B(C6F5)3-Catalyzed Deoxygenation of Sulfoxides and Amine N-Oxides with Hydrosilanes

Article abstract of DOI:10.1002/ejoc.201700489

An efficient strategy for the deoxygenation of sulfoxides and amine N-oxides by using B(C₆F₅)₃ and hydrosilanes was developed. This method provided the corresponding aromatic and aliphatic products in good to high yields and showed good functional-group tolerance under mild conditions.

Full text of DOI:10.1002/ejoc.201700489

A Journal of
Accepted Article
Title: B(C6F5)3-Catalyzed Deoxygenation of Sulfoxides and Amine N-
Oxides with Hydrosilanes
Authors: Fangwei Ding, Yanqiu Jiang, Shaoyan Gan, Robert Li-Yuan
Bao, Kaifeng Lin, and Lei Shi
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700489
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700489
Supported by

10.1002/ejoc.201700489
European Journal of Organic Chemistry
COMMUNICATION
B(C6F5)3-Catalyzed Deoxygenation of Sulfoxides and Amine N-
Oxides with Hydrosilanes
Fangwei Ding,[a,b] Yanqiu Jiang,[a] Shaoyan Gan,[a,b] Robert Li-Yuan Bao,[a,b] Kaifeng Lin,[a] and Lei Shi
[a,b,c]
*
Dedication ((optional))
Abstract: An efficient strategy for the deoxygenation of sulfoxides
and amine N-oxides using B(C6F5)3 and hydrosilanes has been
developed. The method affords the corresponding aromatic or
aliphatic products in good to high yields, and shows good functional
group tolerance under mild conditions.
the model reaction for studying the influence of hydrosilanes,
and critical parameters such as solvents and temperature. In
order to compare the catalytic activities of several hydrosilanes,
phenylsilane, diethylsilane, and triphenylsilane as representative
primary, secondary, and tertiary silanes were investigated.
These reagents had a dramatic effect on the product yields. To
our delight, the addition of small bulk of silane sources such as
tetramethyldisiloxane (TMDS) and diethylsilane had positive
effects. While there was no reaction in the presence of
triphenylsilane, perhaps because the steric hindrance is involved
in the Si–H bond cleavage. Fortunately, using PhSiH3, the
desired product was isolated in 85 % yield (Table 1, entry 2).
The influence of solvents was investigated as well. Since
tetrahydrofuran (THF) could interact with the B(C6F5)3,[21] the
catalyst activity was reduced, giving the desired product in 42 %
yield. Using acetonitrile and 1,2-dichloroethane (DCE) as
solvents, the substrates were converted into the expected
products in 60 % and 75 % yields, respectively (Table 1, entries
8-9). Ultimately, the effect of temperature was studied. The yield
could be slightly increased by elevating the temperature to
100 °C (Table 1, entry 10). However, when the reaction was
carried out at room temperature (Table 1, entry 1), no product
was obtained. Considering lower temperature may be good for
functional group tolerance, and provide a mild condition, 60 °C
was selected as the optimized temperature. As a result, (Table1,
entry 2) was selected as the standard condition.
Introduction
Boron Lewis acids have spurred widespread interest as powerful
tools
for
activation
of
hydrosilanes[1]
and
related
transformations.[2] Meanwhile, hydrosilanes employed as low
toxic, highly active and handling easily substances have also
received considerable attention. Consequently, the combined
use of B(C6F5)3 and hydrosilanes is found to be a method for the
deoxygenation of alcohols[3] and ethers[4] as well as carbonyl
compounds and their derivatives.[5] The past decade has
witnessed spectacular advances in metal-free catalytic
reductions, particularly using B(C6F5)3/silanes.[2] In addition, the
reduction of sulfoxides and amine N-oxides into their
corresponding sulfides and amines is an important reaction due
to its considerable utility in organic synthesis. Over the past
years, many systems have been employed for the
deoxygenation of sulfoxides including reagents such as
silane/MoO2Cl2,[6]
oxo-complexes,[7]
gold
nanoparticle,[8]
Zn(OTf)2/B2(pin)2 or Zn(OTf)2/boranes,[9] SOCl2,[10] Fe powder,[11]
ruthenium nanoparticle,[12] and I2.[13] On the other hand, the
deoxygenation of amine N-oxides involved In,[14] Mo(CO)6,[15]
Cu,[16] NbCl5/Zn,[17] Raney nickel,[18] diboron reagents,[19] and
gold nanoparticle.[20] However, many reagents employed for
these deoxygenation processes are expensive,[6, 8, 12] sensitive to
both air and moisture[15, 17] or using transition metal under harsh
conditions. Herein, a novel method, B(C6F5)3 deoxygenation of
sulfoxides and amine N-oxides with hydrosilanes is presented.
