Resolution-free route to chiral 2,2′-bis(pyridin-2-yl)-1,1′- binaphthyl ligand: Photochemical CpCo(CO)2-mediated cycloaddition of enantiopure 2,2′-dicyano-1,1′-binaphthyl with diynes

Article abstract of DOI:10.1016/j.tetlet.2004.02.155

A resolution-free route to chiral 2,2^′-bis(pyridin-2-yl)- 1,1^′-binaphthyl ligands 2 was developed for the first time based on the photochemical CpCo(CO)₂-mediated cycloaddition reaction of enantiopure 2,2^′-dicyano-1,1^′-binaphthyl 3 with 1,6-heptadiyne, 1,7-octadiyne, 1,8-nonadiyne, and 2,8-decadiyne.

Full text of DOI:10.1016/j.tetlet.2004.02.155

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3489–3491
Resolution-free route to chiral 2,20-bis(pyridin-2-yl)-1,10-binaphthyl
ligand: photochemical CpCo(CO)2-mediated cycloaddition of
enantiopure 2,20-dicyano-1,10-binaphthyl with diynes
Takashi Hoshi,a,* Masayoshi Katano,b Eiji Nozawa,b Toshio Suzukia and
Hisahiro Hagiwarab,*
aFaculty of Engineering, Niigata University, 2-Nocho, Ikarashi, Niigata 950-2181, Japan
bGraduate School of Science and Technology, Niigata University, 2-Nocho, Ikarashi, Niigata 950-2181, Japan
Received 22 January 2004; revised 25 February 2004; accepted 27 February 2004
Abstract—A resolution-free route to chiral 2,20-bis(pyridin-2-yl)-1,10-binaphthyl ligands 2 was developed for the first time based on
the photochemical CpCo(CO)2-mediated cycloaddition reaction of enantiopure 2,20-dicyano-1,10-binaphthyl 3 with 1,6-heptadiyne,
1,7-octadiyne, 1,8-nonadiyne, and 2,8-decadiyne.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Chiral nitrogen ligands have recently attracted much
attention in metal-catalyzed enantioselective processes,
particularly those in which the nitrogen ligands cannot
be replaced by more soft and oxidative phosphine
ligands.1 The bis(oxazoline) ligand represented by an
architecture 1 is the most frequently employed chiral
nitrogen ligand. With respect to neutral, bidentate, sp2-
nitrogen donors, the bis(pyridine) ligand would be a
complementary chiral nitrogen ligand in this class.
However, its application to chiral catalysts is still in its
infancy owing to the difficulties associated with instal-
lation of chirality into the planar pyridine units so that
extensive efforts have been devoted to the design and
synthesis of novel chiral bis(pyridine) ligands.2
are somewhat limited due in part to the inevitable optical
resolution process of the racemic ligand ( )-2a. Thus,
development of a resolution-free route must be indis-
pensable for wide employment of this novel chiral ligand.
As mentioned by Lloyd-Jones, transition metal-cata-
lyzed cross-coupling reactions between optically active
binaphthyl electrophiles and 2-metallopyridine reagents
or reversal of its cross-coupling polarities would be the
most plausible resolution-free route. However, unfortu-
nately, they demonstrated that the steric hindrance of the
binaphthyl reagents made it difficult to form the pyri-
dine-to-naphthalene bond in the cross-coupling reac-
tions.3 Because transition metal-mediated cycloaddition
of a nitrile with two alkynes, especially a diyne, is the
practical protocol for the construction of pyridine rings,
this type of cycloaddition of enantiopure 2,20-dicyano-
1,10-binaphthyl 3 with a diyne would be an alternative
resolution-free route directly accessible to the chiral li-
gand 2. We also assumed that the structural diversity of
ligating pyridine units would be realized by the cyclo-
addition of the binaphthyl template 3 with a variety of
diynes. The purpose of this communication is to describe
the first resolution-free route to the chiral ligand 2 based
on the photochemical CpCo(CO)2-mediated cycloaddi-
tion reaction of enantiopure 3 with diynes.
