Enantioselective synthesis of chiral 1,2-diamines by the catalytic ring opening of azabenzonorbornadienes: Application in the preparation of new chiral ligands

Article abstract of DOI:10.1016/j.tetasy.2005.12.024

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl]₂ and (S,S′)-(R,R′)-C₂-ferriphos- tolyl, the asymmetric ring-opening reaction of N-Boc-azabenzonorbornadienes with dibenzylamine proceeded with excelle

Full text of DOI:10.1016/j.tetasy.2005.12.024

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 17 (2006) 416–427
Enantioselective synthesis of chiral 1,2-diamines by the
catalytic ring opening of azabenzonorbornadienes: application in
the preparation of new chiral ligands
Yong-Hwan Cho, Aude Fayol and Mark Lautens*
Davenport Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5H 3H6
Received 14 December 2005; accepted 20 December 2005
Available online 3 February 2006
Abstract—In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl]2 and (S,S0)-(R,R0)-C2-ferriphos-tolyl,
the asymmetric ring-opening reaction of N-Boc-azabenzonorbornadienes with dibenzylamine proceeded with excellent enantioselec-
tivity (up to >99% ee) to give the corresponding 1,2-diamine scaffolds in high yields. The sequential deprotection of the ring-opened
products and treatment with tartaric acid gave the enantiomerically pure 1,2-diamine tartrate salts. These salts were used for the
preparation of new chiral ligands such as the salen-type ligands and Trost-type ligands.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
catalyzed ring-opening reactions of azabenzonorborna-
dienes with dibenzylamine. Also described is the prepa-
ration of new chiral ligands from the 1,2-diamine
scaffolds thus obtained.
Chiral vicinal 1,2-diamines have been found to be an
important subunit in a large number of bioactive natural
products, such as biotin1 (vitamin H) and several pep-
tidic antibiotics.2 This functionality can also be found
in important medicinal compounds such as 1,2-diamino-
platinum(II) complexes.3
2. Results and discussion
For the catalytic asymmetric synthesis of 1,2-diamine
scaffolds starting from N-Boc protected azabenzonor-
bornadienes, four azabenzonorbornadienes 1a–d were
prepared and reacted (Scheme 1). Since the deprotection
of the Boc group is easier than others and high-yielding,
N-Boc-azabenzonorbornadienes 1 are more versatile
substrates to find efficient conditions for ring-opening
than others. N-Boc-azabenzonorbornadiene 1a and
5,8-dimethyl product 1b were prepared by Diels–Alder
reaction of N-Boc-pyrrole with arynes generated
in situ by diazotization of the corresponding anthranilic
acids8 with isoamyl nitrite followed by heating in 55%
yield and 30% yield, respectively. Also, the Diels–Alder
reaction of N-Boc-pyrrole with arynes generated by
treatment of 1,2-dibromotetramethylbenzene9 and 1,2-
dibromo-4,5-di-methylbenzene10 with n-butyllithium11
gave 5,6,7,8-tetramethyl product 1c and 6,7-dimethyl
product 1d in 36% yield and 33% yield, respectively.
In addition, 1,2-diamines have found extensive use as
chiral auxiliaries for a variety of asymmetric reactions
and scaffolds for the synthesis of chiral ligands,4 such
as the salen-type5 and Trost-type ligands.6 These appli-
cations are brought about considerable attention for
their preparation and the development of synthetic
methods which can realize high diastereoselectivity and
enantioselectivity in the synthesis of vicinal 1,2-diam-
ines.7 There are many methods for the synthesis of chiral
1,2-diamines using stoichiometric amounts of chiral
auxiliaries, however, a catalytic process giving enantio-
merically enriched 1,2-diamines from achiral substrates
using transition metal catalysts still remains to be
developed.
Herein we report the asymmetric synthesis of enantio-
merically pure 1,2-diamine scaffolds by using rhodium-
*
With a range of azabenzonorbornadiene starting materi-
als in hand, we proceeded to study the synthesis of chiral
Corresponding author. Tel.: +1 416 978 6083; fax: +1 416 946
8185; e-mail: mlautens@chem.utoronto.ca
0957-4166/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.12.024

Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
417
O
R1
R1
1.
ONO
O
N
CO2H
NH2
R1
trichloroacetic acid
2. 1,2-dichloroethane, 80
O
C
˚
R1
N
O
1a (R1 = H): 55% yield
1b (R1 = Me): 30% yield
O
R2
O
N
Me
Me
Br
Br
R2
n
-BuLi, toluene, 0 C to rt
˚
Me
O
R2
N
O
Me
R2
Figure 1. Crystal structure of 5a.
1c (R2 = Me): 36% yield
1d (R2 = H): 33% yield
However, this reaction requires relatively high catalytic
loading and excess amount of amine nucleophile. There-
fore, it was necessary to develop new conditions for a
large scale synthesis. We were fortunate to find that
the use of a catalytic amount (20 mol %) of triethylam-
monium hydroiodide (Et3NHI) and N,N-diisopropyl-
ethylamine (i-Pr2NEt) as a base showed a dramatic
improvement in reducing the catalyst loading and
amount of nucleophile in the present reaction (Scheme
2, Table 1). It was found that the combined use of protic
and halide additives effectively alleviate the poisoning of
a catalyst by amines which are known to bind strongly
to the metal center.15 Whereas the reaction of 1a with
dibenzylamine gave 58% yield of 2a in the presence of
2.5 mol % of [Rh(cod)Cl]2 (Table 1, entry 1), the reac-
tion using Et3NHI and i-Pr2NEt proceeded with a lower
catalytic loading (1.0 mol % of [Rh(cod)Cl]2) to give
86% yield of 2a (entry 3).
Scheme 1. Synthesis of N-Boc-azabenzonorbornadienes 1a–d.
1,2-diamine scaffolds using the catalytic asymmetric
ring-opening with several primary and secondary
amines. Amines with removable functional groups were
selected to enable the synthesis of free primary diamines
as the final products. For these studies, we started by
using conditions previously reported by our group utiliz-
ing rhodium catalysts and ferrocenyl phosphine ligands
for the ring opening of azabicyclic alkenes with amine
nucleophiles.12 Among those amines, N,N-dibenzyl-
amine was found to be effective for the present reaction.
The reaction of 1a with primary amines, such as benzyl-
amine and 4-methoxy-benzylamine, used successfully
for the asymmetric ring-opening reaction of oxabenzo-
norbornadiene, did not give the desired ring-opening
product under the same conditions.13 However, in the
presence of 2.5 mol % of [Rh(cod)Cl]2 and 10 mol % of
(S,S0)-(R,R0)-C2-ferriphos 3a,14 the reaction of 1a with
N,N-dibenzylamine (5.0 equiv) at 110 °C for 24 h gave
the corresponding ring-opening product 2a in 80% yield.
The enantiomeric purity of 2a was determined to be 89%
ee by HPLC analysis with a chiral stationary phase col-
umn (Chiralcel OD). The absolute configuration was
determined to be 1S,2S by X-ray analysis of 1,2,3,4-tetra-
hydronaphthyl-1,2-diamine tartrate salt prepared from
2a (see Fig. 1).
O
O
[Rh(cod)Cl]2, dppf
N
Bn2N
O
dibenzylamine, Et3NHI, iPr2NEt
NH
1,4-dioxane, 110 °C
O
1a
( )-2a
Scheme 2. Catalytic ring opening of N-Boc-azabenzonorbornadiene 1a
with dibenzylamine in the presence of Et3NHI.
Table 1. Catalytic ring opening of 1a with dibenzylamine in the presence of triethylammonium iodidea
Entry
[Rh(cod)Cl]2 (mol %)
Et3NHI (mol %)
Concd. (M)
Base
Time (h)
Yieldb (%)
1c
2
3
4
5
6
7
2.5
1.0
1.0
1.0
0.5
0.1
0.1
—
20
20
20
10
2
Neat
0.2
0.2
0.4
0.4
0.4
2.0
—
—
48
48
48
24
24
60
60
58
n.d.
86
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
90
84
38d
25e
2
a The reaction was carried out with 1a (0.25 mmol), dibenzylamine (1.1 equiv), Et3NHI, and i-Pr2NEt (1.1 equiv) in 1,4-dioxane at 110 °C in the
presence of [Rh(cod)Cl]2 and dppf (1.5 equiv to Rh).
bIsolated yield after silica gel column chromatography.
c The reaction was carried out with 5.0 equiv of dibenzylamine without additive and solvent.
d 55% of 1a was recovered.
e 70% of 1a was recovered.

