthyl (2k)
Cy(2l)
2a. c In the air.
4-OMe (1b)
4-OMe (1b)
4-NO2 (1c)
4-NO2 (1c)
4-NO2C6H4 (2a)
3-NO2,4-OMeC6H3 (2i)
4-NO2C6H4 (2a)
3-NO2,4-OMeC6H3 (2i)
48 (3m)
48 (3n)
51 (3o)
47 (3p)
Further optimization involved the screening of reactants
ratios, catalyst loadings, and concentrations. A satisfactory result
was obtained when 4.0 equivalents of 4-nitrobenzaldehyde 2a
was used (Table 2, entry 3). No further improvement in the yield
was observed upon increasing the aldehyde quantity to 5.0
equivalents (Table 2, entry 4). Lowering the reaction
concentration for ten folds led to a dramatically reduced yield
(Table 2, entry 5). A decrease of catalyst loading reduced the
product yield (Table 2, entries 6-7). The optimal reaction
conditions were found consisted of NH-sulfoximine 1 (1.0
equiv.), aldehyde 2 (4.0 equiv.), TBAI (20 mol%), aqueous
a Unless otherwise noted, the reaction was performed under N2 atmosphere,
with NH-sulfoximine 1 (0.3 mmol), aldehyde 2 (4.0 equiv.), TBAI (20 mol%)
and aqueous solution of TBHP (2.0 equiv.), reflux in 1 mL n-hexane for 12
hours. b Isolated yields.

3
To examine the scope of this transformation, the optimized
conditions were applied to the reactions of a variety of NH-
sulfoximine 1 with aldehyde 2. As shown in Table 3, all the
reactions proceeded smoothly to generate N-acylsulfoximine 3 in
moderate to good yields. The electron-deficient aromatic
aldehydes 2a-2c provided higher yields than halo substituted
aromatic aldehydes 2d-2f (Table 3, entries 1-3 vs 4-6). For
electron-donating substituted benzaldehydes 2g and 2h, the
reactions proceeded smoothly to afford the corresponding N-
benzoylsulfoximines 3g and 3h in moderate yields (Table 3,
entries 7-8). Interestingly, a good yield was obtained when nitro
and methoxyl groups were at the 3- and 4-positions of the phenyl
ring (Table 3, entry 9). In addition, electron-neutral benzaldehyde
2j and 1-naphthaldehyde 2k could also be employed, leading to
N-acylsulfoximine 3j in 46% and N-acylsulfoximine 3k in 39%
yields, respectively (Table 3, entries 10-11). Notably, alkyl
aldehydes such as cyclohexanecarboxaldehyde 2l afforded the
desired N-acylsulfoximine 3l in 74% yield (Table 3, entry 11).
Moreover, para-methoxyl and para-nitro substituted NH-
sulfoximines 1b and 1c performed well with 4-substituted or 3,
4-disubstituted benzaldehydes 2a and 2i, furnishing multi-
functionalized N-acylsulfoximines 3m-3p in moderate yields
(Table 3, entries 13-16).
Based on these observations and literature reports, two
ACCEPTED MANUSCRIPT
mechanism pathways were hypothesized. In pathway I (Scheme
2), TBAI was initially oxidized by TBHP to generate
[Bu4N]+[IO]- A or [Bu4N]+[IO2]- B, which subsequently induced
the oxidative C(sp2)-H bond activation of aldehyde 2 to form the
acyl radical C. And the hypoiodite was reduced to TBAI and
water. NH-sulfoximine 1 was liable to be activated by the
hypoiodite species and coupled with acyl radical C, finally
resulted in the formation of the N-acylsulfoximine 3.
Several recent reports have proposed that a radical pathway
and in situ generated ammonium hypoiodite ([Bu4N]+[IO]-) or
iodite ([Bu4N]+[IO2]-) from TBAI are involved in this catalysis
system.8f,9a And in some other reports, tert-butoxyl or tert-
Scheme 2. The proposed pathway I.
