Enantioselective bromoaminocyclization of allyl N-tosylcarbamates catalyzed by a chiral phosphine-Sc(OTf)3 complex

Article abstract of DOI:10.1021/ja4010877

An effective enantioselective bromoaminocyclization of allyl N-tosylcarbamates catalyzed by a chiral phosphine-Sc(OTf)₃ complex is described. A wide variety of optically active oxazolidinone derivatives containing various functional groups can be obtained with high enantioselectivities.

Full text of DOI:10.1021/ja4010877

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Communication
Enantioselective Bromoaminocyclization of Allyl N-
Tosylcarbamates Catalyzed by Chiral Phosphine-Sc(OTf)3 Complex
Deshun Huang, Xiaoqin Liu, Lijun Li, Yudong Cai, Weigang Liu, and Yian Shi
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja4010877 • Publication Date (Web): 09 May 2013
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Enantioselective Bromoaminocyclization of Allyl N-
Tosylcarbamates Catalyzed by Chiral Phosphine-Sc(OTf)3
Complex
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Deshun Huang,a Xiaoqin Liu,a Lijun Li,a Yudong Cai,a Weigang Liu,a and Yian Shi*a,b
a
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Insti-
b
tute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. Department of Chemistry, Colorado State Uni-
versity, Fort Collins, Colorado 80523, United States
Supporting Information Placeholder
Table 1. Studies on reaction conditionsa
ABSTRACT: An effective enantioselective bromo-
O
O
O
2-10 mol % M/L (1:1)
NBS (1.2 equiv)
slovent, t (oC)
aminocyclization of allyl N-tosylcarbamates catalyzed by
chiral phosphine-Sc(OTf)3 is described. A wide variety
of optically active oxazolidinone derivertives containing
various functional groups can be obtained in high enan-
tioselectivities.
NTs
O
NHTs
1a
2a
Br
entry
1
L
M
solvent
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
DCM
CHCl3
THF
t (oC)
0
yield%b
14
ee%c
-7
-6
12
4
L1
L1
L1
L1
L2
L3
L4
L5
L5
L5
-
Cu(OTf)2
Sm(OTf)3
Y(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Y(OTf)3
Cu(OTf)2
-
2
0
72
3
0
68
Electrophilic halogenation of olefins is one of the most
fundamental reactions in organic chemistry and provides
a very effective approach to functionalize the C–C double
bonds.1 Asymmetric halogenation allows the installa-
tion of two chiral C–X bonds simultaneously. The re-
sulting halides can undergo a variety of transformations,
particularly stereoselective nucleophilic substitutions,
which make them extremely versatile chiral building
blocks in organic synthesis. In addition, halogens are
contained in many important natural2 and unnatural
products. Due to its importance, asymmetric halogena-
tion of olefins has received considerable attention. Re-
cently, significant progress has been made in this area.3
A number of catalytic systems including chiral Lewis
acid,4,5 amine,6-11 phosphoric acid,12-14 and Pd(II) com-
plex15 via various asymmetric induction mechanisms,
have been developed. However, there are still many
unsolved challenges. Development of new catalytic sys-
tems with new types of substrates is highly desirable.
During our own efforts on catalytic electrophilic addi-
tions to olefins (Scheme 1),13a,16 we have found that
chiral phosphine-Sc(OTf)3 is an effective catalyst for
asymmetric bromoaminocyclization of allyl N-
tosylcarbamates. Herein, we wish to report our prelimi-
nary studies on this subject.
4
5d
0
55
-30
-30
-30
-30
-30
-30
-30
-30
-30
-30
-30
-30
-40
-50
25
4
6
31
-9
-31
93
-23
3
7
70
8
61
9
54
10
11
12
13
14
15
16
17e
18f
7
trace
trace
54
/
-
Sc(OTf)3
-
/
L5
L5
L5
L5
L5
L5
-2
82
88
80
94
96
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
58
70
10
PhMe
PhMe
60
45
PhMe/DCM
(3:1)
PhMe/DCM
(3:1)
PhMe/DCM
(3:1)
19g
L5
L5
L6
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
-50
-50
-50
63
87
84
96
96
97
20h
21h
a
The reactions were carried out with 1a (0.10 mmol), NBS (0.12
mmol), and M/L (1:1, 0.010 mmol) in solvent (1.0 mL) for 18 h unless
otherwise stated. b Isolated yield. c Determined by chiral HPLC analysis.
d With L2 (0.020 mmol). e For 36 h. f For 72 h. g For 48 h. h With
Sc(OTf)3/L (1:1, 0.0020 mmol) for 48 h.