418
Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
O
The addition of an iodide source led to an increase in
reactivity, which follows the halide effect trends (i.e.,
iodide more reactive than chloride) which have been
observed in the rhodium-catalyzed asymmetric ring
opening of oxabicyclic alkenes.15,16 While the use of
Et3NHI in the catalytic ring opening gave the best
result, the use of triethylamine hydrochloride (Et3NHCl),
which has been found to be an effective additive in the
ring-opening reactions of oxabenzonorbornadiene and
azabenzonorbornadiene, gave only 30% yield under
the same conditions.
[Rh(cod)Cl]2, L*, additive
O
N
dibenzylamine, base, 110 °C, 24 h
Bn2N
O
NH
L* =
Me2N
O
Ph2P
Fe
Ph2P
1a
(S,S)-2a
Me2N
(S,S')-(R,R' )-C2-Ferriphos 3a
Scheme 3. Catalytic asymmetric ring opening of 1a with
dibenzylamine.
It is most likely that the halide exchange between
[Rh(cod)Cl]2 and Et3NHI generates the more stable rho-
dium iodide bridged dimer. The proposed catalytic path-
way for the ring opening of azabenzonorbornadienes
closely follows that put forward regarding oxabicyclic
alkenes17 and dimeric catalyst precursors are implicated
in the reaction pathway. Since it is believed that the
amine-induced cleavage of the dimeric rhodium complex
leads to catalyst poisoning,18 increasing the stability of
the dimeric complex toward the catalyst poisoning could
improve the catalyst activity.19 Also, the use of i-Pr2NEt
is required to ensure high conversion. Without i-Pr2NEt,
the reaction did not proceed with Et3NHI only (entry 2).
Increasing the concentration from 0.2 to 0.4 M reduced
the reaction time, with the reaction for 24 h giving 90%
yield (entries 3 and 4). The reaction with only 0.5 mol %
of [Rh(cod)Cl]2 gave good results (entry 5), but the use
of 0.1 mol % of [Rh(cod)Cl]2 gave an incomplete reac-
tion (entry 6), even when using higher concentration
(2.0 M) (entry 7).
Our experiments indicate that the trends of the halide
effect in the asymmetric ring opening of 1a are strongly
dependent on the nature of phosphine ligands; in fact,
both reactivity and enantioselectivity show different
trends in different systems with respect to the halide.
For example, while the halide effect observed in the
asymmetric ring-opening reaction of oxabenzonorborn-
adiene using PPF-P(t-Bu)2 as a chiral ligand showed
that the reactivity and the enantioselectivity increased
(Cl < Br < I) in the presence of Bu4NX, the reaction
using BPPFA resulted in an inverse trend of the halide
effect with respect to the enantioselectivity.15 These
results show that the halide and phosphine ligand work
at the rhodium metal together to influence the reactivity
and enantioselectivity. The use of Et3NHCl, instead of
Et3NHI, was also tested and gave 83% ee, but the yield
was still very low (entry 2). The increase of the catalytic
loading from 1.0 mol % of [Rh(cod)Cl]2 to 2.5 mol %
gave reasonable yield and higher enantioselectivity
(entry 5). Also, it was found that there are no positive
effects of Et3NHCl (entry 3 vs entry 4) and i- Pr2NEt
(entry 5 vs entry 6) on the asymmetric reaction. The
use of 5.0 equiv of dibenzylamine is required to shorten
the reaction time for complete conversion. In the case of
the reaction using 10 equiv of amine, a slightly lower
enantioselectivity was observed (83% ee) under the same
conditions. It was found that the enantiomeric purity of
2a is dependent on the amount of 3a in the reaction
(Table 3). The use of 1.5 equiv of 3a to rhodium
(7.5 mol %) in the ring-opening reaction gave 78% ee
(Table 3, entry 1), whereas the use of 2.0 equiv
The optimized conditions found for the catalytic ring
opening of 1a with dibenzylamine (1.1 equiv) (Table 1,
entry 4) were applied to the catalytic asymmetric ring
opening of 1a in the presence of [Rh(cod)Cl]2 and
(S,S0)-(R,R0)-C2-ferriphos 3a with the results are sum-
marized in Table 2 (Scheme 3). Using a rhodium catalyst
generated from 1.0 mol % of [Rh(cod)Cl]2 and 3.0
mol % of ligand 3a, the reaction with Et3NHI and
i-Pr2NEt in 1,4-dioxane gave 25% yield of 2a with 22%
ee (entry 1). Considering that the reaction conditions
using Et3NHI and i-Pr2NEt gave 90% yield of 2a in
the reaction of 1a using dppf as a ligand, this low reac-
tivity is rather surprising.
Table 2. Catalytic asymmetric ring opening of N-Boc-azabenzonorbornadiene 1a with dibenzylaminea
Entry
Additive (mol %)
Dibenzylamine (equiv)
Base (equiv)
Yieldb (%)
% eec
1d
2d
3
Et3NHI (20)
Et3NHCl (20)
Et3NHCl (20)
—
—
—
1.2
1.2
2.5
2.5
5.0
5.0
i-Pr2NEt (1.2)
i-Pr2NEt (1.2)
i-Pr2NEt (2.5)
i-Pr2NEt (2.5)
i-Pr2NEt (5.0)
—
25
30
52
61
81
83
22f
83
77
78
82
89
4
5e
6e
a The reaction was carried out with 1a (0.25 mmol), dibenzylamine, additive, and base at 110 °C for 24 h in the presence of 1.0 mol % of [Rh(cod)Cl]2
and 4.0 mol % of ligand 3a (2.0 equiv to Rh).
b Isolated yield after silica gel column chromatography.
c Determined by HPLC analysis of the ring-opened product 2a with chiral stationary column (Chiralcel OD).
d The reaction was performed with 1,4-dioxane (1.0 M).
e The reaction was carried out in the presence of 2.5 mol % of [Rh(cod)Cl]2 and 10.0 mol % of ligand 3a.
f 22% ee of (R,R)-2a was obtained.

Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
419
Table 3. Study of chiral ligands and temperature on the asymmetric ring opening of 1a with dibenzylaminea
Entry
Ligand (equiv to Rh)
Temperature (°C)
Time (h)
Yieldb (%)
% eec
1
2
3
4
5
6
7
8
3a (1.5)
3a (2.0)
3a (2.2)
3a (3.0)
3b (2.2)
3c (2.2)
3b (2.2)
3b (2.2)
110
110
110
110
110
110
80
24
24
24
24
24
24
48
72
84
83
85
80
97
81
98
38d
78
89
92
92
95
81
97
97
60
a The reaction was carried out with 1a (0.25 mmol) and 5.0 equiv of dibenzylamine (1.25 mmol) in the presence of 2.5 mol % of [Rh(cod)Cl]2 and
chiral ligand.
b Isolated yield after silica gel column chromatography.
c Determined by HPLC analysis of the ring-opened product 2a with chiral stationary column (Chiralcel OD).
d 61% of 1a was recovered.
(10 mol %) gave 89% ee (entry 2). Higher enantioselec-
tivity was observed in the reaction using 3.0 equiv of
3a (15 mol %) which gave 92% ee (entry 4). Finally,
the use of 2.2 equiv of 3a (11 mol %) was found to be
most effective (92% ee) for the present asymmetric reac-
tion (entry 3).
of 2a with 97% ee while 61% of the starting material 1a
was recovered (entry 8).
These optimized reaction conditions gave excellent
yields and enantioselectivities in the reactions with aza-
benzonorbornadienes 1a–d (Scheme 5). In the presence
of 2.5 mol % of [Rh(cod)Cl]2 and 11 mol % of 3b, the
ring-opening reaction of 1a with 5.0 equiv of dibenzyl-
amine proceeded at 80 °C for 48 h to give 98% yield of
the corresponding product 2a with 97% ee. The asym-
metric ring-opening reactions of 1b and 1c showed the
highest enantioselectivity but lower reactivity while its
completion needed a longer reaction time. The reaction
of 1b for 96 h gave 91% yield of 2b with 99% ee. In the
case of more bulky 1c, the reaction needed 144 h until
completion to give 70% yield of 2c in 99% ee. The reac-
tion of 1d was completed within 48 h and gave 99% yield
of 2d in 97% ee.
Chiral ligands 3b and 3c were obtained by lithiation
of (S,S)-1,10-bis(a-N,N-dimethylaminoethyl)ferrocene,
whose preparation has been reported by Knochel,14b
followed by the substitution of dilithium salts with the
corresponding diarylchlorophosphines20 (Scheme 4).
Among those chiral ligands prepared here, (S,S0)-
(R,R0)-C2-ferriphos-tolyl 3b showed the best result
(entry 5). In the presence of 2.5 mol % of [Rh(cod)Cl]2
and 11 mol % of (S,S0)-(R,R0)-3b, the reaction at
110 °C for 24 h gave 98% yield of 2a in 95% ee, whereas
the use of C2-ferriphos-xylyl 3c gave only 81% ee (entry
6). The best results were obtained by decreasing the
reaction temperature. The ring-opening reaction pro-
ceeded at 80 °C for 48 h to give 98% yield of 2a in
97% ee (entry 7). At 60 °C, the reaction gave 38% yield
The optically active ring-opening products obtained
here were used for the synthesis of the enantiomerically
pure free 1,2-diamine scaffolds. The reactions starting
Me2N
Me2N
Ar2P
Me
Me
1. n-BuLi, Et2O
2. Ar2PCl
Ar = phenyl
4-methylphenyl
3a
Fe
Fe
Ar2P
3b: 33% yield
Me2N
3,5-dimethylphenyl 3c: 30% yield
Me2N
Scheme 4. Preparation of C2-ferriphos-Ar ligands.
O
R1
2a (R1, R2 = H): 48 h, 98% yield, 97% ee
[Rh(cod)Cl]2 (2.5 mol%)
(S,S' )-(R,R' )-C2-Ferriphos-Tolyl 3b
R2
R2
O
N
R1
2b (R1 = Me, R2 = H): 96 h, 91% yield, 99% ee
2c (R1, R2 = Me): 144 h, 70% yield, 99% ee
2d (R1 = H, R2 = Me): 48 h, 99% yield, 97% ee
R2
R2
Bn2N
O
dibenzylamine (5.0 eq), 80 °C
NH R1
R1
L* =
Me2N
O
Ar2P
Fe
1a (R1, R2 = H)
Ar2P
1b (R1 = Me, R2 = H)
1c (R1, R2 = Me)
Me2N
1d (R1 = H, R2 = Me)
Ar = 4-methylphenyl 3b
Scheme 5. Asymmetric ring opening of N-Boc-azabenzonorbornadienes 1a–d with dibenzylamine under the optimized reaction conditions.

