Chiral: N, N ′-dioxide-iron(iii)-catalyzed asymmetric sulfoxidation with hydrogen peroxide

Article abstract of DOI:10.1039/d0cc00434k

A highly enantioselective sulfoxidation of various sulfides has been achieved by a N,N′-dioxide-iron(iii) complex with 35% aq. H₂O₂ as the oxidant. The utility of the current method was demonstrated by asymmetric gram-scale synthesis of drug molecule (R)-modafinil. Moreover, a possible working mode was provided to elucidate the chiral induction.

Full text of DOI:10.1039/d0cc00434k

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DOI: 10.1039/D0CC00434K
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Chiral N,N-dioxide–iron(III)-catalyzed asymmetric sulfoxidation
with hydrogen peroxide
Fang Wang, Lili Feng, Shunxi Dong,* Xiaohua Liu and Xiaoming Feng*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A highly enantioselective sulfoxidation of various sulfides has been
achieved by a N,N-dioxide–iron(III) complex with 35% aq. H2O2 as
the oxidant. The utility of current method was demonstrated by
asymmetric gram-scale synthesis of drug molecule (R)-modafinil.
Moreover, a possible working mode was provided to elucidate the
chiral induction.
(a) Representative drugs containing sulfoxide moiety
MeO
O
S
O
O
Me
OMe
N
Ph
S
NH2
N
H
Me
Ph
(R)-modafinil
N
O
esomprazole
S
Me
H
O Me
OCH2CF3
N
Optically active sulfoxides are highly important molecules
because of their wide application in asymmetric synthesis1,2 and
frequent existence in many pharmaceuticals (Scheme 1a).3 Over
the past several decades, the synthesis of chiral sulfoxides has
attracted considerable interest and various methods have been
developed.4 Among all strategies established so far, catalytic
asymmetric sulfoxidation of prochiral sulfides by metal-based
catalysts is one of the most attractive and generalized routes for
the preparation of enantioenriched chiral sulfoxides. Since the
pioneered works by Kagan5a-b and Modena,6 a huge spurt of
progress has been made in this research area, and various Lewis
acid salts in combination with chiral diols, Schiff bases, and
salen-type ligands have been employed to promote the reaction
in the presence of different oxidants, supplying numerous
functionalized chiral sulfoxide compounds.4 Remarkably, the
demand of efficient and green catalytic systems for
enantioselective oxidation of sulfides is continuously growing in
line with toughening economic and environmental constraints.
In this context, nontoxic and inexpensive iron complexes7 have
been developed successfully by the group of Bolm8a-c and
S
Me
N
H
N
HOOC
F
(R)-lanoprazole
(R)-sulindac
(b) Asymmetric oxidation of sulfides catalyzed by chiral Fe(OTf)3/N,N'-dioxides complex
R2
S
O
S
R2
FeIII/N,N'-dioxides
S
R2
HO
R1
R1
R1
35% aq. H2O2
O
X
2
1
Fe
O
O
*
31 examples
up to 98% yield
up to 99% ee
*
O
O
Scheme 1. Representative drugs bearing sulfoxide unit and our method for the
asymmetric synthesis of chiral sulfoxides.
recent reports on enantioselective rearrangements10c,d
involving sulfide derivatives, we envisioned that N,N-dioxide–
metal complex11 developed by our group was potential to be an
efficient catalyst for exerting the oxidation of unsymmetric
sulfides. As depicted in Scheme 1b, with H2O2 as the oxidant,
N,N-dioxide–metal–OOH complex could be formed in-situ,
which subsequently works as the possible active specie to
oxidize the prochiral sulfides to chiral sulfoxides by
discriminating the heterotopic lone pairs on sulfur. Herein, we
wish to disclose our effort along this line. Chiral N,N-dioxide–
iron(III) complex12 was found to be efficient as the catalyst to
mediate the proposed sulfoxidation reaction with H2O2 as the
terminal oxidant. Under the optimal conditions, an array of aryl
alkyl sulfides and dialkyl sulfides converted to the
corresponding chiral sulfoxides in moderate to good yield with
high enantioselectivity. The utility of the current method was
9
others,8d-f using environmentally benign H2O2 as a terminal
oxidant. Despite of these significant achievements, there still
leaves room for further improvement in terms of chiral ligands,
catalytic efficiency and substrate scope.
