A facile synthesis of vicinal diamines promoted by low-valent niobium: Preparation of chiral octahydrobiisoquinolines and their application to catalytic asymmetric synthesis

Article abstract of DOI:10.1002/ejoc.200500301

An efficient homocoupling of imines to give vicinal diamines promoted by low-valent niobium, generated by treatment of NbCl₅ with zinc powder, is described. The desired products were obtained in good to excellent yields. Dihydroisoquinoline derivatives also gave the coupling products with good diastereoselectivities (D,L/meso). Optical resolution of the racemic octahydrobiisoquinolines was achieved and their complexes with Cu¹ used in the catalytic asymmetric oxidative coupling of β-naphthols. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500301

FULL PAPER
DOI: 10.1002/ejoc.200500301
A Facile Synthesis of Vicinal Diamines Promoted by Low-Valent Niobium:
Preparation of Chiral Octahydrobiisoquinolines and Their Application to
Catalytic Asymmetric Synthesis
Shigeru Arai,*[a] Satoshi Takita,[a] and Atsushi Nishida*[a]
Keywords: Amines / Asymmetric catalysis / Asymmetric synthesis / Imine coupling / Niobium
An efficient homocoupling of imines to give vicinal diamines
promoted by low-valent niobium, generated by treatment of
NbCl5 with zinc powder, is described. The desired products
were obtained in good to excellent yields. Dihydroisoquino-
line derivatives also gave the coupling products with good
cemic octahydrobiisoquinolines was achieved and their com-
plexes with CuI used in the catalytic asymmetric oxidative
coupling of β-naphthols.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
diastereoselectivities (D,L/meso). Optical resolution of the ra- Germany, 2005)
in yields of 85 and 97%, respectively (entries 2 and 3).
Moreover, smaller amounts of NbCl5 and Zn were suf-
ficient to promote the reaction even at –78 °C in MeOH
(entry 4). As expected, NbV and Zn powder are both essen-
tial in the homocoupling of 1a: reaction in the absence of
NbCl5 or Zn powder gave either no reaction or N-(4-meth-
oxyphenyl)benzylamine (74%), respectively (Scheme 1).
Introduction
Low-valent niobium reagents are well known to react
with unsaturated bonds to give 1,2-dianion equivalents.
Ever since Pedersen and co-workers reported the first suc-
cessful results,[1–3] the chemistry of niobium has been an
attractive area in organic synthesis due to its unique charac-
ter. In fact, the generation of 1,2-dianion equivalents from
imines,[1–3] carbonyl groups,[4–6] and alkynes[7–10] has been
reported for useful chemical transformations, and a Nb–
alkyne complex have been characterized.[11] We therefore
became interested in the unique reactivity of 1,2-dianion
equivalents and began to investigate imine coupling[12–15]
using low-valent Nb reagents.[16]
Table 1. Imine coupling promoted by low-valent Nb.
Results and Discussion
Initially, we surveyed the role of a niobium reagent gen-
erated in situ in imine coupling. Although [NbCl3(DME)]
is known to be a representative NbIII reagent, its prepara-
tion and chemical stability are problematic. Therefore, we
tried to generate a low-valent niobium reagent in situ by a
reported procedure.[10] A solution of 1a in THF was treated
with low-valent niobium generated by the reduction of
NbCl5 with zinc powder, and gave the coupling product 2a
in 94% yield in a ratio of 1.5:1 (,/meso), although the
polymerization of THF was a problem (Table 1, entry 1).
This reaction was carried out under argon in a closed sys-
tem to avoid cleavage of the newly formed carbon–carbon
bonds promoted by a strong Lewis acid in the presence of
trace amounts of molecular oxygen.[17] This homocoupling
reaction also proceeded in CH2Cl2 and MeOH to give 2a
[a] The reaction was carried out at –78 °C.
[a] Graduate School of Pharmaceutical Sciences, Chiba University,
1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Scheme 1. The reaction of 1a without NbCl5 or Zn powder.
5262
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5262–5267

Synthesis of Vicinal Diamines Promoted by Low-Valence Nb
FULL PAPER
Next, we examined the reaction of substrates 1b–e, which sults for the diastereoselective synthesis of 6a have been re-
contain unsaturated bonds around the reaction center, un- ported.[24] On the other hand, only one example of the syn-
der optimized conditions. As shown in Table 2, all of them thesis of 6b has been reported, and this homocoupling reac-
were converted into the corresponding diamines 2b–e in tion, which uses Al(Hg) as a reducing agent, gives only a
good yields. These results suggest that the reaction proceeds 9% yield of the required product together with the meso
via a 1,2-dianion species rather than a radical process.
product in 34% yield.[25]
Table 2. ortho-Substituent effect.
