Enantioselective nitrene transfer to sulfides catalyzed by a chiral iron complex

Article abstract of DOI:10.1002/anie.201304451

Iron works: Enantioselective nitrene transfer to sulfide was accomplished by a chiral iron(III)/PyBOX catalyst (see scheme). Various sulfimides were thus obtained in high enantioselectivities and yields. Applications of this protocol to the syntheses of enantioenriched sulfoximines and an epoxide were also demonstrated. Copyright

Full text of DOI:10.1002/anie.201304451

Angewandte
Chemie
Communications
Sulfimides
Iron works: Enantioselective nitrene
transfer to sulfide was accomplished by
a chiral iron(III)/PyBOX catalyst (see
scheme). Various sulfimides were thus
obtained in high enantioselectivities and
yields. Applications of this protocol to the
syntheses of enantioenriched sulfoxi-
mines and an epoxide were also demon-
strated.
J. Wang, M. Frings,
C. Bolm*
&&&& — &&&&
Enantioselective Nitrene Transfer to
Sulfides Catalyzed by a Chiral Iron
Complex
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
DOI: 10.1002/anie.201304451
Sulfimides
Enantioselective Nitrene Transfer to Sulfides Catalyzed by a Chiral
Iron Complex**
Jun Wang, Marcus Frings, and Carsten Bolm*
Sulfimides are nitrogen analogues of sulfoxides.[1] In organic
synthesis, they serve as useful intermediates[1,2] and have been
applied as efficient ligands for metal catalysts.[3] Because of
their unique biological properties,[1a,4] sulfimides have also
gained considerable attention in agricultural science and
medicinal chemistry. As sulfoxides, sulfimides are chiral and
have a stereogenic center at the sulfur atom if they originate
from unsymmetrically substituted sulfides. Although sulfi-
mides can be easily synthesized by various means,[1,5] their
preparation in enantioenriched form is still challenging. The
most prominent strategies involve the use of chiral auxiliar-
ies[3a,6] or reagents.[7] All of those, however, require stoichio-
metric amounts of chiral compounds that are usually pre-
pared by multi-step syntheses.
and iron(III) acetylacetonate ([Fe(acac)3], 3a) were tested.
Although in most cases the reaction proceeded smoothly to
give the desired product 2a, only (S,S)-2,6-bis(4-phenyl-2-
oxazolinyl)pyridine ((S,S)-Ph-PyBOX, L1) led to a promising
enantiomeric ratio (e.r.) of 77:23 (Table 1, entry 1). Some
other PyBOX ligands were also evaluated (Table 1, entries 2–
5), but the reactions proceeded with poor enantiocontrol,
implying that the phenyl groups in L1 were crucial for
achieving the observed enantioselectivity. Although the use of
iron(II) acetylacetonate ([Fe(acac)2]) instead of [Fe(acac)3]
gave almost the same e.r. (75:25), the reactivity was reduced
(Table 1, entry 6). Essentially racemic products were obtained
with Fe(ClO4)2 and Fe(OTf)2 (Table 1, entries 7 and 8).[13] The
same was true when other metal acetylacetonates ([Cu-
The field of catalytic asymmetric sulfimidation is scarcely
explored, and only very few catalyst systems have been
documented. For example, Uemura, Taylor and their co-
workers disclosed the use of chiral copper(I)/bis(oxazoline)
catalysts.[8] However, only sterically hindered aryl benzyl
sulfides gave satisfying results. Subsequently, Katsuki and co-
workers introduced chiral manganese(III)/salen[9] and ruth-
enium(II)/salen[10] (or salalen)[11] complexes as asymmetric
sulfimidation catalysts. Excellent results were achieved, but
the synthesis of salen ligands proved cumbersome.