Inspired by our previous works on the asymmetric oxidation
of ,-unsaturated carbonyl compounds10a,b as well as our
Key Laboratory of Green Chemistry & Technology, Ministry of Education,
College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
E-mail: dongs@scu.edu.cn, xmfeng@scu.edu.cn； Fax: +86 28 85418249
Electronic Supplementary Information (ESI) available. CCDC 1975799. For ESI and
crystallographic data in CIF or other electronic format see DOI:10.1039/x0xx00000x
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Table 1. Optimization of the reaction conditionsa
T
able 2. Substrate scope of aromatic group in sulfidesa
View Article Online
DOI: 10.1039/D0CC00434K
O
S
O
O
O
Fe(OTf)3/L-PiPr2-Ad
(1:1.2, 5 mol%)
S
S
S
S
ligand/metal salt
R1
R1
35% aq. H2O2 (6 equiv)
THF, 25 °C, 4 h
35% aq. H2O2 (6 equiv)
THF, 25 °C
1b–1v
1a
2b–2v
2a
3a
Entry
1
R1
2-F
2-Cl
2-Br
3-Cl
3-Br
4-F
4-Cl
4-Br
4-Me
4-OMe
4-OH
4-OSi(iPr)3
4-OBn
4-NH2
4-NHBoc
4-NO2
4-CO2Me
4-COMe
2-naphthyl
2-indolyl
5-MeO-1H-
T(C)
25
25
25
25
25
25
25
25
0
t (h)
4
4
4
4
4
4
4
6
12
12
12
14
8
Yield(%)b
91 (2b)
98 (2c)
98 (2d)
90 (2e)
92 (2f)
70 (2g)
81 (2h)
79 (2i)
97 (2j)
96 (2k)
90 (2l)
61 (2m)
86 (2n)
90 (2o)
92 (2p)
66 (2q)
80 (2r)
60 (2s)
76 (2t)
88 (2u)
32 (2v)
ee (%)c
87
84
84
99
99
98
98
99
99
99
83
89
96
72
92
96
98
99
90
90
99
n
n
N
N
O
O
2b
N
N
O
O
O
O
N
N
3
4
5c
H
H
O
O
Ar
Ar
N
N
H
H
L-PrPr2: R = 2,6-iPr2C6H3, n = 1
L-PiEt2: R = 2,6-Et2C6H3, n = 2
L-PiEt2-Me: R = 2,6-Et2-4-MeC6H2, n = 2
L-PiPr2: R = 2,6-iPr2C6H3, n = 2
L-PiPr3: R = 2,4,6-iPr3C6H2, n = 2
L-PiPr2-Ad: R = 2,6-iPr2-4-(1-adamantyl)C6H2, n = 2
Ar
L-RaPr2: Ar = 2,6-iPr2C6H3
Ar
6
7c
8b
Entry
Ligand
L-PiPr2
L-PiPr2
Metal salt
Fe(OTf)3
Fe(ClO4)3·H2O
Fe(acac)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Yield (%)b ee (%)c
9
10
11
12
13
14
15
16b
17
18
19
20
21
0
1
2
3
4
5
6
7
8
9d
10e
52
42
32
30
27
55
61
70
70
80
63
10
0
25
35
35
25
0
35
35
35
35
40
35
L-PiPr2
L-PrPr2
L-RaPr2
L-PiEt2
7
15
4
53
56
87
93
98
98
20
18
20
22
18
48
L-PiPr3
L-PiPr2-Ad
L-PiPr2-Ad
L-PrPr2
Fe(OTf)3
Fe(OTf)3
a The reactions were performed with 1a (0.1 mmol), 35% aq. H2O2 (0.6 mmol), and
ligand/metal salt (1:1, 10 mol%) in THF (1.0 mL) at 25 °C for 4 h. b Isolated yield. c
Determined by HPLC analysis on a chiral stationary phase. Metal salt/ligand
(1:1.2, 10 mol%). e Metal salt/ligand (1:1.2, 5 mol%) in THF (0.2 M).