Scheme 1. Catalytic electrophilic additions to olefins
Nu
R1
R1
R1
R2
Our initial studies were carried out with cis-pent-2-en-
1-yl tosylcarbamate (1a) as substrate and NBS as bro-
mine source (Table 1). A variety of commonly used
NuH
X-Y
R3
R3
R3
R2
R2
catalyst
X
X
X = I, Br, Cl, SR, SeR, etc.
1
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Page 2 of 5
chiral Lewis acids were first examined.17 Only modest
Table 2. Enantioselective bromoaminocyclization of allyl
N-tosylcarbamatesa
ee’s were generally obtained, with M-PyBox (L1)18a
(Figure 1) being among the best (Entries 1-4). Subse-
quently, Lewis acids with chiral phosphine ligands were
investigated (Entries 5-10).18b-f To our delight, oxa-
zolidinone 2a was obtained in 61% yield and 93% ee
1
2
3
4
5
6
7
8
2-5 mol %
O
O
O
Sc(OTf)3/L5 (1:1)
NBS (1.2 equiv)
NTs
R2
R2
O
NHTs
R1
PhMe/DCM (3:1), -50 o
48-72 h
C
R1
Br
2
1
with 10 mol% Sc(OTf)3 and Trost ligand L5 in PhMe
o
entry
substrate
productb
yield%c ee%d
at -30 C (Entry 8). Control experiments showed that
little conversion was observed without Sc(OTf)3 and L5
(Entry 11) or with Sc(OTf)3 alone (Entry 12). However,
ligand L5 itself was able to catalyze the reaction, giving
nearly racemic 2a (Entry 13).19 The reaction was further
optimized with solvent and temperature (Entries 14-19).
Oxazolidinone 2a was obtained in 63% yield and 96%
O
O
9
NTs
O
NHTs
O
R1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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27
28
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30
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R1
Br
1
2
3
4
5
6
7
R1 = Et, 1a
88
80
90
83
77
71
80
96
96
96
93
96
96
94
2a
2b
2c
2d
2e
2f
R1 = n-Bu, 1b
R1 = n-C6H13, 1c
R1 = CH2Bn, 1d
R1 = CH2Cp, 1e
R1 = Cy, 1f
ee with 10 mol% Sc(OTf)3-L5 in PhMe/DCM (3:1) at -
o
50 C (Entry 19). Decreasing the catalyst loading to 2
mol% led to a cleaner reaction, thus increasing the yield
to 87% without loss of ee (Entry 20).20 Similar result
was also obtained with Trost ligand L6 (Entry 21).
Other halogen sources were also examined (Scheme 2).21
Comparable yields and ee’s were obtained with
DBDMH and NBP. However, no reactions were ob-
served with TBCO, NCS, or NIS.
