Asymmetric conjugate addition of thioglycolate to a range of chalcones using tetrahydroisoquinoline (TIQ) N,N′-dioxide ligands

Article abstract of DOI:10.1016/j.tetasy.2012.04.010

A series of novel TIQ based N,N′-oxide ligands were synthesised and screened for their catalytic activity in the enantioselective conjugate addition of thioglycolate to chalcones. Bulky groups on the side chain of the TIQ backbone provided the highest enantioselectivity of up to 88% with 10 mol % catalyst loading. It was also observed that these reactions proceeded optimally in the presence of dichloromethane as a solvent. Screening of various metals emphasized La(OTf)₃ as the ideal pre-catalyst for this particular reaction.

Full text of DOI:10.1016/j.tetasy.2012.04.010

Tetrahedron: Asymmetry 23 (2012) 616–622
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric conjugate addition of thioglycolate to a range of chalcones
using tetrahydroisoquinoline (TIQ) N,N0-dioxide ligands
Sai Kumar Chakka a, Zamani E.D. Cele d, Sphelele C. Sosibo d, Vivian Francis a, Per I. Arvidsson b,c
,
a
d,
Hendrik G. Kruger a, , Glenn E.M. Maguire , Thavendran Govender
⇑
⇑
a School of Chemistry, University of KwaZulu-Natal, Durban, South Africa
b Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden
c Innovative Medicines, CNSP iMed, AstraZeneca R&D Sodertalje, S-151 85 Sodertalje, Sweden
d School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
a r t i c l e i n f o
a b s t r a c t
A series of novel TIQ based N,N0-oxide ligands were synthesised and screened for their catalytic activity in
the enantioselective conjugate addition of thioglycolate to chalcones. Bulky groups on the side chain of
the TIQ backbone provided the highest enantioselectivity of up to 88% with 10 mol % catalyst loading.
It was also observed that these reactions proceeded optimally in the presence of dichloromethane as a
solvent. Screening of various metals emphasized La(OTf)3 as the ideal pre-catalyst for this particular
reaction.
Article history:
Received 11 April 2012
Accepted 17 April 2012
Available online 19 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
O
O
iPr
O
N
O
N
O
O
iPr
The need to synthesise enantiomerically pure compounds is a
driving force for the huge interest in the field of asymmetric catal-
ysis.1–3 Reactions involving C–C bond formation provide methods
by which larger molecules can be synthesised.4–7 In this approach,
important reactions, such as Suzuki couplings,8,9 Heck reac-
tions10,11 and Michael additions12,13 play a significant role in or-
ganic chemistry as well as in asymmetric catalysis.
N
N
H
Ph
NH
iPr
HN
iPr
1
2
The Michael addition is ubiquitous in organic chemistry and has
been utilized to produce a diverse array of compounds for applica-
tions in various fields.12–15 Furthermore, the use of this reaction in
applications other than C–C bond formation opens up avenues by
which molecules that possess unique properties can be prepared.
One such deviation is the addition of sulphur as a nucleophile to
N
N
tBu
nBu
O
O
tBu
nBu
O
O
3
a
,b-unsaturated ketones. This type of conjugate addition has been
widely reported on16–19 and applications in total synthesis have al-
Figure 1. Examples of N-oxide ligands utilized in asymmetric catalysis.
ready been proven.20,21
The use of N-oxide containing ligands in asymmetric catalysis is
well documented with numerous examples of catalytic systems
possessing this chemical moiety.22 Some examples of these mole-
cules are shown in Figure 1. Applications of N-oxide ligands include
enantioselective reactions of allyltrichlorosilane with aldehydes
(ligand 1),23 allylation of aldehydes (ligand 2),24,25 asymmetric al-
dol reactions (ligand 3),26–29 asymmetric opening of meso-epox-
ides,30 cyanosilylation of ketones31,32 and Michael additions.33
The use of the TIQ scaffold in asymmetric catalysis is an ongoing
interest in our research group. Its applications include catalytic
asymmetric transfer hydrogenations (ATH),34,35 high pressure
hydrogenations of unsymmetrical olefins,36 Henry type C–C bond
formations37,38 and an organocatalyst in Diels–Alder reactions.39
Based on the seminal work of Feng et al., 40 we decided to examine
the TIQ based catalyst system to see if it could also be utilized in
similar reactions to Feng’s ligands. We recently reported the use
of TIQ based N-oxides as organocatalysts.41 Herein, we report for
the first time the synthesis and application of TIQ N,N0-dioxide
derivatives for asymmetric catalysis. In this preliminary report
⇑
Corresponding authors.
E-mail address: govenderthav@ukzn.ac.za (T. Govender).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.04.010

S. K. Chakka et al. / Tetrahedron: Asymmetry 23 (2012) 616–622
617
O
O
O
R
R
N
H
i
ii
OH
N
H
NH
N
N
Cbz
Cbz
4
5.
R = Phenyl
10. R = Phenyl
11.
6. R = 2-methyl phenyl
R = 2-methyl phenyl
12. R = 2,6-dimethyl phenyl
7.
8.
R = 2,6-dimethyl phenyl
R = 2,6-diisopropyl phenyl
13.
R = 2,6-diisopropyl phenyl
9. R = Benzyl
14. R = Benzyl
O
O
R
N
R
N
H
H
O
N
N
N
N
iii
iv
O
H
N
R
H
N
R
O
O
15.
20.
21.
R = Phenyl
R = Phenyl
R = 2-methyl phenyl
16. R = 2-methyl phenyl
17.
R = 2,6-dimethyl phenyl
18. R = 2,6-diisopropyl phenyl
19.
22. R = 2,6-dimethyl phenyl
23.
R = 2,6-diisopropyl phenyl
24. R = Benzyl
R = Benzyl
Scheme 1. Reagents for the synthesis of TIQ N-oxide ligands 20–24: (i) ethyl chloroformate, triethylamine, anilines, DCM, 0 °C–rt, 18 h; (ii) 10% wt Pd/C, H2 (1 atm), MeOH/
THF, rt, 3 h; (iii) 1,3-dibromopropane, anhydrous K2CO3, ACN, 80 °C, 12 h; (iv) m-CPBA (70%), DCM, ꢀ20 °C to room temperature 1 h.
we chose the benchmark reaction of the conjugate addition of thi-
oglycolate to chalcone to demonstrate the promising use of this
class of ligand.