benzo[d]imidazolyl
d
a
The reactions were performed with Fe(OTf)3/L-PiPr2-Ad (1:1.2, 5 mol%), 1 (0.1
mmol) and 35% aq. H2O2 (0.6 mmol) in THF (0.5 mL). b Fe(OTf)3/L-PiPr2-Ad (1:1.2,
10 mol%). c Fe(OTf)3/L-PiPr2-Ad (1:1.2, 2.5 mol%).
demonstrated by the asymmetric gram-scale synthesis of drug
molecule (R)-modafinil.
loading was decreased to 5 mol% and reaction concentration
was increased to 0.2 M. Therefore, our optimal reaction
conditions were established as Fe(OTf)3/L-PiPr2-Ad (1:1.2, 5
mol%), sulfide and six equivalents of 35% aq. H2O2 in THF (0.2
M) at 25 C for 4 h. It should be noted that a small amount of
sulfone 3a was generated through over-oxidation in the current
system, which partly contributed to the obtained high
enantioselectivity via kinetic resolution process (for further
details, see ESI, Page 12). The absolute configuration of product
2a was assigned to be (S) by comparing with the optical rotation
value reported in the literature.8c
With the optimized reaction conditions in hand, the substrate
scope of sulfides was then evaluated. As illustrated in Table 2,
various methyl substituted sulfides bearing different aromatic
groups reacted with aqueous hydrogen peroxide smoothly,
providing the respective enantioenriched sulfoxides in
moderate to good yield (60-98%) with high enantioselectivity
(72-99%). Generally, the position of substituents exhibited a
significant effect on the chiral control of the reaction. Meta- and
para-substituted sulfides (1e and 1f, 1g-1k) gave higher
enantioselectivity than orthro-substituted ones (1b-1d).
Although the electronic nature of substituents on the Ar moiety
has limited influence on the enantioselectivity, over-oxidation
was usually heavier for electron-rich sulfides (1j and 1k) than
electron-deficient ones (1g, 1h and 1i). This issue could be partly
solved by lowering the reaction temperature. At 0 °C, the
Initially, phenyl methyl sulfide (1a) was chosen as the model
substrate to optimize the reaction conditions. Various metal
salts were screened by coordinating with L-PiPr2 in THF at 25 C
(For details, See ESI, Page 2). To our delight, promising results
(52% yield with 63% ee) were obtained by using L-PiPr2/Fe(OTf)3
complex as the catalyst (Table 1, entry 1). Further examination

of Fe(III) with different counteranions, for instance, ClO4 and
acac, was carried out, however, no better results were afforded
(Table 1, entries 2 and 3).13 Next, the investigation of the chiral
backbone of the N,N-dioxide ligands showed that S-pipecolic
acid derived L-PiPr2 was superior to L-proline-derived L-PrPr2
and L-ramipril-derived L-RaPr2 in term of enantioselectivity and
reactivity (Table 1, entry 1 vs. entries 4 and 5). Varying the
amide moiety of the N,N-dioxide ligands indicated that with the
increase of steric hindrance of the amide unit, the
enantioselectivity of the reaction increased gradually (Table 1,
entries 6-8). N,N-Dioxide with 2,6-iPr2-4-(1-adamantyl)C6H2
group afforded the corresponding sulfoxide 2a with 70% yield
and 93% ee. Subsequent investigation of the ratio of metal salt
with ligand exhibited that a slight excess of ligand was benefit
to the chiral control (Table 1, entry 12, 70% yield, 98% ee).14
Other parameters including solvent, temperature were
screened as well, but no better results were provided (for
further details, see ESI, Page 3-5). A higher yield (80%) with
maintained enantioselectivity was delivered when the catalyst
2 | J. Name., 2012, 00, 1-3
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Table 3. Substrate scope of methyl groupa
Fe(OTf)3/ent-L-PiEt2-Me
(1:2, 10 mol%)
35% aq. H2O2 (6 equiv)
View Article Online
O
O
O
DOI: 10.1039/D0CC00434K
S
S
O
S
NH2
NH2
Fe(OTf)3/L-PiPr2-Ad
(1:1.2, 10 mol%)
S
MTBE (0.2 M)
35 °C, 8 h
R2
R2
35% aq. H2O2 (6 equiv)
THF, 25 °C
1w-1ad
2w-2ad
1ae
1.028 g, 4.0 mmol
2ae (R)-modafinil
1.004 g, 92% yield, 87% ee
O
S
O
O
S
O
S
S
Et
Bn
11
Scheme 2. Gram-scale synthesis of (R)-modafinil.