Scheme 2. Homocoupling of dihydroisoquinolines.
We initially surveyed the reaction conditions that would
predominantly promote the desired homocoupling. Al-
though the optimized conditions (MeOH, room temp., 3 h)
for 5a allowed the reaction to proceed, the undesired re-
duction to tetrahydroisoquinoline 7a competed with the
coupling to give adduct 6a (,/meso = 1:1). On the other
hand, direct use of NbIII gave better results regarding the
diastereoselectivity of 6a (Table 4, entry 2), although a
problem of reproducibility was observed. Finally, we suc-
ceeded in the development of a ,-selective coupling with
the generation of low-valent Nb in situ in DME/THF, as
shown in entry 3. After washing the crude mixture with
hexane/AcOEt (8:1), racemic 6a was successfully isolated in
50% yield. These results are summarized in Table 4.
Intramolecular diamine coupling with 3 was also investi-
gated. For example, 3a was quantitatively transformed into
the corresponding piperazine 4a as a single isomer (Table 3,
entry 1).[18] A bicyclic piperazine derivative was also ob-
tained from 3b in 98% yield (Table 3, entry 2).[19] However,
attempts to obtain a seven-membered ring were unsuccess-
ful and resulted in oligomerization (Table 3, entry 3).
The optical resolution of ( )-6a was then investigated
(Scheme 3). After a survey of chiral acids, ()-CSA was
found to be the most effective, and the diastereomerically
pure salt of (+)-6a was obtained as a white, crystalline solid
in 29% yield. The optical purity (Ͼ99% ee) was determined
by HPLC analysis using a chiral column after conversion
into the free base. Treatment of the resulting mother liquor
with base, followed by salt formation with ()-CSA, gave
the optically pure salt of (–)-6a (Ͼ99% ee) in 31% yield.
The absolute configuration of (+)-6a was determined to be
(1S,1ЈS) by X-ray crystallographic analysis after transfor-
mation of (+)-6a into the corresponding dibenzamide 8
(Scheme 4). Its structure is shown in Figure 1.
Table 3. Intramolecular diamine coupling using low-valent Nb.[a]
On the other hand, ( )-6b was also successfully prepared
by the modified procedure outlined in Scheme 5. Treatment
of 5b[15] with NbCl5/Zn in DME/THF (1:10) at room temp.
gave 6b in 89% yield as a 1:1 mixture of diastereomers
along with 7b (11% yield), as determined by 1H NMR
analysis. Racemic 6b was isolated by formation of a salt
with ()-CSA, and subsequent treatment with base gave
[a] All reactions were carried out in the presence of NbCl5
(1.2 equiv.) and Zn (3.0 equiv.) in MeOH at room temp. for 1 h.
Next, we turned to the Nb-mediated synthesis of octahy- free ( )-6b in 41% yield. To the best of our knowledge, this
drobiisoquinoline (6) from 5 (Scheme 2).[20,21] Although 6 is the most efficient methodology for the preparation of ( )-
and its derivatives are expected to be biologically important 6b. Optical resolution of ( )-6b was achieved as a salt of
molecules, useful ligands, or nucleophilic catalysts, only a (S)-BNHP (1,1Ј-binaphthyl-2,2Ј-diyl hydrogenphosphate)
few examples of their use in organic synthesis have been to give (–)-6b in 15% yield with greater than 99% ee. Its
reported. A few methods for the preparation of 6a by enantiomer, (+)-6b, was isolated from the mother liquor in
homocoupling of imines are known,[22,23] and excellent re- 24% yield and 98% ee by treatment with 10% NaOH fol-
Eur. J. Org. Chem. 2005, 5262–5267
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5263

S. Arai, S. Takita, A. Nishida
FULL PAPER
Table 4. Synthesis of 6a.
1
[a] Determined by H NMR analysis of the crude mixture. [b] 2.0 g of 5a. [c] The average of four runs is 4.8:1 (,/meso).
Scheme 3. Isolation and optical resolution of 6a.
lowed by formation of the salt using ()-CSA. Although
the absolute configuration of 6b has not yet been deter-
mined, we tentatively assigned the configurations, as shown
in Scheme 5, by comparing the signs of optical rotation to
those in 6a.