R1 = CH2OBn, 1g
2g
O
O
NTs
O
NHTs
X
O
X
Br
8
80
75
75
87
50
97
97
96
96
92
X = OAc, 1h
X = OTs, 1i
X = CN, 1j
X = Cl, 1k
X = NHBoc, 1l
O
2h
2i
9
Ph
O
P
10
11
12
O
O
PPh2
PPh2
N
2j
2k
N
N
N
O
Ph
iPr
iPr
L1
L2
L3
2l
O
NTs
HN
HN
PPh2
PPh2
HN
PPh2
PPh2
O
NHTs
O
Ph
Ph
CH2PPh2
CH2PPh2
13
81
94
O
O
O
O
O
Br
1m
2m
O
HN
O
O
O
NTs
L6
L5
L4
O
NHTs
2
14
15
86
87
95
89
CO2Et
CO2Et
1n
Br
2n
Figure 1. Selected examples of chiral ligands examined
O
O
O
NTs
O
NHTs
Br
Scheme 2. Effect of halogen source
1o
2o
O
O
O
O
O
O
Sc(OTf)3/L5 (1:1) (2 mol %)
halogen source (1.2 equiv)
NTs
O
NHTs
NTs
R1
O
NHTs
PhMe/DCM (3:1), -50 o
48 h
C
R1
Br
1a
2
X
R1 = Me, 1p
16
17
18
81
83
87
83
91
88
2p
2q
O
O
O
R1 = n-Bu, 1q
R1 = i-Bu, 1r
Br
Br
NBr
NBr
2r
NIS
NR
BrN
NCS
NR
O
O
Br
(TBCO)
Br
O
NTs
(DBDMH)
(NBP)
O
n-Pr
O
79%, 92% ee
83%, 96% ee
NR
5
(2s)
90
48
(2s)
20
Br
2s
O
NHTs
19
O
As shown in Table 2, the enantioselective bromoami-
nocyclization can be extended to a wide variety of cis-
allyl N-tosylcarbamates to form the corresponding
oxazolidinones in 50-90% yields and 92-97% ee’s with
2-5 mol% Sc(OTf)3-L5 (Entries 1-14). The substituents
on the olefin can be linear alkyl groups (Entries 1-4) as
well as branched alkyl groups (Entries 5&6). Various
functional groups, such as OBn, OAc, OTs, CN, Cl,
and NHBoc, can be present in the side chains (Entries 7-
12). Alkyne and α,β-unsaturated ester can also be toler-
ated (Entries 13&14). Terminal allyl N-tosylcarbamate
1o was also effective substrate to give oxazolidinone 2o
n-Pr
O
NTs
n-Pr
(2t)
(2t)
1s
Br
2t
a
The reactions were carried out with 1 (0.50 mmol), NBS (0.60
mmol), and Sc(OTf)3/L5 (1:1, 0.010 mmol) in PhMe/DCM (3:1) (5.0 mL)
o
at -50 C for 48 h unless otherwise stated. For entries 14, 17, and 18, the
reactions were carried out for 72 h. For entries 15 and 19, the reactions
were carried our with Sc(OTf)3/L5 (1:1, 0.025 mmol) for 48 h. For
entries 6, 7, and 13, the reactions were carried out with Sc(OTf)3/L5
(1:1, 0.025 mmol) for 72 h. b The absolute configurations of 2a, 2r, and
2t were determined by the X-ray structures. The absolute configurations
of 2g and 2o were determined by comparing the optical rotations with
literature after being converted to the corresponding aziridines. The abso-
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Journal of the American Chemical Society
lute configurations of the others except 2s were tentatively proposed by
tion. The dramatically reduced yields and ee’s obtained
with L9 and L10 (Table 3, entries 3&4) as compared to
L5 (Table 2, entry 1) indicate that the secondary amide
is very important for the reactivity and enantioselectiv-
ity. As shown by the results of L11 and L12 (Table 3,
entries 5&6), the bisphosphine and bisamide moieties
are essential to the reaction efficiency. The catalytic
properties of L7-L12 in the absence of Sc(OTf)3 were
also investigated (Table 3, entries 7-12). In contrast to
L8-L12, no reaction was observed for L7, which sug-
gests that the phosphine is possibly involved in the ac-
tivation of NBS. There are some interactions between
the phosphine and Sc or NBS as detected by 31P NMR
spectra of ligand L5 with Sc(OTf)3 and/or NBS (Sup-
porting Information). It appears that Sc(OTf)3 could
coordinate with both L5 and the substrate to allow the
bromoaminocyclization to occur in a chiral environment
via activation of NBS by the phosphine and/or Sc. A
precise understanding of the reaction mode and the ori-
gin of the enantioselectivity for the current system await
further study.
analogy. The stereochemistry of 2s indicated represents the relative
1
2
3
4
5
6
7
8
d
stereochemistry. c Isolated yield. Determined by chiral HPLC analysis.
in 87% yield and 89% ee (Entry 15). The reaction can
also be applied to (Z)-trisubstituted olefins, giving the
products in 81-87% yields and 83-91% ee’s (Entries 16-
18). In all the cases, the reactions proceeded regioselec-
tively to give the 5-exo products. However, a mixture of
5-exo and 6-endo products with different ee’s were ob-
tained with the trans substrate examined (Entry 19).