Ligand 23, which showed the best activity at a loading of
10 mol % was then used to screen a range of solvents under these
reaction conditions (Table 2). Dicholoromethane provided the best
selectivity whilst other chlorinated solvents such as chloroform
and dichloroethane provided moderate to low selectivities (Table 2,
entries 1, 3 and 5). Non-chlorinated solvents such as tetrahydrofu-
ran and acetonitrile, gave poor selectivity and a racemic mixture,
respectively (Table 2, entries 6, 7).
Having identified the most appropriate solvent, various other
lanthanide group metals were screened to identify the best metal
for our system (Table 3). The metal chosen initially was seen to
be the best choice; although all the other metals showed good
yields and drastically lower selectivities were obtained (Table 3,
entries 2–5). This observation is in agreement with that made by
Feng et al.43
The scope of the substrates was then extended using the results
obtained from the optimized conditions (Table 4). Chalcones with
both electron-donating and withdrawing groups had little influ-
ence on the yield or enantioselectivity (87–95% yield, 70–88% ee;
Table 4, entries 1–4). Substrates with sterically bulky substituents
were also tolerated in terms of activity and selectivity (89% yield,
78% ee; Table 4, entry 5).
2. Results and discussion
The ligands were synthesised as described in Scheme 1. The Cbz
protected TIQ acid 442 underwent amide coupling, facilitated by ac-
tive ester formation with ethyl chloroformate, with various substi-
tuted amines to afford intermediates 5–9.43 The cleavage of the Cbz
group was accomplished with 10% wt palladium on carbon under a
hydrogen atmosphere (1 atm) to afford the free amines 10–14.
Bridging of these free secondary amines was accomplished with
K2CO3 and 1,3-dibromopropane in acetonitrile to yield compounds
15–19, respectively. Finally, intermediates 15–19 were oxidized
with m-chloroperbenzoic acid (m-CPBA) in dichloromethane at
ꢀ20 °C to ambient temperature to afford the final ligands 20–24
in good yields (65–75%).
Ligands 20–24 were evaluated for the conjugate addition of thi-
oglycolate to chalcone (Table 1). The catalytic reaction conditions
chosen were adapted from the literature.33,43,44 Ligand 20, derived
from aniline, provided poor selectivity across all ranges of catalytic
loadings (Table 1, entries 3–5). The employment of substituted ani-
lines resulted in a marked increase in selectivity of the ligands. The
2-methyl aniline derivative 21 resulted in a selectivity of 50% (Ta-
ble 1, entry 8) whilst that of 2,6-dimethyl aniline 22 afforded a selec-
tivity of 71% (Table 1, entry 11). An increase in the steric bulk at the
ortho-positions of the anilines resulted in the highest enantioselec-
tivity of 83% (Table 1, entry 14). Reactions at lower temperatures did
not affect the enantioselectivity (Table 1, entry 15). The use of a ben-
zyl amide group resulted in a complete loss of selectivity (Table 1,
entries 16–18). In order to determine if the conjugate addition could
be organocatalysed, we performed the reaction with the addition of
only the ligand (Table 1, entry 19). Taken together with the results
obtained without the ligand or metal (Table 1, entry 1) and without
the ligand but in the presence of metal (Table 1, entry 2), these re-
sults show that there are considerable background reactions taking
place, which may be detrimental to the enantioselectivity.
3. Conclusion
A series of novel TIQ based N-oxide ligands have been synthes-
ised and evaluated in the conjugate addition of thioglycolate to
chalcones. Complexation of these novel ligands with various met-
als showed lanthanum to be the optimum choice for this particular
reaction. These results show that bulkier substituents on the phe-
nyl amide group afforded the highest enantioselectivity. The choice
of solvent also played an important role in the selectivity of the
reaction with chlorinated solvents, in particular dichloromethane,
being the optimum solvent for the reaction. This conjugate addi-
tion is heavily dependent upon the catalytic loading, since high
enantioselectivities were only achieved with loadings of
10 mol %. Further investigations into this new class of ligands are
currently ongoing.

618
S. K. Chakka et al. / Tetrahedron: Asymmetry 23 (2012) 616–622
Table 1
Asymmetric conjugate addition of thioglycolate 26 to chalcone 25a catalysed by ligands 20–24 with La(OTf)3
O
O
S
*
COOCH3
Ligand, La(
OTf
)
3
HS
COOCH3
Ph
Ph
Ph
Ph
dichloromethane, rt
25a
26
27a
Entrya
Ligand
Mol %
Yieldb (%)
eec (%)
1d
2e
3
4
5
6
7
8
9
10
11
12
13
14
15f
16
17
18
19g
—
—
—
10
1
5
10
1
5
10
1
5
10
1
68
85
75
82
90
65
85
92
69
85
93
78
89
95
64
69
78
93
75
rac
rac
rac
2
20
20
20
21
21
21
22
22
22
23
23
23
23
24
24
24
23
6
11
33
50
28
43
71
32
53
83
80
rac
rac
rac
rac
5
10
10
1
5
10
10
a
b
c
d
e
f
All reactions were performed at 0 °C to room temperature for 12 h.
Isolated by column chromatography.
Determined by HPLC with a chiral column (Chiral Pak-IB).
Neither a ligand nor a metal was used.
With metal but without a ligand.
Reaction performed at 0 °C for 18 h.
g
With ligand but in the absence of metal.
shifts are expressed in ppm downfield from TMS as an internal stan-
dard, and coupling constants are reported in Hz. Thin layer chroma-
tography (TLC) was performed using Merck Kieselgel 60 F254.
Crude compounds were purified with column chromatography
using Silica gel (60–200 mesh unless otherwise stated). All solvents
were dried using standard procedures. All IR spectra were recorded
on a Perkin Elmer spectrum 100 instrument with a universal ATR
attachment. Optical rotations were recorded on a Perkin-Elmer
Polarimeter (Model 341). All melting points are uncorrected. High
resolution mass spectrometric data were obtained using a Bruker
micrOTOF-Q II instrument operating at ambient temperatures,
and a sample concentration of approximately 1 ppm.