With these two chiral diamines in hand, we next planned
to investigate their utility as chiral ligands. Catalytic asym-
metric oxidative coupling of β-naphthols is known to be
one of the most efficient processes for obtaining chiral bi-
Scheme 4. Determination of the absolute stereochemistry of 6a.
naphthol derivatives, which are widely used as chiral ligands
and auxiliaries. In their asymmetric synthesis, some chiral
diamine complexes with CuI have been reported to play im-
portant roles in enantioselectivity.[26–28] First, the coupling
reaction of β-naphthol-2-carboxylate (9) was investigated
under various conditions. The reaction of CuCl with (–)-6a
proceeded smoothly in various solvents under an oxygen
atmosphere, but the yields were poor (Table 5, entries 1–4).
Acetonitrile was found to be the best solvent, and gave the
corresponding coupling product in 66% yield with 28% ee
(entry 4). Product 10 was obtained with 48% ee when the
reaction was conducted at 0 °C. On the other hand, the re-
action with (–)-6b, which possesses methyl groups at the
ring junction, gave 10 in 21% yield with 31% ee (entry 6).
The absolute configuration of 10 was determined by com-
paring its [α]D value and retention time in HPLC analysis
to data in the literature.[27] These results are summarized in
Table 5.
Figure 1. ORTEP diagram showing the X-ray structure of (1S,1SЈ)-
8.
5264
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5262–5267

Synthesis of Vicinal Diamines Promoted by Low-Valence Nb
FULL PAPER
Scheme 5. Synthesis, isolation, and optical resolution of 6b.
Table 5. Catalytic asymmetric oxidative coupling of 9.
internal reference. Mass spectra were measured with a JEOL JMS-
AX500 (for LR-MS) and JEOL JMS-HX110 (for HR-MS).
Conclusions
In summary, we have developed an Nb-promoted imine-
coupling reaction that gives the desired products in good
to excellent yields. Moreover, the practical preparation and
optical resolution of octahydrobiisoquinolines 6a and 6b
have also been successful, and their application to the cata-
lytic asymmetric synthesis has been demonstrated. The fur-
ther application of these unique chiral diamines in organic
synthesis is presently under investigation.
General Procedure for Homocoupling of Imines. Synthesis of 2a:
(Table 1, Entry 3) Zinc powder (47 mg, 0.72 mmol) was added to a
suspension of NbCl5 (78 mg, 0.29 mmol) in MeOH (2.4 mL) under
argon. After stirring the mixture for 30 min, 1a (50 mg, 0.24 mmol)
was added at room temperature and the mixture was stirred for an
additional hour. The reaction was quenched with 10% NaOH
(5 mL) and extracted three times with AcOEt (15 mL). The com-
bined organic layers were washed with brine and dried with
Na2SO4. After removal of the organic solvent in vacuo, flash col-
umn chromatography on silica gel (hexane/AcOEt, 13:1) gave the
desired product 2a (49 mg, 0.116 mmol, 97%) as a yellow, amorph-
Experimental Section
1
ous solid. Diastereoselectivity was determined by H NMR analy-
General Remarks: NbCl5 was purchased from Aldrich and used as
received. All reactions were performed with dry solvents and rea-
gents were purified by the usual methods. Reactions were moni-
tored by thin-layer chromatography carried out on 0.25-mm Merck
silica gel plates (60F-254). Column chromatography was performed
with silica gel (Fuji Silysia, PSQ-60B). IR spectra were recorded on
a JASCO FT/IR-230 Fourier transform spectrophotometer. NMR
spectra were recorded on a JEOL-JMN-Alpha-400 spectrometer,
sis. 2a: CAS registration nos. (,): 35605-52-8; meso: 35583-32-5.
N,NЈ-Diallyl-1,2-diphenyl-1,2-ethylenediamine (2b) [CAS reg. nos.
