Enantioselective synthesis of 2-substitued-tetrahydroisoquinolin-1-yl glycine derivatives via oxidative cross-dehydrogenative coupling of tertiary amines and chiral nickel(II) glycinate

Article abstract of DOI:10.1021/jo401510b

The asymmetric synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycines was achieved by an oxidative cross-dehydrogenative coupling (CDC) reaction. This method for activation of the α-C-H bonds of amines with chiral nickel(II) glycinate using o-chlo

Full text of DOI:10.1021/jo401510b

Article
pubs.acs.org/joc
Enantioselective Synthesis of 2‑Substitued-Tetrahydroisoquinolin-1-
yl Glycine Derivatives via Oxidative Cross-Dehydrogenative Coupling
of Tertiary Amines and Chiral Nickel(II) Glycinate
Shengbin Zhou, Jiang Wang, Daizong Lin, Fei Zhao, and Hong Liu*
CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203,
China
S
* Supporting Information
ABSTRACT: The asymmetric synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycines was achieved by an oxidative cross-
dehydrogenative coupling (CDC) reaction. This method for activation of the α-C-H bonds of amines with chiral nickel(II)
glycinate using o-chloranil as the sole oxidant afforded highly diastereoselective coupling adducts. The decomposition of coupling
adducts readily afforded 2-substituted-tetrahydroisoquinolin-1-yl glycine derivatives.
on catalysis using simple metal salts has received considerable
attention,10 and progress has been made in this fascinating area
since the pioneering studies of oxidative functionalization by
Murahashi et al.11 and CDC by Li et al.12 However,
development of the coupling reactions into a general and
enantioselective process remains a great challenge.13 In
particular, an asymmetric oxidative reaction of tertiary amines
and glycine equivalent has not been achieved.
INTRODUCTION
■
Optically active non-proteinogenic amino acids have crucial
roles in natural products, asymmetric chemical investigations,
medicinal chemistry, and peptide/peptidomimetic agents due
to their wide-ranging biological properties and versatility as
synthetic building blocks.1 Among numerous α,β-diamino
acids,2 substituted tetrahydroisoquinolin-1-yl glycine derivatives
are important building blocks of many bioactive compounds
and natural products, such as ecteinascidin,3 PDE-II,4
indolobenzazocin-8-ones,5 and alkaloids.6 Significant efforts
have focused on the asymmetric preparation of α,β-diamino
acids,2 while few synthetic methods have been developed for
substituted tetrahydroisoquinolin-1-yl glycine derivatives.
These methods have mainly focused on conventional
approaches using functional group chemistry including the
reduction of azides7 and nucleophilic substitution reactions of
prefunctionalized tetrahydroisoquinoline derivatives,4 but only
racemic products were obtained. Asymmetric addition of
glycine equivalents to (dihydro)isoquinolines have also been
limited to few examples.8 Accordingly, the development of a
direct, efficient, and stereoselective synthetic method of
substituted tetrahydroisoquinolin-1-yl glycine derivatives
under mild conditions is of considerable interest in academia
and industry.
Very recently, Wang et al.13a used metals together with chiral
bisoxazoline ligands to realize enantioselective reactions of
activated carbonyl nucleophiles (such as 1,3-dicarbonyls and
acetyl phosphates) to oxidatively generate iminiums or their
analogues. Based on this work, they also used metals/Lewis
acids with bifunctional cinchona alkaloids to realize asymmetric
oxidative cross-coupling reaction of amines and olefins.13b In
addition, Chi et al.13c reported an enantioselective oxidative
reaction of aldehydes and tertiary amines under cooperative
amine and metal catalysis. Despite the considerable enantiose-
lectivities of these reactions, limitations remain: (i) Some
existing problems (e.g., unsatisfactory control of reaction
diastereomeric ratio and instability of coupling products) may
limit their applications.13c (ii) Less reactive and stable
nucleophiles, such as glycine equivalent, cannot react under
these conditions. We describe here a novel oxidative CDC of
tertiary amines with chiral nickel(II) glycinate with high
diastereoselectivities.
Recently, cross-dehydrogenative coupling (CDC) has been a
versatile strategy for C−C bond formations. Direct conversion
of C−H bonds into C−C bonds by CDC allows for the most
efficient synthesis of products.9 Among these reactions,
oxidative coupling of amines with various nucleophiles based
Received: July 11, 2013
Published: October 11, 2013
© 2013 American Chemical Society
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Chiral nickel(II) complexes of glycine Schiff bases have been
used widely to synthesize enantiopure non-proteinogenic
amino acids via aldol,14 Michael addition,15 Mannich,16 and
C-alkylation reactions.17 Given our recent involvement in the
asymmetric synthesis of optically active amino acids via the
nucleophilic reactions of nickel(II) glycinate and electron-
deficient substrates,18 we sought to develop new synthetic
protocols by C−H activation. Recently, we developed an
asymmetric oxidative heterocoupling reaction of a nickel(II)
glycinate and indoles.19 Encouraged by these successful efforts
and aiming to develop other unprecedented transformations,
we describe here our contribution regarding diastereoselectively
oxidative CDC of tertiary amines and chiral nickel(II) glycinate
(Scheme 1). This method possesses four main advantages: (i)
product in 72% yield and in a syn/anti ratio of 2.5:1 with
excellent diastereoselectivity (99%/85% de; Table 1, entries 2−
6). The effect of the solvent was then investigated (Table 1,
entries 7−14). Good diastereoselectivities could be achieved in
1,4-dioxane, chloroform (CHCl3), and dichloromethane
(CH2Cl2) but with moderate yields and a low syn/anti ratio
(Table 1, entries 7−9). In acetonitrile (CH3CN) and toluene,
the reaction gave coupling products with an improved syn/anti
ratio, but lower yields (Table 1, entries 10 and 11). Methanol
(MeOH) and diethyl ether (Et2O) were not appropriate
solvents (Table 1, entries 12 and 13). The reaction in
tetrahydrofuran (THF) afforded the product with good yield,
a moderate syn/anti ratio, and excellent diastereoselectivity
(Table 1, entry 14). Further optimization studies on the
reaction undertaken with the oxidant o-chloranil in THF at
various temperatures suggested that the syn/anti ratio decreased
significantly with increase of temperature and that the desired
product was not obtained at low temperature (Table 1, entries
15 and 16). Better results were not obtained by the screening of
metal catalysts and the equivalent of reactants (see the
Supporting Information for details). The relative and absolute
configuration of major coupling compound 3a-syn was
determined to be (S)(2S,2(1′S)) by X-ray crystallography20
(Figure S2 in the Supporting Information).
Scheme 1. Asymmetric Synthesis of 2-Substituted-
Tetrahydroisoquinolin-1-yl Glycine Derivatives via
Oxidative Cross-Dehydrogenative Coupling of Tertiary
Amines and Chiral Nickel(II) Glycinate
With the best reaction conditions established, the scope of
substrates for the asymmetric oxidative coupling reactions was
then studied. In general, the reaction proceeded well to afford
the desired products in good yields with good to excellent
diastereoselectivities. For the reaction with nickel(II) glycinate-
(S)-1, initial investigation of the steric effect showed that
substituents on the para- and meta- position of the phenyl ring
of 2 were well tolerated in this reaction (Table 2, entries 1−3).
Nevertheless, (S)-1 and aromatic-substituted tetrahydroisoqui-
noline 2d with substituent at the ortho- position of the phenyl
ring did not afford the stable oxidative coupling product due to
the larger steric hindrance. The syn/anti ratio and de values
were not obtained owing to the instability of 3d toward
decompositions (Table 2, entry 4). When methyl group at the
ortho- position of the phenyl ring, the corresponding coupling
product was still obtained in a poor yield due to steric
hindrance (Table 2, entry 5). Then, our focus shifted to
evaluation of the electronic effects on the para- position of the
phenyl ring. Coupling products were obtained in satisfactory
yields of 55−88%, with moderate syn/anti ratio and excellent
diastereoselectivities of 90−99% (Table 2, entries 6−11). The
coupling products of (S)-1 and aromatic-substituted tetrahy-
droisoquinolines 2 with double substituents on the N-aryl ring,
respectively, were also isolated in good yields and high
diastereoselectivities (45−59% yields, up to a 5:1 syn/anti
ratio and 89−99% de; Table 2, entries 12−14). Substituents
with methoxy or methylenedioxy on the 6,7-position of the
tetrahydroisoquinoline ring did not influent reaction outcomes
(Table 2, entries 15 and 16). N-benzyl tetrahydroisoquinoline
and nickel(II) glycinate were used to obtain the corresponding
coupling product in acceptable yield (Table 2, entry 17). The
plausible reaction pathway is postulated to involve a single-
electron transfer (SET) radical mechanism9,13a,c (See Scheme
S1 in the Supporting Information). The relative and absolute
configuration of minor coupling compound 3k-anti was
determined to be (S)(2S,2(1′R)) by X-ray crystallography20
(Figure S3 in the Supporting Information).
formation of C(sp3)-C(sp3) bonds by C(sp3)-H activation
avoiding prefunctionalization of the substrates; (ii) activation of
the α-C-H bonds of amines using o-chloranil as the sole
oxidant; (iii) achieving an asymmetric CDC reaction of amines
with high diastereoselectivities through control of chiral
nickel(II) complexes; (iv) generation of optically active and
potential 2-substituted-tetrahydroisoquinolin-1-yl glycine deriv-
atives in easy and convenient reaction procedures.