2xb, 25 °C, 8 h
60% yield, 76% ee
O
2w, 25 °C, 5 h
84% yield, 92% ee
2y, 0 °C, 24 h
75% yield, 94% ee
2z, 25 °C, 8 h
60% yield, 63% ee
presence of Fe(OTf)3-ent-L-PiEt2-Me (1:2, 10 mol%) in methyl
tert-butyl ether (MTBE) at 35 C for 8 h, and the corresponding
sulfoxide 2ae was yielded in 94% yield with high
enantioselectivity (87% ee). Remarkably, the gram-scale up of
the reactions (4 mmol scale) allows readily preparation of large
quantities of (R)-modafinil (1.004g, 92% yield, 87% ee).
O
O
S
O
S
O
S
S
2
Ar
iBu
Cy
N
H
Ar = 4-CF3OC6H4
2add, 25 °C, 8 h
2aac, 25 °C, 8 h
2acd, 25 °C, 20 h
2ab, 25 °C, 5 h
68% yield, 84% ee 81% yield, 74% ee
65% yield, 56% ee
76% yield, 90% ee
According to the previous reports,15 two possible
intermeidates, either a peroxo FeIII-OOH or high valent iron–
oxido, were postulated to be the catalytically active species. To
gain direct evidence for the mechanism, a series of mechanistic
experiments were performed. Firstly, EPR spectrum of L-PiPr2-
Ad-Fe(OTf)3 (1:1.2) with 20-100 equivalents of 35% aq. H2O2 was
recorded at 120 K (see ESI, Page 7), it was indicated that only a
high spin FeIII specie (g = 4.4) was detected.16 Meanwhile after
addition of H218O even in large excess, the only reaction product
detected by HRMS was PhS(16O)Me (see ESI, Page 9, for
details).17 UV-Vis absorption spectrum showed that the addition
of H2O2 did not lead to new peaks along with decay of the 284
nm absorption in UV-Vis absorption spectrum of L-PiPr2-Ad-
Fe(OTf)3 (1:1.2) in THF at room temperature (see ESI, Page 8),.18
The above results tempted us to conclude that the high spin
FeIII-OOH compound was probably to be the real key active
specie in present system.15b,c,19
Based on the X-ray crystal structure of L-PiPr2-Ad/Fe(OTf)3
complex20 and the configuration of product 2a as well as above
experimental results, a possible transition state model was
proposed as depicted in Scheme 3. The tetradentate L-PiPr2-Ad,
and OOH coordinate with Fe(III) in an octahedral fashion. Due
to the steric repulsion between the aryl groups in the sulfide
with the neighboring 2,6-diisopropyl-4-(1-adamantyl)phenyl
group of the ligand, discrimination of the heterotopic lone pairs
is available and S-configured sulfoxide was formed preferably.