(D,L): 219517-95-0; meso: 219517-92-7] and 1,2-Diphenyl-N,NЈ-
bis(2-vinylphenyl)-1,2-ethylenediamine (2c): IR (KBr): ν = 3353,
˜
3030, 2909, 1600, 1498, 1451, 1311, 748, 702 cm–1. 1H NMR
(CDCl3, 400 MHz): δ = 4.67 (s, 1.5/2.5×2 H), 4.75 (br, 2 H), 4.98
(d, J = 2.5 Hz, 1.0/1.5×2 H), 5.33 (d, J = 12.0 Hz, 2 H), 5.59 (dd,
J = 17.4, 2.0 Hz, 1.5/2.5×2 H), 5.60 (dd, J = 17.4, 2.0 Hz, 1.0/
2.5×2 H), 6.32 (d, J = 7.6 Hz, 1.5/2.5×2 H), 6.35 (d, J = 8.0 Hz,
1
operating at 400 MHz for H NMR and 100 MHz for 13C NMR,
and calibrated relative to the residual undeuterated solvent as an
Eur. J. Org. Chem. 2005, 5262–5267
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5265

S. Arai, S. Takita, A. Nishida
FULL PAPER
1.0/2.5×2 H), 6.66 (t, J = 7.4 Hz, 2 H), 6.76 (dd, J = 16.6, 11.0 Hz,
2 H), 6.92–6.98 (m, 4 H), 7.17–7.26 (m, 10 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 62.5, 63.8, 112.5, 112.6, 116.8, 116.9, 117.8,
118.0, 124.8, 125.3, 127.3, 127.4, 127.5, 127.7, 128.3, 128.5, 128.6,
128.7, 132.7, 132.8, 138.2, 139.7, 143.5, 143.9 ppm. LRMS (FAB):
m/z = 417 [M + H]+. HRMS (FAB): m/z calcd. for C30H29N2
417.2331; found 417.2305.
H2O/MeOH/Et2O (10:1:10, 30 mL) and treated with aq. 10%
NaOH (60 mL) at 0 °C. After stirring the mixture for 30 min, it
was extracted three times with AcOEt (20 mL) and the combined
organic layers were washed with brine, dried with MgSO4, and con-
centrated in vacuo to give (1R,1ЈR)-6a as a yellow solid (1.83 g,
69%, 40% ee). ()–CSA was added, at room temp., (3.22 g,
13.8 mmol) to a solution of the resulting solid in CH2Cl2 (14 mL)
and the mixture was stirred for 30 min. The solvent was evaporated
to give a solid, which was recrystallized three times from iPr2O/
EtOH. The resulting white solid (2.3 g) was dissolved in H2O/
MeOH(Et2O (10:1:10, 30 mL) and treated with 10% aq. NaOH
(60 mL) at 0 °C. The mixture was extracted three times with AcOEt
(20 mL), and the combined organic layers were washed with brine
and dried with MgSO4 to give (1R,1ЈR)-6a as a colorless solid
N,NЈ-Bis(2-allylphenyl)-1,2-diphenyl-1,2-ethylenediamine (2d): IR
(neat): ν = 3414, 3062, 2911, 1603, 1584, 1504, 1452, 1314, 916,
˜
747, 701 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 3.27 (d, J =
6.4 Hz, 1.6/2.6×4 H), 3.31–3.33 (m, 1.0/2.6×4 H), 4.55 (br. s), 4.70
(m, 2 H), 4.96–5.06 (m, 4 H), 5.87–5.96 (m, 2 H), 6.30 (dd, J = 1.2,
8.0 Hz, 1.6/2.6×2 H), 6.34 (dd, J = 0.8, 8.0 Hz, 1.0/2.6×2 H), 6.60–
6.65 (m, 2 H), 6.89–7.04 (m, 6 H), 7.18–7.34 (m, 8 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 36.4, 36.7, 62.1, 63.4, 111.9, 112.3,
116.4, 116.4, 117.4, 117.7, 123.9, 124.5, 127.3, 127.4, 127.5, 127.5,
127.6, 128.2, 128.5, 129.7, 130.0, 135.8, 135.8, 138.4, 139.8, 144.5,
144.8 ppm. LRMS (FAB): m/z = 445 [M + H]+. HRMS (FAB):
m/z calcd. for C32H33N2 445.2644; found 445.2652.
(810 mg, 31%, Ͼ99% ee). IR (KBr): ν = 3284, 3013, 2929, 1495,
˜
1456, 1428, 1125, 865, 762, 739 cm–1. 1H NMR (CDCl3, 400 MHz):
δ = 2.60 (d, J = 15.2 Hz, 2 H), 2.80 (dt, J = 3.2, 11.5 Hz, 2 H),
2.88–2.96 (m, 2 H), 3.18 (ddd, J = 2.4, 5.2, 11.5 Hz, 2 H), 4.68 (s,
2 H), 7.10 (d, J = 7.2 Hz, 2 H), 7.15 (t, J = 7.2 Hz, 2 H), 7.21 (t,
J = 7.6 Hz, 2 H), 7.36 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (CDCl3,
100 MHz): δ = 30.4, 42.8, 60.1, 125.1, 126.0, 126.2, 129.3, 136.6,
137.3 ppm. M.p. 113–114 °C; (1S,1ЈS): [α]2D2 = +254.8 (c = 1.07,
CHCl3) Ͼ99% ee; (1R,1ЈR): [α]2D2 = –251.0 (c = 1.02, CHCl3) Ͼ99%
ee; LRMS (FAB): m/z = 265 [M + H]+. HRMS (FAB): m/z calcd.
