Asymmetric iodoamination of chalcones and 4-aryl-4-oxobutenoates catalyzed by a complex based on scandium(III) and a N,N′-dioxide ligand

Article abstract of DOI:10.1002/chem.201102453

Highly diastereo- and enantioselective iodoamination of chalcones, 4-aryl-4-oxobutenoates, and a trifluoro-substituted enone has been accomplished in the presence of a chiral N,N′-dioxide/[Sc(OTf)₃] complex (0.5-2 mol%), delivering the desired

Full text of DOI:10.1002/chem.201102453

DOI: 10.1002/chem.201102453
Asymmetric Iodoamination of Chalcones and 4-Aryl-4-oxobutenoates
Catalyzed by a Complex Based on ScandiumACTHUNRGTNE(NUG III) and a N,N’-Dioxide Ligand
Yunfei Cai, Xiaohua Liu, Jun Li, Weiliang Chen, Wentao Wang, Lili Lin, and
Xiaoming Feng*[a]
Abstract: Highly diastereo- and enan-
tioselective iodoamination of chal-
cones, 4-aryl-4-oxobutenoates, and a
trifluoro-substituted enone has been
diastereoselectivities (>99:1 d.r.) and
enantioselectivities (up to 99% ee).
Enantiopure syn-a-iodo-b-amino prod-
ucts could also be obtained from the
isomerization of particular iodo com-
pounds. TsNHX species (X=Cl, Br, I),
generated from the reactions between
the halo sources and TsNH2, were fur-
ther confirmed as the active species in
the haloamination reactions involved
in the formation of the key halonium
ion intermediates. A typical haloamina-
tion dependency was observed, with re-
activity decreasing in the order NBS>
NIS@NCS.
accomplished in the presence of
a
chiral N,N’-dioxide/[Sc(OTf)3] complex
AHCTUNGTRENNUNG
(0.5–2 mol%), delivering the desired
vicinal anti-a-iodo-b-amino carbonyl
compounds regioselectively in high
yields (up to 97%) and with excellent
Keywords: asymmetric catalysis
·
dioxides · iodoamination · iodonium
ions · scandium
The intermolecular reactions between olefins and sources
of NÀ and X+ (X=F, Cl, Br, I)—haloamination or amino-
halogenation reactions—are powerful methods for the prep-
aration of vicinal haloamines, which are among the most
versatile building blocks in organic synthesis.[1–4] Diastereo-
selective variants of these reactions for the synthesis of anti-
chloroamines and anti-bromoamines have been well docu-
mented in the last decades.[5–7] A series of transition metal
salts, as well as their complexes, such as CuOTf, CuI,
CuCl2·2H2O, CuCN, Cu
FeCl3, FeCl3/PPh3, Co(OAc)2·4H2O, NiCl2·6H2O, ZnCl2,
LPdCl2 (L=1,10-phenanthroline), Pd/C, [(C3F7CO2)2Rh]2,
and K2OsO2(OH)4/A(DHQ)2PHAL, have been employed as
(OAc)2, V2O5, MnSO4, MnIII/salen,
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
CHTUNGTRENNUNG
catalysts in these reactions.[5,7] Very recently, through the
employment of only 0.05 mol% of a C2-symmetric N,N’-di-
oxide/ScIII complex as the catalyst, we were able to report
the first example of enantioselective bromoamination of
chalcones to deliver anti-a-bromo-b-amino carbonyl com-
pounds with reversed regioselectivity in relation to the prod-
ucts in the previous reports (Scheme 1a).[8a]
Scheme 1. Catalytic asymmetric haloamination reactions.
This catalytic system was subsequently successfully ap-
plied to chloroamination by use of TsNCl2 and TsNH2 as
the chlorine/nitrogen sources (Scheme 1b).[8b] In continua-
tion of our studies on reactions of this kind, involving onium
ion intermediates, we turn our attention to iodoamination.