a The reactions were performed with Fe(OTf)3/L-PiPr2-Ad (1:1.2, 10 mol%), 1 (0.1
mmol) and 35% aq. H2O2 (0.6 mmol) in THF (0.5 mL). b L-PiPr3 was used instead of
L-PiPr2-Ad. c L-PiPr2 was used instead of L-PiPr2-Ad. d Fe(OTf)3/L-PiPr2-Ad (1:1.2, 5
mol%).
reaction of electron-rich sulfide 1j or 1k performed well,
delivering the desired products 2j and 2k with good yield and
high ee value (2j, 97% yield, 99% ee; 2k, 96% yield, 99% ee). For
meta-bromo or para-chloro substituted sulfides 1f and 1h, the
catalyst loading could be reduced to 2.5 mol% with equally good
results (2f, 92% yield, 99% ee; 2h, 81% yield, 98% ee). It should
be noted that many types of functionalized sulfides including
NH2, NHBoc, OH, BnO, OSi(iPr)3, CO2Me and CH3CO groups were
compatible in this transformation, good results were afforded
(2l-2s). In general, the substrates with protected hydroxyl or
amino group yielded the product with higher enantioselectivity
than the ones with hydroxyl or amino group. 2-naphthyl
substituted sulfide 1t was suitable in current system, giving the
expected product 2t in 76% yield with 90% ee. The reaction of
sulfides bearing hetero-aromatic ring, such as indole or 1H-
benzo[d]imidazole moiety, took place well, delivering the
expected products 2u and 2v in high enantioselectivity (90% ee
and 99% ee, respectively).
Further investigation was conducted for phenyl sulfides with
different alkyl substituents. Changing the methyl group to ethyl
or benzyl group, the corresponding products were obtained in
high yield with excellent ee value (Table 3, 92% and 94 % ee for
2w and 2y). Long chain alkyl substituted substrate (1x) as well
as the the substrates with sterically bulky cyclopropyl (1z) or iBu
(1aa) substituent resulted in decreased reactivity (60-65% yield)
and enantioselectivity (56-76% ee). Under slightly modified
conditions, alkene substituted sulfoxides (2ab and 2ac) were
generated in decent yield with reasonable ee value.
Furthermore, the Fe(III)-H2O2-based system was capable of
promoting asymmetric sulfoxidation of alkyl alkyl substituted
sulfides, yielding the desired product 2ad with good results.
The practical synthetic relevance of current method was
demonstrated by enantioselective synthesis of biologically
active sulfoxide (R)-modafinil 2ae (Scheme 2), which is used for
the treatment of sleep disorders. As shown in Scheme 2, the
oxidation of sulfide 1ae with H2O2 occurred smoothly in the
S
HO
O
O
O
HN
N
Fe
O
O
X
NH
N
X = H2O or OTf
Scheme 3. Proposed working model.
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38, 2282; (g) C.-L. Sun, B.-J. Li and Z.-J. Shi, Chem. Rev., 2011,
Conclusions
111, 1293; (h) K. Gopalaiah, Chem. Rev., 2013, 1V1ie3w, A3r2tic4le8O. nline
DOI: 10.1039/D0CC00434K
8
For selected examples, see: (a) J. Legros and C. Bolm, Angew.
Chem., Int. Ed., 2003, 42, 5487; (b) J. Legros and C. Bolm,
Angew. Chem., Int. Ed., 2004, 43, 4225; (c) J. Legros and C.
Bolm, Chem. Eur. J., 2005, 11, 1086; (d) H. Egami and T.
Katsuki, J. Am. Chem. Soc., 2007, 129, 8940; (e) A. Jalba, N.
Régnier and T. Ollevier, Eur. J. Org. Chem., 2017, 1628. (f) J.
Chen, A. Draksharapu, D. Angelone, D. Unjaroen, S. K.