for C18H21N2 265.1705; found 265.1700. HPLC conditions: Daicel
Chiralcel OD, hexane/iPrOH (9:1), flow rate = 0.5 mLmin–1, reten-
tion time: 17.7 (1S,1ЈS), 27.5 min (1R,1ЈR).
Ethyl
3-{2-[2-(2-Ethoxycarbonylvinyl)phenylamino]-1,2-diphenyl-
ethylaminophenyl}acrylate (2e): IR (neat): ν = 3391, 3030, 2980,
˜
1
1713, 1624, 1602, 1505, 1454, 1316, 1265, 1174, 701, 668 cm–1. H
NMR (CDCl3, 400 MHz): δ = 1.30–1.34 (m, 6 H), 4.22–4.29 (m, 4
H), 4.76 (s, 1.5/2.5×2 H), 4.83 (br), 4.94 (s, 1.0/2.5×2 H), 6.31–
6.40 (m, 4 H), 6.68 (t, J = 7.6 Hz, 2 H), 7.01–7.05 (m, 4 H), 7.20–
7.37 (m, 14 H), 7.82 (d, J = 16.0 Hz, 1.5/2.5×2 H), 7.84 (d, J =
16.0 Hz, 1.0/2.5×2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ =
14.3, 14.3, 60.4, 60.4, 62.8, 63.3, 113.3, 113.5, 118.2, 118.3, 119.2,
119.4, 121.0, 121.4, 127.3, 127.3, 128.0, 128.4, 128.6, 128.7, 128.8,
131.0, 131.1, 137.8, 138.7, 140.0, 144.8, 145.1, 166.9, 167.0 ppm.
LRMS (FAB): m/z = 561 [M + H]+. HRMS (FAB): m/z calcd. for
C36H37N2O4 561.2753; found 561.2721.
1,1Ј-Dimethyl-2,3,4,2Ј,3Ј,4Ј-hexahydro-1,1Ј-biisoquinoline
(6b):
DME (68 mL) was slowly added at –40 °C to NbCl5 (22.3 g,
82.6 mmol) in a round-bottomed flask. Zinc powder (13.5 g,
207 mmol) was then slowly added at –40 °C and the mixture was
stirred for a few minutes until the solution turned dark red. The
mixture was stirred for 30 min at room temp. After addition of THF
(600 mL) at –40 °C, the mixture was stirred for 3 h at room temp.
and a THF solution (20 mL) of 5b (10 g, 68.9 mmol) was added.
The mixture was stirred for an additional 14 h. The reaction was
then quenched with aq. 10% NaOH and the resulting mixture was
filtered though a celite pad. The filtrate was extracted three times
with AcOEt (150 mL), and the combined organic layers were
washed with brine, dried with MgSO4, and concentrated in vacuo.
The resulting crude solid was dissolved in CH2Cl2 (100 mL), treated
with ()-CSA (16 g, 68.9 mmol), and the mixture was stirred for
30 min. The solvent was then removed to give a solid which was
suspended in AcOEt (200 mL) and then filtered. The resulting solid
was washed with AcOEt and dissolved in AcOEt/MeOH/H2O
(10:1:10, 200 mL) and 10% aq. NaOH (200 mL). The mixture was
extracted three times with AcOEt (50 mL), and the combined or-
ganic layers were washed with brine, dried with MgSO4, and con-
centrated to give ( )-6b as a yellow solid (4.11 g, 41%).
2,3-Diphenyldecahydroquinoxaline (4b): 1H NMR (CDCl3,
400 MHz): δ = 1.39–1.41 (m, 4 H), 1.71–1.78 (m, 6 H), 2.61 (m, 2
H), 3.82 (s, 2 H), 7.10 (s, 10 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ = 24.9, 31.8, 61.5, 68.5, 127.1, 127.8, 128.0, 141.4 ppm. [α]1D3
–71.7 (c = 0.87, CHCl3). Reg. no. 169532-34-7.