Alternatively, in pathway II (Scheme 3), the tert-butoxyl
radical D and tert-butylperoxy radical E were generated via
iodide/ iodinine catalyzed redox process firstly. Secondly, these
active radical species abstracted a hydrogen atom from the
aldehyde 2 leading to acyl radical C. Similarly, the product N-
acylsulfoximine 3 was formed via N-H bond cleavage of NH-
sulfoximine 1 and C-N bond formation with acyl radical C in the
presence of tert-butoxyl radical D and tert-butylperoxy radical E.
butylperoxyl radicals9c-e
,
generated from TBHP by
iodide/iodinine catalysis cycle, are proposed as active species and
trap H of aldehyde to form the acyl radical.9c To verify the
reaction mechanism above, several control experiments were
carried out (Scheme 1). When a stoichiometric amount of the
radical scavenger 2, 6-di-tert-butyl-4-methylphenol (BHT) was
added to the reaction mixture under the same reaction conditions,
only trace amount of product 3a was observed, which suggested
that the reaction may indeed undergo a radical process (Scheme 1,
A). In addition, The reaction performed well in the presence of
20 mol% of Bu4NOH and iodine (in situ generation of
[Bu4N]+[IO]-), which indicated that hypoiodite or iodite was the
catalytic species (Scheme 1, B). Interestingly, employing iodine
only as the catalyst also afforded the desired product in 65%
yield (Scheme 1, C). This result was significantly different from
those reported by Yu9f, in which replacing Bu4NI with I2 led to no
desired product.
Scheme 3. The proposed pathway II.
3. Conclusion
In conclusion, we have developed the first example of metal-
free direct N-acylation of NH-sulfoximines with aldehydes
catalyzed by TBAI/TBHP oxidation system, affording N-
acylsulfoximines in moderate to good yields. This
straightforward protocol could be served as a practical alternative
to the existing synthetic methods for the preparation of valuable
N-acylsulfoximines.
Two
mechanism
pathways
were
hypothesized, and studies to further elucidate the mechanism and
applications of this reaction are ongoing in our laboratory.
Scheme 1. Investigation of reaction mechanism.

4
Tetrahedron
ACCEPTED MANUSCRIPT
4. Experimental section
4.1. General
7.61 (t, J = 7.6 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 3.46 (s, 3H),
2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.5, 142.9, 139.3,
133.9, 133.1, 129.8, 129.7, 128.9, 127.3, 44.5, 21.8.
5a
1
Melting points were obtained in open capillary tubes using a
micro melting point apparatus SGW X-4, which were
uncalibrated. Mass spectra were recorded by the HP5989A
service; HRMS (EI) spectra were obtained on a Finigann
MAT8401 instrument. 1H nuclear magnetic resonance (NMR)
spectra were recorded using an internal deuterium lock for the
residual protons in CDCl3 (δH=7.26) at ambient temperatures on
the following instruments: Bruker AVANCE DPX-400 (400
MHz). Data are presented as follows: Chemical shift (in ppm on
the scale relative to δTMS=0), integration, multiplicity (s=singlet,
d=doublet, t=triplet, q=quartet and m=multiplet), coupling
constant (J/Hz) and interpretation. 13C NMR spectra were
recorded by broadband spin decoupling using an internal
deuterium lock for CDCl3 (δ=77.2) at ambient temperatures on
the following instruments: Bruker AVANCE DPX-400 (100.6
MHz). Chemical shift values are reported in ppm on the scale
(δTMS=0). All reagents and solvents were used as purchased if not
otherwise stated.
4.4.8. 3h, White solid (60%). Mp: 138-139 ºC; H NMR
(400 MHz, CDCl3) δ 8.13 (d, J = 8.5 Hz, 2H), 8.06 (d, J = 7.7
Hz, 2H), 7.69 (t, J = 7.1 Hz, 1H), 7.61 (t, J = 7.5 Hz, 2H), 6.90
(d, J = 8.6 Hz, 2H), 3.86 (s, 3H), 3.46 (s, 3H).
1
4.4.9. 3i, Yellow oil (70%). H NMR (400 MHz, CDCl3) δ
8.66 (d, J = 2.1 Hz, 1H), 8.31 (dd, J = 8.8, 2.2 Hz, 1H), 8.04 (d, J
= 7.5 Hz, 2H), 7.72 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.5 Hz, 2H),
7.10 (d, J = 8.8 Hz, 1H), 4.02 (s, 3H), 3.47 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 171.7, 155.8, 139.2, 138.7, 135.1, 134.1,
129.9, 128.4, 127.2, 112.9, 56.9, 44.5; HRMS (EI): calcd for
C15H14N2O5S ([M]+): 334.0623, found 334.0625.