Table 1. Optimization studies for the deoxygenation of methyl phenyl
sulfoxide catalyzed by B(C6F5)3.[a]
Entry
Hydrosilane
PhSiH3
PhSiH3
TMDS
Solvent
toluene
toluene
toluene
toluene
toluene
toluene
THF
T [oC]
r.t.
60
Yield [%][b]
trace
85
1
2
3
4
5
6
7
8
9
Results and Discussion
The deoxygenation of methyl phenyl sulfoxide was chosen as
60
75
Et2SiH2
PMHS
60
73
[a]
MIIT Key Laboratory of Critical Materials Technology for New
Energy Conversion and Storage, School of Chemistry and Chemical
Engineering, Harbin Institute of Technology, Harbin 150001, China.
E-mail: lshi@hit.edu.cn http://homepage.hit.edu.cn/shilei
Shenzhen Graduate School, Harbin Institute of Technology,
Shenzhen 518055, China
60
64
Ph3SiH
PhSiH3
PhSiH3
PhSiH3
60
trace
42
[b]
[c]
60
Hubei Key Laboratory of Drug Synthesis and Optimization, Jingchu
University of Technology, Jingmen, 448000, China
MeCN
DCE
60
60
60
75
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700489
European Journal of Organic Chemistry
COMMUNICATION
10
PhSiH3
toluene
100
86
[a] Reaction conditions: sulfoxides (0.5 mmol, 1 equiv.) and PhSiH3 (1 mmol, 2
equiv.) with B(C6F5)3 (5 mol %) in toluene (1.5 mL) at 60 °C for 8 h. [b] Yield of
isolated product.
[a] Reaction conditions: sulfoxide 1a (0.5 mmol, 1 equiv.) and hydrosilane (1
mmol, equiv.) with B(C6F5)3 (5 mol %) in solvent (1.5 mL) at the
2
investigated temperature for 8 h. [b] Yield of isolated product.
Particularly worth mentioning is the case that sulfoxide with –
NO2 was not reduced to –NH2 (Table 2, entry 7), despite the
B(C6F5)3/Et3SiH could reduce of aromatic and aliphatic nitro
groups with hydrosilanes,[23] perhaps because of the
temperature and the amount of hydrosilanes. In other words, S–
O bond is more active than the N–O bond. Furthermore,
To probe the scope of the reaction, we applied the optimized
conditions to a variety of sulfoxides. The deoxygenation of
various sulfoxides to the corresponding sulfides was obtained in
high yields, including sulfides bearing electronwithdrawing or
electrondonating groups (Table 2). As shown in the Table 2, the
deoxygenation of halogenated sulfoxides proceeded smoothly
(Table 2, entries 4-6). Although the B(C6F5)3/Et3SiH was
reported to promote the hydrodefluorination of alkyl fluorides at
room temperature,[22] substrate 1d (Table 2, entry 4) was
tolerated under the standard reaction conditions giving the
desired product 2d in 60 % yield. Chloro and bromo substituted
sulfoxides afforded the corresponding products (2e, 2f, and 2h)
in moderate to high yields, which might be employed for further
structural manipulations such as the coupling reaction.
aliphatic
and
heterocyclic
sulfoxides
all
underwent
deoxygenation sufficiently, providing the corresponding sulfides
in good yields (Table 2, entries 11-12). Sulfoxides with –OH
afforded the desired products (2n and 2o) in high yields. We
also tried the reduction of omeprazole 1p with the
PhSiH3/B(C6F5)3 (5 mol %) system, ufiprazole 2p was obtained
in 71 % yield (Table 2, entry 16).