RESULTS AND DISCUSSION
■
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) has been
used in efficient oxidative coupling reactions involving C(sp3)-
H activation.9f,d,13a We focused initially on the DDQ-oxidized
coupling reaction of chiral nickel(II) glycinate (S)-1 with N-
phenyl tetrahydroisoquinoline 2a at ambient temperature. The
reaction afforded moderate yield and a moderate syn/anti ratio
but good diastereoselectivity (Table 1, entry 1). This suggested
that chiral nickel(II) glycinate has excellent si-face-selectivi-
ty16,18c,19 under oxidative conditions (stereochemistry analysis
see Figure S1 in the Supporting Information). A survey of
oxidants suggested that o-chloranil was a good oxidant for the
nickel(II) glycinate CDC reaction. The reaction mediated by o-
chloranil in dimethyl formamide (DMF) generated the desired
The attempts to liberate 2-substituted-tetrahydroisoquinolin-
1-yl glycine derivatives from coupling products 3 under acidic
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a
Table 1. Optimization of Reaction Conditions
b
c
d
entry
oxidant
DDQ
solvent
yield (%)
syn/anti
de (%) (syn/anti)
1
DMF
50
2.2:1
nd
98/80
nd
2
TBHP
DMF
<5
<5
trace
trace
72
3
DTBP
DMF
nd
nd
4
m-CPBA
DMF
nd
nd
5
Cu(OAc)2
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
o-chloranil
DMF
nd
nd
6
DMF
2.5:1
2.8:1
2.5:1
2.2:1
4.2:1
3.7:1
nd
99/85
99/84
98/84
99/85
99/80
99/82
nd
7
1,4-dioxane
CHCl3
CH2Cl2
CH3CN
toluene
MeOH
Et2O
46
8
45
9
35
10
11
12
13
14
25
33
0
0
nd
nd
THF
64
4.6:1
2.3:1
nd
99/88
96/75
nd
e
15
f
THF
70
16
THF
<10
a
Reaction conditions: (S)-1 (0.1 mmol), 2a (0.12 mmol), oxidant (0.12 mmol), and solvent (1.0 mL) at room temperature for 24 h unless otherwise
b
c
d
1
noted. nd = not determined. Combined yield of isolated 3 (syn and anti). Determined by H NMR spectroscopy. Determined by HPLC on a
chiral stationary phase. 60 °C, 8 h. 0 °C, 36 h.
e
f
conditions resulted in the generation of iminium intermediates
by β-elimination. Next, the basic reaction conditions were
examined. Fortunately, the complexes (S)(2S,2(1′S))-3a and
(S)(2S,2(1′S))-3i were decomposed in a solution of N2H4·H2O
(85%)/EtOH (1/5) with ethylene diamine tetra-acetic acid
(EDTA) under heat to afford the target amino acids 4a and 4i
in 80−85% yields with 90−98% ee values (Scheme 2). The
chiral ligand (S)-BPB was recovered readily in quantitative
yield and could be reused via a simple procedure. The specific
rotation of the recovered (S)-BPB was identical to that of
freshly prepared (S)-BPB.
EXPERIMENTAL SECTION
■
General Information. The reagents (chemicals) were purchased
from commercial sources and used without further purification.
Analytical thin layer chromatography (TLC) was HSGF 254 (0.15−
0.2 mm thickness). All products were characterized by their NMR and
MS spectra. 1H and 13C NMR spectra were recorded in deuterochloro-
form (CDCl3) on a 300 or 400 MHz instrument. Chemical shifts were
reported in parts per million (ppm, δ) downfield from tetramethylsi-
lane. Proton coupling patterns are described as singlet (s), doublet (d),
triplet (t), quartet (q), multiplet (m), and broad (br). High-resolution
mass spectra (HRMS) was measured on Micromass Ultra Q-TOF
spectrometer. Optical rotations were reported as follows: [α]20D (c g/
100 mL, in solvent).
General Procedure for the Synthesis of (S)(2S,2(1′S))-3a. The
nickel(II) complex of glycine (S)-1 (50 mg, 0.1 mmol) was dissolved
in tetrahydrofuran (1.0 mL). After N-phenyl tetrahydroisoquinoline
(2a) (26 mg, 0.12 mmol) and o-chloranil (30 mg, 0.12 mmol) were
added successively, the reaction mixture was stirred for 24 h at room
temperature. After the reaction was complete as indicated by TLC, the
solvent was evaporated under vacuum. The residue was treated with
saturated aqueous Na2CO3, and the mixture was extracted with
dichloromethane (3 mL × 3). The combined organic layers were dried
with MgSO4, concentrated, and purified by column chromatography
on silica gel (dichloromethane/ethyl acetate = 4/1) to give the desired
coupling product 3a (45 mg, yield 64%, syn/anti 4.6:1) as a red solid.
In some cases, some pure syn-3 or anti-3 coupling products could be
isolated by column.
CONCLUSIONS
■
In summary, we developed a novel, direct, and highly
enantioselective route to the synthesis of 2-substituted-
tetrahydroisoquinolin-1-yl glycine derivatives via an asymmetric
oxidative cross-dehydrogenative coupling reaction between
tertiary amines and nickel(II) glycinate. This method provided
an alternative approach for the construction of C(sp3)-C(sp3)
bonds under mild conditions using o-chloranil as the terminal
oxidant with a moderate syn/anti ratio, moderate to good
yields, and excellent diastereoselectivities (up to 99% de). We
showed, for the first time, that the optically active target amino
acids could be obtained by decomposition of nickel(II)
complexes under basic reaction condition with satisfactory
yields and excellent excess enantioselectivity. Moreover, the
described method provided opportunities for the synthesis of
various chiral non-proteinogenic amino acids via the CDC
reaction of extensive sp3 carbons oxidized fragilely and chiral
nickel(II) glycinate.
Nickel(II)-(S)-BPB/2-Amino-2-((S)-2-phenyl-1,2,3,4-tetrahy-
droisoquinolin-1-yl) Acetic Acid Schiff Base Complex 3a. Red
solid (45 mg, yield 64%, syn/anti 4.6:1). Mp 224−226 °C; [α]20
=
D
1
+2113 (c 0.15 g/100 mL, CHCl3). H NMR (400 MHz, CDCl3): δ
syn-isomer 8.32 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 7.1 Hz, 2H), 7.56 (t, J
= 7.7 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H),
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a
Table 2. Investigation of the Scope of the Procedure
b
c
d
entry
1
2, R1, R2
2a, Ph, H
yield (%)
syn/anti
de (%) (syn/anti)
e
64
45
58
20
21
55
59
74
70
72
88
52
45
59
45
57
25
4.6:1 (>10:1)
3.6:1
2.3:1
nd
99/88
96/97
98/98
nd
f
2
2b, 4-OMe-C6H4, H
2c, 3-OMe-C6H4, H
2d, 2-OMe-C6H4, H
2e, 2-Me-C6H4, H
2f, 4-Me-C6H4, H
2g, 4-t-Bu-C6H4, H
2h, 4-CF3-C6H4, H
2i, 4-F-C6H4, H
f
3
f
4
5
nd
nd
6
2.3:1
3.4:1
1.1:1
3.6:1
1.6:1
1.5:1
5.0:1
3.0:1
1:1.2
1.3:1
2.6:1
<1:20
98/98
97/93
90/96
99/98
93/99
98/98
>99/>99
89/96
99/98
97/97
99/98
7
8
9
10
11
2j, 4-Cl-C6H4, H
2k, 4-Br-C6H4, H
f
12
2l, 3,4-di-Me-C6H3, H
2m, 3-Cl-4-Me-C6H3, H
2n, 3,5-di-CF3-C6H3, H
2o, 4-Br-C6H4, OCH2O
2p, 4-Br-C6H4, OMe
2q, Bn, H
13
14
g
15
g
16
17
-/98
a
b
Reaction conditions: (S)-1 (0.1 mmol), 2 (0.12 mmol), o-chloranil (0.12 mmol), and THF (1.0 mL) at room temperature for 24 h. Combined
c
d
e
yield of isolated 3 (syn and anti). Determined by 1H NMR spectroscopy. Determined by HPLC on a chiral stationary phase. Recrystallized with
ethyl acetate. 12 h. 36 h.
f
g
Scheme 2. Disassembling of Nickel(II) Complexes To Release Amino Acids and Recovery of the Ligand (S)-BPB
7.29−7.26 (m, 2H), 7.18−7.05(m, 7H), 6.99−6.95 (m, 1H), 6.82−
6.67 (m, 6H), 6.04 (s, 1H), 5.04 (d, J = 3.1 Hz, 1H), 4.69 (d, J = 3.3
Hz, 1H), 4.35 (d, J = 12.6 Hz, 1H), 3.77−3.66 (m, 2H), 3.43 (d, J =
12.6 Hz, 1H), 3.30−3.25 (m, 2H), 3.07−2.99 (m, 1H), 2.80−2.74 (m,
1H), 2.65−2.59 (m, 1H), 2.22−2.02 (m, 2H), 1.91−1.83 (m, 1H),
1.77−1.69 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): δ 180.2,
177.2, 172.0, 149.7, 143.1, 136.3, 133.9, 133.8, 133.4, 132.7, 131.5,
129.4, 129.1, 128.9, 128.7, 127.9, 127.4, 126.2, 125.9, 123.2, 120.5,
118.6, 113.9, 75.5, 70.6, 66.1, 63.6, 57.4, 42.2, 30.2, 26.3, 23.2 ppm.