To the best of our knowledge, direct synthesis of vicinal
iodoamines through iodoamination or aminoiodination reac-
tions has not previously been reported. We postulated that
the main issues were as follows. Firstly, the iodinating
agents—N-iodosuccinimide (NIS), for example—are simple
and inexpensive, although unlike N-chloro and N-bromo
compounds, N-iodo compounds of this kind immediately hy-
drolyze on contact with water.[9] Because of its large size,
iodine forms relatively weak bonds with most elements. Ad-
ditionally, chiral a-iodinated products are prone to racemi-
zation.[10] Here we describe highly efficient catalytic diaster-
eo- and enantioselective iodoaminations of enones and 4-
aryl-4-oxobutenoates (Scheme 1c).
[a] Y. Cai, Prof. Dr. X. Liu, J. Li, W. Chen, W. Wang, Dr. L. Lin,
Prof. Dr. X. Feng
Key Laboratory of Green Chemistry and Technology
Ministry of Education, College of Chemistry
Sichuan University, Chengdu 610064 (P.R. China)
Fax : (+86)28-8541-8249
E-mail: xmfeng@scu.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201102453.
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FULL PAPER
Results and Discussion
Both H2O and succinimide had considerable negative effects
on the yield (Table 1, entry 5 and entry 6). Meanwhile, the
decomposition of NIS became even more obvious in the
presence of H2O and thus greatly suppressed the reaction,
with a decreased ee value (Table 1, entry 5 vs. entry 2).[9] In
these cases the amounts of by-product 3a did not increase,
which was consisted with transformation of 2a into 3a being
at a relatively sluggish rate.[13] To reduce the disadvantages
of residual H2O in the catalytic system, molecular sieves
(MS, 4 ꢁ) were used as an additive. Pleasingly, the catalytic
efficiency was significantly improved and quantitative con-
version of the chalcone (1a) was observed. The desired
product 2a was obtained in 97% yield, with 96% ee and
over 99:1 d.r., with only a 3% yield of 3a (Table 1, entry 7).
Investigation of the effect of reaction temperature revealed
that the enantioselectivity was increased to 98% ee at 08C,
but that more aziridine 3a was formed during the course of
the prolonged process (Table 1, entry 8). Unfortunately,
simply decreasing the catalyst loading to 0.5 mol% led to a
dramatically decreased yield (Table 1, entry 9). However,
when the reaction was performed under strictly anhydrous
conditions with exclusion of light, the yield and stereoselec-
tivity could be maintained in the presence of 0.5 mol% of
Initially, iodoamination of chalcone (1a, Table 1) with NIS/
TsNH2 was selected as a model reaction for the catalyst
screening. A broad investigation of potential N,N’-dioxide/
Table 1. Optimization of the reaction conditions in the catalytic asym-
metric iodoamination of chalcone (1a) with TsNH2 and NIS.[a]
Entry
n
Additive
Yield
[%][b]
t
ee
d.r.[d]
A
[h]
[%][c]
1
2
3
4
5
6
7
5
5
5
5
5
5
5
5
–
–
–
I2
48 (4)
62 (4)
79 (7)
73 (4)
22 (3)
50 (3)
97 (3)
91 (8)
45 (5)
96 (4)
20
20
48
20
20
20
12
72
20
20
96
96
96
96
91
96
96
98
96
96
>99:1
>99:1
>99:1
97:3
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
H2O
succinimide
MS (4 ꢁ)
MS (4 ꢁ)
MS (4 ꢁ)
MS (4 ꢁ)
8[e]
9[f]
10[g]
0.5
0.5
L1/ScACTHNURTGENNG(U OTf)3 complex and freshly dried MS (4 ꢁ) (96%
[a] Unless otherwise noted, all reactions were performed with L1/[Sc-
ACHTUNGTRENNUNG(OTf)3] (1:1), additive (0.1 mmol) or MS (4 ꢁ, 30 mg), 1a (0.1 mmol),
yield, 96% ee, and >99:1 d.r.; Table 1, entry 10).[14]
TsNH2 (0.12 mmol), NIS (0.11 mmol, purified with CH2Cl2 and Et2O
before use) in CH2Cl2 (0.5 mL) under N2 at 238C for the indicated time.