Due to the compatibility with a range of functional groups
clarified in the reduction of sulfoxides, it seems possible to be
suitable for reduction of other organoheteroatom oxides. To
evaluate the general applicability of the PhSiH3/B(C6F5)3 (5
mol %) system, we also made an investigation of the
deoxygenation of various aromatic and aliphatic amine N-oxides
listed in the Table 3. The deoxygenation of quinoline N-oxide
afforded quinoline 4a in 84 % yield (Table 3, entry 1), and the
reduction of isoquinoline N-oxide provided 4b in 82 % yield
under mild conditions (Table 3, entry 2). The remarkable
functional group tolerance of our experimental conditions was
observed in the deoxygenation of amine N-oxides with functional
groups such as nitro, halogeno and carbonyl groups, to the
corresponding amines in good to excellent yields (Table 3,
entries 4, 6, 11, and 12).
Furthermore, examples for the deoxygenation of aliphatic
amine N-oxides, including alicyclic and phenylic and substituted
phenylic N-oxides to amines showed in high yields (65-75 %;
Table 3, entries 9-11). This methodology had a positive effect on
complex molecules. It worked well when we use this
methodology to obtain complex natural products 4l (Table 3,
entry 12).
[a]
Table 2. Deoxygenation of various sulfoxides catalyzed by B(C6F5)3.
O
B(C6F5)3 (5mol %)
S
S
R1 R2
R1 R2
PhSiH3, toluene
60°C
2
1
Entry
1
Substrate Product Yield[b] (%) Entry
Substrate
Product Yield (%)
O
O
S
85
2a
S
2i
2j
72
Ph
Me
Et
9
Ph
Bn
O
O
S
S
2b
2c
2
3
65
75
Ph
10
Bn
Me
62
60
82
O
O
S
S
Me
Me
Me
2k
2l
11
12
O
S
O
S
Me
2d
2e
2f
60
80
73
4
5
O
F
Based on previous reports[24] and our results, we assume that
the B(C6F5)3 acts as a Lewis acid (Figure 1). Initially, interaction
of the hydrosilane with the Lewis-acidic boronic center activates
the Si–H bond, in order to facilitate sulfoxides attacking at the
silicon atom, thus an activation of the S=O bond occurs.
Subsequently, the complex reacts further with another
equivalent of hydrosilane to afford [R1R2SH]+. Finally,
protonation of [HB(C6F5)3] by the [R1R2SH]+ liberates free H2,
sulfide and B(C6F5)3. This mechanism is closely related to that
described for the deoxygenation of phosphine oxide by
Oestreich and Stephan.[25] In addition, the mechanism for the
deoxygenation of amine N-oxides is similar to that reported by
Namboothiri.[20] The activated silane reacts with the N-oxide
substrate with simultaneous hydrogen transfer at C2. The
transient intermediate then rearomatizes with concomitant
elimination of silanol, affording corresponding products.
O
S
O
S
2m 82
Me
Me
13
Cl
O
S
O
S
81
87
2n
2o
14
15
6
7
HO
B
Br
OH
O
S
O
S
Me
2g
2h
77
87
HO
O2N
Cl
O
O
O
S
Me
N
H
N
2p
71
8
16
S
Cl
N
O
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700489
European Journal of Organic Chemistry
COMMUNICATION
Table 3. Deoxygenation of various amine N-oxides catalyzed by B(C6F5)3.[a]
Conclusions
In conclusion, the PhSiH3/B(C6F5)3 system serves as an efficient
methodology for deoxygenation of a wide range of sulfoxides
and amide N-oxides with other reducible substituents intact
(such as –F and –NO2) in good to excellent yields without any
additives. This approach also features a mild condition, high
chemical selectivity, and good functional group tolerance to
obtain drug intermediate and natural product. This protocol
should be very useful in future because of the ease of operation,
the environmentally friendly reaction conditions, and its wide
scope.
Experimental Section
General Procedure for the Deoxygenation of Sulfoxides and Amine
N-oxides: To a mixture of an appropriate sulfoxides or amine N-oxides
(0.5 mmol) and B(C6F5)3 (5 mol %) in a standard Schlenk tube, 1 mmol of
PhSiH3 for sulfoxides (0.75 mmol for amine N-oxides) was added. The
mixture was evacuated and backfilled with N2 (3 times). Then, the solvent
(1.5 mL) was added via syringe, and the mixture was stirred at 60 °C for
8 h. The resulting reaction mixture was concentrated under reduced
pressure and purified by column chromatography using petroleum
ether/ethyl acetate to afford the corresponding products.