Table 1: Optimization of reaction conditions.[a]
Entry
Metal compound
Ligand
t
Yield [%]
e.r.[b]
1
2
3
4
5
6
7
8
[Fe(acac)3] (3a)
[Fe(acac)3] (3a)
[Fe(acac)3] (3a)
[Fe(acac)3] (3a)
[Fe(acac)3] (3a)
[Fe(acac)2]
Fe(ClO4)2
Fe(OTf)2
[Cu(acac)2]
[Mn(acac)3]
[Ru(acac)3]
3b
(S,S)-L1
(S,S)-L2
(S,S)-L3
(S,S)-L4
(S,S)-L5
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(S,S)-L1
(R,R)-L1
3 h
88
90
94
99
90
75
71
89
63
24
45
97
99
96
99
98
77:23
57:43
56:44
50:50
50:50
75:25
52:48
51:49
52:48
52:48
55:45
82:18
86:14
90:10
91:9
12 h
12 h
5 h
22 h
14 h
1 h
10 min
14 h
4 h
17 h
1 h
Inspired by the early work of Bach[5a,b] and encouraged by
our findings that simple iron(II) and iron(III) compounds
could effectively catalyze non-asymmetric sulfide imida-
tions,[5h–j] we decided to focus our search on chiral iron
complexes for asymmetric versions of such reactions. Herein,
we report that iron(III)/PyBOX combinations are highly
effective catalysts for the aforementioned transformations.
Noteworthy, this is the first iron-catalyzed enantioselective
sulfimidation reported to date, despite many other break-
throughs in asymmetric iron catalysis.[12,13]
9
10
11
12
13
14
15[c]
16[c,d]
3c
3d
3d
3d
6 h
6 h
2 h
16 h
The asymmetric imidation of thioanisole (1a) with N-(p-
=
tolylsulfonyl)imino phenyliodinane (PhI NTs) in acetonitrile
7:93
was selected as the benchmark reaction for our preliminary
screening. Various catalysts formed in situ from chiral ligands
=
[a] Reaction conditions: 1a (0.1 mmol), PhI NTs (0.12 mmol), ligand
(0.01 mmol), metal compound (0.01 mmol), MeCN (1.0 mL), at 08C (no
exclusion of air and moisture). [b] The enantiomeric ratios (e.r.) were
determined by high-performance liquid chromatography (HPLC) analy-
sis using a chiral stationary phase. [c] Acetone was used as solvent.
[d] The reaction was run at À208C. The absolute configuration of the
major enantiomer was determined to be (S) by comparing the specific
rotation with the reported value after transforming 2a to sulfoximine 4a
(Scheme 4).
[*] Dr. J. Wang, M. Frings, Prof. Dr. C. Bolm
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52056 Aachen (Germany)
E-mail: Carsten.Bolm@oc.RWTH-Aachen.de
Homepage: http://bolm.oc.rwth-aachen.de/
[**] J.W. acknowledges support by the Alexander von Humboldt
Foundation. We thank Manuel Jçrres for his help in the HPLC
analyses and Dr. Jing Hu for her kind assistance during this
research. We also appreciate the proofreading of the manuscript by
Dr. Daniel L. Priebbenow, Isabelle Thomꢀ, and Dr. Ingo Schiffers.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201304451.
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
(acac)2], [Mn(acac)3], and [Ru(acac)3]) were applied (Table 1,
entries 9–11).
Next, a series of iron(III) acetylacetonate derivatives (3b–
d) were prepared and investigated (Table 1, entries 12–14).
As expected, the enantioselectivity in the formation of 2a
depended on both the steric and electronic properties of the
acetylacetonate ligand. Finally, iron(III) 4-chloro-2,6-
dimethyl-3,5-heptanedionate ([Fe(dmhdCl)3], 3d) proved
optimal, providing 2a with an e.r. of 90:10 in 96% yield
(Table 1, entry 14).[14] Switching to acetone as a solvent
showed its slight superiority over acetonitrile (Table 1,
entry 15 versus entry 14). The enantioselectivity was further
improved by lowering the reaction temperature to À208C
(Table 1, entry 16).[15] Pleasingly, the reaction could be
performed in air, and no particular protection from moisture
was necessary. Varying the concentration, applying additives,
or using some other iminoiodinane reagents[16] did not lead to
improvements of yield and e.r. Thus, the optimal reaction
conditions involved: [Fe(dmhdCl)3] (10 mol%), (R,R)-Ph-
=
PyBOX (10 mol%), sulfide (1.0 equiv), PhI NTs (1.2 equiv),
Scheme 1. Investigation of the substrate scope (part one).
acetone (0.1m), À208C (without exclusion of moisture and
air).[17]
To evaluate the substrate scope, various alkyl phenyl
sulfides with linear alkyl chains were first subjected to the
optimized reaction conditions (Scheme 1). In general, both
the e.r. values (up to 96:4) and the yields (> 80–98%) were
high. The data remained essentially constant when the length
of the alkyl chain was varied from C1 (methyl) to C8 (octyl).