Table 2
Asymmetric conjugative addition of thioglycolate 26 to chalcone 25a using La(OTf)3
with ligand 23 in different solvents
Entrya
Solvent
Yieldb (%)
eec (%)
1
2
3
4
5
6
ClCH2CH2Cl
ClCH2CH2Cl
CH2Cl2
CHCl3
THF
92
64
95
65
45
35
76
56
83
17
9
CH3CN
rac
a
b
c
All reactions were performed at 0 °C to room temperature.
All products were eluted from column chromatography.
Determined by HPLC on a chiral column (IB-H).
4.2. Typical procedure for the enantioselective conjugate
addition of thioglycolate to chalcones
Table 3
Asymmetric conjugative addition of thioglycolate 26 to chalcone 25a catalysed by
different metals with ligand 23
A
solution of ligand 23 (7.44 mg, 0.001 mmol), La(OTf)3
(5.86 mg, 0.001 mmol) and chalcone (20.8 mg, 0.1 mmol) in anhy-
drous dichloromethane (2 mL) was stirred under microwave irra-
diation at 35 °C for 30 min. The reaction mixture was cooled to
0 °C and the thioglycolate (15.92 mg, 0.15 mmol) was added. The
reaction mixture was then stirred at 0 °C for 2 h, followed by
16 h at room temperature. Solvents were evaporated under re-
duced pressure and the residue was purified by column chroma-
tography using hexane/ethyl acetate, (80:20) to afford the pure
conjugate product. The enantioselectivity was determined by chi-
ral HPLC using the IB column (hexane/2-propanol 90:10,
k = 254 nm); flow rate of 0.8 mL/min. IA column under similar con-
ditions was used for the substrate R1 = Ph, R2 = 4-ClC6H4.
Entrya
Metal
Mol %
Yieldb (%)
eec (%)
1
2
3
4
5
La(OTf)3
Yb(OTf)3
Y(OTf)3
In(OTf)3
Sc(OTf)3
10
10
10
10
10
95
56
35
43
65
83
2
4
1
6
a
b
c
All reactions were performed at 0 °C to room temperature.
All products were eluted from column chromatography.
Determined by HPLC with a chiral column (IB-H).
4. Experimental
4.1. General
4.3. General procedure for the synthesis of amide coupling 5–9
Reagents and solvents were purchased from Aldrich, Merck and
Fluka. All NMR spectra were recorded on Bruker AVANCE III
400 MHz or 600 MHz instruments at room temperature. Chemical
This method was adapted from the literature.43 To a stirred
solution of TIQ Cbz acid 4 (2.0 g, 6.38 mmol) in dichloromethane

S. K. Chakka et al. / Tetrahedron: Asymmetry 23 (2012) 616–622
619
Table 4
Substrate scope for the asymmetric conjugate addition of thioglycolate to chalcones 25
O
O
S
*
COOCH3
Ligand, La(
OTf
)
3
HS
COOCH3
R1
R2
R1
R2
dichloromethane, rt
25
26
27
Entrya
25
R1, R2
Yieldb (%)
eec (%)
1
2
3
4
5
25b
25c
25d
25e
25f
Ph, 4-MeC6H4
4-MeC6H4, Ph
Ph, 4-ClC6H4
Ph, 4-MeOC6H4
Ph, 2-naphthyl
92
88
87
95
89
80
70
88d
88
78
a
b
c
All reactions were performed at 0 °C to room temperature.
All products were eluted from column chromatography.
Determined by HPLC on a chiral column (IB-H).
Determined by HPLC on a chiral column (IA).
d
(20 mL), triethylamine (0.71 g, 7.07 mmol) and ethyl chlorofor-
mate (0.76 g, 7.07 mmol) were added at 0 °C. After 1 h, the substi-
tuted aniline (1.1 equiv) was added and stirred at ambient
temperature for 18 h. Completion of the reaction was monitored
by thin layer chromatography. The reaction mixture was washed
with saturated sodium hydrogen carbonate (20 mL) followed by
brine (10 mL). The organic layer was separated, dried over anhy-
drous magnesium sulphate and purified by column chromatogra-
phy using hexane/ethyl acetate as the mobile phase and silica gel
as the stationary phase.
in one portion and the temperature maintained for 3 h. The reac-
tion mixture was allowed to warm to room temperature and stir-
red for 2 h whilst completion of the reaction was monitored by
TLC. The reaction mixture was diluted with dichloromethane
(5 mL), filtered through a pad of Celite and concentrated under re-
duced pressure to afford the crude N,N0-dioxide compound. The
pure N,N0-dioxide compound was obtained after column chroma-
tography using dichloromethane/methanol as the eluent.
4.7. (S)-Benzyl 3-(phenylcarbamoyl)-3,4-dihydroisoquinoline-
2(1H)-carboxylate 5
4.4. General procedure for the deprotection of the Cbz group
10–14
The synthesis of this compound has already been reported.35
A solution of Cbz-amide (1.0 g) in THF (20 mL) was added to a
suspension of activated Pd/C (500 mg, 10 wt-%) in methanol under
an inert atmosphere. The reaction mixture was connected to an H2
source at 1 atm and stirred at room temperature for 3 h. Comple-
tion of the reaction was monitored by TLC using hexane/ethyl ace-
tate (7:3). The Pd/C was filtered off on a pad of Celite and washed
with ethyl acetate (10 mL) followed by dichloromethane (5 mL).
The filtrate was concentrated under reduced pressure to afford
the crude amide, which was purified by column chromatography
using hexane/ethyl acetate as the mobile phase and silica gel as
the stationary phase.
4.8. (S)-Benzyl 3-(o-tolylcarbamoyl)-3,4-dihydroisoquinoline-
2(1H)-carboxylate 6
Rf = 0.4 (Hexane/ethyl acetate, 7:3). Off white solid (1.7 g, yield
68%); mp: 108–110 °C (hexane/ethyl acetate); ½a D20
¼ ꢀ19:2 (c
ꢂ
0.78, CHCl3); (NMR spectra are reported for a mixture of two rota-
mers). 1H NMR (400 MHz, CDCl3): d 7.74–6.86 (m, 13H), 5.41–4.40
(m, 5H), 3.55–2.99 (m, 2H), 2.05–1.50 (m, 3H); 13C NMR (100 MHz,
CDCl3):d 133.5, 130.3, 128.6, 128.4, 128.1, 127.7, 127.3, 126.8,
126.5, 126.3, 125.4, 123.4, 68.1, 57.1, 49.5, 45.2, 32.1, 16.8; IR
m
max/cmꢀ1 (neat): 3259, 1701, 1661, 1533, 1412, 1202, 760, 698;
HR ESI MS: m/z = 401.1864 [M+H]+ (calcd for C25H25N2O3
4.5. General procedure to form bridge compounds 15–19
401.1860).