LRMS (ESI) m/z [M + Na]+ found: 727.8. HRMS (ESI) m/z calcd
for C42H38N4NiO3Na+ [M + Na]+: 727.2195, found: 727.2152. The de
was determined by HPLC with a Chiralpak AD-H column (n-hexane/
i-PrOH = 75/25, λ = 254 nm, 0.8 mL/min). For the syn-isomer: tR
(major enantiomer) = 31.61 min, tR (minor enantiomer) = 50.85 min,
>99% de; for the anti-isomer: tR (major enantiomer) = 143.18 min, tR
(minor enantiomer) = 43.91 min, 88% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-methoxyphenyl)-1,2,3,4-
tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex
3b. Red solid (33 mg, yield 45%, syn/anti 3.6:1). [α]20 = +1238 (c
D
1
0.16 g/100 mL, CHCl3). H NMR (400 MHz, CDCl3): δ syn-isomer
8.31 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 7.2 Hz, 2H), 4.93 (d, J = 3.2 Hz,
1H), 4.61 (d, J = 3.3 Hz, 1H), 4.38 (d, J = 12.3 Hz, 1H), 3.70 (s, 3H);
anti-isomer 8.22 (d, J = 8.3 Hz, 1H), 8.10 (d, J = 7.4 Hz, 2H), 5.72 (d,
J = 4.9 Hz, 1H), 4.62 (J = 4.9 Hz, 1H), 4.36 (d, J = 12.4 Hz, 1H), 3.71
(s, 3H). Other overlapped peaks: δ 7.58−7.36 (m), 7.34−7.23 (m),
7.19−6.91 (m), 6.82−6.06 (m), 3.74−3.60 (m), 3.48−3.30 (m), 3.15−
2.96 (m), 2.63−2.45 (m), 2.31−2.21 (m), 2.13−2.04 (m), 1.84−1.75
(m) ppm. 13C NMR (125 MHz, CDCl3): δ syn-isomer 179.9, 176.7,
171.3, 152.5, 144.1, 142.7, 120.0, 115.7, 114.4, 75.1, 70.1, 66.3, 63.0,
57.0, 55.4, 42.6, 30.0, 25.5, 22.8; anti-isomer 179.6, 177.5, 171.0, 152.1,
143.3, 142.4, 120.0, 115.2, 114.5, 74.9, 70.5, 66.2, 63.2, 57.0, 55.3, 43.0,
30.6, 25.0, 22.8. Other overlapped peaks: δ 135.8, 135.1, 133.6, 133.5,
133.4, 133.2, 133.1, 133.0, 132.2, 132.0, 131.1, 131.0, 128.9, 128.8,
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128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.9, 127.6, 127.5, 127.1,
126.9, 126.8, 126.0, 125.7, 125.5, 122.8, 122.5 ppm. LRMS (ESI) m/z
found: 741.2336. The de was determined by HPLC with a Chiralpak
IA column (n-hexane/i-PrOH = 60/40, λ = 254 nm, 1.0 mL/min). For
the syn-isomer: tR (major enantiomer) = 22.28 min, tR (minor
enantiomer) = 10.54 min, 98% de; for the anti-isomer: tR (major
enantiomer) = 72.41 min, tR (minor enantiomer) = 14.63 min, 98%
de.
[M
+
Na]+ found: 756.8. HRMS (ESI) m/z calcd for
C43H40N4NiO4Na+ [M + Na]+: 757.2301, found: 757.2289. The de
was determined by HPLC with a Chiralpak IA column (n-hexane/i-
PrOH = 60/40, λ = 254 nm, 1.0 mL/min). For the syn-isomer: tR
(major enantiomer) = 33.68 min, tR (minor enantiomer) = 12.14 min,
96% de; for the anti-isomer: tR (major enantiomer) = 143.25 min, tR
(minor enantiomer) = 17.61 min, 97% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-tert-butylphenyl)-1,2,3,4-
tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex
3g. Red solid (45 mg, yield 59%, syn/anti 3.4:1). [α]20 = +1260 (c
D
1
0.20 g/100 mL, CHCl3). H NMR (500 MHz, CDCl3): δ syn-isomer
Nickel(II)-(S)-BPB/2-Amino-2-(2-(3-methoxyphenyl)-1,2,3,4-
8.31 (d, J = 8.7 Hz, 1H), 8.05 (d, J = 7.2 Hz, 2H), 5.03 (d, J = 2.9 Hz,
1H), 4.68 (d, J = 3.2 Hz, 1H), 4.35 (d, J = 12.6 Hz, 1H), 1.24 (s, 9H);
anti-isomer 8.26 (d, J = 8.7 Hz, 1H), 8.08 (d, J = 7.2 Hz, 2H), 5.68 (d,
J = 4.6 Hz, 1H), 4.65 (d, J = 4.7 Hz, 1H), 4.35 (d, J = 12.6 Hz, 1H),
1.23 (s, 9H). Other overlapped peaks: δ 7.56−7.53 (m), 7.46−7.34
(m), 7.30−7.26 (m), 7.20−7.02 (m), 6.97−6.87 (m), 6.77−6.68 (m),
6.59−6.49 (m), 6.25−6.05 (m), 3.70−3.68 (m), 3.47−3.25 (m), 3.04−
2.98 (m), 2.73−2.59 (m), 2.17−2.04 (m), 1.87−1.64 (m) ppm. 13C
NMR (125 MHz, CDCl3): δ syn-isomer 180.0, 177.2, 147.3, 143.2,
141.2, 136.4, 123.2, 120.4, 113.5, 75.6, 70.5, 66.1, 63.5, 57.4, 42.4, 33.8,
31.5, 30.1, 26.4, 23.2; anti-isomer 180.0, 178.1, 146.8, 143.0, 140.9,
135.6, 122.9, 120.3, 113.5, 75.2, 71.0, 65.4, 63.7, 57.4, 43.0, 33.7, 31.4,
31.2, 25.5, 23.0. Other overlapped peaks: δ 134.1, 133.9, 133.8, 133.7,
133.5, 133.2, 132.6, 132.4, 131.5, 129.3, 129.2, 129.0, 128.8, 128.7,
128.6, 128.5, 128.4, 128.0, 127.9, 127.5, 127.4, 127.3, 127.2, 126.4,
126.3, 126.2, 126.1 ppm. LRMS (ESI) m/z [M + Na]+ found: 782.8.
HRMS (ESI) m/z calcd for C46H46N4NiO3Na+ [M + Na]+: 783.2821,
found 783.2827. The de was determined by HPLC with a Chiralpak IA
column (n-hexane/i-PrOH = 75/25, λ = 254 nm, 1.0 mL/min). For
the syn-isomer: tR (major enantiomer) = 19.09 min, tR (minor
enantiomer) = 10.99 min, 97% de; for the anti-isomer: tR (major
enantiomer) = 72.15 min, tR (minor enantiomer) = 25.54 min, 93%
de.
tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex
3c. Red solid (43 mg, yield 58%, syn/anti 2.3:1). [α]20 = +1325 (c
D
1
0.16 g/100 mL, CHCl3). H NMR (500 MHz, CDCl3): δ syn-isomer
8.34 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 7.3 Hz, 2H), 5.04 (d, J = 2.8 Hz,
1H), 4.66 (d, J = 3.2 Hz, 1H), 4.35 (d, J = 12.6 Hz, 1H), 3.60 (s, 3H);
anti-isomer 8.24 (d, J = 8.6 Hz, 1H), 8.10 (d, J = 7.3 Hz, 2H), 5.94 (d,
J = 5.4 Hz, 1H), 4.63 (d, J = 5.6 Hz, 1H), 4.39 (d, J = 12.6 Hz, 1H),
3.73 (s, 3H). Other overlapped peaks: δ 7.59−7.56 (m), 7.46−7.28
(m),7.20−6.92 (m), 6.83−6.66 (m), 6.59−6.42 (m), 6.32−6.02 (m),
3.76−3.57 (m), 3.48−3.41 (m), 3.30−3.27 (m), 3.06−2.70 (m), 2.63−
2.58 (m), 2.52−2.46 (m), 2.25−1.95 (m), 1.86−1.76 (m) ppm. 13C
NMR (125 MHz, CDCl3): δ syn-isomer 180.2, 177.9, 171.9, 160.9,
151.2, 143.2, 136.2, 126.2, 125.9, 123.2, 120.4, 106.8, 103.6, 100.5,
75.4, 70.6, 66.1, 63.5, 57.4, 55.2, 43.0, 30.4, 26.2, 23.2; anti-isomer
180.0, 177.7, 171.5, 161.0, 150.6, 142.9, 135.4, 126.4, 126.3, 122.9,
120.3, 107.1, 102.9, 100.7, 75.1, 70.9, 65.9, 63.6, 57.4, 55.2, 42.4, 30.9,
25.7, 23.4. Other overlapped peaks: δ 134.0, 133.9, 133.8, 133.7, 133.4,
132.7, 132.4, 131.5, 131.4, 130.2, 130.0, 129.4, 129.2, 129.1, 128.9,
128.8, 128.7, 128.6, 128.5, 128.3, 127.8, 127.5, 127.4, 127.3 ppm.
LRMS (ESI) m/z [M + Na]+ found: 756.8. HRMS (ESI) m/z calcd
for C43H40N4NiO4Na+ [M + Na]+: 757.2301, found: 757.2313, The de
was determined by HPLC with a Chiralpak IA column (n-hexane/i-
PrOH = 60/40, λ = 254 nm, 1.0 mL/min). For the syn-isomer: tR
(major enantiomer) = 38.88 min, tR (minor enantiomer) = 13.48 min,
98% de; for the anti-isomer: tR (major enantiomer) = 164.17 min, tR
(minor enantiomer) = 12.01 min, 98% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-(trifluoromethyl)phenyl)-
1,2,3,4-tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base
Complex 3h. Red solid (57 mg, yield 74%, syn/anti 1.1:1). [α]20
D
= +1357 (c 0.21 g/100 mL, CHCl3). 1H NMR (400 MHz, CDCl3): δ
syn-isomer 8.38 (d, J = 8.6 Hz, 1H), 8.06 (d, J = 6.0 Hz, 2H), 5.25 (d, J
= 3.5 Hz, 1H), 4.83 (d, J = 3.2 Hz, 1H), 4.25 (d, J = 12.6 Hz, 1H);
anti-isomer 8.26 (d, J = 8.5 Hz, 1H), 8.05 (d, J = 7.0 Hz, 2H), 5.48 (d,
J = 5.7 Hz, 1H), 4.67 (d, J = 5.8 Hz, 1H), 4.31 (d, J = 12.6 Hz, 1H).