On the analogy of the highly successful application of
BINAP ligand to chiral catalysts, 2,20-bis(pyridin-2-yl)-
1,10-binaphthyl ligand of general type 2 would be a
candidate for novel chiral bis(pyridine) ligands. The
simplest ligand 2a was recently reported by Lloyd-Jones
and co-workers.3 Quite recently, they also synthesized
the chloro and methyl substituted analogues derived
from 2a and applied them as chiral ligands to the zinc
complex-catalyzed asymmetric allylation of benzalde-
hyde with allyltributyltin.4 However, the structural
diversity and the synthetic application of these ligands
The enantiopure dinitrile (R)-3 was prepared in excellent
yield with no observable racemization starting from the
corresponding enantiopure dicarboxylic acid (R)-4,
which was derived from the optically active dibromide
(R)-5 (Eq. 1).5 In the early stages of this study, we
* Corresponding authors. Tel.: +81-25-262-7401; fax: +81-25-265-7339
(T.H.); tel./fax: +81-25-262-7368 (H.H.); e-mail addresses: hoshi@
gs.niigata-u.ac.jp; hagiwara@gs.niigata-u.ac.jp
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.155

3490
T. Hoshi et al. / Tetrahedron Letters 45 (2004) 3489–3491
investigated a more straightforward route based on the
dicyanation reaction of (R)-5 (Eq. 2). A mixture of (R)-5
(79% ee) and 2.4 equiv of CuCN in DMF was heated to
reflux for 48 h to afford the optically active (R)-3 (73%
ee) in 79% yield. Though racemization slightly occurred
during the cyanation reaction, erosion of enantiopurity
was at an acceptable level. In addition, the high yield
achieved in this dicyanation reaction was beyond our
O
O
N
N
N
N
R
R
1
2a
ꢀ
expectation because Putala and Karak recently reported
that the diiodide analogue did not give any cyanation
products under the same conditions.6 However, a more
amenable protocol was desired to afford enantiopure
(R)-3 because the contamination with the minor enan-
tiomer could not be removed by recrystallization.
Actually, we surveyed a variety of solvents (cyclohexane,
toluene, EtOH, CH3CN, n-Bu2O, Et2O–CH2Cl2 ¼ 10:1,
i-Pr2O–CHCl3 ¼ 5:1) and found no condition that was
sufficient to effect an increase in enantiomeric excess of
the optically active (R)-3. The full details of the devel-
N
N
N
N
2c
2b
N
N
N
N
1) SOCl2, reflux,
10 min
2) NH3, THF, 0 °C,
CO2H
CO2H
CN
CN
2e
2d
15 min
ð1Þ
ð2Þ
3) NEt3, Tf2O, 0 °C,
40 min
(R)-4 (>99% ee)
(R)-3 (>99% ee)
(R)-3 (73% ee)
97% (3 steps)
opment of the synthesis of enantiopure (R)-3 starting
from (R)-4 are presented in our preceding letter.5
Because Co complexes have proven to be the most
effective reagents for the transition metal-mediated
cycloaddition of a nitrile and a diyne,1e;7 our investiga-
tion of the preparation of 2,20-bis(pyridin-2-yl)-1,10-bi-
naphthyl ligand 2 was based on the CpCo(CO)2-
mediated cycloaddition reaction of (R)-3 (>99% ee) with
a diyne (Table 1). Initially, the reaction with 1,7-octa-
diyne was chosen to examine this cycloaddition reaction.
2.4 eq CuCN
Br
Br
DMF, reflux, 48 h
79%
(R)-5 (79% ee)
H
To
a solution of enantiopure (R)-3 in toluene
+
(1.7 · 10À3 M) was added 180 mol % of CpCo(CO)2 and
6-fold excess of 1,7-octadiyne, and then the reaction
mixture was heated to reflux under irradiation using a
200 W tungsten lamp. After 120 h, the dinitrile (R)-3 was
completely consumed and the desired ligand (R)-2b was
obtained in 40% yield (entry 1).8 HPLC analysis of (R)-
2b revealed that the reaction proceeded with complete
retention of the axial chirality. On the other hand, both
CN
1.7 × 10–3
H
1 equiv.