This method was adapted from the literature.43 To a solution of
deprotected amine (0.20 g) in acetonitrile (10 mL), anhydrous
K2CO3 (5.0 equiv) followed by 1,3-dibromopropane (1.1 equiv)
was added and stirred under a microwave reactor at 100 °C for
12 h. Completion of the reaction was monitored by TLC using hex-
ane/ethyl acetate. The solvent was evaporated and the crude prod-
uct taken up in ethyl acetate (20 mL), and washed with water
(2 ꢁ 10 mL) followed by brine (10 mL). The organic layer was sep-
arated, dried over anhydrous magnesium sulphate and concen-
trated under reduced pressure to afford the crude bridge
compound, which was purified by column chromatography using
hexane/ethyl acetate as the eluent to give the pure bridged amide
compound.
4.9. (S)-Benzyl 3-(2,6-dimethylphenylcarbamoyl)-3,4-dihydro-
isoquinoline-2(1H)-carboxylate 7
Rf = 0.5 (Hexane/ethyl acetate, 70:30). Off white solid (1.6 g,
yield 48%); mp: 143–145 °C (hexane/ethyl acetate); ½a D20
¼ ꢀ32:0
ꢂ
(c 0.50, CHCl3); (NMR spectra are reported for a mixture of two
rotamers). 1H NMR (400 MHz, CDCl3): d 7.59–6.82 (m, 12H),
5.43–4.91 (m, 3H), 4.91–4.41 (m, 2H), 3.49 (m, 1H), 3.16 (m, 1H),
1.93–1.53 (m, 6H); 13C NMR (100 MHz, CDCl3): d 169.7, 135.4,
133.8, 133.0, 128.8, 128.6, 128.1, 127.4, 126.6, 126.4, 68.3, 56.7,
45.9, 32.5, 17.8; IR
m
max/cmꢀ1 (neat): 3275, 1697, 1650, 1526,
1417, 1207, 1123, 1093, 739; HR ESI MS: m/z = 415.2016 [M+H]+
(calcd for C26H27N2O3 415.2016).
4.6. General procedure to form N-oxide compounds 20–24
4.10. (S)-Benzyl 3-(2,6-diisopropylphenylcarbamoyl)-3,4-dihy-
droisoquinoline-2(1H)-carboxylate 8
To a solution of bridge amide (0.2 g) in dichloromethane
(10 mL) was added anhydrous K2CO3 (5.0 equiv) and the reaction
mixture was cooled to ꢀ20 °C. Next, m-CPBA (2.2 equiv) was added
Rf = 0.4 (Hexane/ethyl acetate, 70:30). Off white solid (1.5 g,
yield 51%); mp: 60–62 °C (hexane/ethyl acetate); ½a D20
¼ ꢀ11:3 (c
ꢂ

620
S. K. Chakka et al. / Tetrahedron: Asymmetry 23 (2012) 616–622
0.53, CHCl3); (NMR spectra are reported for a mixture of two rota-
mers). 1H NMR (400 MHz, CDCl3): d 7.52–6.93 (m, 12H), 5.58–5.00
(m, 3H), 4.93–4.52 (m, 2H), 3.53 (m, 1H), 3.12 (m, 1H), 1.22 (m,
2H), 0.88 (m, 12H); 13C NMR (100 MHz, CDCl3): d 170.6, 146.1,
132.6, 128.7, 128.4, 127.9, 123.2, 68.2, 56.6, 45.9, 32.2, 28.2, 23.6;
4.17. (3S,30S)-2,20-(Propane-1,3-diyl)bis(N-phenyl-1,2,3,4-tetra-
hydroisoquinoline-3-carboxamide) 15
Rf = 0.5 (Hexane/ethyl acetate, 1:1). Colourless oil (0.16 g, yield
68%); ½a 2D0
ꢂ
¼ ꢀ28:6 (c 0.35, CH2Cl2); 1H NMR (400 MHz, CDCl3): d
IR
755, 694; HR ESI MS: m/z = 471.2639 [M+H]+ (calcd for
30H35N2O3 471.2642).
m
max/cmꢀ1 (neat): 3280, 1643, 1547, 1453, 1222, 1029, 963,
9.11 (s, 2H), 7.43 (d, J = 7.84 Hz, 4H), 7.26 (t, J = 7.44 Hz, 4H),
7.22–7.12 (m, 6H), 7.11–7.01 (m, 4H), 3.92 (d, J = 15.00 Hz, 2H),
3.72 (d, J = 14.84 Hz, 2H), 3.47 (t, J = 6.78 Hz, 2H), 3.17–3.04 (m,
4H), 2.71–2.57 (m, 4H), 1.85 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 171.4, 137.6, 134.5, 134.2, 129.1, 128.2, 127.4, 126.6, 126.4,
C
4.11. (S)-Benzyl 3-(benzylcarbamoyl)-3,4-dihydroisoquinoline-
2(1H)-carboxylate 935
124.2, 119.3, 63.3, 52.0, 28.3, 26.5; IR
m
max/cmꢀ1 (neat): 3281,
2955, 2926, 1684, 1599, 1517, 1440, 1287, 1123, 1075, 743, 692;
HR ESI MS: m/z = 545.2917 [M+H]+ (calcd for C35H37N4O2
545.2911).