9
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12
13
14
15
16
17
18
19
20
21
22
23
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49
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58
59
60
The reaction can be carried out on a relatively large
scale. For example, 4.43 g oxazolidinone 2a was ob-
tained in 82% yield and 99% ee after recrystallization
(Scheme 3). The resulting bromide can be displaced by
nucleophiles, such as azide, benzenethiolate, and chlo-
ride with inversion of configuration (Scheme 4). Treat-
ing bromide 2a with K2CO3 in MeOH led to cis-
aziridine 6a,22 which can undergo aza-Payne rearrange-
ment23 to form epoxide 7a. Both 6a and 7a are highly
useful intermediates.23,24 Like bromide 2a, chloride 5a
can be converted to the corresponding trans-aziridine 8a.
To certain extent, the availability of chloride 5a pro-
vides an alternative solution to trans substrates, which
are not effective with the current catalytic system. As
exemplified by aziridine 6f in Scheme 5, the Ts group
can be readily removed without loss of ee with Mg in
MeOH under sonication.
Table 3. The structural effect of liganda
2 mol %
Sc(OTf)3/L (1:1)
O
O
O
NTs
NBS (1.2 equiv)
O
NHTs
PhMe/DCM (3:1), -50 o
48 h
C
1a
2a
Br
PPh2
Scheme 3. Bromoaminocyclization on gram scale
HN
HN
HN
HN
X
PPh2
PPh2
HN
PPh2
2 mol % Sc(OTf)3/L5 (1:1)
O
O
O
O
O
O
O
O
O
O
NBS (1.2 equiv)
PhMe/DCM (3:1)
-50 oC, 48 h
NTs
O
NHTs
Y
X
after recrystallization
82% yield, 99% ee
Br
2a
4.43 g
1a
PPh2
L11: Y = NHCOPh
L12: Y = H
L9: X = NMe
L10: X = O
L7
L8
Scheme 4. Synthetic transformations of bromide 2a
entry ML
yield%b
NR
8
ee%c
entry
L
yield%b
ee%c
O
O
O
O
O
O
1a
2a
3a
4a
5a
6a
L7
L8
/
-6
40
2
7d
8d
9d
10d
11d
12d
L7
NR
12
39
43
45
57
/
-8
4
5
0
/
NTs
NTs
NTs
LiCl
DMF, 80 o
NaX
DMF, 80 o
C
C
L8
9 h, 72%
2a
5a
Cl
X
Br
99% ee
99% ee
L9
14
L9
3a, X = N3, 60%, 99% ee
4a, X = SPh, 69%, 99% ee
L10
L11
L12
7
L10
L11
L12
K2CO3
K2CO3
MeOH, rt
50 min, 70%
MeOH, rt
1 h, 93%
47
9
Ts
N
trace
/
Ts
N
O
NaH
HO
a
HO
The reactions were carried out with 1a (0.50 mmol), NBS (0.60
THF, rt
4 h, 71%
7a NHTs
99% ee
6a
99% ee
8a
mmol), and Sc(OTf)3/L (1:1, 0.010 mmol) in PhMe/DCM (3:1) (5.0 mL)
99% ee
at -50 C for 48 h unless otherwise stated. b Isolated yield. c Determined
o
by chiral HPLC analysis. d Without Sc(OTf)3.
Scheme 5. Removal of Ts group
O
In summary, we have developed an efficient
enantioselective bromoaminocyclization of allyl N-tosyl-
carbamates using NBS as bromine source and Sc(OTf)3-
L5 complex as catalyst. A wide variety of oxazolidi-
nones with various functional groups can be obtained in
generally good yields and high enantioselectivities. The
reaction can be performed on a gram scale. Further
transformations of these compounds provide access to
useful intermediates with diverse functionality. Future
efforts will be devoted to understanding the reaction
mechanism, expanding the substrate scope, and explor-
ing additional electrophilic addition processes.
Ts
H
N
N
NTs
K2CO3
Mg, MeOH
HO
HO
O
Cy
Cy
Cy
Sonication, rt
2 h, 94%
MeOH, rt
1 h, 89%
Br
2f
96% ee
9f
96% ee
6f
96% ee
To gain some mechanistic insights into this catalytic
system, several analogues (L7-L12) of ligand L5 were
prepared and examined for the reaction with substrate 1a
(Table 3). Little or low yield and ee were obtained with
L7 and L8 (Table 3, entries 1&2), illustrating that the
phoshine group and its position are crucial for the reac-
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(8) For leading references on chiral amine catalyzed enantiose-
lective halocyclization using amides or sulfonamides, see: (a) Jaga-
nathan, A.; Garzan, A.; Whitehead, D. C.; Staples, R. J.; Borhan, B.