Padamati, R. Hage, M. Swart, C. Duboc and W. R. Browne, ACS
In summary, we have developed an efficient chiral N,N-
dioxide/Fe(OTf)3 complex catalytic system for the asymmetric
sulfoxidation of a series of alkyl aryl sulfides. The corresponding
sulfoxides were obtained in moderate to high yield (60-98%)
and ee value (56-99%), and the reaction is suitable for the
asymmetric synthesis of bioactive drug (R)-modafinil.21 Further
exploration of the reaction mechanism is currently underway.
We acknowledge the National Natural Science Foundation of
China (No. 21801175) for financial support.
Catal., 2018, 8, 9665
.
9
For a recent review on catalytic asymmetric oxygenation with
H2O2, see: K. P. Bryliakov, Chem. Rev., 2017, 117, 11406.
10 (a) Y. Y. Chu, X. H. Liu, W. Li, X. L. Hu, L. L. Lin and X. M. Feng,
Chem. Sci., 2012, 3, 1996; (b) Y. Y. Chu, X. Y. Hao, L. L. Lin, W.
L. Chen, W. Li, F. Tan, X. H. Liu and X. M. Feng, Adv. Synth.
Catal., 2014, 356, 2214; (c) X. B. Lin, Y. Tang, W. Yang, F. Tan,
L. L. Lin, X. H. Liu and X. M. Feng, J. Am. Chem. Soc., 2018, 140,
3299; (d) X. B. Lin, W. Yang, W. K. Yang, X. H. Liu and X. M.
Feng, Angew. Chem., Int. Ed., 2019, 58, 13492.
Conflicts of interest
There are no conflicts to declare.
11 For reviews of the metal/N,N′-dioxide complex: (a) X. H. Liu,
L. L. Lin and X. M. Feng, Acc. Chem. Res., 2011, 44, 574; (b) X.
H. Liu, L. L. Lin and X. M. Feng, Org. Chem. Front., 2014, 1, 298;
(c) X. H. Liu, H. F. Zheng, Y. Xia, L. L. Lin and X. M. Feng, Acc.
Chem. Res., 2017, 50, 2621; (d) X. H. Liu, S. X. Dong, L. L. Lin
and X. M. Feng, Chin. J. Chem., 2018, 36, 791.
12 For our previous work on iron catalysis: (a) P. F. Zhou, Y. F. Cai,
X. Zhong, W. W. Luo, T. F. Kang, J. Li, X. H. Liu, L. L. Lin and X.
M. Feng, ACS Catal., 2016, 6, 7778; (b) P. F. Zhou, L. L. Lin, L.
Chen, X. Zhong, X. H. Liu and X. M. Feng, J. Am. Chem. Soc.,
2017, 139, 13414; (c) T. Y. Huang, X. H. Liu, J. W. Lang, J. Xu, L.
L. Lin and X. M. Feng, ACS Catal., 2017, 7, 5654; (d) W. D. Cao,
X. H. Liu, R. X. Peng, P. He, L. L. Lin and X. M. Feng, Chem.
Commun., 2013, 49, 3470.
13 At current stage, we have no clear-cut explanation on the
vastly different reaction outcomes caused by counteranions
in iron salts. Several possible reasons are provided: (1) the
different Lewis acidity of the iron salt with diverse
counterions, (2) the dissociation ability of counteranions and
(3) OTf may take part in the following chiral determining step
through interaction with H2O2.
14 We thought that excess ligand was used to coordinate trace
amount Fe(OTf)3 to suppress its racemic background reaction.
15 For the mechanistic studies on iron-catalyzed sulfoxidation
with H2O2, see: (a) G. Roelfes, M. Lubben, R. Hafe, L. Q., Jr. and
B. L. Feringa, Chem. Eur. J., 2000, 6, 2152; (b) J. Cho, S. Jeon, S.
A. Wilson, L. V. Liu, E. A. Kang, J. J. Braymer, M. H. Lim, B.
Hedman, K. O. Hodgson, J. S. Valentine, E. I. Solomon and W.