420
Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
R1
R1
R2
R1
R1
R2
R2
R2
R2
R2
Pd/C, HCO2NH4
MeOH/EtOAc
H2N
O
Bn2N
K2CO3, EtOH, H2O, reflux
OH
NH R1
N
N
5a-d
O
NH R1
O
O
t-Bu
OH HO
t-Bu
t-Bu
t-Bu
t-Bu
CHO
2a (R1, R2 = H): 97% ee
benzoyl chloride
pyridine, THF
(2.0 eq)
2b (R1 = Me, R2 = H): 99% ee
2c (R1, R2 = Me): 99% ee
2d (R1 = H, R2 = Me): 97% ee
t-Bu
R1, R2 = H
R1 = H, R2 = Me 6b 84% yield
R1, R2 = Me
6c 86% yield
R1 = Me, R2 = H 6d 96% yield
6a 91% yield
R1
R2
R1
R1
R2
R2
R2
1. 50% HCl aq.
2. L-tartaric acid
EtOH/H2O (10/1)
Ph
H3N
O2C
Scheme 7. Synthesis of salen-type ligands 5a–d.
NH NH
NH3 R1
CO2 H2O
O
O
O
HO
Jacobsen-type salen ligands 6a–d.23 In the presence of
K2CO3, treatment of the (S,S)-diamine (R,R)-tartrates
with 3,5-di-tert-butylsalicylaldehyde in ethanol/H2O at
80 °C gave the corresponding salen products 6a–d in
84–96% yield (Scheme 7).
OH
5a (R1, R2 = H): 85% yield
4a (R1, R2 = H): 70% yield
5b (R1 = Me, R2 = H): 75% yield
5c (R1, R2 = Me): 71% yield
5d (R1 = H, R2 = Me): 80% yield
4b (R1 = Me, R2 = H): 68% yield
4c (R1, R2 = Me): 65% yield
4d (R1 = H, R2 = Me): 65% yield
Scheme 6. Synthesis of 1,2-diamine scaffolds 5a–d.
The preparation of new Trost-type ligands from the 1,2-
diamine derivatives obtained here was also attempted.
For the successful amide bond formation, diphenylchlo-
rophosphate was employed as the coupling reagent to
activate the carboxylic acid.6c The method of amide
bond formation promoted by DCC6b was examined
for this reaction but did not give the desired product.
After the reaction of 2-(diphenylphosphino)benzoic acid
with triethylamine and diphenylchlorophosphate in
CH2Cl2 at room temperature for 15 h, (1S,2S)-1,2-dia-
minotetrahydro-naphthalenes, obtained by treatment
of (S,S)-diamine (R,R)-tartrates 5 with 4 M NaOH aq,
were added in the mixture. The amide-forming reactions
proceeded in the presence of DMAP for 24 h to give bis-
phosphine ligands 7a–d (Scheme 8). An X-ray structure
of the ligand 7a is shown in Figure 2.24
from (1S,2S)-2a–d are summarized in Scheme 6. The
reduction of the double bond and debenzylation of the
dibenzylamino group were carried out at the same time
by catalytic hydrogenation of 2a–d with ammonium for-
mate in the presence of 30 mol % of Pd/C at 60 °C in
methanol/ethyl acetate.21 In order to facilitate the puri-
fication of these polar substrates, the resulting debenzyl-
ated products were converted into the corresponding
benzoylamides 4a–d by acylation with benzoyl chloride.
Recrystallization of 4a–d from ethanol or 2-propanol
gave the enantiomerically pure (>99% ee) products in
65–70% yield. Treatment of 4a–d with 50% aq HCl at
100 °C for 48 h gave unstable free 1,2-diamines with
the resulting 1,2-diamines immediately converted into
the storable tartrate salts 5a–d. The reaction of 1,2-dia-
mino-1,2,3,4-tetrahydronaphthalenes with L-tartaric
acid gave (S,S)-5a–d. The absolute configuration was
determined to be 1S,2S by X-ray analysis of 5a
(Fig. 1).22
3. Conclusion
In conclusion, we have developed new reaction condi-
tions for the catalytic asymmetric ring-opening reaction
of azabenzonorbornadienes 1a–d with dibenzylamine,
giving the optically active 1,2-diamine derivatives 2a–d
in high yields and excellent enantioselectivity (up to
>99% ee). (S,S0)-(R,R0)-C2-ferriphos-tolyl 3b was found
These bench-stable salts were used as synthetic inter-
mediates for the preparation of new chiral ligands.
The resulting tartrates 5a–d were easily converted into
R1
R2
R1
R2
R1
H2N
R2
R2
NH2 R1
7a (R1, R2 = H): 88% yield
O
PPh2
7b (R1 = Me, R2 = H): 77% yield
7c (R1, R2 = Me): 76% yield
7d (R1 = H, R2 = Me): 80% yield
Ph2P
NH NH
O
(PhO)2P(O)Cl, Et3N
CH2Cl2, 0 ˚C to rt, 15 h
DMAP, rt, 24 h
CO2H
Ph2P
Scheme 8. Synthesis of Trost-type ligands 7a–d.

Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
421
precipitate of benzenediazonium-2-carboxylate was
collected by filtration and washed with cold THF using
minimal suction for draining so as to prevent complete
drying. The salt was immediately transferred to a flask
and 1,2-dichloroethane (100 mL) and N-tert-butyl pyr-
role 1-carboxylate (7.8 mL, 46.7 mmol) were added.
The mixture was heated at 60 °C for 45 min and the
black mixture was cooled to room temperature. After
concentration under reduced pressure, the residue was
purified by flash column chromatography (hexane/ethyl
acetate = 95/5) and recrystallization with hexane to give
7.8 g of N-Boc-azabicycle 1a (55% yield). Mp 70–72 °C
(lit.25 mp 72–73 °C for 1a); IR (NaCl, cmꢀ1) 2976,
2931, 1708, 1455, 1367, 1332, 1252, 1167, 1074, 857,
1
830, 782, 748, 694, 643. H NMR (CDCl3): d 1.37 (s,
9H), 5.48 (br s, 2H), 6.94–6.98 (m, 4H), 7.22–7.29 (m,
2H); 13C NMR (CDCl3): d 155.3, 148.5, 143.1 (d,
J = 85.0 Hz), 125.1, 121.0 (d, J = 31.5 Hz), 80.7, 66.7
(d, J = 47.3 Hz), 28.3.
Figure 2. Crystal structure of 7a. Solvent (CH2Cl2) is omitted for
clarity.
4.1.2. 5,8-Dimethyl-N-Boc-azabenzonorbornadienes, 1b.
To a stirred solution of 3,6-dimethylanthranilic acid8
(14.0 g, 84.7 mmol) and trichloroacetic acid (0.2 g,
0.9 mmol) in dry THF (100 mL) was slowly added iso-
amyl nitrite (14 mL, 101.7 mmol) at ꢀ20 °C for 40 min
by syringe pump under nitrogen atmosphere. The mix-
ture was allowed to stir at ꢀ20 °C for another 2 h. Then,
N-tert-butyl pyrrole 1-carboxylate (11 mL, 67.8 mmol)
and 1,2-dichloroethane (100 mL) were added and the
mixture heated immediately at 80 °C for 30 min. The
resulting mixture was then cooled to room temperature
and all volatile substrates removed under reduced
pressure. The residue was purified by flash column
chromatography (hexane/ethyl acetate = 95/5) and
recrystallization with hexane to give 6.9 g (30% yield)
of 1b. Mp 95–97 °C; IR (NaCl, cmꢀ1) 2974, 1709,
1490, 1455, 1366, 1329, 1253, 1167, 1073. 1H NMR
(CDCl3): d 1.38 (s, 9H), 2.29 (s, 6H), 5.53–5.57 (m,
2H), 6.67 (s, 2H), 6.95–6.99 (m, 2H); 13C NMR
(CDCl3): d 155.5, 146.3, 142.9 (d, J = 97.9 Hz), 127.9
(d, J = 38.5 Hz), 126.6, 80.6, 65.2 (d, J = 42.9 Hz),
28.3, 17.9. Anal. Calcd for C17H21NO2: C, 75.25; H,
7.80; N, 5.16. Found: C, 75.19; H, 7.71; N, 5.19.
to be the best enantioselective ligand. The sequential
deprotection of the ring-opening products 2 and treat-
ment with tartaric acid gave the enantiomerically pure
1,2-diamine salts 5 that are stable and easy to handle.
These 1,2-amine derivatives were used for the prepara-
tion of new chiral ligands, such as the salen-type ligands
6 and Trost-type ligands 7. Applications of these ligands
in catalytic asymmetric synthesis are currently being
investigated.
4. Experimental
All moisture and air-sensitive manipulations were
carried out under a dried nitrogen atmosphere. NMR
spectra were recorded on a Varian Mercury NMR spec-
trometer (300 MHz for 1H, 75 MHz for 13C, and
121 MHz for 31P). Chemical shifts are reported in d
ppm referenced to SiMe4 or DMSO-d6 (2.50 ppm) as
the internal standard for 1H NMR, chloroform-d (d
77.0) or DMSO-d6 (39.52 ppm) for 13C NMR, and an
external 85% H3PO4 standard for 31P NMR. IR spectra
were obtained using a Perkin–Elmer Spectrum 1000 FT-
IR spectrometer as a neat film on a NaCl plate. High
resolution mass spectra were obtained from a Micro-
mass 70S-250 mass spectrometer (EI) or an ABI/Sciex
Qstar mass spectrometer (ESI). Optical rotations were
measured on a Perkin–Elmer Model 243 Polarimeter
and melting points were taken on a Fisher–Johns melt-
ing point apparatus. HPLC analysis was performed on
an Agilent 1100 Series HPLC with Chiralcel OD or
AD columns.
4.1.3. 5,6,7,8-Tetramethyl-N-Boc-azabenzonorbornadi-
enes, 1c. To a solution of 1,2-dibromotetramethylbenz-
ene9 (20.0 g, 68.5 mmol) prepared from commercially
available 1,2,3,4-tetramethylbenzene according to previ-
ously reported procedure10 in dry toluene (200 mL) was
slowly added n-butyllithium solution in hexane (95 mL,
150.7 mmol) diluted with dry toluene (24 mL) and N-
tert-butyl pyrrole 1-carboxylate solution in dry toluene
(14 mL, 82.2 mmol in 110 mL of toluene) at 0 °C by syr-
inge pump for 3 h under a nitrogen atmosphere. The
mixture was allowed to stir at room temperature for
48 h and quenched with water. The resulting mixture
was extracted with ethyl acetate and the organic phase
dried over anhydrous MgSO4. After removal of all vola-
tile solvents under reduced pressure, flash column chro-
matography on silica gel (hexane/ethyl acetate = 95/5)
and recrystallization with hexane gave 7.0 g (34% yield)
of 1c. Mp 125–127 °C; IR (NaCl, cmꢀ1) 2973, 1708,
1366, 1330, 1257, 1167, 1073. 1H NMR (CDCl3): d
4.1. Preparation of azabenzonorbornadienes
4.1.1. N-Boc-Azabenzonorbornadienes, 1a. To a stirred
solution of anthranilic acid (8.0 g, 58.3 mmol) and tri-
chloroacetic acid (67 mg, 0.4 mmol) in dry THF
(120 mL) was slowly added isoamyl nitrite (13 mL,
93.3 mmol) at 0 °C for 30 min and the mixture was
stirred at room temperature for 1.5 h. The dark yellow