Other overlapped peaks: δ 7.59−7.56 (m), 7.50−7.28 (m), 7.25−7.04
(m), 6.90−6.83 (m), 6.70−6.45 (m), 3.62−3.22 (m), 3.08−2.91 (m),
2.64−2.60 (m), 2.13−2.03 (m), 1.75−1.67 (m) ppm. 13C NMR (125
MHz, CDCl3): δ syn-isomer 180.2, 176.8, 171.4, 151.0, 143.2, 136.6,
122.7, 120.5, 72.7, 70.8, 65.2, 64.0, 57.7, 43.4, 30.7, 27.3, 23.4; anti-
isomer 179.9, 177.8, 171.4, 150.9, 143.0, 135.7, 123.0, 120.5, 74.1, 70.6,
63.8, 63.7, 57.1, 43.8, 30.8, 26.4, 23.1. Other overlapped peaks: δ
134.1, 134.0, 133.5, 133.4, 133.3, 133.1, 132.8, 131.4, 131.3, 129.7,
129.6, 129.1, 129.0, 128.8, 128.6, 128.2, 128.0, 127.8, 127.2, 126.9,
126.7, 126.4, 125.9, 125.7 ppm. LRMS (ESI) m/z [M + Na]+ found:
794.8. HRMS (ESI) m/z calcd for C43H37F3N4NiO3Na+ [M + Na]+:
795.2069, found: 795.2076. The de was determined by HPLC with a
Chiralpak AD-H column (n-hexane/i-PrOH = 80/20, λ = 254 nm, 0.8
mL/min). For the syn-isomer: tR (major enantiomer) = 31.64 min, tR
(minor enantiomer) = 23.18 min, 90% de; for the anti-isomer: tR
(major enantiomer) = 95.10 min, tR (minor enantiomer) = 66.38 min,
96% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(2-methylphenyl)-1,2,3,4-
tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex
3e. Red solid (15 mg, yield 21%). [α]20D = +2105 (c 0.15 g/100 mL,
1
CHCl3). H NMR (500 MHz, CDCl3): δ syn-isomer 8.29 (d, J = 8.4
Hz, 1H), 8.06 (d, J = 7.2 Hz, 2H), 7.45−6.92 (m, 16H), 6.68−6.50
(m, 3H), 5.49 (s, 1H), 5.36 (s, 1H), 4.42 (d, J = 12.5 Hz, 1H), 4.25−
3.98 (m, 1H), 3.55−3.21 (m, 6H), 2.79−2.49 (m, 5H), 2.20−1.98 (m,
3H). 13C NMR (125 MHz, CDCl3) δ 180.4, 177.4, 170.8, 150.3, 142.6,
136.9, 134.2, 134.0, 133.8, 133.7, 133.3, 132.4, 131.6, 131.3, 129.5,
129.4, 128.8, 128.7, 128.4, 128.0, 127.7, 127.4, 127.3, 126.7, 126.2,
126.0, 125.8, 123.7, 123.2, 122.7, 120.6, 74.0, 70.4, 63.2, 57.1, 44.3,
30.7, 24.2, 24.0, 18.6. LRMS (ESI) m/z [M + Na]+ found: 741.2.
HRMS (ESI) m/z calcd for C43H40N4NiO3Na+ [M + Na]+: 741.2352,
found: 741.2346.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-methylphenyl)-1,2,3,4-
tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex
3f. Red solid (40 mg, yield 55%, syn/anti 2.3:1). [α]20 = +1412 (c
D
1
0.17 g/100 mL, CHCl3). H NMR (400 MHz, CDCl3): δ syn-isomer
8.31 (d, J = 8.7 Hz, 1H), 8.06 (d, J = 7.1 Hz, 2H), 4.97 (d, J = 3.1 Hz,
1H), 4.64 (d, J = 3.3 Hz, 1H), 4.37 (d, J = 12.4 Hz, 1H), 2.19 (s, 3H);
anti-isomer 8.21 (d, J = 8.7 Hz, 1H), 8.11 (d, J = 7.0 Hz, 2H), 5.93 (d,
J = 5.8 Hz, 1H), 4.61 (d, J = 5.8 Hz, 1H), 4.38 (d, J = 12.8 Hz, 1H),
2.18 (s, 3H). Other overlapped peaks: δ 7.59−7.27 (m), 7.20−7.04
(m), 7.02−6.84 (m), 6.78−6.48 (m), 3.77−3.66 (m), 3.52−3.27 (m),
3.07−2.93 (m), 2.70−2.41 (m), 2.22−1.75 (m) ppm. 13C NMR (125
MHz, CDCl3): syn-isomer: δ 180.3, 177.2, 171.7, 147.9, 143.1, 136.2,
126.1, 126.0, 123.3, 120.5, 113.9, 75.6, 70.5, 66.4, 63.4, 57.3, 42.3, 30.3,
26.0, 23.1, 20.2; anti-isomer 180.0, 177.7, 171.3, 147.1, 142.8, 135.5,
126.4, 126.3, 123.0, 120.4, 114.4, 75.1, 70.9, 66.4, 63.6, 57.4, 42.7, 31.0,
25.6, 23.4, 20.2. Other overlapped peaks: δ 134.0, 133.8, 133.7, 133.5,
133.4, 132.6, 132.4, 131.6, 131.4, 130.0, 129.8, 129.4, 129.2, 129.1,
129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 128.3, 128.0, 127.8, 127.6,
127.5, 127.4, 127.2 ppm. LRMS (ESI) m/z [M + Na]+ found: 740.8.
HRMS (ESI) m/z calcd for C43H40N4NiO3Na+ [M + Na]+: 741.2352,
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-fluorophenyl)-1,2,3,4-tet-
rahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex 3i.
Red solid (51 mg, yield 70%, syn/anti 3.6:1). [α]20 = +1171 (c 0.14
D
1
g/100 mL, CHCl3). H NMR (400 MHz, CDCl3): δ syn-isomer 8.35
(d, J = 8.6 Hz, 1H), 8.06 (d, J = 7.1 Hz, 2H), 5.02 (d, J = 3.6 Hz, 1H),
4.68 (d, J = 3.7 Hz, 1H), 4.33 (d, J = 12.5 Hz, 1H); anti-isomer 8.23
(d, J = 8.7 Hz, 1H), 8.08 (d, J = 7.5 Hz, 2H), 5.63 (d, J = 5.4 Hz, 1H),
4.63 (d, J = 5.3 Hz, 1H), 4.35 (d, J = 12.5 Hz, 1H). Other overlapped
peaks: δ 7.53−7.37 (m), 7.33−7.22 (m), 7.18−6.96 (m), 6.87−6.84
(m), 6.73−6.65 (m), 6.62−6.49 (m), 6.35−6.31 (m), 3.64−3.53 (m),
3.48−3.40 (m), 3.36−3.29 (m), 3.25−3.19 (m), 3.01−2.41 (m), 2.31−
2.23 (m), 2.12−2.05 (m), 1.80−1.72 (m) ppm. 13C NMR (125 MHz,
11208
dx.doi.org/10.1021/jo401510b | J. Org. Chem. 2013, 78, 11204−11212

The Journal of Organic Chemistry
Article
CDCl3): δ syn-isomer 180.2, 177.0, 157.3, 146.2, 143.1, 136.4, 123.0,
120.5, 115.7, 115.6, 114.9, 114.8, 75.0, 70.6, 66.4, 63.7, 57.5, 43.2, 30.6,
26.4, 23.3; anti-isomer 180.0, 177.9, 155.4, 145.7, 142.9, 135.5, 122.9,
120.4, 116.0, 115.8, 114.7, 74.6, 70.8, 65.8, 63.7, 57.4, 43.5, 30.9, 25.6,
23.2. Other overlapped peaks: δ 134.0, 133.9, 133.8, 133.7, 133.6,
133.4, 132.8, 132.6, 131.5, 131.4, 129.4, 129.3, 129.0, 128.9, 128.8,
128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 127.8, 127.6, 127.4, 126.5,
126.4, 126.2, 125.8 ppm. LRMS (ESI) m/z [M + Na]+ found: 745.8.
HRMS (ESI) m/z calcd for C42H37FN4NiO3Na+ [M + Na]+:
745.2101, found: 745.2115. The de was determined by HPLC with
a Chiralpak IA column (n-hexane/i-PrOH = 60/40, λ = 254 nm, 1.0
mL/min). For the syn-isomer: tR (major enantiomer) = 25.49 min, tR
(minor enantiomer) = 12.21 min, 99% de; for the anti-isomer: tR
(major enantiomer) = 147.17 min, tR (minor enantiomer) = 14.68
min, > 98% de.
PrOH = 60/40, λ = 254 nm, 1.0 mL/min). For the syn-isomer: tR
(major enantiomer) = 24.87 min, tR (minor enantiomer) = 12.95 min,
98% de; for the anti-isomer: tR (major enantiomer) = 80.08 min, tR
(minor enantiomer) = 19.35 min, 98% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(3,4-dimethylphenyl)-
1,2,3,4-tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base
Complex 3l. Red solid (38 mg, yield 52%, syn/anti 5.0:1). [α]20
=
D
1
+1746 (c 0.14 g/100 mL, CHCl3). H NMR (400 MHz, CDCl3): δ
syn-isomer 8.34 (d, J = 8.6 Hz, 1H), 8.04 (d, J = 7.4 Hz, 2H), 4.91 (s,
1H), 4.63 (s, 1H), 4.40 (d, J = 12.8 Hz, 1H), 2.10 (s, 3H), 1.89 (s,
3H); anti-isomer 8.26 (d, J = 8.7 Hz, 1H), 8.13 (d, J = 7.8 Hz, 2H),
6.05 (d, J = 5.4 Hz, 1H), 4.60 (d, J = 5.6 Hz, 1H), 4.40 (d, J = 12.8 Hz,
1H), 2.14 (s, 3H), 1.89 (s, 3H). Other overlapped peaks: δ 7.69−7.28
(m), 7.23−6.97 (m), 6.97−6.63 (m), 6.62−6.29 (m), 3.89−3.71 (m),
3.52−3.24 (m), 3.12−2.83 (m), 2.63−2.43 (m), 2.19−2.00 (m), 1.82−
1.75 (m) ppm. 13C NMR (125 MHz, CDCl3): δ syn-isomer 180.2,
177.2, 171.2, 148.5, 143.3, 137.6, 123.4, 120.4, 117.0, 111.4, 75.9, 70.4,
66.6, 63.2, 57.1, 41.8, 30.1, 25.8, 23.0, 20.1, 18.5; anti-isomer 180.2,
177.6, 171.3, 147.6, 142.8, 137.6, 123.0, 120.4, 115.8, 111.8, 75.3, 70.9,
67.0, 63.5, 57.4, 42.2, 31.0, 25.4, 23.5, 20.3, 18.6. Other overlapped
peaks: δ 136.0, 135.3, 134.2, 134.0, 133.7, 133.6, 133.3, 132.6, 132.4,
131.6, 131.4, 130.5, 130.3, 129.6, 129.5, 129.2, 129.1, 129.0, 128.8,
128.7, 128.4, 128.2, 127.9, 127.7, 127.6, 127.4, 127.3, 127.0, 126.7,
126.5, 126.4, 126.1, 125.9 ppm. LRMS (ESI) m/z [M + Na]+ found:
754.8. HRMS (ESI) m/z calcd for C44H42N4NiO3Na+ [M + Na]+:
755.2508, found: 755.2512. The de was determined by HPLC with a
Chiralpak IA column (n-hexane/i-PrOH = 60/40, λ = 254 nm, 1.0
mL/min). For the syn-isomer: tR (major enantiomer) = 14.83 min, tR
(minor enantiomer) = 7.97 min, > 99% de; for the anti-isomer: tR
(major enantiomer) = 49.99 min, tR (minor enantiomer) = 8.70 min, >
99% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-chlorophenyl)-1,2,3,4-tet-
rahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex 3j.