5a
1
4.4.10. 3j, White solid (46%). Mp: 122-123 ºC; H NMR
(400 MHz, CDCl3) δ 8.18 (d, J = 7.8 Hz, 2H), 8.07 (d, J = 7.8
Hz, 2H), 7.70 (t, J = 7.1 Hz, 1H), 7.62 (t, J = 7.6 Hz, 2H), 7.52 (t,
J = 7.0 Hz, 1H), 7.42 (t, J = 7.5 Hz, 2H), 3.47 (s, 3H).
5a
4.4.11. 3k,
Colorless oil (39%). 1H NMR (400 MHz,
CDCl3) δ 9.00 (d, J = 8.6 Hz, 1H), 8.35 (d, J = 6.3 Hz, 1H), 8.10
(d, J = 7.2 Hz, 2H), 7.96 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 7.6 Hz,
1H), 7.68 (d, J = 6.6 Hz, 1H), 7.67-7.58 (m, 2H), 7.57-7.46 (m,
3H), 3.49 (s, 3H).
4.2. General procedure for synthesis of N-acylsulfoximine 3
To a flame-dried 10 mL Schlenk tube under N2 was added
NH-sulfoximine 1 (0.3 mmol), aldehyde 3 (4.0 equiv.) and TBAI
(20 mol%), followed by n-hexane (1 mL). TBHP (2.0 equiv.,
70% aqueous solution) was added after the starting materials
were dissolved. The reaction mixture was then heated to reflux.
After completion, the reaction was cooled to room temperature
and quenched with saturated Na2S2O3, extracted by EA. The
organic layer was washed by saturated brine, dried over
anhydrous sodium sulfate. After the mixture was filtered and
evaporated, the residue was purified by flash column
chromatography to afford the desired N-acylsulfoximine 3.
4
1
4.4.12. 3l, Colorless oil (74%). H NMR (400 MHz, CDCl3)
δ 8.03 (d, J = 6.9 Hz, 1H), 7.91 (d, J = 7.0 Hz, 1H), 7.68-7.51 (m,
3H), 3.13 (s, 3H), 2.37 (m, 1H), 1.98-1.85 (m, 2H), 1.81-1.59 (m,
2H), 1.59-1.17 (m, 6H).
1
4.4.13. 3m, White solid (48%). Mp: 141-142 ºC; H NMR
(400 MHz, CDCl3) δ 8.31 (d, J = 8.9 Hz, 2H), 8.25 (d, J = 8.9
Hz, 2H), 7.59 (d, J = 7.9 Hz, 1H), 7.57-7.51 (m, 2H), 7.22 (d, J =
8.0 Hz, 1H), 3.90 (s, 3H), 3.49 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 172.2, 160.5, 150.2, 131.1, 130.6, 123.4, 120.4, 119.1,
112.3, 56.0, 44.5; HRMS (EI): calcd for C15H14N2O5S ([M]+):
334.0623, found 334.0622.
5a
1
4.4.1. 3a, Yellow solid (90%). Mp: 146-147 ºC; H NMR
(400 MHz, CDCl3) δ 8.31 (d, J = 8.3 Hz, 2H), 8.25 (d, J = 8.0
Hz, 2H), 8.06 (d, J = 7.7 Hz, 2H), 7.73 (t, J = 7.0 Hz, 1H), 7.66
(t, J = 7.2 Hz, 2H), 3.51 (s, 3H).
1
4.4.14. 3n, Yellow oil (48%). H NMR (400 MHz, CDCl3) δ
8.67 (d, J = 2.1 Hz, 1H), 8.31 (dd, J = 8.8, 2.2 Hz, 1H), 7.63-7.47
(m, 3H), 7.23-7.17 (m, 1H), 7.10 (d, J = 8.8 Hz, 1H), 4.02 (s,
3H), 3.90 (s, 3H), 3.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
171.7, 160.5, 155.7, 139.9, 135.2, 131.0, 127.3, 120.3, 119.1,
112.9, 112.2, 56.9, 55.9, 44.6; HRMS (EI): calcd for
C16H16N2O6S ([M]+): 364.0729, found 364.0729.