The synthesis of this compound has already been reported.35
4.12. (S)-N-Phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxa-
mide 1035
4.18. (3S,30S)-2,20-(Propane-1,3-diyl)bis(N-o-tolyl-1,2,3,4-tetra-
hydroisoquinoline-3-carboxamide) 16
The synthesis of this compound has already been reported.35
Rf = 0.4 (Hexane/ethyl acetate, 1:1). Yellow oil (0.16 g, yield
4.13. (S)-N-o-Tolyl-1,2,3,4-tetrahydroisoquinoline-3-carboxa-
mide 11
69%); ½a 2D0
ꢂ
¼ ꢀ15:15 (c 0.33 in CHCl3); 1H NMR (400 MHz, CDCl3):
d 9.14 (s, 2H), 7.92 (d, J = 7.96 Hz, 2H), 7.22–7.12 (m, 8H), 7.11–7.04
(m, 4H), 7.03–6.96 (m, 2H), 3.92 (d, J = 14.12 Hz, 2H), 3.71 (d,
J = 14.12 Hz, 2H), 3.53 (t, J = 6.12 Hz, 2H), 3.13 (d, J = 6.12 Hz, 4H),
2.80–2.62 (m, 4H), 1.95–1.85 (m, 8H); 13C NMR (100 MHz, CDCl3):
d 171.5, 135.8, 135.2, 134.4, 130.4, 128.1, 127.6, 126.9, 126.7,
Rf = 0.3 (Hexane/ethyl acetate, 7:3). Off white solid (0.6 g, yield
90%); mp: 124–126 °C (hexane/ethyl acetate); ½a D20
¼ ꢀ60:0 (c
ꢂ
0.50, CHCl3); 1H NMR (400 MHz, CDCl3): d 9.40 (s, 1H), 8.08 (d,
J = 7.96 Hz, 2H), 7.25–7.15 (m, 3H), 7.09 (m, 1H), 7.04 (m, 1H),
4.06 (d, J = 9.96 Hz, 2H), 3.74 (q, J = 9.98, 5.58 Hz, 1H), 3.35 (dd,
J = 16.28, 5.56 Hz, 1H), 2.94 (dd, J = 16.28, 10.22 Hz, 1H), 2.27 (s,
3H); 13C NMR (100 MHz, CDCl3): d 171.4, 136.4, 135.9, 134.6,
130.4, 129.2, 127.8, 127.0, 126.9, 126.5, 125.6, 124.5, 121.4, 57.0,
126.2, 124.5, 121.3, 63.5, 54.0, 51.9, 29.4, 26.7, 17.5; IR mmax
/
cmꢀ1 (neat): 3287, 2955, 2926, 1724, 1686, 1586, 1518, 1454,
1289, 1120, 745; HR ESI MS: m/z = 573.3228 [M+H]+ (calcd for
C37H41N4O2 573.3224).
47.4, 30.8, 17.8; IR
m
max/cmꢀ1 (neat): 3280, 2905, 1659, 1587,
4.19. (3S,30S)-2,20-(Propane-1,3-diyl)bis(N-(2,6-dimethylphenyl)-1,
1531, 1455, 1125, 1042, 807, 724, 715; HR ESI MS: m/
2,3,4-tetrahydroisoquinoline-3-carboxamide) 17
z = 267.1491 [M+H]+ (calcd for C17H19N2O 267.1492).
Rf = 0.4 (Hexane/ethyl acetate, 1:1). Pale yellow oil (.15 g, yield
4.14. (S)-N-(2,6-Dimethylphenyl)-1,2,3,4-tetrahydroisoquinoline-
3-carboxamide 12
65%); ½a 2D0
ꢂ
¼ ꢀ35:7 (c 0.14, CH2Cl2); 1H NMR (400 MHz, CDCl3): d
8.7 (s, 2H), 7.24–7.11 (m, 8H), 7.08–6.89 (m, 6H), 3.98 (d,
J = 13.12 Hz, 2H), 3.71 (d, J = 13.08 Hz, 2H), 3.60 (q, J = 7.16,
3.44 Hz, 2H), 3.26 (dd, J = 15.28, 3.44 Hz, 2H), 3.13 (dd, J = 15.16,
7.24 Hz, 2H), 2.91–2.75 (m, 4H), 2.04 (m, 2H), 1.90 (s, 12H); 13C
NMR (100 MHz, CDCl3): d 171.7, 135.6, 134.7, 133.7, 128.2, 128.0,
127.7, 127.1, 126.8, 126.1, 63.1, 54.7, 52.1, 30.4, 26.5, 18.4; IR
Rf = 0.4 (Hexane/ethyl acetate, 7:3). Off white solid (0.61 g, yield
91%); mp: 195–197 °C (hexane/ethyl acetate); ½a D20
¼ ꢀ78:8 (c
ꢂ
0.33, CHCl3); 1H NMR (400 MHz, CDCl3): d 8.76 (s, 1H), 7.24–7.16
(m, 3H), 7.13–7.03 (m, 4H), 4.09 (d, J = 10.48 Hz, 2H), 3.80 (q,
J = 9.38, 5.62 Hz, 1H), 3.33 (dd, J = 16.14, 5.58 Hz, 1H), 3.01 (dd,
J = 16.08, 9.40 Hz, 1H), 2.17 (s, 6H); 13C NMR (100 MHz, CDCl3): d
171.8, 136.3, 135.1, 134.6, 133.9, 129.1, 128.2, 127.1, 127.0,
m
max/cmꢀ1 (neat): 3205, 2955, 1725, 1646, 1520, 1263, 1135, 764,
728; HR ESI MS: m/z = 601.3538 [M+H]+ (calcd for C39H45N4O2
601.3537).
126.5, 125.7, 56.5, 47.3, 31.3, 18.5; IR
m
max/cmꢀ1 (neat): 3250,
2928, 1670, 1594, 1525, 1466, 1220, 761, 742, 713; HR ESI MS:
4.20. (3S,30S)-2,20-(Propane-1,3-diyl)bis(N-(2,6-diisopropylphe-
nyl)-1,2,3,4-tetrahydroisoquinolin-e-3-carboxamide) 18
m/z = 281.1648 [M+H]+ (calcd for C18H21N2O 281.1649).