Red solid (53 mg, yield 72%, syn/anti 1.6:1). [α]20 = +1114 (c 0.22
D
1
g/100 mL, CHCl3). H NMR (400 MHz, CDCl3): δ syn-isomer 8.36
(d, J = 8.8 Hz, 1H), 8.06 (d, J = 6.9 Hz, 2H), 5.07 (d, J = 3.6 Hz, 1H),
4.72 (d, J = 3.7 Hz, 1H), 4.30 (d, J = 12.6 Hz, 1H); anti-isomer 8.23
(d, J = 8.7 Hz, 1H), 8.08 (d, J = 6.0 Hz, 2H), 5.61 (d, J = 5.5 Hz, 1H),
4.64 (d, J = 5.6 Hz, 1H), 4.34 (d, J = 12.7 Hz, 1H). Other overlapped
peaks: δ 7.51−7.46 (m), 7.37−7.19 (m), 7.16−6.99 (m), 6.83−6.41
(m), 3.57−3.16 (m), 3.00−2.91 (m), 2.77−2.24 (m), 2.12−2.05 (m),
1.76−1.69 (m) ppm. 13C NMR (125 MHz, CDCl3): δ syn-isomer
180.2, 176.9, 171.4, 147.6, 147.2, 136.4, 123.2, 122.9, 120.5, 114.4,
74.7, 70.7, 65.9, 63.8, 57.6, 43.4, 30.6, 25.9, 23.3; anti-isomer 179.9,
177.8, 172.6, 148.0, 142.9, 135.6, 123.0, 122.8, 120.5, 114.5, 73.9, 70.7,
63.7, 60.1, 57.4, 43.1, 30.9, 26.7, 23.3. Other overlapped peaks: δ
134.0, 133.6, 133.4, 132.9, 132.6, 131.4, 129.5, 129.3, 129.2, 129.0,
128.9, 128.8, 128.7, 128.6, 128.3, 128.1, 127.8, 127.6, 127.3, 126.6,
126.4, 126.2, 125.8 ppm. LRMS (ESI) m/z [M + Na]+ found: 760.8.
HRMS (ESI) m/z calcd for C42H37ClN4NiO3Na+ [M + Na]+:
761.1805, found: 761.1785. The de was determined by HPLC with a
Chiralpak IA column (n-hexane/i-PrOH = 60/40, λ = 254 nm, 1.0
mL/min). For the syn-isomer: tR (major enantiomer) = 27.55 min, tR
(minor enantiomer) = 12.54 min, 93% de; for the anti-isomer: tR
(major enantiomer) = 100.13 min, tR (minor enantiomer) = 18.98
min, > 99% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(3-chloro-4-methylphenyl)-
1,2,3,4-tetrahydroisoquinolin-1-yl) Acetic Acid Schiff Base
Complex 3m. Red solid (34 mg, yield 45%, syn/anti 3.0:1). [α]20
D
= +1446 (c 0.16 g/100 mL, CHCl3). 1H NMR (400 MHz, CDCl3): δ
syn-isomer 8.36 (d, J = 8.7 Hz, 1H), 8.06 (d, J = 7.7 Hz, 2H), 5.08 (d, J
= 2.7 Hz, 1H), 4.67 (d, J = 3.3 Hz, 1H), 4.34 (d, J = 12.7 Hz, 1H), 2.21
(s, 3H); anti-isomer 8.25 (d, J = 8.6 Hz, 1H), 8.11 (d, J = 7.9 Hz, 2H),
5.93 (d, J = 6.1 Hz, 1H), 4.59 (d, J = 6.0 Hz, 1H), 4.39 (d, J = 12.4 Hz,
1H), 2.18 (s, 3H). Other overlapped peaks: δ 7.56−7.26 (m), 7.23−
6.99 (m), 6.93−6.81 (m), 6.73−6.50 (m), 6.37−6.29 (m), 3.62−3.59
(m), 3.50−3.42 (m), 3.34−3.26 (m), 3.01−2.85 (m), 2.60−2.54 (m),
2.32−2.05 (m), 1.85−1.80 (m) ppm. 13C NMR (125 MHz, CDCl3): δ
syn-isomer 180.3, 176.9, 172.1, 148.7, 143.2, 136.2, 123.0, 120.5, 114.4,
112.2, 70.6, 65.9, 63.5, 57.4, 42.6, 30.5, 26.4, 23.4, 18.7; anti-isomer
180.3, 177.4, 171.4, 148.3, 142.9, 135.2, 123.0, 120.4, 113.9, 112.6,
70.8, 66.1, 63.5, 57.4, 42.8, 30.9, 25.7, 23.6, 18.8. Other overlapped
peaks: δ 135.1, 135.0, 134.0, 133.8, 133.5, 133.4, 133.3, 132.8, 132.6,
131.6, 131.5, 131.4, 131.2, 129.4, 129.3, 129.1, 128.9, 128.8, 128.7,
128.6, 128.5, 128.1, 128.0, 127.7, 127.6, 127.5, 126.4, 126.3, 126.2,
125.8, 125.4, 125.2 ppm. LRMS (ESI) m/z [M + Na]+ found: 774.8.
HRMS (ESI) m/z calcd for C43H39ClN4NiO3Na+ [M + Na]+:
775.1962, found: 775.1945. The de was determined by HPLC with a
Chiralpak IA column (n-hexane/i-PrOH = 60/40, λ = 254 nm, 1.0
mL/min). For the syn-isomer: tR (major enantiomer) = 28.47 min, tR
(minor enantiomer) = 11.21 min, 89% de; for the anti-isomer: tR
(major enantiomer) = 132.25 min, tR (minor enantiomer) = 13.93
min, 96% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-bromophenyl)-1,2,3,4-tet-
rahydroisoquinolin-1-yl) Acetic Acid Schiff Base Complex 3k.
Red solid (69 mg, yield 88%, syn/anti 1.5:1). 3k-syn: Mp 178−180 °C.
[α]20D = +1429 (c 0.17 g/100 mL, CHCl3). 3k-anti: Mp 176−178 °C .