[b] Yields of isolated product 2a. The data in parentheses are isolated
yields of 3a. [c] Determined by HPLC analysis on a chiral stationary
phase with a Chiralcel AD-H column. [d] Determined by HPLC and
1H NMR analysis. [e] The reaction was carried out at 08C. [f] Commer-
cially available NIS was used without purification. [g] The reaction was
performed with exclusion of light with freshly activated MS (4 ꢁ, dried
at 5008C for 5 h).
With the optimized reaction conditions in hand (Table 1,
entry 10), the substrate scope of chalcone derivatives was
examined and the results are listed in Table 2. In all cases,
diastereomeric ratios of over 95:5 were obtained and less
than 5% yields of syn products were detected for all evalu-
ated substrates. Excellent yields (85–97%) and enantioselec-
tivities (93–99% ee) were obtained, regardless of the elec-
tronic natures or positions of the substituents on the phenyl
ring (Table 2, entries 1–8 and 12–15). Moreover, fused-ring
chalcones as well as cinnamyl-, heteroaromatic-, and multi-
substituted ones were also suitable substrates for the reac-
tion (90–95% yields, 98% ee, >95:5 d.r.; Table 2, entries 9
and 16–19). Remarkably, (E)-1-phenylbut-2-enone and 1-
phenylprop-2-enone were also usable with this catalytic
system and delivered the corresponding products in 86%
yield with 94% ee and in 90% yield with 90% ee, respec-
tively (Table 2, entries 10 and 11). Notably, a chalcone deriv-
ative with a para-methoxy substituent on the b-phenyl
group was also shown to be a competent candidate in this
reaction (95% ee, >95:5 d.r.; Table 2, entry 7), which im-
plied that no racemization of the iodonium ion intermediate
was in evidence, unlike in the cases of bromonium and
chloronium ions.[15] The absolute configuration of the prod-
uct 2h (1R,2R) was determined by X-ray crystallography
(Figure 1),[16] which also confirmed the anti configuration
and the stereostructure assignment.
ScIII complexes[11] (see the Supporting Information for de-
tails) showed that the scandium complex of the N,N’-dioxide
L1 (Scheme 1), derived from (S)-pipecolic acid, could pro-
duce the trans-a-iodo-b-amino product 2a with 96% ee and
a diastereomeric ratio (d.r.) of over 99:1, but only in 48%
yield (Table 1, entry 1). At the same time, the corresponding
aziridine 3a was generated in 4% yield and with the same
stereoselectivity as that of 2a, and these transformations
were also accompanied by the decomposition of NIS to gen-
erate I2. With use of NIS that had previously been purified
with CH2Cl2 and Et2O, the yield increased to 62% (Table 1,
entry 2). Prolonging the reaction time was not appropriate
for improvement of the yield of 2a because of increased
amounts of side product (Table 1, entry 3).
The factors potentially disadvantageous to the yield and
enantiomeric purity of the iodoaminated product were then
investigated. When stoichiometric amounts of I2 were
added, the yield of 2a increased from 62 to 73% but the
diastereoselectivity decreased a little (Table 1, entry 4 vs.