422
Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
1
1.39 (s, 9H), 2.11 (s, 6H), 2.24 (s, 6H), 5.56–5.60 (m,
2H), 6.94–6.98 (m, 2H); 13C NMR (CDCl3): d 155.3,
143.5, 143.1 (d, J = 101.6 Hz), 131.6, 127.2 (d,
J = 40.1 Hz), 80.5, 65.8 (d, J = 46.1 Hz), 28.4, 16.5,
16.0. Anal. Calcd for C19H25NO2: C, 76.32; H, 8.42;
N, 4.68. Found: C, 76.71; H, 8.59; N, 4.65.
1228, 1163. H NMR (CDCl3): d 1.40 (s, 9H), 2.29 (s,
3H), 2.38 (s, 3H), 3.39 (br s, 1H), 3.43 (d, J = 13.8 Hz,
2H), 3.53 (d, J = 13.5 Hz, 2H), 4.43 (d, J = 9.0 Hz,
1H), 5.32 (d, J = 9.9 Hz, 1H), 5.87 (dd, J = 10.2,
6.0 Hz, 1H), 6.88 (d, J = 10.2 Hz, 1H), 6.95–7.01 (m,
2H), 7.15–7.27 (m, 6H), 7.35 (d, J = 6.9 Hz, 4H); 13C
NMR (CDCl3): d 154.5, 140.4, 134.2, 132.3, 131.7,
130.1, 129.6, 129.0, 127.9, 126.6, 126.2, 125.8, 79.2,
58.5, 53.5, 43.9, 28.3, 18.9, 18.6. HRMS (ESI) calcd
for C31H37N2O2 ([MH]+): 469.2849. Found: 469.2833.
4.1.4. 6,7-Dimethyl-N-Boc-azabenzonorbornadienes, 1d.
Prepared from 1,2-dibromo-4,5-dimethylbenzene10 in a
similar manner to 1a in 35% yield. Mp 93–95 °C; IR
(NaCl, cmꢀ1) 2974, 1706, 1593, 1455, 1366, 1328,
1
1251, 1167, 1071. H NMR (CDCl3): d 1.38 (s, 9H),
4.2.3. (1S,2S)-(2-N,N-Dibenzylamino-1,2-dihydro-5,6,7,
8-tetramethylnaphthalen-1-yl)-carbamic acid tert-butyl
ester, 2c. Ee (99%) by HPLC analysis with a chiral col-
umn (Chiralcel AD, hexane/2-propanol = 99/1, 0.5 mL/
2.17 (s, 6H), 5.42 (m, 2H), 6.95 (m, 2H), 7.05 (s, 2H);
13C NMR (CDCl3):
d
155.2, 146.0, 143.3 (d,
J = 81.2 Hz), 132.6, 122.9 (d, J = 27.1 Hz), 80.6, 66.4
(d, J = 47.5 Hz), 28.4, 19.9. Anal. Calcd for
C17H21NO2: C, 75.25; H, 7.80; N, 5.16. Found: C,
75.10; H, 7.89; N, 5.07.
min), tR (S)-(+), 9.6 min (major); (R)-(ꢀ), 12.0 min
25
(minor). ½aꢁD ¼ þ265:8 (c 1.00, CHCl3) for 2c of 99%
ee; IR (NaCl, cmꢀ1) 3418, 2925, 2358, 1705, 1489,
1
1365, 1165, 1047. H NMR (CDCl3): d 1.39 (s, 9H),
4.2. Rhodium-catalyzed asymmetric ring opening of 1a–d
with dibenzylamine
2.21 (s, 3H), 2.25 (s, 6H), 2.33 (s, 3H), 3.38 (d,
J = 5.4 Hz, 1H), 3.44 (d, J = 13.5 Hz, 2H), 3.52
(d, J = 13.8 Hz, 2H), 4.42 (d, J = 9.0 Hz, 1H), 5.38 (d,
J = 9.6 Hz, 1H), 5.83 (dd, J = 9.3, 5.1 Hz, 1H), 7.01
(d, J = 10.2 Hz, 1H), 7.14–7.25 (m, 6H), 7.35 (d,
J = 7.2 Hz, 4H); 13C NMR (CDCl3): d 154.7, 140.7,
135.8, 135.0, 132.5, 130.4, 130.2, 129.2, 128.1, 127.9,
127.3, 126.7, 124.8, 79.2, 58.6, 53.7, 44.9, 28.5, 17.2,
17.0, 15.4, 15.2. HRMS (ESI) calcd for C33H41N2O2
([MH]+): 497.3162. Found: 497.3174.
A typical procedure is given for the reaction of 1a with
5.0 equiv of N,N-dibenzylamine in the presence of
2.5 mol % of [Rh(cod)Cl]2 and 11.0 mol % of 3b (Table
3, entry 7).
To a 10 mL round bottom flask were added N-Boc-aza-
benzonorbornadiene
1a
(80 mg,
0.33 mmol),
[Rh(cod)Cl]2 (4 mg, 8 lmol), and (S,S)-(R,R)-C2-ferri-
phos-tolyl 3b (27 mg, 36 lmol) under a nitrogen atmo-
sphere. Then, dibenzylamine (0.3 mL, 1.6 mmol) was
added and the mixture allowed to stir at 80 °C for
48 h. The resulting mixture was cooled to room temper-
ature and diluted in CH2Cl2. The black solution was fil-
tered through Celite and the filtrate concentrated under
reduced pressure. The residue was purified by flash col-
umn chromatography (hexane/ethyl acetate = 95/5) to
give 142 mg (98% yield) of 2a as a semisolid.
4.2.4.
(1S,2S)-(2-N,N-Dibenzylamino-1,2-dihydro-6,7-
dimethylnaphthalen-1-yl)-carbamic acid tert-butyl ester,
2d. Ee (97%) by HPLC analysis with a chiral column
(Chiralcel OD, hexane/2-propanol = 99/1, 0.5 mL/
min), tR (S)-(+), 14.2 min (major); (R)-(ꢀ), 18.7 min
25
(minor). ½aꢁD ¼ þ135:8 (c 1.00, CHCl3) for 2d of 97%
ee; IR (NaCl, cmꢀ1) 3415, 2973, 1713, 1494, 1364,
1
1245, 1166. H NMR (CDCl3): d 1.51 (s, 9H), 2.19 (s,
3H), 2.23 (s, 3H), 3.41 (br s, 1H), 3.53 (d, J = 13.5 Hz,
2H), 3.70 (d, J = 13.8 Hz, 2H), 4.43–4.46 (m, 1H), 5.18
(m, 1H), 5.93–5.96 (m, 1H), 6,54 (dd, J = 9.9, 1.8 Hz,
1H), 6.82 (s, 1H), 7.08 (s, 1H), 7.15–7.28 (m, 6H), 7.37
(d, J = 6.9 Hz, 4H); 13C NMR (CDCl3): d 155.6,
140.3, 136.6, 136.1, 133.1, 130.3, 129.4, 129.3, 128.9,
128.3, 128.1, 127.0, 125.8, 79.5, 59.5, 54.0, 48.9, 28.7,
19.9, 19.5. HRMS (ESI) calcd for C31H37N2O2
([MH]+): 469.2849. Found: 469.2849.
4.2.1. (1S,2S)-(2-N,N-Dibenzylamino-1,2-dihydro-naph-
thalen-1-yl)-carbamic acid tert-butyl ester, 2a. Ee
(97%) by HPLC analysis with a chiral column (Chiralcel
OD, hexane/2-propanol = 99/1, 0.5 mL/min), tR (S)-
25
(+), 15.4 min (major); (R)-(ꢀ), 17.0 min (minor). ½aꢁD
¼
þ150:4 (c 1.00, CHCl3) for 2a of 97% ee. (lit.12
25
½aꢁD ¼ þ96:1 (c 1.06, CCl4) for 2a of 89% ee); 1H NMR
(CDCl3): d 1.53 (s, 9H), 3.43–3.50 (m, 1H), 3.55
(d, J = 13.5 Hz, 2H), 3.74 (d, J = 13.5 Hz, 2H), 4.48
(d, J = 9.0 Hz, 1H), 5.24 (t, J = 9.0 Hz, 1H), 6.05 (dd,
J = 9.9, 3.3 Hz, 1H), 6.59 (dd, J = 9.9, 1.8 Hz, 1H),
7.02–7.05 (m, 1H), 7.18–7.33 (m, 9H), 7.37 (d,
J = 6.9 Hz, 4H); 13C NMR (CDCl3): d 155.7, 140.0,
135.8, 132.6, 129.5, 129.2, 129.1, 128.3, 128.1, 127.9,
127.4, 127.0, 126.9, 126.7, 79.5, 59.5, 54.0, 49.4, 28.6, 28.5.
4.3. Preparation of chiral ferrocenyl phosphine ligands 3b
and 3c
4.3.1. C2-Ferriphos-tolyl, 3b. To a solution of (S,S)-
1,10-bis(a-N,N-dimethylaminoethyl)ferrocene (1.2 g, 3.6
mmol) prepared according to the reported procedure
by Knochel14b in dry ether was slowly added n-butyl-
lithium solution in hexane (6.9 mL, 10.9 mmol) by syr-
inge pump at room temperature for 45 min under a
nitrogen atmosphere. The reaction mixture was allowed
to stir at room temperature for 2.5 h and di(4-methyl-
phenyl)chlorophosphine20 (2.9 g, 11.7 mmol) was slowly
added at room temperature. The mixture was refluxed
for another 15 h. The resulting mixture was quenched
with saturated NaHCO3 solution and extracted with
4.2.2.
(1S,2S)-(2-N,N-Dibenzylamino-1,2-dihydro-5,8-
dimethylnaphthalen-1-yl)-carbamic acid tert-butyl ester,
2b. Ee (99%) by HPLC analysis with a chiral column
(Chiralcel AD, hexane/2-propanol = 99/1, 0.5 mL/
min), tR (S)-(+), 13.3 min (major); (R)-(ꢀ), 15.3 min
25
(minor). ½aꢁD ¼ þ175:8 (c 1.00, CHCl3) for 2b of 99%
ee; IR (NaCl, cmꢀ1) 3408, 2974, 1707, 1493, 1365,

Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
423
benzene. The separated organic layer was dried over
anhydrous MgSO4 and evaporated under reduced pres-
sure. The residue was purified by flash column chroma-
tography on silica gel (hexane/ethyl acetate = 50/50) to
(m, 4H), 7.88 (d, J = 6.9 Hz, 2H); 13C NMR (CDCl3):
d 28.5, 28.7, 29.0, 54.3, 55.0, 80.5, 126.5, 127.1, 127.3,
127.7, 128.6, 129.1, 131.6, 134.3, 135.4, 136.9, 158.0,
167.5. Anal. Calcd for C22H26N2O3: C, 72.11; H, 7.15;
N, 7.64. Found: C, 72.32; H, 7.26; N, 7.67.
give 0.9 g (33% yield) of ferrocenyl bisphosphine 3b.
25
½aꢁD ¼ þ460:2 (c 1.00, CHCl3). Mp 174–176 °C; IR
(NaCl, cmꢀ1) 2966, 2929, 2812, 2796, 1596, 1496, 1447,
4.4.2. (1S,2S)-(2-Benzoylamino-1,2,3,4-tetrahydro-5,8-
dimethylnaphthalen-1-yl)-carbamic acid tert-butyl ester,
4b. Prepared from 2b in a similar manner to 4a in 68%
yield. Ee (>99%) by HPLC analysis with a chiral column
(Chiralcel AD, hexane/2-propanol = 90/10, 1.0 mL/
1
1271, 1242, 1184, 1093, 1019, 929, 804, 756, 623. H
NMR (CDCl3): d 1.27 (d, J = 6.3 Hz, 6H), 1.73 (s, 12
H), 2.25 (s, 6H), 2.34 (s, 6H), 3.03 (s, 2H), 4.00–4.09
(m, 2H), 4.13 (s, 2H), 4.34 (s, 2H), 6.93–6.97 (m, 12H),
7.19 (t, J = 7.7 Hz, 4H); 31P NMR (CDCl3): d ꢀ25.5.
Anal. Calcd for C46H54FeN2P2: C, 73.40; H, 7.23; N,
3.72. Found: C, 73.53; H, 7.31; N, 3.72.
min), tR (R)-(ꢀ), 7.3 min (minor); (S)-(+), 8.4 min
25
(major). ½aꢁD ¼ þ129:6 (c 1.00, CHCl3) for 4b of >99%
ee. Mp 132–134 °C; IR (NaCl, cmꢀ1) 3313, 2974, 1688,
1
1639, 1532, 1315, 1247, 1166, 1046. H NMR (CDCl3):
4.3.2. C2-Ferriphos-xylyl, 3c. Prepared from 3c in a
d 1.42 (s, 9H), 1.75–2.07 (m, 1H), 2.17–2.30 (m, 7H),
2.60–2.83 (m, 2H), 4.40 (m, 1H), 4.65 (d, J = 8.1 Hz,
1H), 4.89 (t, J = 7.2 Hz, 1H), 6.50 (m, 1H), 6.99 (d,
J = 7.5 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H), 7.35–7.49
(m, 3H), 7.75 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3):
d 167.7, 155.9, 136.3, 134.7, 134.4, 132.2, 131.5, 130.2,
129.4, 128.9, 128.6, 128.5, 127.2, 80.1, 52.6, 51.4, 28.5,
24.3, 19.7, 19.4. HRMS (ESI) calcd for C24H30N2O3Na
([MNa]+): 417.2148. Found: 417.2138.
25
similar manner to 3b in 30% yield. ½aꢁD ¼ þ366:2 (c
1.00, CHCl3). Mp 248–250 °C (decomp); IR (NaCl,
cmꢀ1) 2965, 2927, 2852, 2812, 2769, 1598, 1582, 1453,
1362, 1272, 1242, 1167, 1125, 1095, 1065, 1038, 929,
846, 824, 756, 693. 1H NMR (CDCl3): d 1.27 (d,
J = 6.3 Hz, 6H), 1.69 (s, 12H), 2.17 (s, 12H), 2.23 (s,
12H), 3.03 (s, 2H), 3.95–4.09 (m, 2H), 4.16 (s, 2H),
4.31 (s, 2H), 6.72 (d, J = 8.4 Hz, 4H), 6.77 (s, 2H),
6.83 (s, 2H), 6.95 (d, J = 8.1 Hz, 4H); 31P NMR
(CDCl3): d ꢀ23.1. Anal. Calcd for C50H62FeN2P2: C,
74.25; H, 7.73; N, 3.64. Found: C, 74.93; H, 7.87; N,
3.41.
4.4.3. (1S,2S)-(2-Benzoylamino-1,2,3,4-tetrahydro-5,6,7,
8-tetramethylnaphthalen-1-yl)-carbamic acid tert-butyl
ester, 4c. Prepared from 2c in a similar manner to 4a
in 56% yield. Ee (>99%) by HPLC analysis with a chiral
column (Chiralcel AD, hexane/2-propanol = 90/10,
4.4. Synthesis of benzoylamides 4a–d
1.0 mL/min), tR (R)-(ꢀ), 6.9 min (minor); (S)-(+),
25
4.4.1. (1S,2S)-(2-Benzoylamino-1,2,3,4-tetrahydro-naph-
thalen-1-yl)-carbamic acid tert-butyl ester, 4a. To a stir-
red solution of 2a (8.3 g, 18.8 mmol) in ethyl acetate
(80 mL) and methanol (160 mL) was added ammonium
formate (11.9 g, 188.3 mmol) and 30 mol % of Pd/C
(10 wt %, 6.0 g, 5.6 mmol). The mixture was refluxed
for 25 min and cooled to room temperature. The result-
ing black suspension was filtered through Celite and the
Celite cake washed with triethylamine/methanol (1/
1 = v/v) several times. The filtrate was concentrated
under reduced pressure. The residue was dissolved with
dry THF (100 mL) and pyridine (4.6 mL, 56.5 mmol)
was added. Then, benzoyl chloride (2.7 mL, 22.6 mmol)
was slowly added at 0 °C and the mixture stirred at
room temperature for 15 h under a nitrogen atmo-
sphere. The resulting mixture was quenched with 1 N
NaOH solution and was extracted with ether. The sepa-
rated organic layer was dried over anhydrous MgSO4
and evaporated under reduced pressure. Flash column
chromatography on silica gel (hexane/ethyl acetate =
70/30) and recrystallization with 2-propanol gave 5.0 g
(72% yield) of 4a. Ee (>99%) by HPLC analysis with a
chiral column (Chiralcel AD, hexane/2-propanol =
11.2 min (major). ½aꢁD ¼ þ137:2 (c 1.00, CHCl3) for 4c
of >99% ee. Mp 174–175 °C; IR (NaCl, cmꢀ1) 3307,
2928, 1695, 1653, 1528, 1314, 1245, 1168, 1017, 753.
1H NMR (CDCl3): d 1.42 (s, 9H), 1.92–2.04 (m, 1H),
2.18–2.26 (m, 8H), 2.65–2.87 (m, 2H), 4.34 (m, 1H),
4.63 (d, J = 7.8 Hz, 1H), 4.92 (t, J = 7.4 Hz, 1H), 6.56
(d, J = 7.5 Hz, 1H), 7.35–7.48 (m, 3H), 7.76 (d,
J = 7.2 Hz, 2H); 13C NMR (CDCl3): d 167.7, 156.0,
135.0, 134.8, 134.3, 134.2, 133.3, 132.4, 131.4, 129.8,
128.5, 127.2, 80.0, 52.9, 51.9, 28.5, 25.3, 24.5, 16.9,
16.8, 16.4, 15.9. Anal. Calcd for C26H34N2O3: C,
73.90; H, 8.11; N, 6.63. Found: C, 73.85; H, 8.10; N,
6.48.
4.4.4. (1S,2S)-(2-Benzoylamino-1,2,3,4-tetrahydro-6,7-
dimethylnaphthalen-1-yl)-carbamic acid tert-butyl ester,
4d. Prepared from 2d in a similar manner to 4a in 70%
yield. Ee (>99%) by HPLC analysis with a chiral column
(Chiralcel AD, hexane/2-propanol = 90/10, 1.0 mL/
min), tR (R)-(ꢀ), 10.8 min (minor); (S)-(+), 15.1 min
25
(major). ½aꢁD ¼ þ57:0 (c 1.00, CHCl3) for 4d of >99%
ee. Mp 191–194 °C; IR (NaCl, cmꢀ1) 3325, 2927, 1683,
1
1639, 1540, 1315, 1248, 1169, 1023. H NMR (CDCl3):
90/10, 1.0 mL/min), tR (R)-(ꢀ), 9.4 min (minor); (S)-
d 1.39 (s, 9H), 1.67–1.82 (m, 1H), 2.22 (s, 3H), 2.25 (s,
3H), 2.41–2.48 (m, 1H), 2.76–2.83 (m, 1H), 2.95–3.07
(m, 1H), 4.06–4.17 (m, 1H), 4.83–4.96 (m, 2H), 6.90 (s,
1H), 7.13 (s, 1H), 7.38–7.50 (m, 3H), 7.87 (d,
J = 7.3 Hz, 1H); 13C NMR (CDCl3): d 167.4, 158.0,
136.2, 134.8, 134.3, 134.2, 132.5, 131.5, 130.2, 128.5,
128.0, 127.3, 80.4, 55.5, 53.9, 29.1, 28.5, 28.1, 19.6,
19.4. HRMS (ESI) calcd for C24H30N2O3Na
([MNa]+): 417.2148. Found: 417.2149.
25
(+), 11.5 min (major). ½aꢁD ¼ þ58:2 (c 1.00, CHCl3)
for 4a of >99% ee. Mp 185–187 °C; IR (NaCl, cmꢀ1
)
3320, 2977, 1682, 1638, 1537, 1489, 1365, 1318, 1250,
1173, 1018, 691. 1H NMR (CDCl3): d 1.38 (s, 9H),
1.80 (dq, J = 12.3, 5.1 Hz, 1H), 2.43–2.49 (m, 1H),
2.87 (dd, J = 17.3, 3.2 Hz, 1H), 3.07 (ddd, J = 17.3,
12.3, 5.1 Hz, 1H), 4.11–4.22 (m, 1H), 4.97–5.02 (m,
2H), 7.10–7.13 (m, 1H), 7.18–7.25 (m, 3H), 7.38–7.50