Nam, Nature, 2011, 478, 502; (c) Y. M. Kim, K.-B. Cho, J. Cho,
B. Wang, C. Li, S. Shaik and W. Nam, J. Am. Chem. Soc., 2013,
135, 8838.
16 (a) R. D. Dowsing and J. F. Gibson, J. Chem. Phys., 1969, 50,
294; (b) C. A. Reed and F. Guiset, J. Am. Chem. Soc., 1996, 118,
3281; (c) L. Simkhovich, I. Goldberg and Z. Gross, Inorg. Chem.,
2002, 41, 5433.
17 (a) L. P. Hager, D. L. Doubek, R. M. Silverstein, J. H. Hargis and
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19 Molecular ion peak of [L-PiPr2-Ad/Fe-OOH/OTf/CH3OH] was
found in the spectrum of HRMS, See ESI page 10 for details.
20 CCDC 1975799 [L-PiPr2-Ad/Fe(OTf)3 complex].
21 As suggested by one reviewer, a detailed comparison of
current method with other iron-based catalyst system was
provided in ESI, Page 28.
Notes and references
1
For selected reviews on the application of chiral sulfoxides as
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Rev., 1995, 95, 1717; (b) H. Pellissier, Tetrahedron, 2006, 62,
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Klose, R. Oost, J. Neuhaus and N. Maulide, Chem. Rev., 2019,
119, 8701.
For selected reviews on the application of chiral sulfoxides as
chiral ligands or catalysts, see: (a) R. Tokunoh, M. Sodeoka, K.-
i. Aoe and M. Shibasaki, Tetrahedron Lett., 1995, 36, 8035; (b)
H. Pellissier, Tetrahedron, 2007, 63, 1297; (c) M. Mellah, A.
Voituriez and E. Schulz, Chem. Rev., 2007, 107, 5133; (d) G.
Sipos, E. E. Drinkel and R. Dorta, Chem. Soc. Rev., 2015, 44,
3834; (e) S. Otocka, M. Kwiatkowska, L. Madalińska and P.
Kiełbasiński, Chem. Rev., 2017, 117, 4147.
2
3
4
For a summary of sulfur containing pharmaceuticals, see:
https://njardarson.lab.arizona.edu/sites/njardarson.lab.arizo
na.edu/files/Sulfur%20Containing%20Pharmaceuticals2.pdf.
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(b) J. Legros, J. R. Dehli and C. Bolm, Adv. Synth. Catal., 2005,
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For selected reviews on the synthesis of optically active
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2003, 103, 3651; (b) E. Wojaczyńska and J. Wojaczyński,
Chem. Rev., 2010, 110, 4303; (c) G. E. O’Mahony, P. Kelly, S. E.
Lawrence and A. R. Maguire, ARKIVOC, 2011, i, 1; (d) G. E.
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5
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Kagan, J. Am. Chem. Soc., 1984, 106, 8188.
6
7
F. D. Furia, G. Modena and R. Seraglia, Synthesis, 1984, 325.
For books on iron catalysis, see: (a) B. Plietker, Iron Catalysis
in Organic Chemistry: Reactions and Applications, Wiley-VCH,
Weinheim, 2008; (b) J. I. PadrÓn and V. S. MartÍn, in Topics in
Organometallic Chemsitry, Iron Catalysis: Fundamentals and
Applications, Springer-VBH, 2011. For selected reviews on
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4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0CC00434K
O
S
S
R2
R2
Fe(OTf)3/L-PiPr2-Ad
R1
R1
35% H2O2,THF( 0.2 M)
31 examples, up to
98% yield, 99% ee
N
N
O
O
O
O
N
N
H
H
Ar
Ar
L-PiPr2-Ad: Ar = 2,6-iPr2-4-(1-adamantyl)C6H2
Gram-scale synthesis of drug molecule (R)-modafinil was accomplished by chiral N,N-
dioxide–iron(III) complex catalyzed asymmetric sulfoxidation.