The asymmetric imidation of phenyl tetradecanyl sulfide (1i)
to give sulfimide 2i (e.r. of 91:9; 23% yield) was less effective
with respect to the yield, which was probably due to the poor
solubility of the sulfide under the reaction conditions. A
terminal phenyl group at an n-propyl substitu-
ent (as in 1j) had no negative effect, and the
corresponding product 2j was obtained with
an e.r. of 94:6 in 82% yield. As exemplified by
the asymmetric imidation of sulfides 1c and
1d, a reduction of the catalyst loading from
10 mol% to 5 mol% was tolerated. Compara-
ble yields and slightly decreased enantioselec-
tivities in the respective formation of 2c and
2d were observed.
sulfides 1n–s, the catalyst tolerated all substitution patterns.
Generally, electronic properties only slightly affected the
enantiocontrol of the reaction. However, the presence of the
strongly electron-withdrawing nitro group in sulfide 1v
resulted in a lower enantioselectivity in the formation of the
corresponding sulfimide 2v (e.r. of 83:17). The reduced
electron density around the sulfur atom caused by the nitro
group could be partially compensated by a positive inductive
effect achieved by chain extension of the alkyl substituent.
Thus, compared with the formation of methyl-substituted 2v,
Finally, branched-alkyl phenyl sulfides
were tested in this series. While 3-methylbutyl
phenyl sulfide (1l) was imidated to give 2l with
an e.r. value and yield in the expected range
(94:6; 86%), the nitrene transfer to isopropyl
phenyl sulfide (1k) appeared to be hampered
by the branching at the a position leading to
sulfimide 2k with an e.r. of only 80:20. This
value as well as the moderate yield (49%)
indicate the significant influence of steric
effects during the asymmetric imidation by
the chiral iron catalyst.
Next, various alkyl aryl sulfides bearing
electron-donating or electron-withdrawing
substituents on the arene were tested
(Scheme 2). As revealed by the results of
reactions with ortho-, meta-, or para-tolyl alkyl Scheme 2. Investigation of the substrate scope (part two).
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
a higher enantioselectvity was observed in the imidation of n-
propyl-bearing sulfide 1w to give 2w (e.r. of 83:17 vs. e.r. of
89:11).
ment of this product with concentrated sulfuric acid (followed
by basification with sodium hydroxide) gave N-unprotected
sulfoximine 5a in 94% yield.[22] Analyzing the e.r. values of
each compound confirmed the stereospecificity of both
synthetic steps, the oxidation and the deprotection.[20]
Finally, condensed aromatic, heteroaryl, and sterically
constrained substrates were investigated. 2-Naphthyl n-
propyl sulfide (1z) could be converted to sulfimide 2z with
an e.r. of 91:9 in 70% yield. To our delight, 2-(alkylthio)pyr-
idines 1aa and 1ab were also applicable, affording the
corresponding sulfimides 2aa and 2ab with an e.r. of 92:8
and an e.r. of 91:9, respectively.[18] Although the yield (49%)
was only moderate because of a competing imidation of the
sulfur atom in the thiophene ring, 2-(methylthio)thiophene
(1ac) was converted to 2ac with high enantioselectivity (e.r.
of 93:7). Catalyses using 2,3-dihydrobenzothiophene (1ad),
benzyl methyl sulfide (1ae), and cyclohexyl methyl sulfide
(1af) as starting materials gave the corresponding products in
low to moderate yields and enantioselectivities.