M
ð3Þ
30 mol% CpCo(CO)2
hν, toluene,
reflux, 48 h
N
69%
Table 1. CpCo(CO)2-mediated cycloaddition reaction of (R)-3 with diynes
CpCo(CO)2
hν, toluene, reflux
+ Diyne
(R)-3 (>99% ee)
(1.7 × 10–3 M)
(R)-2 (>99% ee)
Entry
Reagent
6 equiv 1,7-octadiyne, 180 mol % CpCo(CO)2
Time (h)
Product
Yield (%)
1
120
120
72
(R)-2b
(R)-2b
(R)-2b
(R)-2b
(R)-2b
(R)-2c
(R)-2d
40
62
70
26
69
87
9
2
2 equiv 1,7-octadiyne · 3/48 h, 60 mol % CpCo(CO)2 · 3/48 h
2 equiv 1,7-octadiyne · 3/24 h, 60 mol % CpCo(CO)2 · 3/24 h
2 equiv 1,7-octadiyne · 3/24 h, 60 mol % CpCo(CO)2 · 3/24 h
2 equiv 1,7-octadiyne · 3/24 h, 60 mol % CpCo(CO)2 · 3/24 h
2 equiv 1,6-heptadiyne · 3/24 h, 60 mol % CpCo(CO)2 · 3/24 h
2 equiv 1,8-nonadiyne · 7/24 h, 60 mol % CpCo(CO)2 · 7/24 h
3
4a
5b
6
72
72
72
168
7
a The reaction was carried out in the absence of light.
b Xylene was used as a solvent.

T. Hoshi et al. / Tetrahedron Letters 45 (2004) 3489–3491
3491
the reaction rate and yield were not satisfactory com-
References and notes
pared to those of the model reaction of benzonitrile
(Eq. 3). We then focused on finding a better condition
for this cycloaddition reaction. Because the high dilution
condition has been precedented to suppress intermo-
lecular side reactions competitive with the pyridine ring
formation, CpCo(CO)2 and 1,7-octadiyne were added
portionwise at intervals of 48 h in order to keep the
dilution condition higher than that of entry 1 (entry 2).
Though the reaction rate was still sluggish, the chemical
yield was increased to 62% yield. The shortening addi-
tion intervals by half were more effective to improve
both the reaction rate (72 h) and yield (70% yield) (entry
3). Along with the high dilution condition, irradiation
was also essential in this cycloaddition reaction. In fact,
when the reaction was carried out in the absence of light,
(R)-2b was obtained in only 26% yield (entry 4). Ele-
vated reaction temperature had little effect on this
cycloaddition reaction at least within a range from tol-
uene to xylene (entry 5). Next, in order to investigate the
generality of this cycloaddition reaction, we evaluated
use of 1,6-heptadiyne, 1,8-nonadiyne, and 2,8-deca-
diyne. The reaction with 1,6-heptadiyne afforded the
desired ligand (R)-2c in excellent yield (entry 6). In
contrast, the reaction with more flexible 1,8-nonadiyne
was much slower than with other terminal diynes and
the cycloaddition product (R)-2d was obtained in
only 9% yield (entry 7). 2,8-Decadiyne, which is a
dimethyl substituted analogue of highly reactive
1,7-octadiyne, was used with the expectation of incor-
poration of more sterically demanding substituents than
hydrogen in proximity to ligating nitrogen donors of
the pyridine rings. However, only a trace of the desired
ligand (R)-2e was detected by mass spectrometry after
the dinitrile (R)-3 was completely consumed. These
results suggested that the photochemical CpCo(CO)2-
mediated cycloaddition reaction of (R)-3 with diynes
was sensitive to both the entropy factor and the steric
factor of diynes.
1. For reviews see: (a) Chelucci, G.; Thummel, R. P. Chem.
Rev. 2002, 102, 3129–3170; (b) Eames, J.; Watkinson, M.
Angew. Chem., Int. Ed. 2001, 40, 3567–3571; (c) Fache, F.;
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2000, 100, 2159–2231; (d) Ghosh, A.; Mathivanan, P.;
Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1–45; (e)
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2. For recent examples, see: (a) Hamada, T.; Manabe, K.;
Ishikawa, S.; Nagayama, S.; Shiro, M.; Kobayashi, S. J.