4.15. (S)-N-(2,6-Diisopropylphenyl)-1,2,3,4-tetrahydroisoquino-
line-3-carboxamide 13
Rf = 0.4 (Hexane/ethyl acetate, 7:3); Colourless oil (0.17 g, yield
75%); ½a 2D0
ꢂ
¼ ꢀ12:5 (c 0.16, CH2Cl2); 1H NMR (400 MHz, CDCl3): d
8.73 (s, 2H), 7.31–7.14 (m, 9H), 7.11–6.98 (m, 5H), 4.00 (d,
J = 13.12 Hz, 2H), 3.69 (d, J = 13.12 Hz, 2H), 3.62 (q, J = 7.14,
2.42 Hz, 2H), 3.31 (dd, J = 15.05, 3.10 Hz, 2H), 3.1 (dd, J = 15.14,
7.22 Hz, 2H), 2.99–2.77 (m, 4H), 2.14–2.04 (m, 2H), 1.64 (m, 4H),
1.03 (m, 24H); 13C NMR (100 MHz, CDCl3): d 173.1, 145.7, 136.0,
135.0, 131.2, 128.1, 127.87, 127.80, 126.8, 126.1, 123.4, 63.3,
Rf = 0.4 (Hexane/ethyl acetate, 7:3). Off white solid (0.66 g, yield
93%); mp: 142–144 °C (hexane/ethyl acetate); ½a D20
¼ ꢀ58:3 (c
ꢂ
0.48, CHCl3); 1H NMR (400 MHz, CDCl3): d 8.76 (s, 1H), 7.29–7.06
(m, 7H), 4.09 (d, J = 15.72 Hz, 2H), 3.85 (q, J = 8.84, 5.76 Hz, 1H),
3.31 (dd, J = 16.0, 5.72 Hz, 1H), 3.05 (dd, J = 15.98, 8.90 Hz, 1H),
2.88 (m, 2H), 1.15 (d, J = 6.88 Hz, 12H); 13C NMR (100 MHz, CDCl3):
d 172.9, 145.9, 136.4, 134.8, 131.3, 129.0, 128.1, 127.0, 126.5,
55.4, 51.9, 30.6, 28.6, 26.8, 23.8, 23.7; IR m
max/cmꢀ1 (neat): 3269,
2958, 2925, 1664, 1486, 1472, 1256, 1129, 1098, 797, 738, 510;
HR ESI MS: m/z = 713.4794 [M+H]+ (calcd for C47H61N4O2
713.4789).
125.7, 123.4, 56.3, 47.2, 31.2, 28.9, 23.7; IR
m
max/cmꢀ1 (neat):
3234, 2958, 1671, 1494, 1454, 1471, 799, 742; HR ESI MS: m/
z = 337.2274 [M+H]+ (calcd for C22H29N2O 337.2273).
4.21. (3S,30S)-2,20-(Propane-1,3-diyl)bis(N-benzyl-1,2,3,4-tetra-
4.16. (S)-N-Benzyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
hydroisoquinoline-3-carboxamide) 19
1435
Rf = 0.4 (Hexane/ethyl acetate, 3:2). Yellow oil (0.16 g, yield
The synthesis of this compound has already been reported.35
69%); ½a 2D0
ꢂ
¼ ꢀ5:9 (c 0.17, CHCl3); 1H NMR (400 MHz, CDCl3): d

S. K. Chakka et al. / Tetrahedron: Asymmetry 23 (2012) 616–622
621
7.50 (m, 2H), 7.25–7.15 (m, 13H), 7.05 (d, J = 6.52 Hz, 2H), 6.92 (m,
3H), 4.45 (dd, J = 15.04, 6.88 Hz, 2H), 4.18 (dd, J = 15.04, 5.28 Hz,
2H), 3.77 (d, J = 14.32 Hz, 2H), 3.54 (d, J = 14.53 Hz, 2H), 3.38 (t,
J = 6.33 Hz, 2H), 3.11 (dd, J = 15.99, 6.08 Hz, 2H), 3.03 (dd,
J = 15.82, 6.60 Hz, 2H), 2.48 (t, J = 7.26 Hz, 4H), 1.64 (m, 2H); 13C
NMR (100 MHz, CDCl3): d 173.2, 138.3, 135.1, 134.4, 128.5, 128.0,
(dd, J = 17.06, 4.74 Hz, 2H), 3.19–3.02 (m, 4H), 2.31 (m, 2H),
1.31–1.11 (m, 24H); 13C NMR (100 MHz, CDCl3): d 169.6, 166.5,
164.7, 145.9, 145.2, 136.0, 133.0, 131.0, 129.9, 128.9, 128.3,
128.0, 127.4, 126.5, 123.5, 72.6, 66.5, 60.7, 45.3, 31.8, 29.8, 29.1,
23.8, 23.6, 22.5; IR
m
max/cmꢀ1 (neat): 3248, 2960, 2927, 2868,
1724, 1681, 1500, 1458, 1383, 1272, 1122, 797, 740; HR ESI MS:
127.2, 126.4, 126.2, 62.6, 53.1, 52.0, 42.8, 29.3, 26.1; IR mmax
/
m/z = 745.4686 [M+H]+ (calcd for C47H61N4O4 745.4686).
cmꢀ1 (neat): 3298, 2928, 1650, 1517, 1496, 1453, 1257, 1029,
742, 698; HR ESI MS: m/z = 573.3227 [M+H]+ (calcd for
4.26. (3S,30S)-2,20-(Propane-1,3-diyl)bis(3-(benzylcarbamoyl)-1,
C37H41N4O2 573.3224).
2,3,4-tetrahydroisoquinoline 2-oxide) 24
4.22. (3S,30S)-2,20-(Propane-1,3-diyl)bis(3-(phenylcarbamoyl)-1,
2,3,4-tetrahydroisoquinoline 2-oxide) 20
Rf = 0.4 (CH2Cl2/MeOH, 9.8:0.2). Off white solid (0.17 g, yield
81%); mp: 72–74 °C (DCM/MeOH); ½a D20
¼ ꢀ22:2 (c 0.18, CH2Cl2);
ꢂ
1H NMR (400 MHz, CDCl3): d 10.46 (s, 2H), 7.83–6.68 (m, 18H),
4.80–4.14 (m, 8H), 3.68–2.84 (m, 6H), 2.80–1.93 (m, 6H); 13C
NMR (100 MHz, CDCl3): d 167.2, 138.2, 130.9, 130.1, 128.7, 128.6,
128.4, 128.2, 128.0, 127.9, 127.6, 127.4, 127.1, 126.5, 72.8, 66.1,
Rf = 0.4 (CH2Cl2/MeOH, 9.8:0.2). White solid (0.15 g, yield 71%);
mp: 100–102 °C (DCM/MeOH); ½a D20
ꢂ
¼ ꢀ27:3 (c 0.11, CH2Cl2); 1H
NMR (400 MHz, CDCl3): d 12.62 (s, 2H), 7.67–7.46 (m, 4H), 7.36–
6.92 (m, 14H), 4.82–4.37 (m, 4H), 4.35–4.01 (m, 2H), 3.99–3.47
(m, 4H), 3.48–3.11 (m, 4H), 2.78–2.25 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 165.0, 137.9, 129.9, 129.7, 129.0, 128.9,
128.5, 128.4, 128.2, 127.8, 127.6, 127.3, 126.7, 126.3, 124.5,
65.2, 43.0, 29.6, 16.5; IR
m
max/cmꢀ1 (neat): 3230, 2927, 1727,
1670, 1542, 1497, 1454, 1271, 1120, 1029, 919, 740, 699; HR ESI
MS: m/z = 605.3129 [M+H]+ (calcd for C37H41N4O4 605.3122).