Angew. Chem., Int. Ed. 2011, 50, 2593. (b) Zhou, L.; Chen, J.; Tan,
C. K.; Yeung, Y.-Y. J. Am. Chem. Soc. 2011, 133, 9164.
(9) For leading references on chiral amine catalyzed enantiose-
lective fluorination of olefins, see: (a) Ishimaru, T.; Shibata, N.;
Horikawa, T.; Yasuda, N.; Nakamura, S.; Toru, T.; Shiro, M. Angew.
Chem., Int. Ed. 2008, 47, 4157. (b) Lozano, O.; Blessley, G.; Marti-
nez del Campo, T.; Thompson, A. L.; Giuffredi, G. T.; Bettati, M.;
Walker, M.; Borman, R.; Gouverneur, V. Angew. Chem., Int. Ed.
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1
2
3
4
5
6
7
8
ASSOCIATED CONTENT
Supporting Information.
Experimental procedures, characterization data, X-ray struc-
tures, data for determination of enantiomeric excess, and
NMR spectra. This information is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
9
(10) For a leading reference on chiral amine catalyzed dichlori-
nation of allylic alcohols, see: Nicolaou, K. C.; Simmons, N. L.;
Ying, Y.; Heretsch, P. M.; Chen, J. S. J. Am. Chem. Soc. 2011, 133,
8134.
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W.; Chen, Z. H.; Li, H.; Tu, Y. Q.; Zhang, F. M.; Tian, J. M. J. Am.
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hedron 2012, 68, 2728.
(17) For leading references on Lewis acid catalyzed halogena-
tion of olefins, see: (a) Hajra, S.; Maji, B.; Karmakar, A. Tetrahe-
dron Lett. 2005, 46, 8599. (b) Yeung, Y.-Y.; Gao, X.; Corey, E. J. J.
Am. Chem. Soc. 2006, 128, 9644.
(18) For leading references on ligands, see: L1: (a) Nishiyama,
H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo, M.; Itoh, K.
Organometallics 1989, 8, 846. L2: (b) de Vries, A. H. M.; Meetsma,
A.; Feringa, B. L. Angew. Chem., Int. Ed. 1996, 35, 2374. (c) Se-
wald, N.; Wendisch, V. Tetrahedron: Asymmetry 1998, 9, 1341. L3:
(d) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Sou-
chi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. L4: (e)
Dang, T. P.; Kagan, H. B. Chem. Commun. 1971, 481. L5 and L6:
(f) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc.
1992, 114, 9327.
Corresponding Author
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yian@lamar.colostate.edu
No competing financial interests have been declared.
ACKNOWLEDGMENT
We gratefully acknowledge the National Basic Research
Program of China (973 program, 2011CB808600), the
National Natural Science Foundation of China (21172221),
and the Chinese Academy of Sciences for the financial sup-
port.
REFERENCES
(1) For leading reviews on halogenation of olefins, see: (a)
Dowle, M. D.; Davies, D. I. Chem. Soc. Rev. 1979, 8, 171. (b) Li,
G.; Kotti, S. R. S. S.; Timmons, C. Eur. J. Org. Chem. 2007, 2745.
(2) For a leading review, see: Vaillancourt, F. H.; Yeh, E.; Vos-
burg, D. A.; Garneau-Tsodikova, S.; Walsh, C. T. Chem. Rev. 2006,
106, 3364.
(3) For leading reviews on asymmetric halogenation of olefins,
see: (a) French, A. N.; Bissmire, S.; Wirth, T. Chem. Soc. Rev. 2004,
33, 354. (b) Chen, G. F.; Ma, S. M. Angew. Chem., Int. Ed. 2010, 49,
2. (c) Castellanos, A.; Fletcher, S. P. Chem.—Eur. J. 2011, 17, 5766.
(d) Tan, C. K.; Zhou, L.; Yeung, Y.-Y. Synlett 2011, 1335. (e) Hen-
necke, U. Chem.—Asian J. 2012, 7, 456. (f) Denmark, S. E.;
Kuester, W. E.; Burk, M. T. Angew. Chem., Int. Ed. 2012, 51, 10938.