entry 2). It is worth pointing out that in the presence of I2,
the diastereomerization of the major product anti-2a at the
carbon atom adjacent to the iodo group was accelerated,
leading to the formation of the corresponding syn-2a.[12]
Encouraged by the successful iodoaminations of chal-
cones, we also investigated the substrate scope of 4-aryl-4-
oxobutenoates 4, which deliver the useful b-iodo-a-amino
acid derivatives 5. As shown in Table 3, the ee values (93–
98% ee) were excellent and the yields (88–97%) were as
well, except in the cases of the substrates with bulky groups
Chem. Eur. J. 2011, 17, 14916 – 14921
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14917

X. Feng et al.
Table 2. Substrate scope in the catalytic asymmetric iodoamination of enones with
TsNH2 and NIS.[a]
Haloamination of the trifluoro-substituted enone
6 (Scheme 2) was also explored. With judicious
choice of nitrogen and halogen sources (X=I, Br,
Cl), the desired haloaminated products 7 were ob-
tained in excellent yields, with 93 to 98% ee and
over 95:5 d.r..[18]
Entry[a]
R1
R2
t
Yield
[%][b]
ee
d.r.[d]
To show the synthetic utility of the catalyst
system, the iodoamination of chalcone (1a) was ex-
panded to a gram scale. As shown in Scheme 3a,
the desired anti-iodoamine 2a was obtained in 96%
yield with 97% ee, with the use of only 0.5 mol%
[h]
[%][c]
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
20
48
20
48
20
48
72
24
48
12
12
72
48
48
72
48
24
10
96 (2a)
95 (2b)
96 (2c)
86 (2d)
85 (2e)
95 (2 f)
90 (2g)
92 (2h)
90 (2i)
90 (2j)
86 (2k)
93 (2l)
97 (2m)
96 (2n)
91 (2o)
92 (2p)
90 (2q)
93 (2r)
96
98
98
98
97
98
95
98[g]
98
90
94
97
97
98
98
98[h]
98
98
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>95:5
>99:1
>99:1
–
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
2[e,f]
3
2-CH3C6H4
3-CH3C6H4
4-CH3C6H4
4-FC6H4
4-ClC6H4
4-MeOC6H4
3-NO2C6H4
3,4-Cl2C6H3
H
Me
Ph
Ph
Ph
4[f]
of L1/[ScACTHNURGTNEUNG(OTf)3] catalyst. Unexpectedly, in the pres-
5
ence of I2 the anti-2a could be gradually trans-
formed into syn-2a, which could be obtained exclu-
sively in 85% yield and with 99% ee through spon-
taneous racemization and crystallization-induced
resolution (Scheme 3b).[19] Compound cis-3a could
then be obtained from the resulting syn-2a.
To examine the possible nitrogen/iodine sources
in the iodoamination reactions, other N-iodo reac-
tants were examined. No reactivity was found with
use of I2 directly, which established that I2 generat-
ed from the decomposition of NIS was not the
active species involved in formation of the key
iodonium ion intermediate (Scheme 4, (1) vs.
Table 1, entry 10). With the employment of 1,3-
6[e,f]
7[e,f]
8
9[e,f]
10[e,f]
11[e]
12[e,f]
13[f]
14[e,f]
15[e,f]
16[e,f]
17[e,f]
18[e,i]
Ph
Ph
Ph
4-CH3C6H4
4-FC6H4
4-ClC6H4
4-MeOC6H4
2-naphthyl
2-furyl
Ph
Ph
Ph
Ph
À
PhCHCH
19[e]
20
95 (2s)
99
96:4
diiodo-5,5-dimethylhydantoin
(DIH,
either
[a] Unless specified, the reactions were performed with 1 (0.1 mmol), L1/[ScACHTNUTGRNEUNG(OTf)3]
1.1 equiv or 0.6 equiv), containing two activated
iodo groups, 2a could be obtained in nearly quanti-
tative yields with the same stereoselectivities as in
the case of NIS, which indicated that the same
active species—TsNHI produced by I-transfer—
might be involved in this iodoamination reaction
(Scheme 4, (2)).[20] The combination of TsNH2 and
N-iodosaccharin (NISC) produced a mixture of io-
doaminated products 2a and 8a, with no enantiose-
(0.5 mol%, 1:1) and MS (4 ꢁ, 30 mg), TsNH2 (0.12 mmol), and NIS (0.11 mmol) in
CH2Cl2 (0.5 mL) at 238C for the indicated time. [b] Yields of isolated products. [c] De-
termined by HPLC analysis (see the Supporting Information for details). [d] Deter-
1
mined by HPLC and H NMR analysis. [e] 2.0 mol% of catalyst was used. [f] Reaction
was carried out at 08C. [g] The absolute configuration of 2h (1R,2R) was determined
by X-ray crystallography. [h] Determined by HPLC after transformation into the cor-
responding aziridine product. [i] Further prolonging of the reaction time led to the
transformation of anti-2r into syn-2r after the complete conversion of 1r.