4.4.15. 3o, White solid (51%). 1H NMR (400 MHz,
Acetone-D6) δ 8.54 (d, J = 9.0 Hz, 2H), 8.42 (d, J = 9.0 Hz,
2H), 8.36-8.29 (m, 4H), 3.76 (s, 3H); 13C NMR (100 MHz,
DMSO-D6) δ 171.3, 151.0, 150.2, 144.4, 140.9, 130.7, 129.5,
125.9, 124.0, 43.0; HRMS (EI): calcd for C14H11N3O6S ([M]+):
349.0369, found 349.0368.
4.4.16. 3p, Yellow solid (47%). 1H NMR (400 MHz,
Acetone-D6) δ 8.54 (s, 1H), 8.51 (s, 1H), 8.49 (d, J = 2.1 Hz,
1H), 8.39 (d, J = 9.0 Hz, 2H), 8.29 (dd, J = 8.8, 2.1 Hz, 1H),
7.42 (d, J = 9.0 Hz, 1H), 4.06 (s, 3H), 3.71 (s, 3H); 13C NMR
(100 MHz, DMSO-D6) δ 175.5, 160.2, 155.7, 149.5, 143.8,
139.9, 134.3, 132.5, 130.9, 129.9, 119.4, 62.4, 47.9; HRMS
(EI): calcd for C15H13N3O7S ([M]+): 379.0474, found 379.0473.
5a
1
4.4.2. 3b, Yellow solid (66%). Mp: 123-124 ºC; H NMR
(400 MHz, CDCl3) δ 8.98 (s, 1H), 8.46 (d, J = 7.5 Hz, 1H), 8.35
(d, J = 7.7 Hz, 1H), 8.06 (d, J = 7.5 Hz, 2H), 7.77-7.69 (m, 1H),
7.69-7.55 (m, 3H), 3.51 (s, 3H).
2c
1
4.4.3. 3c, White solid (67%). Mp: 117-118 ºC; H NMR
(400 MHz, CDCl3) δ 8.27 (d, J = 7.9 Hz, 2H), 8.05 (d, J = 7.7
Hz, 2H), 7.75 – 7.60 (m, 5H), 3.48 (s, 3H).
5a
1
4.4.4. 3d, White solid (35%). Mp: 128-129 ºC; H NMR
(400 MHz, CDCl3) δ 8.22-8.14 (m, 2H), 8.05 (d, J = 7.8 Hz, 2H),
7.70 (t, J = 7.1 Hz, 1H), 7.62 (t, J = 7.5 Hz, 2H), 7.07 (t, J = 8.3
Hz, 2H), 3.46 (s, 3H).
5a
1
4.4.5. 3e, White solid (49%). Mp: 113-114 ºC; H NMR
(400 MHz, CDCl3) δ 8.10 (d, J = 8.2 Hz, 2H), 8.05 (d, J = 7.8
Hz, 2H), 7.70 (t, J = 7.0 Hz, 1H), 7.63 (t, J = 7.5 Hz, 2H), 7.38
(d, J = 8.2 Hz, 2H), 3.47 (s, 3H).
5c
1
4.4.6. 3f, White solid (59%). Mp: 117-118 ºC; H NMR
(400 MHz, CDCl3) δ 8.08-7.99 (m, 4H), 7.70 (t, J = 7.3 Hz, 1H),
7.62 (t, J = 7.5 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 3.46 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 173.5, 138.9, 134.6, 134.1, 131.4,
131.2, 129.9, 127.3, 127.2, 44.5.
Acknowledgments
This work was supported by the Fundamental Research Funds for
the Central Universities, and the Shanghai Committee of Science
and Technology (No. 14431902500).
2a
1
4.4.7. 3g, White solid (56%). Mp: 168-169 ºC; H NMR
(400 MHz, CDCl3) δ 8.09-8.03 (m, 4H), 7.69 (t, J = 7.3 Hz, 1H),

5
8. For recent selected examples see: (a) Froehr, T.; Sindlinger, C.
References and notes
ACCEPTED MANUSCRIPT
P.; Kloeckner, U.; Finkbeiner, P.; Nachtsheim, B. J. Org. Lett.,
2011, 13, 3754–3757. (b) Ma, L.; Wang, X.; Yu, W.; Han, B.