Recently, we prepared a series of bioactive sulfoximines
and demonstrated their potential applications in medicinal
chemistry.[23] It was shown that the biological response
significantly depended on the absolute configuration of the
stereogenic sulfur atom.[23c] For obtaining those results,
racemic compounds were prepared, which subsequently had
to be resolved by HPLC using a chiral stationary phase. We
now utilized our newly devised protocol for the iron-catalyzed
asymmetric imidation in the synthesis of enantioenriched
Vioxx analogue 5ah (Scheme 5). To our delight, the enantio-
selective sulfimidation of 1ah[24] proceeded smoothly, gener-
ating sulfimide 2ah with high enantioselectivity (e.r. of 94:6)
in excellent yield (28 h, 96%). Because the oxidation of
sulfimide 2ah to sulfoximine 4ah with NaIO4/RuCl3 proved
In accord with previous findings,[8a,b,10b,c] imidation of
crotyl phenyl sulfide (1ag) resulted in a product that under-
went immediate [2,3]-sigmatropic rearrangement to afford
sulfenamide 2ag (26 h; e.r. of 90:10; 73% yield; Scheme 3).[19]
=
problematic (because of partial C C bond oxidation),
mCPBA was applied as oxidant. In this manner, sulfoximine
4ah was formed chemoselectively in 81% yield. Removal of
the tosyl group with concentrated H2SO4 occurred effortlessly
without affecting any other functional groups, furnishing the
desired sulfoximine 5ah with an e.r. of 90:10 in 99% yield
(Scheme 5).
Scheme 3. Asymmetric imidation of crotyl phenyl sulfide (1ag) fol-
lowed by an immediate [2,3]-sigmatropic rearrangement to give 2ag.
In order to establish the stereochemical path of the
asymmetric catalysis and to demonstrate the synthetic utility
of the method, a few transformations of the sulfimide
products were investigated. Cram and co-workers had
oxidized sulfimide 2n with mCPBA and isolated the corre-
sponding sulfoximine 4n in modest yield (65%) after 24 h.[20]
With the goal to improve the yield and hoping to shorten the
reaction time, we applied NaIO4 as oxidant and a catalytic
amount of RuCl3 for the same transformation, starting from
2n, which was obtained from the catalysis with FeIII/(R,R)-
L1.[21] Product 4n was formed stereospecifically, and the yield
was essentially quantitative (Scheme 4). Comparing the
optical rotations of 2n and 4n with the respective reported
values proved that the oxidation had proceeded with reten-
tion of configuration. Hence, sulfimide (S)-2n resulted in
sulfoximine (R)-4n and for both the e.r. was 93:7. Sulfimide
2a, prepared from thioanisole (1a), was elaborated to N-
tosyl-protected sulfoximine 4a in the same manner. Treat-
Scheme 5. Asymmetric synthesis of sulfoximine-based Vioxx analogue
5ah.
Another application of the iron-catalyzed asymmetric
imidation was illustrated by the enantioselective synthesis of
unsaturated epoxide 6m (Scheme 6).[25] Starting from homo-
allyl phenyl sulfide (1m), the corresponding sulfimide 2m was
obtained with high enantioselectivity (e.r. of 95:5) in 87%
yield after 28 h. The absence of an aziridine confirmed the full
chemoselectivity of the nitrogen transfer (sulfur atom vs.
double bond).[26] Treatment of a mixture of 2m and benzal-
dehyde with NaH gave epoxide 6m with good diastereose-
lectivity (trans:cis = 87:13) and enantioselectivity (e.r. of
88:12 for the trans isomer). Thus, the chirality transfer from
the stereogenic sulfur atom to the two newly generated
stereogenic carbon centers took place with high enantiospe-
cificity (es = 84%).[27]
Scheme 4. Transformation of sulfimides to the corresponding NTs and
NH sulfoximines.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
[4] R. Vanacore, A.-J. L. Ham, M. Voehler, C. R. Sanders, T. P.
Conrads, T. D. Veenstra, K. B. Sharpless, P. E. Dawson, B. G.
Hudson, Science 2009, 325, 1230.
[5] For selected examples, see: a) T. Bach, C. Kçrber, Tetrahedron
Lett. 1998, 39, 5015; b) T. Bach, C. Kçrber, Eur. J. Org. Chem.