Am. Chem. Soc. 2003, 125, 2989–2996; (b) Malkov, A. V.;
Pernazza, D. P.; Bell, M.; Bella, M.; Massa, A.; Teply, F.;
Meghani, P.; Kocovsky, P. J. Org. Chem. 2003, 68, 4727–
4742; (c) Trost, B. M.; Dogra, K.; Hachiya, I.; Emura, T.;
Hughes, D. L.; Krska, S.; Reamer, R. A.; Palucki, M.;
Yasuda, N.; Reider, P. J. Angew. Chem., Int. Ed. 2002, 41,
1929–1931; (d) Chelucci, G.; Loriga, G.; Murineddu, G.;
Pinna, G. A. Tetrahedron Lett. 2002, 43, 8599–8602; (e)
Malkov, A. V.; Baxendale, L. R.; Bella, M.; Langer, V.;
Fawcett, J.; Russell, D. R.; Mansfield, D. J.; Valko, M.;
Kocovsky, P. Organometallics 2001, 20, 673–690; (f)
€
Lotscher, D.; Rupprecht, S.; Collomb, P.; Belser, P.;
Viebrock, H.; von Zelewsky, A. v. Inorg. Chem. 2001, 50,
5675–5681; (g) Kolp, B.; Abeln, D.; Stoeckli-Evans, H.;
Zelewsky, A. v. Eur. J. Inorg. Chem. 2001, 1207; (h)
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M.-C.; Fu, G. C. Chem. Commun. 2000, 377–378.
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G. C.; Murray, M.; Nowak, T. J. Chem. Soc., Dalton
Trans. 2000, 1723–1732.
4. Charmant, J . P. H.; Hunt, N. J .; Lloyd-J ones, G. C.; Nowak,
T. Collect. Czech. Chem. Commun. 2003, 68, 865–884.
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ꢀ
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ꢀ
7. For a recent review: (a) Varela, J. A.; Castedo, L.; Saa, C.
Chem. Rev. 2003, 103, 3787–3801; For pioneering works
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€
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In conclusion, we have developed the first resolution-
free route to the enantiopure 2,20-bis(pyridin-2-yl)-1,10-
binaphthyl ligands 2 via the photochemical CpCo(CO)2-
mediated cycloaddition reaction of the enantiopure
dinitrile 3 with terminal diynes. Application of chiral
ligand 2 to catalytic asymmetric syntheses is currently
under investigation in our laboratory.
539–556, and references cited therein.
8. (R)-2b (>99% ee): mp ¼ 95–97 ꢁC; ½aŠ 3.99 (c 1.00,
20
D
CHCl3); 1H NMR (500 MHz, CDCl3) d 1.48–1.74 (m, 8H),
2.04–2.18 (m, 4H), 2.50–2.64 (m, 4H), 6.31 (s, 2H), 7.26
(ddd, J ¼ 8:7, 6.7, 1.2 Hz, 2H), 7.38 (d, J ¼ 8:7 Hz, 2H),
7.44 (ddd, J ¼ 8:2, 6.7, 1.2 Hz, 2H), 7.82 (d, J ¼ 8:5 Hz,
2H), 7.91 (d, J ¼ 8:2 Hz, 2H), 7.96 (d, J ¼ 8:5 Hz, 2H),
8.06 (s, 2H); 13C NMR (125 MHz, CDCl3) d 22.1, 22.4,
25.7, 28.2, 123.9, 125.7, 126.3, 127.2, 127.8, 127.9, 130.4,
132.7, 133.7, 134.3, 138.5, 144.9, 149.29, 149.31, 154.7; Ms,
m=z (%) 516 (Mþ, 93), 384 (100); HRMS Found: 516.2563.
Calcd for C38H32N2: 516.2565. The enantiomeric excess of
(R)-2b was determined by HPLC using a Daicel Chiralcel
AD-H (0.46 cm / ꢀ 25 cm), hexane–i-PrOH ¼ 9:1, wave-
length: 320 nm, flow rate: 1.0 mL/min, retention time:
9.48 min (S), 20.78 min (R).
Acknowledgements
This work was partially supported by a Grant-in-Aid for
Young Scientists (B) (No. 1474033) from the Ministry of
Education, Culture, Sports, Science and Technology of
Japan and Grant for Promotion of Niigata University
Research Projects (to T.H.).