lectivity being observed in either case (Scheme 4, (3)). The
amount of product 8a exceeded that of 2a more than two-
fold. Moreover, NISC itself could be used as the iodo-
amination reagent, affording racemic 8a in 92% yield
(Scheme 4, (4)). It would thus appear that the TsNHI spe-
cies (generated from TsNH2/NIS) or the NISC species might
be the real active reactants involved in formation of the
iodonium intermediates.[21] Accordingly, TsNHBr (generated
from TsNH2/NBS) might be the active species in the bro-
1
moamination reaction.[8b] Additionally, H NMR analysis of
mixtures of NIS and TsNH2 or of NBS and TsNH2 con-
firmed the existence of TsNHI (see the Supporting Informa-
tion) or TsNHBr.[5g]
Figure 1. X-ray crystallographic structure of 2h.
A proposed possible reaction process for the haloamina-
tion reaction, based on the above results and on previous
mechanistic studies on the chloroamination and bromoami-
nation reactions,[8] is shown in Scheme 5. Initially, TsNHX
(X=I, Br, Cl) could be generated through the reaction of
TsNH2 and the halo source, such as DIH, NIS, NBS, or
TsNCl2. Then, in the presence of the chiral N,N’-dioxide/ScIII
complex, TsNHX could stereoselectively attack the enones
on the ester moiety (73–85% yields, Table 3, entries 4 and
5). The steric hindrance of ester moieties and the electronic
properties of the substituents on the aromatic ring had little
influence on the diastereoselectivities (>95:5 d.r.;
Table 3).[17]
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Asymmetric Iodoamination Catalyzed by a ScandiumACTHNUTRGNE(UNG III) Complex
FULL PAPER
Table 3. Substrate scope in the catalytic asymmetric iodoamination of 4-
aryl-4-oxobutenoates with TsNH2 and NIS.[a]
Entry[a]
R3
R4
t
Yield
[%][b]
ee
d.r.[d]
98:2
99:1
99:1
>99:1
>95:5
98:2
97:3
98:2
98:2
97:3
[h]
[%][c]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Me
Et
8
8
96 (6a)
96 (6b)
83 (6c)
75 (6d)
90 (6e)
94 (6 f)
92 (6g)
89 (6h)
97 (6i)
95 (6j)
88 (6k)
90 (6l)
92 (6m)
96
98
96
97
97
97
95
96
97
96
97
98
97
iPr
tBu
Ph
Bn
Et
Et
Et
Et
Et
20
20
16
12
20
20
6
4-MeOC6H4
4-MeC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
3-MeOC6H4
3,4-Cl2C6H3
9
10
11
12
13
6
8
8
8
98:2
>95:5
98:2
Et
Et
Scheme 3. The synthetic utility of the catalytic reactions. a) Asymmetric
iodoamination of chalcone on a gram scale. b) Unexpected transforma-
tion of anti product to syn product.
[a] Unless specified, the reactions were performed with 4 (0.1 mmol) ,
L1/[Sc(OTf)3] (0.5 mol%, 1:1) and MS (4 ꢁ, 30 mg), TsNH2 (0.12 mmol),
ACHTUNGTRENNUNG
and NIS (0.11 mmol) in CH2Cl2 (0.5 mL) under N2 at 238C for the indi-
cated time (see the Supporting Information for details). [b] Yields of iso-
lated products. [c] Determined by HPLC analysis (see the Supporting In-
formation). [d] Determined by 1H NMR spectroscopy and HPLC with a
chiral stationary phase.