1
[α]20 = +2088 (c 0.16 g/100 mL, CHCl3). H NMR (400 MHz,
D
CDCl3): δ syn-isomer 8.36 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 7.1 Hz,
2H), 7.49 (t, J = 7.5 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.31−7.24 (m,
4H), 7.18−7.01 (m, 7H), 6.73−6.50 (m, 6H), 5.08 (d, J = 3.5 Hz,
1H), 4.73 (d, J = 3.7 Hz, 1H), 4.30 (d, J = 12.6 Hz, 1H), 3.59−3.46
(m, 2H), 3.39 (d, J = 12.6 Hz, 1H), 3.33−3.28 (m, 1H), 3.19−3.14
(m, 1H), 2.98−2.91 (m, 1H), 2.63−2.58 (m, 2H), 2.33−2.24 (m, 1H),
2.11−2.05 (m, 2H), 1.77−1.66 (m, 1H) ppm; anti-isomer 8.23 (d, J =
8.7 Hz, 1H), 8.08 (d, J = 7.0 Hz, 2H), 7.53−7.47 (m, 2H), 7.33−7.27
(m, 2H), 7.25−7.07 (m, 8H), 7.02 (t, J = 7.4 Hz, 1H), 6.83 (d, J = 7.6
Hz, 1H), 6.67 (d, J = 9.1 Hz, 2H), 6.64−6.60 (m, 1H), 6.51 (dd, J =
8.3, 1.6 Hz, 1H), 6.44 (d, J = 7.6 Hz, 1H), 5.59 (d, J = 5.6 Hz, 1H),
4.63 (d, J = 5.7 Hz, 1H), 4.33 (d, J = 12.6 Hz, 1H), 3.53−3.39 (m,
3H), 3.34−3.28 (m, 1H), 3.24−3.18 (m, 1H), 3.00−2.93 (m, 1H),
2.81−2.72 (m, 2H), 2.54−2.38 (m, 2H), 2.12−2.05 (m, 1H), 1.82−
1.73 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ syn-isomer 180.2,
176.9, 172.7, 148.4, 143.1, 136.4, 134.0, 133.6, 133.5, 133.4, 132.9,
131.8, 131.4, 129.3, 129.0, 128.9, 128.8, 128.7, 128.1, 127.9, 127.3,
126.6, 125.8, 122.9, 120.5, 115.0, 110.3, 74.6, 70.7, 65.8, 63.8, 57.6,
43.0, 30.6, 26.7, 23.3 ppm; anti-isomer 180.0, 177.8, 171.4, 148.0,
142.9, 135.6, 134.0, 133.5, 133.4, 132.7, 132.1, 131.4, 129.5, 128.8,
128.7, 128.6, 128.4, 127.8, 127.6, 126.5, 126.1, 123.0, 120.5, 114.8,
109.9, 73.7, 70.7, 64.9, 63.7, 57.4, 43.3, 30.9, 25.9, 23.3 ppm. LRMS
(ESI) m/z [M + Na]+ found: 804.7. HRMS (ESI) m/z calcd for
C42H37BrN4NiO3Na+ [M + Na]+: 805.1300, found 805.1348. The de
was determined by HPLC with a Chiralpak IA column (n-hexane/i-
Nickel(II)-(S)-BPB/2-Amino-2-(2-(3,5-bis(trifluoromethyl)-
phenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl) Acetic Acid Schiff
Base Complex 3n. Red solid (50 mg, yield 59%, syn/anti 1:1.2). 3n-
syn: Mp 164−166 °C. [α]20D = +1140 (c 0.10 g/100 mL, CHCl3). 3n-
anti: Mp 157−159 °C. [α]20D = +1267 (c 0.21 g/100 mL, CHCl3). 1H
NMR (400 MHz, CDCl3): δ syn-isomer 8.38 (d, J = 8.7 Hz, 1H), 8.06
(d, J = 7.4 Hz, 2H), 7.50−7.46 (m, 1H), 7.32−7.24 (m, 6H), 7.19−
6.89 (m, 8H), 6.67−6.31 (m, 2H), 6.37 (s, 1H), 5.31 (d, J = 2.8 Hz
1H), 4.77 (d, J = 2 Hz, 1H), 4.30 (d, J = 12.2 Hz, 1H), 3.56 (s, 2H),
3.40 (d, J = 12.4 Hz, 1H), 3.32 (t, J = 8.6 Hz, 1H), 3.18 (s, 1H), 3.05−
2.88 (m, 1H), 2.66−2.62 (m, 2H), 2.36−2.31 (m, 1H), 2.12−2.07 (m,
2H), 1.83 (s, 1H); anti-isomer 8.34 (d, J = 8.7 Hz, 1H), 8.09 (d, J = 7.4
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Hz, 2H), 7.47−7.24 (m, 7H), 7.15−7.02 (m, 5H), 6.97−6.89 (m, 2H),
6.79 (d, J = 7.6 Hz, 1H), 6.59 (t, J = 7.4 Hz, 1H), 6.47 (d, J = 8.2 Hz,
1H), 6.03 (d, J = 7.5 Hz, 1H), 5.76 (d, J = 4.0 Hz, 1H), 4.74 (d, J = 4.2
Hz, 1H), 4.36 (d, J = 12.5 Hz, 1H), 3.87 (d, J = 13.3 Hz, 1H), 3.46−
3.41 (m, 2H), 3.37−3.17 (m, 2H), 3.10−2.93 (m, 1H), 2.88−2.80 (m,
1H), 2.66−2.57 (m, 2H), 2.50−2.41 (m, 1H), 2.09−2.02 (m, 1H),
1.80−1.77 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): δ syn-isomer
180.2, 176.4, 172.8, 149.6, 143.4, 136.0, 134.0, 133.5, 133.4, 133.1,
133.0, 132.5, 132.2, 131.4, 129.3, 129.0, 128.9, 128.8, 128.7, 128.3,
128.0, 127.6, 126.8, 125.6, 124.5, 122.9, 122.3, 120.5, 112.2, 111.0,
73.5, 70.8, 65.2, 63.8, 57.6, 43.0, 30.7, 26.8, 23.5; anti-isomer 180.2,
177.1, 172.0, 149.7, 143.1, 136.3, 133.9, 133.8, 133.4, 132.7, 131.5,
129.4, 129.1, 128.9, 128.7, 127.8, 127.5, 127.4, 126.2, 125.9, 123.2,
120.5, 118.5, 113.9, 75.5, 70.6, 66.1, 63.6, 57.4, 42.2, 30.2, 26.3, 23.2
ppm. LRMS (ESI) m/z [M + Na]+ found: 862.8. HRMS (ESI) m/z
calcd for C44H36F6N4NiO3Na+ [M + Na]+: 863.1943, found 863.1915.
The de was determined by HPLC with a Chiralpak IA column (n-
hexane/i-PrOH = 60/40, λ = 254 nm, 1.0 mL/min). For the syn-
isomer: tR (major enantiomer) = 19.40 min, tR (minor enantiomer) =
9.08 min, 99% de; for the anti-isomer: tR (major enantiomer) = 17.52
min, tR (minor enantiomer) = 6.98 min, 98% de.
865.1511, found: 865.1505. The de was determined by HPLC with a
Chiralpak AD-H column (n-hexane/i-PrOH = 75/25, λ = 254 nm, 1.0
mL/min). For the syn-isomer: tR (major enantiomer) = 80.42 min, tR
(minor enantiomer) = 39.52 min, 99% de; for the anti-isomer: tR
(major enantiomer) = 46.22 min, tR (minor enantiomer) = 54.76 min,
98% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-benzyl-1,2,3,4-tetrahydroi-
soquinolin-1-yl) Acetic Acid Schiff Base Complex 3q. Red solid
(18 mg, yield 25%, syn/anti < 1:20). Mp 124−126 °C. [α]20D = +1496
(c 0.14 g/100 mL, CHCl3). 1H NMR (400 MHz, CDCl3): anti-isomer
8.34 (d, J = 8.8 Hz, 1H), 8.15 (d, J = 7.1 Hz, 2H), 7.76 (d, J = 6.4 Hz,
2H), 7.55−7.45 (m, 3H), 7.37 (t, J = 7.6 Hz, 2H), 7.25−6.96 (m, 7H),
6.88−6.82 (m, 4H), 6.63 (t, J = 7.6 Hz, 1H), 6.42 (dd, J = 8.2, 1.4 Hz,
1H), 5.02 (d, J = 7.8 Hz, 1H), 4.56 (d, J = 12.7 Hz, 1H), 4.44−4.20
(m, 1H), 4.16 (d, J = 13.4 Hz, 1H), 4.07 (d, J = 3.9 Hz, 1H), 3.93−
3.76 (m, 1H), 3.71 (d, J = 13.3 Hz, 1H), 3.64 (d, J = 4.8 Hz, 1H), 3.61
(d, J = 4.9 Hz, 1H), 3.58 (d, J = 12.6 Hz, 1H), 3.49−3.44 (m, 1H),
3.17−3.09 (m, 1H), 2.86−2.70 (m, 1H), 2.61−2.48 (m, 2H), 2.27−
2.12 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ 180.8, 177.4,
170.3, 150.0, 142.8, 138.7, 134.4, 134.0, 133.4, 133.0, 132.0, 131.8,
131.6, 129.3, 129.1, 129.0, 128.8, 128.7, 128.4, 127.6, 127.4, 127.2,
126.6, 126.3, 126.0, 123.5, 120.3, 75.0, 69.8, 62.9, 61.7, 59.1, 57.3, 45.9,
30.8, 23.5, 21.9 ppm. LRMS (ESI) m/z [M + Na]+ found: 740.8.
HRMS (ESI) m/z calcd for C43H40N4NiO3Na+ [M + Na]+: 741.2352,
found: 741.2361. The de was determined by HPLC with a Chiralpak
IA column (n-hexane/i-PrOH = 80/20, λ = 254 nm, 1.0 mL/min). For
the anti-isomer: tR (major enantiomer) = 32.57 min, tR (minor
enantiomer) = 19.99 min, 98% de.
Procedure for the Synthesis of (2S,2(1′S))-4a. The crystallized
complex (S)(2S,2(1′S))-3a (1 g, 1.42 mmol) and EDTA (0.83 g, 2.82
mmol) were suspended in a mixture of aqueous N2H4 (85% in water, 5
mL) and EtOH (25 mL) and stirred at 80 °C for 4 h, until the red
color of the solution disappeared. The reaction was cooled to room
temperature and then evaporated to dryness. Water (20 mL) was
added to the residue to form a clear solution, and the solution was
extracted with CH2Cl2 (3 times). The aqueous layer was purified to
give the desired amino acids, while the organic layer was evaporated to
dryness and treated with 6 N HCl for recovering the ligand (S)-BPB
(525 mg, 96%). The aqueous layer was adjusted pH to 7 with aqueous
6 N HCl and then evaporated to dryness. The residue was treated with
MeOH (40 mL) and an amount of precipitation was produced. After
filtering, the solution was concentrated and separated by column
chromatography on C18-reversed phase (230−400 mesh) silica gel.
Water/MeOH (1:1) was used to obtain product 4a (340 mg, yield
85%, syn:anti 9:1). The organic layer was evaporated to dryness, and
MeOH (10 mL) and 6 N HCl (10 mL) were added and then stirred
for 2 h at room temperature. After the reaction was complete as
indicated by TLC, the solution was extracted with dichloromethane
(20 mL × 3). The combined organic layers were dried with anhydrous
Na2SO4, concentrated, and purified by column chromatography on
silica gel (petroleum ether/ethyl acetate = 4/1) to give the ligand (S)-
BPB (525 mg, yield 96%).
Nickel(II)-(S)-BPB/2-Amino-2-((6-(4-bromophenyl)-5,6,7,8-
tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl) Acetic Acid
Schiff Base Complex 3o. Red solid (37 mg, yield 45%, syn/anti
1
1.3:1). [α]20 = +1331 (c 0.13 g/100 mL, CHCl3). H NMR (400
D
MHz, CDCl3): δ syn-isomer 8.34 (d, J = 8.7 Hz, 1H), 8.05 (d, J = 7.3
Hz, 2H), 5.89 (s, 1H), 5.85 (s, 1H), 4.77 (d, J = 2.5 Hz, 1H), 4.64 (d, J
= 2.2 Hz, 1H), 4.33 (d, J = 12.5 Hz, 1H); anti-isomer 8.22 (d, J = 8.6
Hz, 1H), 8.09 (d, J = 7.3 Hz, 2H), 5.90 (s, 1H), 5.82 (s, 1H), 5.47 (d, J
= 4.3 Hz, 1H), 4.63 (d, J = 4.3 Hz, 1H), 4.34 (d, J = 12.6 Hz, 1H).