(4) For leading references on Lewis acid catalyzed enantioselec-
tive iodocyclization, see: (a) Inoue, T.; Kitagawa, O.; Ochiai, O.;
Shiro, M.; Taguchi, T. Tetrahedron Lett. 1995, 36, 9333. (b) Kang,
S. H.; Lee, S. B.; Park, C. M. J. Am. Chem. Soc. 2003, 125, 15748.
(c) Ning, Z.; Jin, R.; Ding, J.; Gao, L. Synlett 2009, 2291.
(5) For leading references on Lewis acid catalyzed intermolecu-
lar enantioselective halogenation of olefins, see: (a) Sakurada, I.;
Yamasaki, S.; Gottlich, R.; Iida, T.; Kanai, M.; Shibasaki, M. J. Am.
Chem. Soc. 2000, 122, 1245. (b) Cai, Y. F.; Liu, X. H.; Hui, Y. H.;
Jiang, J.; Wang, W. T.; Chen, W. L.; Lin, L. L.; Feng, X. M. Angew.
Chem., Int. Ed. 2010, 49, 6160.
(6) For leading references on chiral amine-based catalytic enan-
tioselective halolactonization, see: (a) Wang, M.; Gao, L. X.; Mai,
W. P.; Xia, A. X.; Wang, F.; Zhang, S. B. J. Org. Chem. 2004, 69,
2874. (b) Whitehead, D. C.; Yousefi, R.; Jaganathan, A.; Borhan, B.
J. Am. Chem. Soc. 2010, 132, 3298. (c) Zhou, L.; Tan, C. K.; Jiang,
X.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2010, 132, 15474. (d)
Veitch, G. E.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2010, 49, 7332.
(e) Murai, K.; Matsushita, T.; Nakamura, A.; Fukushima, S.; Shi-
mura, M.; Fujioka, H. Angew. Chem., Int. Ed. 2010, 49, 9174. (f)
Zhang, W.; Zheng, S.; Liu, N.; Werness, J. B.; Guzei, I. A.; Tang,
W. P. J. Am. Chem. Soc. 2010, 132, 3664. (g) Jiang, X.; Tan, C. K.;
Zhou, L.; Yeung, Y.-Y. Angew. Chem., Int. Ed. 2012, 51, 7771. (h)
Dobish, M. C.; Johnston, J. N. J. Am. Chem. Soc. 2012, 134, 6808.
(i) Paull, D. H.; Fang, C.; Donald, J. R.; Pansick, A. D.; Martin, S. F.
J. Am. Chem. Soc. 2012, 134, 11128. (j) Tungen, J. E.; Nolsøe, J. M.
J.; Hansen, T. V. Org. Lett. 2012, 14, 5884.
(19) Ligands L1-L4 and L6 can also catalyze this reaction but
with low ee’s (Table S1 in Supporting Information).
(20) No decomposition was observed when oxazolidinone 2a was
subjected to the reaction conditions.
(21) The reactions were carried out with 1a (0.50 mmol), halogen
source (0.60 mmol), and Sc(OTf)3/L5 (1:1, 0.010 mmol) in
PhMe/DCM (3:1) (5.0 mL) at -50 oC for 48 h.
(22) Hirama, M.; Iwashita, M.; Yamazaki, Y.; Itô, S. Tetrahedron
Lett. 1984, 25, 4963.
(23) For a leading review, see: Ibuka, T. Chem. Soc. Rev. 1998,
27, 145.
(24) (a) Hodgson, D. M.; Fleming, M. J.; Xu, Z.; Lin, C.; Stanway,
S. J. Chem. Commun. 2006, 3226. (b) Schomaker, J. M.; Bhattachar-
jee, S.; Yan, J.; Borhan, B. J. Am. Chem. Soc. 2007, 129, 1996.
(7) For a leading reference on chiral amine catalyzed desym-
metrization via bromolactonization, see: Ikeuchi, K.; Ido, S.;
Yoshimura, S.; Asakawa, T.; Inai, M.; Hamashima, Y.; Kan, T. Org.
Lett. 2012, 14, 6016.
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O
O
NH HN
L*
Ph2P
O
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O
PPh2
NTs
R2
R2
O
NHTs
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R1
2-5 mol % Sc(OTf)3/L*
NBS (1.2 equiv)
R1
PhMe/DCM (3:1), -50 oC
up to 90% yield, 97% ee
Br
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