120.1, 73.0, 68.0, 66.1, 29.6, 29.3, 29.0, 25.7, 17.3; IR
m
max/cmꢀ1
Acknowledgements
(neat): 2958, 1726, 1683, 1597, 1552, 1497, 1290, 1077, 906,
753, 692; HR ESI MS: m/z = 577.2808 [M+H]+ (calcd for
This work is supported by the UKZN productivity research grant
and Aspen Pharmacare, SA. The NRF is thanked for their support.
C35H37N4O4 577.2809).
4.23. (3S,30S)-2,20-(Propane-1,3-diyl)bis(3-(o-tolylcarbamoyl)-1,
2,3,4-tetrahydroisoquinoline 2-oxide) 21
References
1. Noyori, R. John Wiley & Sons: New York, 1994.
2. Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Comprehensive Asymmetric Catalysis;
Springer: New York, 1999.
3. Blaser, H.-U.; Schmidt, E. Asymmetric Catalysis on Industrial Scale; Wiley-VCH
GmbH & Co.: KGaA, 2004.
4. Hou, X. L.; You, S. L.; Tu, T.; Deng, W. P.; Wu, X. W.; Li, M.; Yuan, K.; Zhang, T. Z.;
Dai, L. X. Top. Catal. 2005, 35, 87–103.
5. Oppolzer, W. Sel., Goal Synth. Effic., Proc. Workshop Conf. Hoechst, 14th 1984,
137–167.
6. Noyori, R.; Kitamura, M. Mod. Synth. Methods 1989, 5, 115–198.
7. Sukumaran, J.; Hanefeld, U. Chem. Soc. Rev. 2005, 34, 530–542.
8. Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2009, 48, 3565–3568.
9. Molander, G. A.; Bernardi, C. R. J. Org. Chem. 2002, 67, 8424–8429.
10. Ruan, J. W.; Saidi, O.; Iggo, J. A.; Xiao, J. L. J. Am. Chem. Soc. 2008, 130, 10510.
11. Chandrasekhar, S.; Narsihmulu, C.; Sultana, S. S.; Reddy, N. R. Org. Lett. 2002, 4,
4399–4401.
12. Angelo, J. D.; Cave, C.; Desmaele, D.; Dumas, F. Trends Org. Chem. 1993, 4, 555–
616.
13. D’Angelo, J.; Desmaele, D.; Dumas, F.; Guingant, A. Tetrahedron: Asymmetry
1992, 3, 459–505.
14. Takemoto, Y. Chem. Pharm. Bull. (Tokyo) 2010, 58, 593–601.
15. Garcia, J. M.; Oiarbide, M.; Palomo, C. Catal. Asymmetric Friedel-Crafts
Alkylations 2009, 17–99.
16. Marigo, M.; Schulte, T.; Franzen, J.; Jorgensen, K. A. J. Am. Chem. Soc. 2005, 127,
15710–15711.
17. Emori, E.; Arai, T.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 4043–
4044.
18. Abe, A. M. M.; Sauerland, S. J. K.; Koskinen, A. M. P. J. Org. Chem. 2007, 72, 5411–
5413.
19. Liu, Y.; Sun, B. F.; Wang, B. M.; Wakem, M.; Deng, L. J. Am. Chem. Soc. 2009, 131,
418.
20. Trost, B. M.; Keeley, D. E. J. Org. Chem. 1975, 40, 2014.
21. Shono, T.; Matsumura, Y.; Kashimura, S.; Hatanaka, K. J. Am. Chem. Soc. 1979,
101, 4752–4753.
22. Malkov, A. V.; Kocovsky, P. Eur. J. Org. Chem. 2007, 29–36.
23. Traverse, J. F.; Zhao, Y.; Hoveyda, A. H.; Snapper, M. L. Org. Lett. 2005, 7, 3151–
3154.
24. Nakajima, M.; Saito, M.; Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120,
6419–6420.
Rf = 0.4 (CH2Cl2/MeOH, 9.8:0.2). White solid (0.14 g, yield 66%);
mp: 112–114 °C (DCM/MeOH); ½a D20
ꢂ
¼ ꢀ20:0 (c 0.1, CH2Cl2); 1H
NMR (400 MHz, CDCl3): d 12.63 (s, 2H), 8.05 (d, J = 8.04 Hz, 2H),
7.34–6.93 (m, 14H), 4.67 (d, J = 15.16 Hz, 2H), 4.48 (d,
J = 15.16 Hz, 2H), 3.95 (dd, J = 17.16, 8.56 Hz, 2H), 3.78–3.62 (m,
4H), 3.24 (dd, J = 16.90, 4.58 Hz, 2H), 2.99–2.86 (m, 2H), 2.28–
2.15 (m, 8H); 13C NMR (100 MHz, CDCl3): d 165.0, 136.1, 130.4,
129.9, 128.9, 128.4, 128.3, 128.2, 128.0, 127.5, 127.4, 127.2,
126.7, 126.5, 124.4, 120.9, 72.7, 66.2, 66.0, 50.6, 29.7, 29.4, 29.0,
18.3, 17.3; IR
m
max/cmꢀ1 (neat): 2918, 1677, 1588, 1547, 1458,
1290, 753; HR ESI MS: m/z = 605.3118 [M+H]+ (calcd for
C37H41N4O4 605.3122).