Chem. Commun., 2011, 7, 11333–11335. (c) Liu, Z.; Zhang, J.;
Chen, S.; Shi, E.; Xu, Y.; Wan, X. Angew. Chem., Int. Ed., 2012,
51, 3231-3235. (d) Mai, W.-P.; Wang, H.-H.; Li, Z.-C.; Yuan, J.-
W.; Xiao, Y.-M.; Yang, L.-R.; Mao, P.; Qu, L.-B. Chem.
Commun., 2012, 48, 10117–10119. (e) Xie, J.; Jiang, H.; Cheng,
Y.; Zhu, C. Chem. Commun., 2012, 48, 979–981. (f) Xue, Q.; Xie,
J.; Li, H.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 49, 3700-
3702. (g) Lv, Y.; Li, Y.; Xiong, T.; Lu, Y.; Liu Q.; Zhang, Q.
Chem. Commun., 2014, 50, 2367–2369.
1. (a) Zhu, Y.; Loso, M. R.; Watson, G. B.; Sparks, T. C.; Rogers, R.
B.; Huang, J. X.; Gerwick, B. C.; Babcock, J. M.; Kelley, D.;
Hegde, V. B.; Nugent, B. M.; Renga, J. M.; Denholm, I.; Gorman,
K.; DeBoer, G. J.; Hasler, J.; Meade, T.; Thomas, J. D. J. Agric.
Food. Chem. 2011, 59, 2950-2957. (b) Pandya, V.; Jain, M.;
Chakrabarti, G.; Soni, H.; Parmar, B.; Chaugule, B.; Patel, J.;
Jarag, T.; Joshi, J.; Joshi, N.; Rath, A.; Unadkat, V.; Sharma, B.;
Ajani, H.; Kumar, J.; Sairam, K. V. V. M.; Patel, H.; Patel, P. Eur.
J. Med. Chem. 2012, 58, 136-152. (c) Lücking, U. Angew. Chem.
Int. Ed. 2013, 52, 9399-9408. (d) Lücking, U.; Jautelat, R.;
Krüger, M.; Brumby, T.; Lienau, P.; Schäfer, M.; Briem, H.;
Schulze, J.; Hillisch, A.; Reichel, A.; Wengner, A. M.; Siemeister,
G. ChemMedChem 2013, 8, 1067-1085. (e) Park, S. J.; Baars, H.;
Mersmann, S.; Buschmann, H.; Baron, J. M.; Amann, P. M.;
Czaja, K.; Hollert, H.; Bluhm, K.; Redelstein, R.; Bolm, C.
ChemMedChem 2013, 8, 217-220.
2. (a) Yadav, M. R.; Rit, R. K.; Sahoo, A. K. Chem. Eur. J. 2012, 18,
5541-5545. (b) Rit, R. K.; Yadav, M. R.; Sahoo, A. K. Org. Lett.
2012, 14, 3724-3727. (c) Yadav, M. R.; Rit, R. K.; Sahoo, A. K.
Org. Lett. 2013, 15, 1638-1641. (d) Rit, R. K.; Yadav, M. R.;
Sahoo, A. K. Org. Lett. 2014, 16, 968-971.
3. (a) Bolm, C.; Hackenberger, C. P. R.; Simic, O.; Verrucci, M.;
Müller, D.; Bienewald, F. Synthesis 2002, 7, 879-887. (b) Siu, T.;
Yudin, A. K. Org. Lett. 2002, 4, 1839-1842. (c) Hackenberger, C.
P. R.; Raabe, G.; Bolm, C. Chem. Eur. J. 2004, 10, 2942-2952. (d)
Cho, G. Y.; Bolm, C. Org. Lett. 2005, 7, 1351-1354.
9. For recent selected examples see: (a) Uyanik, M.; Okamoto, H.;
Yasui, T.; Ishihara, K. Science 2010, 328, 1376-1379. (b) Uyanik,
M.; Suzuki, D.; Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed.,
2011, 50, 5331–5334. (c) Wei, W.; Zhang, C.; Xu, Y.; Wan, X.