=
Synthesis of ( )-1,2,3,4,1Ј,2Ј,3Ј,4Ј-Octahydro-1,1Ј-biisoquinoline
(6a): Zinc powder (1.5 g, 22.8 mmol) was added, at 0 °C, to a sus-
pension of NbCl5 (6.2 g, 15.2 mmol) in DME (15 mL). After stir-
ring this mixture for 30 min, it was diluted with THF (115 mL)
and a THF solution of 5a (2.0 g/20 mL) was added. Stirring was
continued for an additional 3 h at room temp. The reaction was
quenched with 10% aq. NaOH (50 mL) at 0 °C, and the mixture
was filtered through a celite pad. The filtrate was separated and
the aqueous layer was extracted three times with AcOEt (50 mL).
The combined organic layers were washed with brine and dried
with MgSO4. After removal of the solvent in vacuo, the residue
was treated with a mixture of hexane and AcOEt (8:1) to give ( )-
6a (1.0 g, 50%) as crystals.
Optical Resolution of ( )-6b: (S)-BNHP (1.77 g, 5.0 mmol) was
added to a solution of ( )-6b (736 mg, 2.5 mmol) in CH2Cl2
(25 mL) and MeOH (3.5 mL), and the mixture was stirred for
30 min at room temp. After removal of the solvent, recrystallization
of the crude product from EtOH gave a white solid. Finally,
recrystallization of the solid from EtOH gave a colorless solid
Optical Resolution of 6a: ()-CSA (4.66 g, 20 mmol) was added to
a solution of ( )–6a (2.65 g, 10 mmol) in CH2Cl2 (20 mL) and the
mixture was stirred for 30 min at room temp. After removal of the
solvent in vacuo, the resulting crude product was recrystallized
from iPr2O/EtOH (3 times) to give the salt as a white, crystalline (920 mg). The resulting solid was dissolved in 10% aq. K2CO3
solid (2.2 g). This was dissolved in H2O/MeOH/Et2O (10:1:10,
50 mL), neutralized by the addition of aq. 10% NaOH (60 mL) at
0 °C, and the free amine was extracted three times with AcOEt
(20 mL,). The combined organic layers were washed with brine,
dried with MgSO4, and concentrated in vacuo to give (1S,1ЈS)-6a
as a white solid (775 mg, 29%, Ͼ99% ee). The organic solvent was
removed from the mother liquor, and the residue was dissolved in
(10 mL) and the mixture was extracted three times with AcOEt
(10 mL). The combined organic layers were washed with brine,
dried with MgSO4, and concentrated in vacuo. Purification by col-
umn chromatography on basic alumina (hexane/AcOEt, 1:1) gave
(–)-6b as a colorless solid (109 mg, 15%, Ͼ99% ee). The mother
liquor was treated with 10% aq. K2CO3 (30 mL) and AcOEt
(10 mL), and the mixture was stirred for 1 h. After extraction three
5266
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 5262–5267

Synthesis of Vicinal Diamines Promoted by Low-Valence Nb
FULL PAPER
times with AcOEt (20 mL), the combined organic layers were
washed with brine, dried with Na2SO4, and concentrated in vacuo
to give a yellow solid with the mixture of BNHP (554 mg, Ͻ75%,
49% ee). ()-CSA (885 mg, 3.8 mmol) was added to a solution of
the resulting yellow solid in CH2Cl2 (19 mL) and the mixture was
stirred for 30 min. After removal of the solvent in vacuo, the re-
sulting solid was washed with AcOEt and the mother liquor was
treated with 10% aq. NaOH (30 mL). The mixture was extracted
three times with AcOEt (15 mL), and the combined organic layers
were washed with brine, dried with Na2SO4, and concentrated in
vacuo. Purification by column chromatography on basic alumina
0.025 mmol) in CH3CN (0.25 mL) was stirred for 30 min and then
CH3CN (2.3 mL) was added. After addition of 9 (50 mg, 0.25 mmol)
at 0 °C, the mixture was stirred for an additional 48 h. The reaction
was quenched with 1  HCl (5.0 mL) and extracted three times with
AcOEt (10 mL). The combined organic layers were washed with
brine and concentrated in vacuo to give the crude product. Purifica-
tion by flash column chromatography on silica gel (hexane/AcOEt,
8:1) gave 10 as a yellow solid (30.0 mg, 0.15 mmol, 60%, 48% ee).