1999, 1033; c) W. Ou, Z.-C. Chen, Synth. Commun. 1999, 29,
4443; d) A. L. Marzinzik, K. B. Sharpless, J. Org. Chem. 2001, 66,
594; e) H. Okamura, C. Bolm, Org. Lett. 2004, 6, 1305; f) G. Y.
Cho, C. Bolm, Org. Lett. 2005, 7, 4983; g) G. Y. Cho, C. Bolm,
Tetrahedron Lett. 2005, 46, 8007; h) O. Garcꢀa MancheÇo, C.
Bolm, Org. Lett. 2006, 8, 2349; i) O. Garcꢀa MancheÇo, C. Bolm,
Chem. Eur. J. 2007, 13, 6674; j) O. Garcꢀa MancheÇo, J.
Dallimore, A. Plant, C. Bolm, Org. Lett. 2009, 11, 2429; k) O.
Garcꢀa MancheÇo, J. Dallimore, A. Plant, C. Bolm, Adv. Synth.
Catal. 2010, 352, 309; l) A. Pandey, C. Bolm, Synthesis 2010,
2922.
Scheme 6. Synthesis of the enantioenriched allyl epoxide 6m.
In summary, we have developed the first iron-catalyzed
asymmetric imidation of sulfides with a broad substrate scope.
A variety of optically active sulfimides were prepared in good
yields and enantioselectivities. Both ligand and iron precata-
lyst are readily available. Acetone is used as a cheap solvent
with low toxicity. The reaction is easy to manipulate, as air and
moisture do not have to be excluded. Finally, applications of
the new protocol to the preparation of synthetically relevant
products were demonstrated.
[6] a) G. Celentano, S. Colonna, Chem. Commun. 1998, 701; b) H.
Takada, K. Ohe, S. Uemura, Angew. Chem. 1999, 111, 1367;
Angew. Chem. Int. Ed. 1999, 38, 1288.
[7] a) G. Guanti, C. DellꢁErba, G. Gaiani, Phosphorus Sulfur Relat.
Elem. 1976, 1, 179; b) R. Annunziata, M. Cinquini, S. Colonna, F.
Cozzi, J. Chem. Soc. Perkin Trans. 1 1981, 3118; c) C. DellꢁErba,
M. Novi, G. Garbarino, G. P. Corallo, Tetrahedron Lett. 1983, 24,
1191; d) C. S. Tomooka, E. M. Carreira, Helv. Chim. Acta 2002,
85, 3773; e) F. Collet, R. H. Dodd, P. Dauban, Org. Lett. 2008, 10,
5473.
[8] a) H. Takada, Y. Nishibayashi, K. Ohe, S. Uemura, Chem.
Commun. 1996, 931; b) H. Takada, Y. Nishibayashi, K. Ohe, S.
Uemura, C. P. Baird, T. J. Sparey, P. C. Taylor, J. Org. Chem.
1997, 62, 6512; c) Y. Miyake, H. Takada, K. Ohe, S. Uemura, J.
Chem. Soc. Perkin Trans. 1 1998, 2373.
[9] a) H. Nishikori, C. Ohta, E. Oberlin, R. Irie, T. Katsuki,
Tetrahedron 1999, 55, 13937; b) H. Nishikori, T. Katsuki, Appl.
Catal. A 2000, 194 – 195, 475; c) C. Ohta, T. Katsuki, Tetrahedron
Lett. 2001, 42, 3885.
[10] a) M. Murakami, T. Uchida, T. Katsuki, Tetrahedron Lett. 2001,
42, 7071; b) M. Murakami, T. Katsuki, Tetrahedron Lett. 2002,
43, 3947; c) M. Murakami, T. Uchida, B. Saito, T. Katsuki,
Chirality 2003, 15, 116; d) T. Uchida, Y. Tamura, M. Ohba, T.
Katsuki, Tetrahedron Lett. 2003, 44, 7965; e) Y. Tamura, T.
Uchida, T. Katsuki, Tetrahedron Lett. 2003, 44, 3301.
[11] H. Fujita, T. Uchida, R. Irie, T. Katsuki, Chem. Lett. 2007, 36,
1092.