Acknowledgements
The work was financially supported by the “Hundred Talents
Program” of Harbin Institute of Technology (HIT), the
“Fundamental
Research
Funds
for
the
Central
University”(HIT.BRETIV.201502), the NSFC (21202027), the
NCET (NCET-12-0145), Open Project Program of Hubei Key
Laboratory of Drug Synthesis and Optimization, Jingchu
University of Technology (No.OPP2015ZD01), and the
“Technology Foundation for Selected Overseas Chinese
Scholar” of Ministry of Human Resources and Social Security of
China (MOHRSS).
[a] Reaction conditions: amine N-oxides (0.5 mmol, 1 equiv.) and PhSiH3 (0.75
mmol, 1.5 equiv.) with B(C6F5)3 (5 mol %) in DCM (1.5 mL) at 60 °C for 8 h.
[b] Yield of isolated product.
B(C6F5)3
S
B(C6F5)3
R1 R2
Keywords: Deoxygenation • B(C6F5)3 • Hydrosilane • Sulfide •
R3SiH
N
+
Amine
R3SiOH
R1R2SH
H B(C6F5)3
[1]
[2]
[3]
[4]
Y. Ma, B. Wang, L. Zhang, Z. Hou, J. Am. Chem. Soc. 2016, 138,
3663-3666.
R3Si
H B(C6F5)3
H
H
N
O
R3Si H B(C6F5)3
SiR3
M. Oestreich, J. Hermeke, J. Mohr, Chem. Soc. Rev. 2015, 44, 2202-
2220.
(R3Si)2O
V. Gevorgyan, J.-X. Liu, M. Rubin, S. Benson, Y. Yamamoto,
Tetrahedron Lett. 1999, 40, 8919-8922.
R1
SiR3
N
O
H
S O
O
S
R3SiH
R2
+
SiR3
a) V. Gevorgyan, M. Rubin, J.-X. Liu, Y. Yamamoto, J. Org. Chem.
2001, 66, 1672-1675; b) L. L. Adduci, M. P. McLaughlin, T. A. Bender, J.
J. Becker, M. R. Gagné, Angew. Chem. Int. Ed. 2014, 53, 1646-1649;
Angew. Chem. 2014, 126, 1672-1675. c) K. Saito, K. Kondo, T.
Akiyama, Org. Lett. 2015, 17, 3366-3369.
R1 R2
N
O
H
B(C6F5)3
B(C6F5)3
Figure 1. Proposed catalytic cycle for the reduction of sulfoxides and N-oxides.
[5]
a) R. D. Nimmagadda, C. McRae, Tetrahedron Lett. 2006, 47, 5755-
5758; b) M. Tan, Y. Zhang. Tetrahedron Lett. 2009, 50, 4912-4915; c)
D. Bezier, S. Park, M. Brookhart, Org. Lett. 2013, 15, 496-499; d) K.
Sakata, H. Fujimoto, J. Org. Chem. 2013, 78, 12505-12512; e) E.
Blondiaux, T. Cantat, Chem. commun. 2014, 50, 9349-9352; f) R. C.
Chadwick, V. Kardelis, P. Lim, A. Adronov, J. Org. Chem. 2014, 79,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700489
European Journal of Organic Chemistry
COMMUNICATION
7728-7733; g) M. Mehta, M. H. Holthausen, I. Mallov, M. Perez, Z.-W.
Qu, S. Grimme, D. W. Stephan, Angew.Chem.Int. Ed. 2015, 54, 8250-
8254; Angew. Chem. 2015, 127, 8368-8372.
[15] B. W. Yoo, J. W. Choi, C. M. Yoon, Tetrahedron Lett. 2006, 47, 125-
126.
[16] S. K. Singh, M. S. Reddy, M. Mangle, K. R. Ganesh, Tetrahedron 2007,
63, 126-130.