Scheme 2. Haloamination of the trifluoro-substituted enone 6.
to form chiral halonium ion intermediates,[22] followed in-
stantly by nucleophilic attack of negative nitrogen to deliver
the final enantiomerically enriched product. With the use of
NISC (which could act as an active species itself in the iodo-
amination reaction) as the reactant, the disparity of enantio-
selectivity might be a consequence of its steric hindrance.
To compare the relative activities of haloamination reac-
tions, reactions of chalcone (1a) with TsNH2 and NXS (X=
C, B, I) under the same reaction conditions were carried out
(Scheme 6). No reaction took place with TsNH2/NCS as re-
actants, which indicated that chloroamination exhibited the
lowest reactivity. With the combined use of TsNH2
(1.0 equiv), NIS (0.5 equiv), and NBS (0.5 equiv) as re-
agents, the amount of the bromoaminated product 2aa ex-
ceeded that of the iodoaminated product 2a by more than
threefold after 16 h.[23] Typical haloamination dependency is
therefore, observed with reactivity decreasing in the order
NBS>NIS@NCS.
Scheme 4. Iodoamination of chalcone (1a) with use of other I sources.
Conclusion
In summary, we have developed highly efficient enantiose-
lective iodoamination reactions of chalcones and 4-aryl-4-
oxobutenoates, as well as of a trifluoro-substituted enone. In
the presence of the chiral ScIII/N,N’-dioxide complex (0.5–
2 mol%), the reactions performed well over a series of sub-
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14919

X. Feng et al.
stirring at 08C or 238C for the indicated time. The residue was purified
by flash chromatography on silica gel to afford the desired product. The
enantiomeric excess (ee) was determined by high-performance liquid
chromatography (HPLC) with Chiralcel AD-H, Chiralcel IA, Chiralce-
l OD-H, or Chiralcel IB. The diastereomeric ratio (d.r.) was determined
1
by H NMR spectroscopy and HPLC analysis.
General procedure for the reaction with 2 mol% catalyst loading:
CH2Cl2 (0.3 mL) was added under N2 to a dry reaction tube charged with
L1 (0.002 mmol, 1.1 mg) and [ScACTHNUTRGNE(NUG OTf)3] (0.002 mmol, 1.0 mg). The mix-
ture was stirred under N2 at 358C for 0.5 h. The solvent was then re-
moved in vacuo. The substrate 1 or 4 (0.1 mmol), para-toluenesulfona-
mide (TsNH2, 20.5 mg, 0.12 mmol), and N-iodosuccinimide (NIS,
24.7 mg, 0.11 mmol, purified with CH2Cl2 and Et2O before use to remove
trace amounts of I2 and H2O) was weighed into this tube, followed by ad-
dition of CH2Cl2 (0.5 mL). Under N2 and with exclusion of light, the reac-
tion mixture was stirred at 08C or 238C for the indicated time. The resi-
due was purified by flash chromatography on silica gel to afford the de-
sired product. The ee value was determined by high-performance liquid
Scheme 5. Proposed mechanism of the haloamination reaction.
chromatography
(HPLC)
with
Chiralcel AD-H,
Chiralcel IA,
Chiralcel OD-H, or Chiralcel IB. The d.r. was determined by 1H NMR
spectroscopy and HPLC analysis.