Chem. Commun. 2011, 47, 10827-10829. (d) Chen, L.; Shi, E.;
Liu, Z.; Chen, S.; Wei, W.; Li, H.; Xu, K.; Wan, X. Chem. Eur. J.
2011, 17, 4085-4089. (e) Tan, B.; Toda, N.; Barbas, C. F. Angew.
Chem. Int. Ed. 2012, 51, 12538-12541. (f) Feng, J.; Liang, S.;
Chen, S.-Y.; Zhang, J.; Fu, S.-S.; Yu, X.-Q. Adv. Synth. Catal.
2012, 354, 1287-1292. (g) Shi, E.; Shao, Y.; Chen, S.; Hu, H.; Liu,
Z.; Zhang, J.; Wan, X. Org. Lett., 2012, 14, 3384-3387. (h) Huang,
J.; Li, L.-T.; Li, H.-Y.; Husan, E.; Wang, P.; Wang, B. Chem.
Commun., 2012, 48, 10204-10206. (i) Majji, G.; Guin, S.; Gogoi,
A.; Rout, S. K.; Patel, B. K. Chem. Commun. 2013, 49, 3031-3033.
10. For recent selected examples see: (a) Li, X.; Xu, X.; Zhou, C.
Chem. Commun., 2012, 48, 12240-12242. (b) Xiao, F.; Chen, H.;
Xie, H.; Chen, S.; Yang, L.; Deng, G.-J. Org. Lett., 2014, 16, 50–
53. (c) Zhang, J.; Shao, Y.; Wang, H.; Luo, Q.; Chen, J.; Xu, D.;
Wan, X. Org. Lett., 2014, 16, 3312-3315. (d) Qiu, J.-K.; Hao, W.-
J.; Wang, D.-C.; Wei, P.; Sun, J.; Jiang, B.; Tu, S.-J. Chem.
Commun. 2014, 50, 14782-14785.
4. Garimallaprabhakaran, A.; Harmata, M. Synlett 2011, 3, 361-364.
5. (a) Wang, L.; Priebbenow, D. L.; Zou, L.-H.; Bolm, C. Adv. Synth.
Catal. 2013, 355, 1490-1494. (b) Wang, L; Huang, H;
Priebbenow, D. L.; Pan, F.-F.; Bolm, C. Angew. Chem. Int. Ed.
2013, 52, 3478-3480. (c) Priebbenow, D. L.; Bolm, C. Org. Lett.
2014, 16, 1650-1652.
Supplementary Material
6. For recent review see: (a) Uyanik, M.; Ishihara, K.
ChemCatChem, 2012, 4, 177-185. (b) Wu, X.-F.; Gong, J.-L.; Qi,
X. Org. Biomol. Chem. 2014, 12, 5807-5817.
7. For recent selected examples see: (a) Li, L.-T.; Huang, J.; Li, H.-
Y.; Wen, L.-J.; Wang, P.; Wang, B. Chem. Commun., 2012, 48,
5187–5189. (b) Nobuta, T.; Tada, N.; Fujiya, A.; Kariya, A.;
Miura, T.; Itoh, A. Org. Lett., 2013, 15, 574–577. (c) Kloeckner,
U.; Finkbeiner, P.; Nachtsheim, B. J. J. Org. Chem., 2013, 78,
2751–2756. (d) Jia, Z.; Nagano, T.; Li, X.; Chan, A. S. C. Eur. J.
Org. Chem. 2013, 5, 858-861.
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TBHP/ TBAI catalyzed direct N-acylation of sulfoximines
with aldehydes
Wen-Jing Qin, Yi Li, Xingxin Yu and Wei-Ping Deng
Shanghai Key Laboratory of New Drug Design & School of Pharmacy, East China University of Science and
Technology, 130 Meilong Road, Shanghai 200237, China
xxyu@ecust.edu.cn; weiping_deng@ecust.edu.cn
Supplementary Material
1H NMR and 13C NMR spectra of N-acylsulfoximine 3
Corresponding author. Tel.: +86-21-64252431; fax: +86-21-64252431; e-mail: xxyu@ecust.edu.cn;
weiping_deng@ecust.edu.cn

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