[6]
[7]
A. C. Fernandes, C. C. Romão, Tetrahedron 2006, 62, 9650-9654.
a) S. C. A. Sousa, A. C. Fernandes, Tetrahedron Lett. 2010, 51, 6132-
6135; b) S. C. A. Sousa, J. R. Bernardo, M. Wolff, B. Machura, A. C.
Fernandes, Eur. J. Org. Chem. 2014, 1855-1859.
[17] K. Oh, W. E. Knabe, Tetrahedron 2009, 65, 2966-2974.
[18] N. B. Gowda, G. K. Rao, R. A. Ramakrishna, Tetrahedron Lett. 2010,
51, 5690-5693.
[8]
[9]
Y. Mikami, A. Noujima, T. Mitsudome, T. Mizugaki, K. Jitsukawa, K.
Kaneda, Chem. Eur. J. 2011, 17, 1768-1772.
[19] H. P. Kokatla, P. F. Thomson, S. Bae, V. R. Doddi, M. K. Lakshman, J.
Org. Chem. 2011, 76, 7842-7848.
a) S. Enthaler, Catal. Lett.2012, 142, 1306-1311; b) S. Enthaler, S.
Krackl, E. Irran, S. Inoue, Catal Lett. 2012, 142, 1003-1010.
[20] S. Donck, E. Gravel, N. Shah, D. V. Jawale, E. Doris, I. N. N.
Namboothiri, RSC Adv. 2015, 5, 50865-50868.
[10] Y. Jang, K. T. Kim, H. B. Jeon, J. Org. Chem. 2013, 78, 6328-6331.
[11] R. Ma, A.-H. Liu, C.-B. Huang, X.-D. Li, L.-N. He, Green Chem. 2013,
15, 1274-1279.
[21] D. W. Stephan, G. Erker, Angew. Chem. Int. Ed. 2010, 49, 46-76;
Angew. Chem. 2010, 122, 50-81.
[22] C. B. Caputo, D. W. Stephan, Organometallics 2012, 31, 27-30.
[23] D. Porwal, M. Oestreich, Eur. J. Org. Chem. 2016, 3307-3309.
[24] a) D. J. Parks, W. E. Piers, J. Am. Chem. Soc. 1996, 118, 9440-9441;
b) D. J. Parks, J. M. Blackwell, Warren E. Piers, J. Org. Chem. 2000,
65, 3090-3098; c) J. M. Blackwell, E. R. Sonmor, T. Scoccitti, W. E.
Piers, Org. Lett. 2000, 24, 3921-3923; d) J. Hermeke, M. Mewald, M.
Oestreich, J. Am. Chem. Soc. 2013, 135, 17537-17546.
[25] M. Mehta, I. Garcia de la Arada, M. Perez, D. Porwal, M. Oestreich, D.
W. Stephan, Organometallics 2016, 35, 1030-1035.
[12] T. Mitsudome, Y. Takahashi, T. Mizugaki, K. Jitsukawa, K. Kaneda,
Angew. Chem. Int. Ed. 2014, 53, 8348-8351; Angew. Chem. 2014, 126,
8488-8491.
[13] M. Abbasi, M. R. Mohammadizadeh, Z. Moradi, Tetrahedron Lett. 2015,
56, 6610-6613.
[14] J. S. Yadav, B. V. S. Reddy, M. M. Reddy, Tetrahedron Lett. 2000, 41,
2663-2665.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700489
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
An efficient strategy for the
Deoxygenation
deoxygenation of sulfoxides and
amine N-oxides using B(C6F5)3 and
hydrosilanes has been developed.
Fangwei Ding, Yanqiu Jiang, Shaoyan
Gan, Robert Li-Yuan Bao, Kaifeng Lin,
and Lei Shi *
Page No. – Page No.
B(C6F5)3-Catalyzed Deoxygenation of
Sulfoxides and Amine N-Oxides with
Hydrosilanes
*one or two words that highlight the emphasis of the paper or the field of the study
Layout 2:
COMMUNICATION
Key Topic*
Author(s), Corresponding Author(s)*
((Insert TOC Graphic here; max. width: 11.5 cm; max. height: 2.5 cm; NOTE: the
final letter height should not be less than 2 mm.))
Page No. – Page No.
Title
Text for Table of Contents
*one or two words that highlight the emphasis of the paper or the field of the study
This article is protected by copyright. All rights reserved.