Mild copper-TBAF-catalyzed N-arylation of sulfoximines with aryl siloxanes

Article abstract of DOI:10.1021/ol502174n

An efficient copper-TBAF-catalyzed C-N bond formation of sulfoximines with arylsiloxanes in dichloromethane at room temperature, affording the desired N-aryl sulfoximines in good to excellent yields under an oxygen atmosphere, is reported. This method complements the existing synthetic approaches due to some advantageous properties of arylsiloxanes such as availability, low toxicity, ease of handling, high stability, and environmental benignity under mild reaction conditions, thus opening a new approach to practical C-N bond formation.

Full text of DOI:10.1021/ol502174n

Letter
pubs.acs.org/OrgLett
Mild Copper−TBAF-Catalyzed N‑Arylation of Sulfoximines with Aryl
Siloxanes
Jaeeun Kim, Jinpyo Ok, Sanghyuck Kim, Wonseok Choi, and Phil Ho Lee*
Department of Chemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea
S
* Supporting Information
ABSTRACT: An efficient copper−TBAF-catalyzed C−N bond formation of sulfoximines with arylsiloxanes in dichloromethane
at room temperature, affording the desired N-aryl sulfoximines in good to excellent yields under an oxygen atmosphere, is
reported. This method complements the existing synthetic approaches due to some advantageous properties of arylsiloxanes such
as availability, low toxicity, ease of handling, high stability, and environmental benignity under mild reaction conditions, thus
opening a new approach to practical C−N bond formation.
ecause sulfoximines are valuable privileged structures that
have been applied as biologically active compounds1 and
However, because sulfoximines exhibit lower nucleophilic
character at the nitrogen than amines and imines, development
of a new C−N bond formation of sulfoximines still represents a
formidable challenge. Recently, Cheng and co-workers reported
an efficient C−N bond formation via Cu−TBAF-catalyzed
arylation of amines and amides with aryl trimethoxysilane.8
Therefore, we envisioned that organosilicon reagents would be
excellent coupling partners in transition-metal-catalyzed N-
arylation of sulfoximines due to their significant advantages
involving low toxicity, ease of handling, high stability, and
environmental benignity.9 Recently, we were interested in a
transition-metal-catalyzed C−N bond formation.10 These
results prompted us to investigate the feasibility of an
organosilicon reagent in reaction with sulfoximines for C−N
bond formation. In this paper, we report an efficient copper-
TBAF-catalyzed N-arylation of sulfoximines with aryl siloxanes
under mild conditions (eq 5).
B
chiral auxiliaries and ligands in asymmetric synthesis,2 the
development of novel synthetic methodologies for preparing
sulfoximines and their functionalizations is extremely desirable.
Thus, functionalization of sulfoximines via the reaction with
easily available starting materials has been continuously
investigated.3 Since 1998, Bolm and co-workers have reported
a variety of N-arylation of sulfoximines via transition-metal-
catalyzed cross-coupling reactions (Scheme 1): N-arylation of
Scheme 1. Metal-Catalyzed Synthesis of N-Arylsulfoximines
First, we started our investigation with an N-arylation
reaction of sulfoximine (1a) with trimethoxyphenylsilane (2a)
under an oxygen atmosphere (Table 1, see the Supporting
Information). When CuI and tetrabutylammonium fluoride
trihydrate (TBAF·3H2O) (10 mol % each) as catalyst were
used, dichloromethane (DCM) gave the best result (84%)
among solvents such as dichloroethane (DCE), toluene,
MeOH, DMSO, and DCM (entries 1−5). CuI provided most
the desirable result among the catalysts such as CuI, CuBr,
CuCl, CuOAc, and Cu(OAc)2 in the presence of (TBAF·
3H2O) (10 mol %) in DCM (entries 5−9). The N-arylation
reaction did not take place without (TBAF·3H2O) (entry 10).