The enantioselectivity was determined by chiral HPLC analysis on
a Daicel Chiralpak AD column [hexane/iPrOH (9:1), 254 nm, flow
rate: 1.0 mLmin–1; retention times: 9.4 min (S form: minor) and
(hexane/AcOEt, 1:1) gave (+)-6b as a yellow solid (180 mg, 24%, 15.5 min (R form: major)]. The absolute stereochemistry was deter-
98% ee). IR (KBr): ν = 2990, 2948, 2900, 2827, 1490, 1457, 1148,
mined based on the optical rotation value (see ref.[27]).
˜
765, 736 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 1.66 (s, 6 H), 1.90
(br. s, 2 H), 2.44–2.49 (m, 2 H), 2.86–2.94 (m, 4 H), 3.10–3.15 (m,
2 H), 6.86 (d, J = 7.2 Hz, 2 H), 6.95–7.03 (m, 4 H), 7.86 (d, J =
7.6 Hz, 2 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 25.7, 31.7,
40.0, 63.5, 124.6, 125.4, 128.2, 128.5, 137.0, 141.5 ppm. M.p. 115–
116 °C. [α]1D1 = –120.9 (c = 1.02, CHCl3) Ͼ99% ee (1R,1ЈR), [α]1D3
= +112.9 (c = 1.06, CHCl3) 98% ee (1S,1ЈS). LRMS (FAB): m/z =
293 [M + H]+. HRMS (FAB): m/z calcd. for C20H25N2 293.2018;
found 293.2004. HPLC conditions: Daicel Chiralcel OD-H, 0.1%
Et2NH in hexane/iPrOH (99:1), flow rate: 0.5 mLmin–1, retention
time: 13.4 min for (–)-form, 14.2 min for (+)-form.
[1] E. J. Roskamp, S. F. Pedersen, J. Am. Chem. Soc. 1987, 109,
3152–3154.
[2] E. J. Roskamp, S. F. Pedersen, J. Am. Chem. Soc. 1987, 109,
6551–6553.
[3] E. J. Roskamp, P. S. Dragovich, J. B. Hartung, S. F. Pedersen,
J. Org. Chem. 1989, 54, 4736–4737.
[4] J. Syzmoniak, J. Besançon, C. Moïse, Tetrahedron 1992, 48,
3867–3876.
[5] J. Syzmoniak, J. Besançon, C. Moïse, Tetrahedron 1994, 50,
2841–2848.
[6] S. Arai, Y. Sudo, A. Nishida, Chem. Pharm. Bull. 2004, 52,
[N,NЈ-(4-Bromobenzoyl)-1,2,3,4,1Ј,2Ј,3Ј,4Ј-octahydro-1,1Ј-biisoquin-
olin-2-yl]-4-bromophenylmethanone (8): NEt3 (79 µL, 0.57 mmol),
DMAP (7 mg, 0.05 mmol), and p-bromobenzoyl chloride (91.8 mg,
0.42 mmol) were added, at room temp., to a solution of (+)-6a
(50 mg, 0.19 mmol) in CH2Cl2 (3.8 mL) and the reaction mixture
was stirred for 40 min. The reaction was quenched by the addition
of sat. NaHCO3 (3 mL) and the mixture was extracted three times
with AcOEt (10 mL). The combined organic layers were washed
with brine and dried with MgSO4. After removal of the solvent in
vacuo, the resulting residue was purified by flash column
chromatography on silica gel (hexane/AcOEt, 8:1) to give 8 as a
colorless solid (68.3 mg, 57%). M.p. 221–222 °C (EtOAc). IR
287–288.
[7] J. B. Hartung, S. F. Pedersen, J. Am. Chem. Soc. 1989, 111,
5468–5469.
[8] Y. Kataoka, K. Takai, K. Ohshima, K. Utimoto, Tetrahedron
Lett. 1990, 31, 365–368.
[9] Y. Kataoka, J. Miyai, M. Tezuka, K. Takai, K. Ohshima, K.
Utimoto, Tetrahedron Lett. 1990, 31, 369–372.
[10] Y. Kataoka, K. Takai, K. Ohshima, K. Utimoto, J. Org. Chem.
1992, 57, 1615–1618.
[11] J. B. Hartung, S. F. Pedersen, Organometallics 1990, 9, 1414–
1417.
[12] M. Ortega, M. A. Rodriguez, P. J. Campos, Tetrahedron 2004,
60, 6475–6478.