Experimental Section
Procedure for the iron(III)-catalyzed asymmetric sulfimidation:
[Fe(dmhdCl)3] (0.01 mmol, 6.2 mg), (R,R)-Ph-PyBOX (0.01 mmol,
3.7 mg), and acetone (1 mL) were placed in a test tube equipped with
a magnetic stir bar. The mixture was stirred at room temperature for
30 min. Then, the sulfide (0.1 mmol) was added by syringe. After the
=
mixture was cooled to À208C, PhI NTs (45 mg, 0.12 mmol) was
added in one portion as a solid. The reaction mixture was stirred at
À208C and monitored by thin-layer chromatography (TLC). When
the reaction was finished, the solvent was removed under reduced
pressure, and the sulfimide was purified by column chromatography
on silica gel (60–200 mm). The enantiomeric ratio was determined by
HPLC analysis using a chiral stationary phase.
Received: May 23, 2013
Published online: && &&, &&&&
[12] a) C. Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004, 104,
6217; b) A. Correa, O. Garcꢀa MancheÇo, C. Bolm, Chem. Soc.
Rev. 2008, 37, 1108; c) E. B. Bauer, Curr. Org. Chem. 2008, 12,
1341; d) C. Bolm, Nat. Chem. 2009, 1, 420; e) R. H. Morris,
Chem. Soc. Rev. 2009, 38, 2282; f) K. Junge, K. Schrçder, M.
Beller, Chem. Commun. 2011, 47, 4849; g) M. Darwish, M. Wills,
Catal. Sci. Technol. 2012, 2, 243; h) K. Gopalaiah, Chem. Rev.
2013, 113, 3248.
Keywords: asymmetric catalysis · iron · sulfides · sulfimides ·
.
sulfoximines
[13] For the use of chiral FeII/PyBOX combinations in asymmetric
aziridine formations, see: a) M. Redlich, M. M. Hossain, Tetra-
hedron Lett. 2004, 45, 8987 (additions of diazo compounds to
imines); b) M. Nakanishi, A.-F. Salit, C. Bolm, Adv. Synth. Catal.
[1] a) T. L. Gilchrist, C. J. Moody, Chem. Rev. 1977, 77, 409; b) N.
Furukawa, S. Oae, Ind. Eng. Chem. Prod. Res. Dev. 1981, 20, 260;
c) I. V. Koval, Sulfur Rep. 1993, 14, 149; d) P. C. Taylor, Sulfur
Rep. 1999, 21, 241.
=
2008, 350, 1835 (additions of PhI NTs to olefins).
[2] a) S. Raghavan, S. R. Reddy, K. A. Tony, C. N. Kumar, S. Nanda,
Synlett 2001, 851; b) J. P. Marino, N. Zou, Org. Lett. 2005, 7, 1915;
c) A. Padwa, S. Nara, Q. Wang, J. Org. Chem. 2005, 70, 8538;
d) Q. Wang, S. Nara, A. Padwa, Org. Lett. 2005, 7, 839; e) A.
Padwa, S. Nara, Q. Wang, Tetrahedron Lett. 2006, 47, 595; f) S.
Raghavan, C. N. Kumar, Tetrahedron Lett. 2006, 47, 1585; g) M.
Candy, C. Guyon, S. Mersmann, J.-R. Chen, C. Bolm, Angew.
Chem. 2012, 124, 4516; Angew. Chem. Int. Ed. 2012, 51, 4440;
h) G. P. Silveira, J. P. Marino, J. Org. Chem. 2013, 78, 3379.
[3] a) H. Takada, M. Oda, A. Oyamada, K. Ohe, S. Uemura,
Chirality 2000, 12, 299; b) V. V. Thakur, N. S. C. R. Kumar, A.
Sudalai, Tetrahedron Lett. 2004, 45, 2915.
[14] Attempts to prepare [Fe(tBuCOCClCOtBu)3] failed. As [Fe(Ph-
COCHCOPh)3] gave an inferior result (24 h, 97% yield, e.r. of
80:20) compared with [Fe(iPrCOCHCOiPr)3] (6 h, 99% yield,
e.r. of 86:14) in MeCN at 08C, the use of [Fe(PhCOCClCOPh)3]
was not investigated.