Typical procedure for the scale-up reaction: CH2Cl2 (5.0 mL) was added
under N2 to a 25 mL flask charged with L1 (0.025 mmol, 13.5 mg), [Sc-
AHCTUNGRTEG(NNNU OTf)3] (0.025 mmol, 12.2 mg), and freshly activated MS (4 ꢁ, 1.0 g,
dried at 5008C for 5 h before use). The mixture was stirred under N2 at
358C for 1 h. The solvent was then removed in vacuo. The substrate 1a
(1.04 g, 5 mmol), para-toluenesulfonamide (TsNH2, 1.03 g, 6 mmol), and
N-iodosuccinimide (NIS, 1.23 g, 5.5 mmol, purified with CH2Cl2 and Et2O
before use to remove trace amounts of I2 and H2O) was weighed into this
flask, followed by addition of CH2Cl2 (12.5 mL). Under N2 and with ex-
clusion of light, the reaction mixture was stirred at 238C for 12 h. The
residue was purified by flash chromatography on silica gel (ethyl acetate/
petroleum ether, 1:4) to afford the desired product 2a as a white solid
(2.45 g, 96% yield, 97% ee, and >99:1 d.r.).
Scheme 6. Contrast in the reactivities of haloamination reactions.
strates, delivering the desired vicinal anti-a-iodo-b-amino
products regioselectively in excellent yields (up to 97%),
and with excellent diastereoselectivities (>99:1) and enan-
tioselectivities (up to 99% ees). Enantiopure syn-a-iodo-b-
amino products could also be obtained from the isomeriza-
tion of particular iodo compounds. TsNHX generated from
the reactions between the halo sources and TsNH2 was fur-
ther confirmed as the active species involved in the forma-
tion of the key halonium ion intermediates. Additionally, a
typical haloamination dependency was observed, with reac-
tivity decreasing in the order NBS> NIS@ NCS. Further
development of catalytic asymmetric fluoroamination reac-
tions and application of these haloamination reactions are
underway.
Acknowledgements
We thank the National Natural Science Foundation of China
(Nos. 20732003, 21021001, and 20872097) and the National Basic Re-
search Program of China (973 Program: No. 2010CB833300) for financial
support. We also thank Sichuan University Analytical and Testing Center
for NMR analysis and the State Key Laboratory of Biotherapy for
HRMS analysis.
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Experimental Section
Preparation of the catalyst: CH2Cl2 (5.0 mL) was added under N2 to a
10 mL flask charged with L1 (0.01 mmol, 5.4 mg), [ScACTHNURGTNEUNG(OTf)3] (0.01 mmol,
4.9 mg), and freshly activated MS (4 ꢁ, 600 mg, dried at 5008C for 5 h
before use). The mixture was stirred under N2 at 358C for 1 h. The sol-
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The catalyst was stored under N2 at room temperature and used for
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0.5 mol%), a substrate 1, 4, or 6 (0.1 mmol), para-toluenesulfonamide
(TsNH2, 20.5 mg, 0.12 mmol), and N-iodosuccinimide (NIS, 24.7 mg,
0.11 mmol, purified with CH2Cl2 and Et2O before use to remove trace
amounts of I2 and H2O) under N2 and with exclusion of light. CH2Cl2
(0.5 mL) was then added at 08C or 238C. The reaction mixture was kept
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 14916 – 14921

Asymmetric Iodoamination Catalyzed by a ScandiumACTHNUTRGNE(UNG III) Complex
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[12] The control experiments showed that i) 8% yield of syn-2a was ob-
tained after stirting of anti-2a (0.1 mmol) in CH2Cl2 (0.5 mL) for
24 h under 1.0 equiv of I2; ii) 32% yield anti-2a was obtained after
stirting of syn-2a (0.1 mmol) in CH2Cl2 (0.5 mL) for 24 h under
1.0 equiv of I2. Notably, catalytic amount of I2 which was easily in-
troduced to the solid product due to unavoidable decomposition of
NIS could also enhance this isomerization.
1
[23] The ratio between 2a and 2aa was determined by H NMR analysis
on the isolated mixture of the products (for details, see the Support-
ing Information).
Received: August 8, 2011
Published online: December 8, 2011
Chem. Eur. J. 2011, 17, 14916 – 14921
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14921