Other overlapped peaks: δ 7.66−7.37 (m), 7.37−7.25 (m), 7.22−7.01
(m), 6.91−6.84 (m), 6.78−6.57 (m), 6.51−6.42 (m), 3.85−3.50 (m),
3.50−3.36 (m), 3.36−3.14 (m), 3.02−2.68 (m), 2.67−2.38 (m), 2.61−
2.44(m), 2.16−1.94 (m), 1.80−1.75 (m) ppm. 13C NMR (125 MHz,
CDCl3): δ syn-isomer 180.1, 177.0, 171.8, 148.4, 147.1, 146.3, 143.2,
122.9, 120.5, 115.6, 110.4, 108.5, 107.2, 101.0, 74.9, 70.6, 65.6, 63.6,
57.4, 43.1, 30.4, 25.2, 23.0; anti-isomer 180.0, 178.0, 172.2, 148.7,
147.3, 146.2, 142.9, 123.0, 120.5, 115.4, 110.6, 108.1, 107.5, 100.9,
75.6, 70.9, 66.1, 63.8, 57.4, 42.7, 31.1, 26.3, 23.1. Other overlapped
peaks: δ 134.1, 133.8, 133.7, 133.4, 132.9, 132.7, 132.2, 131.9, 131.4,
129.6, 129.4, 129.3, 129.2, 128.8, 128.7, 128.6, 128.4, 128.0, 127.8,
127.4, 127.2, 126.7, 126.2, 126.1, 125.8 ppm. LRMS (ESI) m/z [M +
Na]+ found: 848.8. HRMS (ESI) m/z calcd for C43H37BrN4NiO5Na+
[M + Na]+: 849.1198, found: 849.1250. The de was determined by
HPLC with a Chiralpak IA column (n-hexane/i-PrOH = 60/40, λ =
254 nm, 1.0 mL/min). For the syn-isomer: tR (major enantiomer) =
45.36 min, tR (minor enantiomer) = 22.48 min, 97% de; for the anti-
isomer: tR (major enantiomer) = 57.83 min, tR (minor enantiomer) =
28.42 min, 97% de.
Nickel(II)-(S)-BPB/2-Amino-2-(2-(4-bromophenyl)-6,7-dime-
thoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) Acetic Acid Schiff
Base Complex 3p. Red solid (48 mg, yield 57%, syn/anti 2.6:1).
1
[α]20 = +1900 (c 0.12 g/100 mL, CHCl3). H NMR (400 MHz,
D
(S)-2-Amino-2-((S)-2-phenyl-1,2,3,4-tetrahydroisoquinolin-
CDCl3): δ syn-isomer 8.35 (d, J = 8.7 Hz, 1H), 8.07 (d, J = 7.5 Hz,
2H), 5.12 (s, 1H), 4.66 (s, 1H), 4.31 (d, J = 12.5 Hz, 1H), 3.88 (s,
3H), 3.63 (s, 3H); anti-isomer 8.28 (d, J = 8.7 Hz, 1H), 8.09 (d, J = 7.2
Hz, 2H), 5.33 (d, J = 2.6 Hz, 1H), 4.70 (d, J = 2.6 Hz, 1H), 4.31 (d, J
= 12.5 Hz, 1H), 3.83 (s, 3H), 3.46 (s, 3H). Other overlapped peaks: δ
7.47−7.42 (m), 7.39−7.24 (m), 7.17−7.02 (m), 6.96−6.87 (m), 6.74−
5.90 (m), 3.45−3.25 (m), 3.05−2.99 (m), 2.87−2.83 (m), 2.58−2.30
(m), 2.23−1.97 (m), 1.85−1.80 (m) ppm. 13C NMR (125 MHz,
CDCl3): δ syn-isomer 180.2, 177.0, 172.3, 148.7, 148.5, 147.5, 122.7,
120.5, 116.1, 111.2, 110.6, 110.5, 74.1, 70.8, 65.3, 63.8, 57.7, 56.2, 55.8,
43.1, 30.9, 29.7, 23.3; anti-isomer 180.0, 178.5, 172.3, 148.8, 148.3,
147.5, 122.8, 120.4, 115.2, 110.9, 110.4, 109.2, 75.6, 71.1, 65.5, 63.9,
57.4, 55.9, 55.3, 43.1, 31.1, 24.3, 22.7. Other overlapped peaks: δ
134.2, 134.0, 133.7, 133.6, 132.9, 132.7, 132.3, 131.8, 131.4, 129.3,
128.9, 128.8, 128.7, 128.6, 128.5, 128.3, 128.1, 127.3, 127.2, 126.9,
126.2, 125.9, 125.5, 125.0 ppm. LRMS (ESI) m/z [M + Na]+ found:
864.8. HRMS (ESI) m/z calcd for C44H41BrN4NiO5Na+ [M + Na]+:
1-yl) Acetic Acid 4a. White solid (340 mg, yield 85%, syn/anti 9:1).
1
Mp > 300 °C. [α]20 = +59 (c 0.30 g/100 mL, CH3OH). H NMR
D
(400 MHz, D2O) δ 7.32−7.21 (m, 3H), 7.19−7.16 (m, 3H), 7.06 (d, J
= 8.0 Hz, 2H), 6.94 (t, J = 7.4 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 4.34
(d, J = 5.3 Hz, 1H), 3.65−3.55 (m, 1H), 3.34−3.28 (m, 1H), 2.89−
2.76 (m, 2H) ppm. 13C NMR (125 MHz, D2O/MeOD) δ 171.3,
149.3, 137.3, 130.7, 130.3, 129.6, 128.3, 127.9, 122.7, 119.6, 60.1, 57.2,
46.8, 27.2 ppm. LRMS (ESI) m/z [M + H]+ found: 283.0. HRMS
+
(ESI) m/z calcd for C17H19N2O2 [M + H]+: 283.1441, found:
283.1451. The enantiomeric excess was determined by HPLC with a
Chirobiotic T column (25 cm × 4.6 mm, 5 μm) (H2O/MeOH = 60/
40, λ = 254 nm, 0.5 mL/min). For the syn-isomer: tR (major
enantiomer) = 15.32 min, tR (minor enantiomer) = 18.13 min, 98% ee;
for the anti-isomer: tR (major enantiomer) = 12.68 min, tR (minor
enantiomer) = 13.68 min, 80% ee.
(S)-2-Amino-2-((S)-2-(4-fluorophenyl)-1,2,3,4-tetrahydroiso-
quinolin-1-yl) Acetic Acid 4i. White solid (332 mg, yield 80%, syn/
11210
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Article
anti 3.6:1). Mp > 300 °C. [α]20 = +42 (c 0.20 g/100 mL, CH3OH).
(9) For recent reviews on CDC, see: (a) Li, C. J.; Li, Z. P. Pure Appl.
Chem. 2006, 78, 935−945. (b) Li, C. J. Acc. Chem. Res. 2009, 42, 335−
344. (c) Scheuermann, C. J. Chem. Asian J. 2010, 5, 436−451.
(d) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011,
40, 5068−5083. (e) Wendlandt, A. E.; Suess, A. M.; Stahl, S. S. Angew.
Chem., Int. Ed. 2011, 50, 11062−11087. (f) Yeung, C. S.; Dong, V. M.
Chem. Rev. 2011, 111, 1215−1292.
(10) Selected reviews on oxidative coupling of amines: (a) Jones, K.
M.; Klussmann, M. Synlett 2012, 159−162. (b) Campos, K. R. Chem.
Soc. Rev. 2007, 36, 1069−1084. (c) Murahashi, S. I.; Zhang, D. Chem.
Soc. Rev. 2008, 37, 1490−1501.
(11) (a) Murahashi, S. I.; Komiya, N.; Terai, H.; Nakae, T. J. Am.
Chem. Soc. 2003, 125, 15312−15313. (b) Murahashi, S. I.; Komiya, N.;
Terai, H. Angew. Chem., Int. Ed. 2005, 44, 6931−6933. (c) Murahashi,
S. I.; Nakae, T.; Terai, H.; Komiya, N. J. Am. Chem. Soc. 2008, 130,
11005−11012.
D
1H NMR (500 MHz, MeOD): δ 7.43−6.91 (m, 8H), 5.40 (s, 1H),
3.95 (s, 1H), 3.75−3.65 (m 1H), 3.25−3.07 (m, 2H), 2.92−2.80 (m,
1
1H) ppm. 13C NMR (125 MHz, MeOD): δ 172.6, 159.7 (d, JCF
=
238 Hz), 147.7, 138.1, 132.5, 130.0, 129.2, 128.8, 127.7, 122.6 (d, 3JCF
2
= 7.4 Hz), 116.9 (d, JCF = 22 Hz), 61.4, 59.5, 46.0, 25.6 ppm. LRMS
(ESI) m/z [M − H]− found: 299.1. HRMS (ESI) m/z calcd for
−
C17H16FN2O2 [M − H]−: 299.1196, found: 299.1202. The
enantiomeric excess was determined by HPLC with a Chirobiotic T
column (25 cm × 4.6 mm, 5 μm) (H2O/MeOH = 50/50, λ = 254 nm,
0.5 mL/min). For the syn-isomer: tR (major enantiomer) = 19.59 min,
tR (minor enantiomer) = 21.73 min, 90% ee; for the anti-isomer: tR
(major enantiomer) = 16.17 min, tR (minor enantiomer) = 16.94 min,
73% ee.