4.24. (3S,30S)-2,20-(Propane-1,3-diyl)bis(3-(2,6-dimethylphenyl-
carbamoyl)-1,2,3,4-tetrahydroisoquinoline 2-oxide) 22
Rf = 0.4 (CH2Cl2/MeOH, 9.8:0.2). Off white solid (0.13 g, yield
62%); mp: 106–108 °C (DCM/MeOH);
½
a 2D0
ꢂ
¼ ꢀ26:7 (c 0.15,
CH2Cl2); 1H NMR (400 MHz, CDCl3): d 11.82 (s, 2H), 7.34–7.19
(m, 5H), 7.14–6.95 (m, 9H), 4.82 (d, J = 15.20 Hz, 2H), 4.54 (d,
J = 15.24 Hz, 2H), 4.03 (dd, J = 17.10, 8.30 Hz, 2H), 3.95–3.68 (m,
4H), 3.31 (dd, J = 17.08, 4.88 Hz, 2H), 3.00 (m, 2H), 2.21 (s, 12H),
2.30–2.12 (m, 2H); 13C NMR (100 MHz, CDCl3): d165.1, 134.1,
133.5, 130.9, 129.8, 128.8, 128.3, 128.2, 128.1, 127.4, 127.2, 27.1,
126.9, 126.6, 72.9, 66.0, 65.6, 29.9, 19.0, 18.4; IR m
max/cmꢀ1 (neat):
2958, 2926, 1728, 1682, 1522, 1470, 1377, 1285, 1123, 1073, 767,
741; HR ESI MS: m/z = 633.3435 [M+H]+ (calcd for C39H45N4O4
633.3435).
4.25. (3S,30S)-2,20-(Propane-1,3-diyl)bis(3-(2,6-diisopropylphe-
nylcarbamoyl)-1,2,3,4-tetrahydroisoquinoline 2-oxide) 23
25. Malkov, A. V.; Bell, M.; Orsini, M.; Pernazza, D.; Massa, A.; Herrmann, P.;
Meghani, P.; Kocovsky, P. J. Org. Chem. 2003, 68, 9659–9668.
26. Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2002, 124, 4233–4235.
27. Denmark, S. E.; Fujimori, S.; Pham, S. M. J. Org. Chem. 2005, 70, 10823–10840.
28. Wang, F.; Liu, X. H.; Zhang, Y. L.; Lin, L. L.; Feng, X. M. Chem. Commun. 2009,
7297–7299.
29. Qin, B.; Xiao, X.; Liu, X. H.; Huang, J. L.; Wen, Y. H.; Feng, X. M. J. Org. Chem.
2007, 72, 9323–9328.
30. Gao, B.; Wen, Y.; Yang, Z.; Huang, X.; Liu, X.; Feng, X. Adv. Synth. Catal. 2008,
350, 385–390.
Rf = 0.4 (CH2Cl2/MeOH, 9.8:0.2). Off white solid (0.16 g, yield
77%); mp: 78–80 °C (DCM/MeOH); ½a D20
¼ ꢀ38:5 (c 0.13, CH2Cl2);
ꢂ
1H NMR (400 MHz, CDCl3): d 11.96 (s, 2H), 7.33–7.13 (m, 9H),
7.04 (m, 5H), 4.81 (d, J = 15.40 Hz, 2H), 4.56 (d, J = 15.40 Hz, 2H),
4.18–4.02 (m, 2H), 3.90 (m, 2H), 3.65 (m, 2H), 3.46 (m, 2H), 3.31

622
S. K. Chakka et al. / Tetrahedron: Asymmetry 23 (2012) 616–622
31. Chen, F. X.; Feng, X. M.; Qin, B.; Zhang, G. L.; Jiang, Y. Z. Org. Lett. 2003, 5, 949–
952.
38. Pawar, S. S.; Chakka, S. K.; Andersson, P. G.; Kruger, H. G.; Maguire, G. E. M.;
Govender, T. S. Afr. J. Chem. 2012, 65, 23–29.
32. Chen, F. X.; Qin, B.; Feng, X. M.; Zhang, G. L.; Jiang, Y. Z. Tetrahedron 2004, 60,
10449–10460.
33. Wang, Z.; Chen, D. H.; Yang, Z. G.; Bai, S.; Liu, X. H.; Lin, L. L.; Feng, X. M. Chem.
Eur. J. 2010, 16, 10130–10136.
39. Naicker, T.; Petzold, K.; Singh, T.; Arvidsson, P. I.; Kruger, H. G.; Maguire, G. E.
M.; Govender, T. Tetrahedron: Asymmetry 2010, 21, 2859–2867.
40. Yu, Z.; Liu, X.; Dong, Z.; Xie, M.; Feng, X. Angew. Chem. Int. Ed. 2008, 47, 1308–
1311.
34. Chakka, S. K.; Andersson, P. G.; Maguire, G. E. M.; Kruger, H. G.; Govender, T.
Eur. J. Org. Chem. 2010, 972–980.
41. Naicker, T.; Arvidsson, P. I.; Kruger, H. G.; Maguire, G. E. M.; Govender, T. Eur. J.
Org. Chem. 2011, 6923–6932.
35. Peters, B. K.; Chakka, S. K.; Naicker, T.; Maguire, G. E. M.; Kruger, H. G.;
Andersson, P. G.; Govender, T. Tetrahedron: Asymmetry 2010, 21, 679–687.
36. Chakka, S. K.; Peters, B. K.; Andersson, P. G.; Maguire, G. E. M.; Kruger, H. G.;
Govender, T. Tetrahedron: Asymmetry 2010, 21, 2295–2301.
37. Kawthekar, R. B.; Chakka, S. K.; Francis, V.; Andersson, P. G.; Kruger, H. G.;
Maguire, G. E. M.; Govender, T. Tetrahedron: Asymmetry 2010, 21, 846–852.
42. Tarver, J. E., Jr.; Pfizenmayer, A. J.; Joullie, M. M. J. Org. Chem. 2001, 66, 7575–
7587.
43. Hui, Y. H.; Jiang, J.; Wang, W. T.; Chen, W. L.; Cai, Y. F.; Lin, L. L.; Liu, X. H.; Feng,
X. M. Angew. Chem., Int. Ed. 2010, 49, 4290–4293.
44. Wen, Y. H.; Gao, B.; Fu, Y. Z.; Dong, S. X.; Liu, X. H.; Feng, X. M. Chem. Eur. J.
2008, 14, 6789–6795.