424
Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
4.5. Preparation of the tartrates 5a–d
1H), 3.85 (s, 2H), 5.50 (br s, 10H), 6.84 (s, 1H), 7.34
(s, 1H); 13C NMR (DMSO-d6): d 174.5, 134.8, 134.7,
133.7, 132.5, 129.1, 128.5, 71.4, 53.4, 53.3, 26.6, 26.5,
19.1, 18.8. Anal. Calcd for C16H26N2O7: C, 53.62; H,
7.31; N, 7.82. Found: C, 53.56; H, 7.31; N, 7.74.
4.5.1. (1S,2S)-Diamine (R,R)-tartrate, 5a. To 50%
hydrochloric acid (120 mL) was added 4a (3.0 g,
8.2 mmol) and the mixture was refluxed for 48 h. The
reaction mixture was cooled to room temperature and
the acidic solution was washed with ether several times.
Then, to the separated aqueous solution was slowly
added 4 N NaOH solution at 0 °C for 30 min and its
pH was adjusted around pH 11. The resulting basic
solution was extracted with CH2Cl2 and dried over
anhydrous MgSO4. After removal of all volatile solvents
under reduced pressure, the crude solid was dissolved
with ethanol (80 mL) and H2O (10 mL) and L-(+)-tar-
taric acid (1.1 g, 7.4 mmol) solution in ethanol (20 mL)
was slowly added. The resulting suspension was refluxed
for 18 h and was slowly cooled to room temperature.
The precipitate was collected by filtration and the col-
lected solid was washed with cold methanol. After dry-
4.6. Synthesis of the salen-type ligands 6a–d
4.6.1. Salen-type ligand, 6a. (S,S)-Diamine (R,R)-tar-
trate 5a (0.9 g, 2.9 mmol, >99% ee) and K2CO3 (0.8 g,
5.7 mmol) were dissolved with H2O (4 mL) and ethanol
(10 mL) then a solution of 3,5-di-tert-butylsalicylalde-
hyde (1.3 g, 5.5 mmol) in ethanol (40 mL) was slowly
added at 80 °C by syringe pump for 40 min to the sus-
pension. The yellow suspension was refluxed for 2 h,
cooled to room temperature, and stirred at room tem-
perature for another 15 h. The resulting mixture was
quenched with H2O and stored in ice bath for 1 h. The
yellow solid was collected by filtration and dissolved
with CH2Cl2. The organic solution was washed with
H2O and brine, dried over MgSO4, and evaporated
under reduced pressure. The crude solid was purified
ing under vacuum, 2.1 g (82% yield) of (S,S)-diamine
25
(R,R)-tartrate 5a was obtained. ½aꢁD ¼ þ27:2 (c 1.00,
H2O) for 5a of >99% ee. Mp 238–240 °C (decomp);
1H NMR (DMSO-d6): d 1.71–1.85 (m, 1H), 2.08–2.16
(m, 1H), 2.80–2.84 (m, 2H), 3.02–3.10 (m, 1H), 3.80
(d, J = 9.0 Hz, 1H), 5.18 (br s, 10H), 7.09 (d,
J = 7.2 Hz, 1H), 7.15–7.24 (m, 2H), 7.60 (d,
J = 6.9 Hz, 1H); 13C NMR (DMSO-d6): d 174.5,
138.1, 135.3, 128.1, 127.6, 126.8, 126.1, 71.4, 53.5,
53.4, 27.0, 26.4. Anal. Calcd for C14H22N2O7: C,
50.90; H, 6.71; N, 8.48. Found: C, 51.13; H, 6.70; N,
8.44.
by recrystallization with methanol to give 1.6 g (91%
25
yield) of salen 6a as a light yellow solid. ½aꢁD ¼ þ265:8
(c 1.00, CHCl3) for 6a of >99% ee. Mp 197–198 °C;
IR (NaCl, cmꢀ1) 2935, 1623, 1437, 1361, 1273, 1249,
1
1173, 749. H NMR (CDCl3): d 1.24 (s, 9H), 1.26 (s,
9H), 1.40 (s, 9H), 1.42 (s, 9H), 2.14–2.32 (m, 2H),
3.00–3.18 (m, 2H), 3.74 (ddd, J = 10.5, 6.3, 4.2 Hz,
1H), 4.59 (d, J = 13.5 Hz, 1H), 6.99 (d, J = 2.4 Hz,
1H), 7.07 (d, J = 2.4 Hz, 1H), 7.12–7.23 (m, 4H), 7.34
(dd, J = 6.6, 4.2 Hz, 2H), 8.37 (s, 1H), 8.46 (s, 1H),
13.47 (br s, 1H), 13.53 (br s, 1H); 13C NMR (CDCl3):
d 168.55, 166.95, 158.34, 158.13, 140.32, 140.27,
136.75, 136.69, 135.86, 135.61, 128.92, 128.49, 127.50,
127.41, 127.25, 126.61, 126.53, 126.46, 118.05, 117.88,
73.75, 70.42, 35.21, 34.29, 31.64, 30.07, 29.65, 28.34.
Anal. Calcd for C40H54N2O2: C, 80.76; H, 9.15; N,
4.71. Found: C, 81.02; H, 8.96; N, 4.72.
4.5.2. (1S,2S)-Diamine (R,R)-tartrate, 5b. Prepared
from 4b in a similar manner to 5a in 86% yield.
25
½aꢁD ¼ þ7:6 (c 1.00, DMSO) for 5b of >99% ee. Mp
198–201 °C (decomp); 1H NMR (DMSO-d6): d 1.81–
1.91 (m, 1H), 2.14 (s, 3H), 2.23–2.32 (m, 1H), 2.35 (s,
3H), 2.51–2.69 (m, 2H), 3.42 (m, 1H), 3.86 (s, 2H),
4.07 (m, 1H), 5.16 (br s, 10H), 6.96 (d, J = 7.8 Hz,
1H), 7.01 (d, J = 7.8 Hz, 1H); 13C NMR (DMSO-d6):
d 174.6, 135.2, 133.7, 133.4, 133.2, 128.3, 127.8, 71.5,
71.3, 50.8, 48.4, 20.9, 19.8, 19.1, 18.4. Anal. Calcd for
C16H26N2O7: C, 53.62; H, 7.31; N, 7.82. Found: C,
53.60; H, 7.06; N, 7.66.
4.6.2. Salen-type ligand, 6b. Prepared from 5b in a sim-
25
ilar manner to 6a in 86% yield. ½aꢁD ¼ þ219:8 (c 1.00,
CHCl3) for 6b of >99% ee. Mp 135–137 °C; IR (NaCl,
cmꢀ1) 2955, 1623, 1465, 1439, 1361, 1272, 1249, 1171,
1
807, 772. H NMR (CDCl3): d 1.26 (s, 9H), 1.29 (s,
4.5.3. (1S,2S)-Diamine (R,R)-tartrate, 5c. Prepared
9H), 1.39 (s, 9H), 1.43 (s, 9H), 1.92–2.08 (m, 1H),
2.13–2.25 (m, 4H), 2.30 (s, 3H), 2.71–2.94 (m, 2H),
3.88 (m, 1H), 4.87 (d, J = 8.4 Hz, 1H), 6.96–6.98 (m,
2H), 7.07–7.09 (m, 2H), 7.36 (t, J = 2.4 Hz, 2H), 8.12
(s, 1H), 8.53 (s, 1H), 13.23 (br s, 1H), 13.82 (br s, 1H);
13C NMR (CDCl3): d 166.43, 158.36, 158.07, 140.31,
140.20, 136.84, 136.21, 135.98, 134.20, 131.22, 129.28,
128.47, 127.34, 127.27, 126.51, 126.35, 118.09, 118.05,
69.41, 68.45, 35.24, 34.34, 31.70, 29.67, 29.62, 25.63,
23.97, 20.06, 19.88. Anal. Calcd for C42H58N2O2: C,
80.98; H, 9.38; N, 4.50. Found: C, 80.79; H, 9.48; N,
4.45.
from 4c in a similar manner to 5a in 75% yield.
25
½aꢁD ¼ þ0:8 (c 1.00, DMSO) for 5c of >99% ee. Mp
198–201 °C (decomp); 1H NMR (DMSO-d6): d 1.80–
1.85 (m, 1H), 2.09 (s, 3H), 2.16–2.29 (m, 10H), 2.51–
2.69 (m, 2H), 3.38 (m, 1H), 3.82 (s, 2H), 4.10 (m, 1H),
4.81 (br s, 10H); 13C NMR (DMSO-d6): d 174.5,
133.4, 132.8, 132.7, 131.3, 130.5, 71.3, 54.9, 51.1, 49.2,
21.9, 20.4, 16.4, 15.4, 15.2. Anal. Calcd for
C18H30N2O7: C, 55.94; H, 7.82; N, 7.25. Found: C,
56.13; H, 7.81; N, 7.29.
4.5.4. (1S,2S)-Diamine (R,R)-tartrate, 5d. Prepared
from 4d in a similar manner to 5a in 80% yield.
4.6.3. Salen-type ligand, 6c. Prepared from 5c in a sim-
25
25
½aꢁD ¼ ꢀ44:2 (c 1.00, DMSO) for 5d of >99% ee. Mp
ilar manner to 6a in 94% yield. ½aꢁD ¼ þ185:0 (c 1.00,
235–237 °C (decomp); 1H NMR (DMSO-d6): d 1.65–
1.79 (m, 1H), 2.06–2.14 (m, 1H), 2.16 (s, 3H), 2.18 (s,
3H), 2.73 (m, 2H), 3.01 (m, 1H), 3.75 (d, J = 8.7 Hz,
CHCl3) for 6c of >99% ee. Mp 210–212 °C; IR (NaCl,
cmꢀ1) 2954, 1625, 1439, 1360, 1273, 1250, 1171, 773.
1H NMR (CDCl3): d 1.24 (s, 9H), 1.29 (s, 9H), 1.40 (s,

Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
425
9H), 1.43 (s, 9H), 1,94–2.15 (m, 5H), 2.22 (s, 3H), 2.26
(s, 3H), 2.30 (s, 3H), 2.73–2.96 (m, 2H), 3.84 (m, 1H),
5.01 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 4.0 Hz, 1H), 7.08
(d, J = 2.7 Hz, 1H), 7.36 (d, J = 2.1 Hz, 2H), 8.08 (s,
1H), 8.53 (s, 1H), 13.32 (br s, 1H), 13.95 (br s, 1H);
13C NMR (CDCl3): d 166.41, 166.24, 158.43, 158.06,
140.28, 140.05, 136.82, 136.77, 134.60, 133.89, 133.54,
133.49, 132.13, 128.55, 127.20, 126.49, 126.36, 118.13,
69.63, 68.59, 35.25, 35.23, 34.32, 31.70, 29.68, 29.63,
25.99, 25.00, 17.07, 16.92, 15.99. Anal. Calcd for
C44H62N2O2: C, 81.18; H, 9.60; N, 4.30. Found: C,
81.24; H, 9.53; N, 4.29.
J = 22.5 Hz), 136.58, 135.18, 134.77, 134.35, 134.09 (d,
J = 20.2 Hz), 133.99 (d, J = 20.2 Hz), 130.63, 130.32,
129.11, 128.94, 128.75, 128.66, 128.59, 128.51, 127.95,
127.73, 127.45, 126.53, 53.55, 53.29, 28.65, 28.50. 31P
NMR (CDCl3): d ꢀ10.3, ꢀ11.5. Anal. Calcd for
C48H40N2O2P2: C, 78.03; H, 5.46; N, 3.79. Found: C,
78.23; H, 5.60; N, 3.76.
4.7.2. Trost-type ligand, 7b. Prepared from 5b in a simi-
25
lar manner to 7a in 77% yield. ½aꢁD ¼ þ94:0 (c 1.00,
CHCl3). Mp 119–123 °C (decomp); IR (NaCl, cmꢀ1
)
3398, 3300, 3053, 2931, 1647, 1522, 1433, 1321, 1258,
1
1217, 1156, 1090, 1026, 745, 696. H NMR (CDCl3): d
4.6.4. Salen-type ligand, 6d. Prepared from 5d in a simi-
1.57–1.68 (m, 1H), 1.91–2.03 (m, 1H), 2.14 (s, 3H),
2.28 (s, 3H), 2.35–2.59 (m, 2H), 4.24–4.32 (m, 1H),
5.21 (dd, J = 8.4, 4.2 Hz, 1H), 5.88 (d, J = 8.4 Hz,
1H), 6.04 (d, J = 6.9 Hz, 1H), 6.87–6.96 (m, 3H), 6.99–
7.08 (m, 3H), 7.12–7.38 (m, 22H), 7.56–7.63 (m, 2H);
13C NMR (CDCl3): d 168.80, 167.76, 141.68 (d, J =
25.4 Hz), 141.32 (d, J = 25.4 Hz), 137.31 (d,
J = 11.3 Hz), 137.20 (d, J = 11.3 Hz), 137.08 (d, J =
11.8 Hz), 136.94 (d, J = 11.8 Hz), 136.82, 135.98 (d,
J = 21.5 Hz), 135.92, 135.81 (d, J = 21.5 Hz), 134.60,
134.23, 133.96 (d, J = 20.6 Hz), 133.95 (d, J =
20.6 Hz), 133.89 (d, J = 19.7 Hz), 133.85 (d, J =
19.7 Hz), 130.87, 130.50, 130.10, 129.43, 129.09,
128.93, 128.87, 128.84, 128.81, 128.76, 128.71, 128.66,
128.63, 128.57, 128.49, 128.42, 128.35, 50.15, 49.14,
23.04 (d, J = 2.8 Hz), 22.51, 19.64, 19.50 (d,
J = 4.5 Hz); 31P NMR (CDCl3): d ꢀ11.9, ꢀ12.3. Anal.
Calcd for C50H44N2O2P2: C, 78.31; H, 5.78; N, 3.65.
Found: C, 78.29; H, 5.91; N, 3.46.
25
lar manner to 6a in 84% yield. ½aꢁD ¼ þ220:2 (c 1.00,
CHCl3) for 6d of >99% ee. Mp 132–135 °C; IR (NaCl,
cmꢀ1) 2955, 2358, 1626, 1439, 1361, 1250, 1173, 879,
1
772. H NMR (CDCl3): d 1.24 (s, 9H), 1.26 (s, 9H),
1.40 (s, 9H), 1.42 (s, 9H), 2.13–2.22 (m, 5H), 2.24 (s,
3H), 2.92–3.04 (m, 2H), 3.70 (ddd, J = 10.5, 6.9,
4.2 Hz, 1H), 4.53 (d, J = 8.4 Hz, 1H), 6.87 (s, 1), 6.98
(m, 2H), 7.08 (d, J = 2.4 Hz, 1H), 7.34 (dd, J = 8.1,
2.4 Hz, 2H), 8.37 (s, 1H), 8.45 (s, 1H), 13.12 (br s,
1H), 13.56 (br s, 1H); 13C NMR (CDCl3): d 168.17,
166.85, 158.42, 158.14, 140.28, 140.17, 136.77, 136.66,
135.99, 134.85, 133.11, 132.86, 130.05, 129.41, 127.32,
127.18, 126.59, 126.44, 118.09, 117.93, 73.64, 70.71,
35.22, 35.20, 34.30, 34.28, 31.65, 30.24, 29.65, 27.90,
19.61, 19.56. Anal. Calcd for C42H58N2O2: C, 80.98;
H, 9.38; N, 4.50. Found: C, 80.94; H, 9.50; N, 4.45.
4.7. Synthesis of the Trost ligands 7a–d
4.7.1. Trost-type ligand, 7a. To a stirred solution of 2-
(diphenylphosphino)benzoic acid (2.6 g, 8.4 mmol) and
triethylamine (3.5 mL, 25.2 mmol) in anhydrous CH2Cl2
was slowly added diphenylchlorophosphate (1.9 mL,
9.2 mmol) at 0 °C for 10 min under a nitrogen atmo-
sphere. The mixture was warmed to room temperature
and stirred for 15 h. Then a solution of (S,S)-1,2,3,4-tet-
rahydronaphthalen-1,2-diamine 5a (0.6 g, 3.8 mmol)
and DMAP (47 mg, 0.4 mmol) in anhydrous CH2Cl2
was added by cannula and the mixture was stirred at
room temperature for another 24 h. The reaction was
quenched with saturated NaHCO3 solution and extr-
acted with CH2Cl2. The separated organic layer was
washed with brine and dried over anhydrous MgSO4.
After concentration under reduced pressure, the residue
was purified by flash column chromatography (hexane/
4.7.3. Trost-type ligand, 7c. Prepared from 5c in a simi-
25
lar manner to 7a in 76% yield. ½aꢁD ¼ þ58:4 (c 1.00,
CHCl3). Mp 116–120 °C (decomp); IR (NaCl, cmꢀ1
)
3404, 3314, 3052, 2925, 1643, 1521, 1458, 1433, 1321,
1089, 744, 695. 1H NMR (CDCl3): d 1.65–1.77 (m,
1H), 1.85–1.95 (m, 1H), 2.11 (s, 3H), 2.17 (s, 3H), 2.20
(s, 3H), 2.24 (s, 3H), 2.42–2.64 (m, 2H), 4.22–4.28 (m,
1H), 5.25 (dd, J = 8.1, 5.1 Hz, 1H), 5.89 (d,
J = 8.1 Hz, 1H), 6.09 (d, J = 7.8 Hz, 1H), 6.86–6.95
(m, 2H), 7.07 (t, J = 7.8 Hz, 2H), 7.14–7.36 (m, 22H),
7.55–7.59 (m, 2H); 13C NMR (CDCl3): d 168.94,
167.84, 141.80 (d, J = 26.5 Hz), 141.41 (d, J = 26.5
Hz), 137.62 (d, J = 11.5 Hz), 137.46 (d, J = 11.7 Hz),
137.31 (d, J = 11.5 Hz), 137.26 (d, J = 11.7 Hz), 136.30
(d, J = 21.3 Hz), 135.97 (d, J = 21.3 Hz), 134.98,
134.69, 134.58, 133.98 (d, J = 20.1 Hz), 133.94 (d,
J = 20.1 Hz), 133.92, 133.17, 132.34, 130.49, 130.05,
129.81 (d, J = 4.3 Hz), 129.04, 128.91, 128.81, 128.75,
128.72, 128.66, 128.62, 128.56, 128.31 (d, J = 4.3 Hz),
128.19, 128.11, 50.87, 50.09, 24.35, 23.17, 16.94, 16.88,
16.48 (d, J = 4.1 Hz), 15.82. 31P NMR (CDCl3): d
ꢀ11.7, ꢀ12.2. Anal. Calcd for C52H48N2O2P2: C,
78.57; H, 6.09; N, 3.52. Found: C, 78.22; H, 6.40; N,
3.47.
ethyl acetate = 70/30) to give 2.6 g of 7a (93% yield) as
25
a white solid. ½aꢁD ¼ ꢀ29:8 (c 1.00, CHCl3). Mp 129–
135 °C (decomp); IR (NaCl, cmꢀ1) 3311, 3051, 2925,
1635, 1583, 1528, 1433, 1325, 1156, 1087, 1026, 743,
695. 1H NMR (CDCl3): d 1.48–1.62 (m, 1H), 2.01–
2.13 (m, 1H), 2.73–2.79 (m, 1H), 2.88–2.97 (m, 1H),
4.09–4.23 (m, 1H), 5.30 (t, J = 9.3 Hz, 1H), 6.34 (d,
J = 9.3 Hz, 1H), 6.63 (d, J = 7.8 Hz, 1H), 6.88–6.93
(m, 1H), 6.98–7.02 (m, 1H), 7.04–7.15 (m, 4H), 7.18–
7.34 (m, 24H), 7.64–7.68 (m, 2H); 13C NMR (CDCl3):
d 170.41, 169.41, 140.77 (d, J = 24.5 Hz), 140.60
(d, J = 24.5 Hz), 138.13 (d, J = 11.5 Hz), 137.98
(d, J = 11.5 Hz), 137.83 (d, J = 12.2 Hz), 137.77 (d,
J = 12.2 Hz), 137.25 (d, J = 22.5 Hz), 136.94 (d,
4.7.4. Trost-type ligand, 7d. Prepared from 5d in a simi-
25
lar manner to 7a in 80% yield. ½aꢁD ¼ ꢀ28:9 (c 1.00,
CHCl3). Mp 131–136 °C (decomp); IR (NaCl, cmꢀ1
)
3417, 3304, 3052, 2922, 1638, 1522, 1433, 1320, 1187,
1158, 1088, 962, 744, 695. 1H NMR (CDCl3): d