(KBr): ν = 1634, 1429, 1321, 1186, 1108, 1067, 1011, 839, 756 cm–1.
˜
[13] M. Shimizu, I. Suzuki, H. Makino, Synlett 2003, 1635–1638.
[14] N. Kise, H. Oike, E. Okazaki, T. Yoshimoto, T. Shono, J. Org.
Chem. 1995, 60, 3980–3982.
[15] D. Lucet, T. Le Gall, C. Mioskowski, Angew. Chem. Int. Ed.
1998, 37, 2580–2627.
[16] K. Fuchibe, T. Akiyama, Synlett 2004, 1282–1284.
[17] M. Shimizu, H. Makino, Tetrahedron Lett. 2001, 42, 8865–
8868.
[18] G. J. Marcer, M. S. Sigman, Org. Lett. 2003, 5, 1591–1594.
[19] T. Shono, N. Kise, E. Shirakawa, H. Matsumoto, E. Okazaki,
J. Org. Chem. 1991, 56, 3063–3067.
1H NMR (CDCl3, 400 MHz): δ =2.90 (ddd, J = 8.4, 8.4, 16.4 Hz,
2 H), 3.20 (ddd, J = 6.0, 6.0, 16.4 Hz, 2 H), 3.69 (ddd, J = 6.0, 6.0,
13.0 Hz, 2 H), 4.22 (ddd, J = 6.0, 8.4, 13.0 Hz, 2 H), 6.08 (d, J =
7.6 Hz, 2 H), 6.13 (s, 2 H), 6.83–6.87 (m, 2 H), 7.16–7.21 (m, 4 H),
7.28 (d, J = 8.8 Hz, 4 H), 7.50 (d, J = 8.8 Hz, 4 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 28.4, 43.2, 55.7, 123.8, 125.1, 127.7, 128.2,
128.4, 130.5, 131.8, 132.5, 134.2, 135.2, 170.5 ppm. [α]1D8 = –110.1
(c
= 1.0, CHCl3). LRMS (FAB): m/z = 629, 631, 633
[M + H]+. HRMS (FAB): m/z calcd. for C32H27Br2N2O2 629.0439;
found 629.0422. Crystal data: C32H26N2O2Br2, mol. wt. = 630.38,
monoclinic system, space group P21 (no. 4), a = 9.839 (2), b =
[20] For 5a:I. S. Cho, C. P. Lee, P. S. Mariano, Tetrahedron Lett.
1989, 30, 799–802.
[21] For 5b: F. S. Sancho, E. Mann, B. Herradon, Synlett 2000,
10.145 (2) c = 14.133 (3) Å, V = 1373.5 (4)3 Å, Z = 2, Dcalcd.
=
1.524 gcm–3, F(000) = 636.00, µ(Mo-Ka) = 29.92 cm–1.
509–513.
[22] A. T. Nielsen, J. Org. Chem. 1970, 35, 2498–2503.
[23] M. C. Elliott, E. Williams, S. T. Howard, J. Chem. Soc., Perkin
Trans. 2 2002, 201–203.
Lattice constants and intensity data were measured using graphite-
monochromated Mo-Kα radiation (λ = 0.71069 Å). Of the 8293
reflections that were collected, 3410 were unique (Rint = 0.037).
Observations were made on a Rikagaku/MSC Mercury dif-
fractometer. The structure was solved by direct methods using
SIR97 and refined to a final R value of 0.041 and Rw = 0.059.
CCDC-286847 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[24] M. C. Elliott, E. Williams, Org. Biomol. Chem. 2003, 1, 3038–
3047.
[25] P. Cerutti, H. Schmid, Helv. Chim. Acta 1964, 47, 203–213.
[26] M. Nakajima, K. Kanayama, S. Hashimoto, Tetrahedron Lett.
1995, 36, 9519–9520.
[27] M. Nakajima, I. Miyoshi, K. Kanayama, S. Hashimoto, M.
Noji, K. Koga, J. Org. Chem. 1999, 64, 2264–2271.
[28] X. Li, J. B. Hergley, C. A. Mulrooney, J. Yang, M. C. Kozlow-
ski, J. Org. Chem. 2003, 68, 5500–5511.
General Procedure for the Oxidative Coupling of 9: (Table 3, Entry
5) A solution of CuCl (2.5 mg, 0.025 mmol) and diamine 6a (6.5 mg,
Received: April 28, 2005
Published Online: October 27, 2005
Eur. J. Org. Chem. 2005, 5262–5267
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5267