[15] Further lowering of the reaction temperature to À308C did not
enhance the enantioselectivity, but dramatically reduced the
reaction rate.
[16] Under the reaction conditions shown in Table 1, entry 16, use of
=
4-NO2C6H4SO2N IPh gave the corresponding product in 52%
=
yield and an e.r. of 84:16. When 4-tBuC6H4SO2N IPh was
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
applied, the product was obtained in 60% yield and an e.r. of
Synthesis (Eds.: T. Toru, C. Bolm), Wiley-VCH, Weinheim, 2008,
pp. 209 – 229.
=
=
90:10. Generating PhI NTs in situ by combining PhI O and
TsNH2 at À208C led to a similar enantioselectivity, but a lower
reactivity, which was attributed to an inefficient formation of
[23] a) S. J. Park, H. Buschmann, C. Bolm, Bioorg. Med. Chem. Lett.
2011, 21, 4888; b) X. Y. Chen, H. Buschmann, C. Bolm, Synlett
2012, 2808; c) S. J. Park, H. Baars, S. Mersmann, H. Buschmann,
J. M. Baron, P. M. Amann, K. Czaja, H. Hollert, K. Bluhm, R.
Redelstein, C. Bolm, ChemMedChem 2013, 8, 217.
[24] Sulfide 1ah was prepared according to the reported procedure:
R. Desmond, U. Dolling, B. Marcune, R. Tillyer, D. Tschaen
(Merck and Co., Inc.), US005585504A, 1996.
[25] For previous reports on the reactions of sulfimides with
aldehydes or ketones to generate epoxides, see: a) Y. Tamura,
S. M. Bayomi, K. Sumoto, M. Ikeda, Synthesis 1977, 693; b) C. P.
Baird, P. C. Taylor, J. Chem. Soc. Chem. Commun. 1995, 893;
c) C. P. Baird, P. C. Taylor, J. Chem. Soc. Perkin Trans. 1 1998,
3399.
=
PhI NTs under those conditions.
[17] No background reaction was observed in the absence of the
chiral iron(III) catalyst at À208C.
[18] With 4-(n-propylthio)pyridine as substrate, the catalysis was
almost inhibited, which was attributed to a strong coordination
of the sterically unshielded basic pyridine nitrogen atom to the
iron(III) catalyst.
[19] Although sulfenamide 2ag possesses two stereochemical ele-
ments, namely a) a stereogenic carbon center and b) an axis of
À
chirality because of the S N bond (L. Craine, M. Raban, Chem.
Rev. 1989, 89, 689), only one pair of peaks was observed when an
HPLC analysis of a racemic sample of 2ag was conducted on
a chiral stationary phase at 208C. This result implies that the
[26] For iron-catalyzed aziridinations starting from olefins, see:
a) A. C. Mayer, A.-F. Salit, C. Bolm, Chem. Commun. 2008,
5975; for related theoretical studies, see: b) Y. Moreau, H. Chen,
E. Derat, H. Hirao, C. Bolm, S. Shaik, J. Phys. Chem. B 2007,
111, 10288.
À
torsional barrier of the S N bond was easily overcome at that
temperature. In line with this result is the observed broadening
of some peaks in 1H NMR and 13C NMR spectra recorded at
258C.
[20] D. J. Cram, J. Day, D. R. Rayner, D. M. von Schriltz, D. J.
Duchamp, D. C. Garwood, J. Am. Chem. Soc. 1970, 92, 7369.
[21] For the synthesis of racemic sulfoximines using this approach,
see: D. Craig, S. J. Gore, M. I. Lansdell, S. E. Lewis, A. V. W.
Mayweg, A. J. P. White, Chem. Commun. 2010, 46, 4991.
[22] For a recent overview on sulfoximine chemistry, see: C. Worch,
A. C. Mayer, C. Bolm in Organosulfur Chemistry in Asymmetric
[27] The enantiospecificity was calculated according to the following
equation: es [%] = (enantiomeric excess of epoxide 6m/enan-
tiomeric excess of sulfimide 2m) ꢂ 100%. For the first use of this
term, see: S. E. Denmark, T. Vogler, Chem. Eur. J. 2009, 15,
11737.
6
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!