426
Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
4320; (i) Yoon, T. P.; Jacobsen, E. N. Science 2003, 299,
1691.
1.42–1.58 (m, 1H), 2.01–2.11 (m, 1H), 2.18 (s, 3H), 2.20
(s, 3H), 2.65–2.71 (m, 1H), 2.83–2.91 (m, 1H), 4.08–4.17
(m, 1H), 5.27 (t, J = 9.3 Hz, 1H), 6.30 (d, J = 9.3 Hz,
1H), 6.64 (d, J = 7.8 Hz, 1H), 6.85 (s, 1H), 6.88–6.92
(m, 1H), 7.01–7.06 (m, 1H), 7.19–7.39 (m, 25H), 7.63–
7.69 (m, 2H); 13C NMR (CDCl3): d 170.35, 169.39,
141.49 (d, J = 25.6 Hz), 140.89 (d, J = 25.6 Hz), 138.15
(d, J = 12.2 Hz), 138.06 (d, J = 11.5 Hz), 138.03 (d,
J = 12.2 Hz), 137.87 (d, J = 11.5 Hz), 137.12 (d,
J = 21.8 Hz), 136.91 (d, J = 21.8 Hz), 136.09, 135.10,
134.87, 134.14 (d, J = 20.5 Hz), 134.10 (d,
J = 20.5 Hz), 133.92 (d, J = 19.8 Hz), 133.84 (d,
J = 19.8 Hz), 132.39, 130.65, 130.31, 129.99, 129.23,
128.94, 128.77, 128.72, 128.67, 128.62, 128.58, 128.52,
128.06 (d, J = 4.2 Hz), 127.99 (d, J = 4.2 Hz), 53.71,
53.30, 28.57, 28.11, 19.60, 19.47. 31P NMR (CDCl3): d
ꢀ10.2, ꢀ11.9. Anal. Calcd for C50H44N2O2P2: C,
78.31; H, 5.78; N, 3.65. Found: C, 78.46; H, 6.02; N,
3.53.
6. (a) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96,
395; (b) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J.
Am. Chem. Soc. 1992, 114, 9327; (c) Trost, B. M.; Bunt, R.
C.; Lemoine, R. C.; Calkins, T. L. J. Am. Chem. Soc.
2000, 122, 5968.
7. Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem., Int.
Ed. 1998, 37, 2580, and references cited therein.
8. (a) Newman, M. S.; Cella, J. A. J. Org. Chem. 1973, 38,
3482; (b) Wilcox, C. F., Jr.; Farley, E. J. Am. Chem. Soc.
1984, 106, 7195.
9. Kajigaeshi, S.; Kakinami, T.; Moriwaki, M.; Tanaka, T.;
Fujisaki, S.; Okamoto, T. Bull. Chem. Soc. Jpn. 1989, 62,
439.
10. Caster, K. C.; Keck, C. G.; Walls, R. D. J. Org. Chem.
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11. Ashton, P. R.; Girreser, U.; Giuffrida, D.; Kohnke, F. H.;
Mathias, J. P.; Raymo, F. M.; Slawin, A. M. Z.; Stoddart,
J. F.; Williams, D. J. J. Am. Chem. Soc. 1993, 115, 5422.
12. Lautens, M.; Fagnou, K.; Zunic, V. Org. Lett. 2002, 4,
3465.
13. We also examined the ring-opening reactions of 1a with
benzophenone imine and benzamide under the same
conditions. Those reactions did not give the ring-opening
products.
14. (a) Hayashi, T.; Yamamoto, A.; Hojo, M.; Kishi, K.; Ito,
Y.; Nishioka, E.; Miura, H.; Yanagi, K. J. Organomet.
Chem. 1989, 370, 129; (b) Schwink, L.; Knochel, P. Chem.
Eur. J. 1998, 4, 950.
15. Lautens, M.; Fagnou, K.; Yang, D. J. Am. Chem. Soc.
2003, 125, 14884.
16. (a) Lautens, M.; Fagnou, K. J. Am. Chem. Soc. 2001, 123,
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2002, 41, 26.
Acknowledgements
We thank NSERC, the University of Toronto and
AstraZeneca Research Centre in Montreal, for financial
´
support. A.F. thanks ‘Le Ministere de Affaires Etrang-
eres Francais’, for a Bourse Lavoisier postdoctoral fel-
lowship. We thank Dr. Alan J. Lough, for his
assistance with crystallographic analysis. We also thank
Mr. Chris Dockendorff for valuable discussions and use-
ful suggestions during the writing of this manuscript.
17. (a) Fagnou, K. In Modern Rhodium-Catalyzed Organic
Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim,
2005; pp 173–190, Chapter 9; (b) Lautens, M.; Fagnou, K.
Proc. Natl. Acad. Sci. USA 2004, 101, 5455.
18. Comprehensive Organometallic Chemistry; Wilkinson, G.,
Ed.; Pergamon Press: Elmsford, NY, 1982; Vol. 5.
19. Buchwald found that cleavage of palladium iodide bridged
dimer complex was slower that chloro bridged dimer
complex and others have also reported similar results. See:
(a) Widenhoefer, R. A.; Buchwald, S. L. Organometallics
1996, 15, 2755; (b) Widenhoefer, R. A.; Zhong, A. H.;
Buchwald, S. L. Organometallics 1996, 15, 2745; (c)
Bennett, M. A.; Longstaff, P. A. J. Am. Chem. Soc.
1969, 91, 6266; (d) Chatt, J.; Venanzi, L. M. J. Chem. Soc.
1957, 2445.
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22. Crystal data for 5a: C14H22N2O7, M = 330.34, mono-
˚
clinic, space group P2 (no 1), a = 8.4869(4) A,
˚
˚
b = 7.0103(3) A,
c = 12.8152(6) A,
a = 90°,
b =
3
˚
104.569(2)°, c = 90°, V = 737.93(6) A , Z = 2, Dc =
1.487 Mg/m3, m = (Cu-Ka) = 0.120 mmꢀ1, F(000) = 352
reflections were collected, of which 4704 were considered
to be observed with I > 2r(I). The structure was deter-
mined by direct methods using the SHELXTLTM suite of
programs. Hydrogen atoms were placed in calculated
positions. Full-matrix least squares refinement based on F2
with anisotropic thermal parameters for the non-hydrogen
atoms led to agreement factors R1 = 0.0345 and
wR2 = 0.0773. Crystallographic data (excluding structure

Y.-H. Cho et al. / Tetrahedron: Asymmetry 17 (2006) 416–427
427
factors) for the structure reported in this paper have been
deposited at the Cambridge Crystallographic Data Centre
as supplementary material No. CCDC-288672.
2056 reflections were collected, of which 38,687 were
considered to be observed with I > 2r(I). Full-matrix least
squares refinement based on F2 with anisotropic thermal
parameters for the non-hydrogen atoms led to agreement
factors R1 = 0.0754 and wR2 = 0.2138. Crystallographic
data for the structure reported in this paper have been
deposited at the Cambridge Crystallographic Data Centre
as supplementary material No. CCDC-288671.
23. Larrow, J. F.; Jacobsen, E. N. Org. Synth. 1998, 75, 1.
24. Crystal data for 7a: C51H46Cl6N2O2P2, M = 993.54,
˚
monoclinic, space group P21/c, a = 15.5347(4) A,
˚
˚
b = 12.3346(4) A,
6.0330(15)°, c = 90°, V = 4912.5(2) A , Z = 4, Dc =
1.343 Mg/m3, m = (Cu-Ka) = 0.457 mmꢀ1
F(000) =
c = 25.7800(6) A,
a = 90°,
b =
3
˚
,
25. Carpino, L. A.; Barr, D. E. J. Org. Chem. 1966, 31, 764.