ASSOCIATED CONTENT
* Supporting Information
■
(12) (a) Li, Z. P.; Li, C. J. J. Am. Chem. Soc. 2004, 126, 11810−
11811. (b) Li, Z. P.; Li, C. J. Eur. J. Org. Chem. 2005, 3173−3176.
(c) Li, Z. P.; Li, C. J. J. Am. Chem. Soc. 2005, 127, 6968−6969. (d) Li,
Z. P.; Li, C. J. J. Am. Chem. Soc. 2005, 127, 3672−3673. (e) Li, Z. P.;
Bohle, D. S.; Li, C. J. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 8928−
8933. (f) Li, Z. P.; Li, C. J. J. Am. Chem. Soc. 2006, 128, 56−57.
S
Experiment details including X-ray crystal, product character-
ization, and NMR and chiral HPLC experiments. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: hliu@mail.shcnc.ac.cn.
́
(g) Basle, O.; Li, C. J. Green Chem. 2007, 9, 1047−1050. (h) Basle, O.;
■
Li, C. J. Chem. Commun. 2009, 27, 4124−4126. (i) Basle, O.; Borduas,
N.; Dubois, P.; Chapuzet, J. M.; Chan, T. H.; Lessard, J.; Li, C. J.
Chem.Eur. J. 2010, 16, 8162−8166. (j) Girard, S. A.; Hu, X.;
Knauber, T.; Zhou, F.; Simon, M. O.; Deng, G. J.; Li, C. J. Org. Lett.
2012, 14, 5606−5609.
Notes
The authors declare no competing financial interest.
(13) Selective examples of enantioselective CDC reactions of tertiary
amines: (a) Zhang, G.; Zhang, Y.; Wang, R. Angew. Chem., Int. Ed.
2011, 50, 10429−10432. (b) Zhang, G.; Ma, Y.; Wang, S.; Zhang, Y.;
Wang, R. J. Am. Chem. Soc. 2012, 134, 12334−12337. (c) Zhang, J.;
Tiwari, B.; Xing, C.; Chen, X.; Chi, Y. R. Angew. Chem., Int. Ed. 2012,
51, 3649−3652. (d) Li, Z. P.; Li, C. J. Org. Lett. 2004, 6, 4997−4999.
(e) Li, Z. P.; MacLeod, P. D.; Li, C. J. Tetrahedron: Asymmetry 2006,
17, 590−597.
(14) (a) Belokon, Y. N.; Bulychev, A. G.; Vitt, S. V.; Struchkov, Y. T.;
Batsanov, A. S.; Timofeeva, T. V.; Tsyryapkin, V. A.; Ryzhov, M. G.;
Lysova, L. A.; Bakhmutov, V. I.; Belikov, V. M. J. Am. Chem. Soc. 1985,
107, 4252−4259. (b) Belokon, Y. N.; Kochetkov, K. A.; Ikonnikov, N.
S.; Strelkova, T. V.; Harutyunyan, S. R.; Saghiyan, A. S. Tetrahedron:
Asymmetry 2001, 12, 481−485. (c) Soloshonok, V. A.; Avilov, D. V.;
Kukhar, V. P. Tetrahedron: Asymmetry 1996, 7, 1547−1550. (d) Solo-
shonok, V. A.; Avilov, D. V.; Kukhar, V. P.; Tararov, V. I.; Saveleva, T.
F.; Churkina, T. D.; Ikonnikov, N. S.; Kochetkov, K. A.; Orlova, S. A.;
Pysarevsky, A. P.; Struchkov, Y. T.; Raevsky, N. I.; Belokon, Y. N.
Tetrahedron: Asymmetry 1995, 6, 1741−1756.
(15) (a) Soloshonok, V. A.; Cai, C. Z.; Hruby, V. J. Tetrahedron:
Asymmetry 1999, 10, 4265−4269. (b) Soloshonok, V. A.; Cai, C. Z.;
Yamada, T.; Ueki, H.; Ohfune, Y.; Hruby, V. J. J. Am. Chem. Soc. 2005,
127, 15296−15303. (c) Belokon, Y. N.; Bespalova, N. B.; Churkina, T.
D.; Cisarova, I.; Ezernitskaya, M. G.; Harutyunyan, S. R.; Hrdina, R.;
Kagan, H. B.; Kocovsky, P.; Kochetkov, K. A.; Larionov, O. V.;
Lyssenko, K. A.; North, M.; Polasek, M.; Peregudov, A. S.;
Prisyazhnyuk, V. V.; Vyskocil, S. J. Am. Chem. Soc. 2003, 125,
12860−12871. (d) Belokon, Y. N.; Maleev, V. I.; Savel’eva, T. F.;
Moskalenko, M. A.; Pripadchev, D. A.; Khrustalev, V. N.; Saghiyan, A.
S. Amino Acids 2010, 39, 1171−1176.
(16) Soloshonok, V. A.; Avilov, D. V.; Kukhar, V. P.; VanMeervelt,
L.; Mischenko, N. Tetrahedron Lett. 1997, 38, 4671−4674.
(17) (a) Qiu, W.; Soloshonok, V. A.; Cai, C. Z.; Tang, X. J.; Hruby,
V. J. Tetrahedron 2000, 56, 2577−2582. (b) Soloshonok, V. A.; Tang,
X. J.; Hruby, V. J. Tetrahedron 2001, 57, 6375−6382. (c) Soloshonok,
V. A.; Tang, X. J.; Hruby, V. J.; Meervelt, L. Org. Lett. 2001, 3, 341−
343.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (Grants 21021063,
91229204, 81302633, and 81025017), National S&T Major
Projects (2012ZX09103101-072 and 2012ZX09301001-005).
REFERENCES
■
(1) For a recent book, see: Amino Acids, Peptides and Proteins in
Organic Chemistry; Hughes, A. B., Ed; Wiley-VCH: Weinheim,
Germany, 2009; Vols. 1 and 2. For leading reviews on synthesis of
chiral α-amino acids, see: (a) Liu, Z. H.; Mehta, S. J.; Hruby, V. J. Org.
Prep. Proced. Int. 2012, 44, 222−255. (b) Luo, Y. C.; Zhang, H. H.;
Wang, Y.; Xu, P. F. Acc. Chem. Res. 2010, 43, 1317−1330. (c) Michaux,
J.; Niel, G.; Campagne, J. M. Chem. Soc. Rev. 2009, 38, 2093−2116.
(d) Najera, C.; Sansano, J. M. Chem. Rev. 2007, 107, 4584−4671.
(2) For selected reviews on the synthesis and biological significance
of α,β-diamino acids, see: (a) Weiner, B.; Szymanski, W.; Janssen, D.
B.; Minnaard, A. J.; Feringa, B. L. Chem. Soc. Rev. 2010, 39, 1656−
1691. (b) Arrayas, R. G.; Carretero, J. C. Chem. Soc. Rev. 2009, 38,
1940−1948. (c) Viso, A.; Pradilla, R. F.; Garcia, A.; Flores, A. Chem.
Rev. 2005, 105, 3167−3196.
(3) (a) Chen, J.; Chen, X.; Willot, M.; Zhu, J. Angew. Chem., Int. Ed.
2006, 45, 8028−8032. (b) Zheng, S.; Chan, C.; Furuuchi, T.; Wright,
B. J.; Zhou, B.; Guo, J.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2006,
45, 1754−1759. (c) Chen, J.; Chen, X.; Bois-Choussy, M.; Zhu, J. J.
Am. Chem. Soc. 2006, 128, 87−89. (d) Endo, A.; Yanagisawa, A.; Abe,
M.; Tohma, S.; Kan, T.; Fukuyama, T. J. Am. Chem. Soc. 2002, 124,
6552−6554.
(4) Okano, K.; Mitsuhashi, N.; Tokuyama, H. Chem. Commun. 2010,
46, 2641−2643.
(5) Gai, X.; Grigg, R.; Rajviroongit, S.; Songarsa, S.; Sridharan, V.
Tetrahedron Lett. 2005, 46, 5899−5902.
(6) Gandasegui, M. T.; Alvarezbuilla, J.; Florencio, F. Heterocycles
1994, 37, 1747−1759.
(7) Gober, B.; Bauer, G.; Pfeifer, S.; Dube, G.; Engelhar., G.; Jancke,
H. Pharmazie 1973, 28, 221−232.
(18) (a) Wang, J.; Zhou, S. B.; Lin, D. Z.; Ding, X.; Jiang, H. L.; Liu,
H. Chem. Commun. 2011, 47, 8355−8357. (b) Wang, J.; Lin, D. Z.;
Zhou, S. B.; Ding, X.; Soloshonok, V. A.; Liu, H. J. Org. Chem. 2011,
76, 684−687. (c) Wang, J.; Shi, T.; Deng, G. H.; Jiang, H. L.; Liu, H. J.
(8) (a) De, C. K.; Mittal, N.; Seidel, D. J. Am. Chem. Soc. 2011, 133,
16802−16805. (b) Polniaszek, R. P.; Bell, S. J. Tetrahedron Lett. 1996,
37, 575−578.
11211
dx.doi.org/10.1021/jo401510b | J. Org. Chem. 2013, 78, 11204−11212

The Journal of Organic Chemistry
Article
Org. Chem. 2008, 73, 8563−8570. (d) Wang, J.; Shi, J. M.; Zhang, X.
D.; Lin, D. Z.; Jiang, H. L.; Liu, H. Synthesis 2009, 1744−1752.
(e) Wang, J.; Lin, D. Z.; Shi, J. M.; Ding, X.; Zhang, L.; Jiang, H. L.;
Liu, H. Synthesis 2010, 1205−1208.
(19) Lin, D. Z.; Wang, J.; Zhang, X.; Zhou, S. B.; Lian, J.; Jiang, H. L.;
Liu, H. Chem. Commun. 2013, 49, 2575−2577.
(20) CCDC 927172 and CCDC 962699 contain the supplementary
crystallographic data for this paper.
11212
dx.doi.org/10.1021/jo401510b | J. Org. Chem. 2013, 78, 11204−11212