The use of CuI is critically significant for a successful N-
arylation (entry 12). The use of molecular oxygen was also
essential for the reaction to proceed. Hence, the N-arylation did
sulfoximines using aryl triflates, nonaflates, tosylates, iodides,
and bromides under palladium, copper, nickel, and iron
catalysis (eq 1)4 and copper-catalyzed N-arylation of
sulfoximines using aryl boronic acids (eq 2).5 Recently,
Varma and co-workers described the copper-catalyzed N-
arylation of sulfoximines using diaryliodonium triflates and
ultrasound (eq 3).6 Moreover, Bolm and Miura have developed
N-arylation of sulfoximines via copper-catalyzed C−H
activation with azoles and polyfluoroarenes (eq 4).7
Received: July 23, 2014
Published: August 21, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
a
Table 1. Optimization of N-Arylation of Sulfoximines
Scheme 2. N-Arylation of Substituted Sulfoximines with
a
Trimethoxyphenylsilane
b
entry
cat.
solvent
yield (%)
1
2
CuI, TBAF·3H2O
CuI, TBAF·3H2O
CuI, TBAF·3H2O
CuI, TBAF·3H2O
CuI, TBAF·3H2O
CuOAc, TBAF·3H2O
CuBr, TBAF·3H2O
CuCl, TBAF·3H2O
Cu(OAc)2, TBAF·3H2O
CuI
DCE
78
0
toluene
MeOH
DMSO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
3
0
4
42
84
72
50
61
5
6
7
8
c
9
57 (36)
10
0
d
e
11
CuI, TBAF·3H2O
TBAF·3H2O
CuI, TBAF·3H2O
CuI, TBAF·3H2O
91 (90)
12
0
0
0
f
13
g
14
a
Reactions were carried out with 1a (0.2 mmol), 2a (0.3 mmol, 1.5
equiv), TBAF·3H2O, and Cu catalyst (10 mol % each) in solvent (1.0
b
mL) under O2 at room temperature for 12 h. NMR yield using
c
d
CH2Br2 as an internal standard. NMR yield of 1a. 2a (0.35 mmol,
e
f
g
1.75 equiv) was used. Isolated yield. Under N2. Under air.
not occur under nitrogen and air atmosphere (entries 13 and
14). The optimal reaction conditions could be obtained from
the reaction of 1a (1 equiv) with 2a (1.75 equiv) in the
presence of CuI and (TBAF·3H2O) (10 mol % each) in DCM
for 12 h at room temperature under an oxygen atmosphere (1
atm), leading to the formation of 3aa in 90% isolated yield
(entry 11).
a
Reaction conditions: 1a (0.2 mmol), 2 (1.75 equiv), CuI, TBAF·
3H2O (10 mol % each), and CH2Cl2 (1 mL) under O2 at room
temperature for 12 h. Reaction scale is 2 mmol. CuI (20 mol %) was
used for 24 h.
b
c
On the basis of the optimal reaction conditions, we next
examined the scope and limitations of the N-arylation with
respect to sulfoximines 1 to react with trimethoxyphenylsilane
(2a) in Scheme 2. Electronic variation of a wide range of
substituents on the arene moiety of sulfoximines 1 had little
effect on the reaction efficiency. In fact, sulfoximines (1b, 1c,
and 1d) having electron-donating p-, m-, and o-methyl groups
on the phenyl ring were smoothly transformed to the desirable
S-aryl-N-phenylsulfoximines (3ba, 3ca, and 3da) in good to
excellent yields under mild conditions. 3,5-Dimethylsulfoximine
(1e) was less reactive and then provided 3ea in 76% yield with
CuI (20 mol %). 4- and 3-methoxyphenyl-substituted
sulfoximines (1f and 1g) underwent the N-arylation reaction,
producing N-phenylsulfoximines (3fa and 3ga) in 78% and
81% yields, respectively. Sulfoximines bearing chloro (1h and
1i) and bromo (1j and 1k) groups were all smoothly N-arylated
to afford 3ha−ka in high yields ranging from 84% to 89%. The
tolerance of chloro and bromo groups is especially significant,
as sequentially catalytic cross-coupling reactions are possible.
Despite the presence of strong electron-withdrawing nitro and
trifluoromethyl groups, the N-phenylated sulfoximines (3la and
3ma) were obtained in 88% and 89% yields, respectively. N-
Phenylation also took place in S-2-naphthyl sulfoximine (1n),
leading to the formation of S-2-naphthyl-N-phenylsulfoximine
(3na) in 76% yield. Likewise, phenyl ethyl sulfoximine (1o)
worked well with CuI (20 mol %). S,S-Dimethylsulfoximine
(1p) also was N-arylated, producing the desired product 3pa in
81% yield.
nylsilane 2a (1.75 equiv) in the presence of CuI and TBAF·
3H2O (10 mol % each) under the optimal conditions,
producing the N-arylated compound 3aa in 86% yield (0.40 g).
Next, we turned our attention to the N-arylation of S-methyl-
S-phenylsulfoximine 1a with a broad range of aryltrimethox-
ysilanes 2, and the results are summarized in Scheme 3. The
electronic nature of aryl substituents in aryltrimethoxysilanes
Scheme 3. N-Arylation of Sulfoximine with Various
Organosilanes
To demonstrate the applicability of the present method to a
larger scale processes, a 2.0 mmol scale reaction of phenyl-
sulfoximine 1a (0.31 g) was undertaken with trimethoxyphe-
a
CuI (20 mol %) was used for 24 h. Recovery yield of starting
material.
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Letter
had little effect on the reaction efficiency. Thus, the N-arylation
products were produced in good to excellent yields from
aryltrimethoxysilanes having not only electron-donating methyl
and methoxy but also electron-withdrawing chloro and fluoro
groups. It was noteworthy that the chloro group in 4-
chlorophenyltrimethoxysilane 2f could be tolerated under the
reaction conditions, enabling further functional group trans-
formation. On the other hand, an o-methyl group at the phenyl
ring of trimethoxy-2-methylphenylsilane 2c slightly decreased
the reactivity, presumably due to steric reasons, and then
produced 3ac in 66% yield together with 1a (15%) with 20 mol
% of CuI. Trimethoxy-2-thienylsilane 2h could also be used as
the cross-coupling partner and delivered the N-2-thienylated
product 3ah in quantitative yield.
lane 2a was subjected to S-4-methoxyphenyl-S-methylsulfox-
imine 1f and S-methyl-S-4-nitrophenylsulfoximine 1l to provide
the N-arylation products 3fa (34%) and 3la (72%). A
competition experiment between aryltrimethoxysilanes (2d
and 2g) having 4-methoxy and 4-fluoro groups produced the
N-aryl-S-methyl-S-phenylsulfoximines 3ad (37%) and 3ag
(59%) (b). These results indicate that electron-deficient
sulfoximines and arylsiloxanes are more reactive in C−N
bond formation.
Because the catalytic cycle of copper and TBAF is unclear at
the present stage, the elucidation of the detailed reaction
mechanism must wait further study.
In conclusion, we have developed an efficient copper−
TBAF-catalyzed coupling reaction of sulfoximines with
arylsiloxanes in dichloromethane at room temperature to
produce the desired N-arylsulfoximines in good to excellent
yields under an oxygen atmosphere. The present method
complements the previously reported synthetic approaches due
to some advantageous properties of aryl siloxanes such as
availability, low toxicity, ease of handling, high stability, and
environmentally benignity under mild conditions, thus opening
a new approach to practical C−N bond formation.
The scope and limitations of the N-arylation reaction with
respect to a myriad of S-aryl-S-methylsulfoximines 1 and
aryltrimethoxysilanes 2 were next investigated under optimal
conditions (Scheme 4). When trimethoxy-4-methylphenylsilane
Scheme 4. N-Arylation of Substituted Sulfoximines with
Organosilanes
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, characterization data, and 1H and 13
■
S
C
NMR spectra for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
2b was treated with 4-methyl-, 4-methoxy-, and 3-chloro-
substituted sulfoximines, the N-arylation proceeded smoothly
to afford the desired products (3bb, 3fb, and 3ib). Likewise,
aryltrimethoxysilanes (2f and 2g) having chloro and fluoro
substituents underwent effectively the N-arylation reaction, thus
producing the corresponding products in good yields ranging
from 75% and 88%.
*E-mail: phlee@kangwon.ac.kr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Research Foundation
of Korea (NRF) grant funded by the Korea government
(MSIP) (No. 2014001403).
Competition experiments between S-aryl-S-methylsulfoxi-
mines 1 were examined [Scheme 5, (a)]. Trimethoxyphenylsi-
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