Enantioselective synthesis of C2-symmetric spirobipyridine ligands through cationic Rh(I)/modified-BINAP-catalyzed double [2 + 2 + 2] cycloaddition

Article abstract of DOI:10.1021/ol070129e

Figure presented Enantioenriched C₂-symmetric spirobipyridine ligands were efficiently synthesized through a cationic rhodium(I)/(R)-Segphos or (R)-H₈-BINAP complex-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycload

Full text of DOI:10.1021/ol070129e

ORGANIC
LETTERS
2007
Vol. 9, No. 7
1295-1298
Enantioselective Synthesis of
C2-Symmetric Spirobipyridine Ligands
through Cationic Rh(I)/Modified-BINAP-
Catalyzed Double [2
Azusa Wada,† Keiichi Noguchi,‡ Masao Hirano,† and Ken Tanaka*,†
+ 2 + 2] Cycloaddition
Department of Applied Chemistry, Graduate School of Engineering, and
Instrumentation Analysis Center, Tokyo UniVersity of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received January 19, 2007
ABSTRACT
Enantioenriched C2-symmetric spirobipyridine ligands were efficiently synthesized through a cationic rhodium(I)/(R)-Segphos or (R)-H8-BINAP
complex-catalyzed enantioselective intramolecular double [2
+
2
+
2] cycloaddition of bis-diynenitriles.
C2-Symmetric spiranes having stable axial chirality are
valuable structures for efficient chiral ligands because
heteroatoms containing chiral spiranes easily form well-
defined chelate complexes with many metals.1-3 Chan, Jiang,
and co-workers synthesized the spirophosphinite ligands
through phosphinylation of enantiopure spiro[4.4]nonane-
1,6-diol.1 Zhou and co-workers synthesized the chiral spiro-
phosphine ligands through phosphinylation of enantiopure
1,1′-spirobiindane-7,7′-diol.2 Sasai and co-workers synthe-
sized the chiral spiro ligands bearing nitrogen heterocycles
through double annulation reaction followed by separation
of diastereomers and/or enantiomers.3 However, a catalytic
enantioselective synthesis of C2-symmetric spiranes is scarce.4
A novel catalytic enantioselective synthesis of a C2-sym-
metric spirane, 1,1′-spirobi(indan-3,3′-dione), was developed
by Hashimoto and co-workers through a rhodium(II)-
catalyzed double intramolecular C-H bond insertion.4a On
the other hand, Saa´ and co-workers developed an elegant
approach to spirobipyridine ligands, which is based on a
cobalt(I)-catalyzed double [2 + 2 + 2] cycloaddition of bis-
alkynenitriles with monoalkynes, although the synthesis
† Department of Applied Chemistry.
‡ Instrumentation Analysis Center.
(1) (a) Chan, A. S. C.; Hu, W.; Pai, C.-C.; Lau, C.-P.; Jiang, Y.; Mi, A.;
Yan, M.; Sun, J.; Lou, R.; Deng, J. J. Am. Chem. Soc. 1997, 119, 9570. (b)
Jiang, Y.; Xue, S.; Li, Z.; Deng, J.; Mi, A.; Chan, A. S. C. Tetrahedron:
Asymmetry 1998, 9, 3185.
(2) (a) Fu, Y.; Xie, J.-H.; Hu, A.-G.; Zhou, H.; Wang, L.-X.; Zhou, Q.-
L. Chem. Commun. 2002, 480. (b) Hu, A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.;
Wang, L.-X.; Zhou, Q.-L. Angew. Chem., Int. Ed. 2002, 41, 2348. (c) Xie,
J.-H.; Wang, L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou,
Q.-L. J. Am. Chem. Soc. 2003, 125, 4404. (d) Zhu, S.-F.; Yang, Y.; Wang,
L.-X.; Liu, B.; Zhou, Q.-L. Org. Lett. 2005, 7, 2333. (e) Zhu, S. F.; Xie,
J.-B.; Zhang, Y.-Z.; Li, S.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 12886.
(f) Cheng, X.; Zhang, Q.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. Angew.
Chem., Int. Ed. 2005, 44, 1118.
(3) (a) Arai, M. A.; Arai, T.; Sasai, H. Org. Lett. 1999, 1, 1795. (b)
Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H. J. Am. Chem. Soc. 2001,
123, 2907. (c) Shinohara, T.; Wakita, T.; Arai, M. A.; Arai, T.; Sasai, H.
Heterocycles 2003, 59, 587. (d) Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai,
H. Chirality 2003, 15, 101. (e) Takizawa, S.; Honda, Y.; Arai, M. A.; Kato,
T.; Sasai, H. Heterocycles 2003, 60, 2551. (f) Wakita, K.; Arai, M. A.;
Kato, T.; Shinohara, T.; Sasai, H. Heterocycles 2004, 62, 831. (g) Kato,
T.; Marubayashi, K.; Takizawa, S.; Sasai, H. Tetrahedron: Asymmetry 2004,
15, 3693.
(4) (a) Takahashi, T.; Tsutsui, H.; Tamura, M.; Kitagaki, S.; Nakajima,
M.; Hashimoto, S. Chem. Commun. 2001, 1604. (b) Tanaka, M.; Takahashi,
M.; Sakamoto, E.; Imai, M.; Matsui, A.; Fujio, M.; Sakai, K.; Suemune,
H. Tetrahedron 2001, 57, 1197.
10.1021/ol070129e CCC: $37.00
© 2007 American Chemical Society
Published on Web 03/08/2007

provides racemates and the product yields are not sufficient
(6-33% yields).5 They also demonstrated that a racemic C2-
symmetric spirobipyridine ligand can quantitatively coordi-
nate to [Cu(CH3CN)4]PF6, which represents the potential util-
ity of chiral spirobipyridine ligands for asymmetric catalysis.5
Our research group first demonstrated that cationic rhod-
ium(I)/modified-BINAP complexes can efficiently catalyze
both inter- and intramolecular [2 + 2 + 2] cycloaddition of
various unsaturated compounds with high chemo-, regio-,
and enantioselectivities.6,7 Recently, we have applied these
catalysts to [2 + 2 + 2] cycloaddition involving nitriles
leading to substituted pyridines,7h,8-13 and the work was
further extended to the axially chiral bipyridine synthesis
through double [2 + 2 + 2] cycloaddition.7f,14 In this
communication, we describe an enantioselective synthesis
of C2-symmetric spirobipyridine ligands through a cationic
rhodium(I)/modified-BINAP complex-catalyzed double [2 +
2 + 2] cycloaddition.
We have already reported that the reaction of substituted
malononitrile 1 with 1,6-diyne 2 in the presence of 5% [Rh-
(cod)2]BF4/(R)-BINAP selectively afforded the corresponding
enantioenriched monopyridine 3 having a quaternary ste-
reocenter without the formation of a bipyridine (Scheme 1).7h
Scheme 1
This successful enantioselective construction of a quater-
nary stereocenter prompted our investigation into a chiral
spirobipyridine synthesis. First, we applied the above-
mentioned catalyst to intermolecular double [2 + 2 + 2]
cycloaddition of bis-alkynenitrile 4 with monoalkyne 5, but
spirobipyridine 6 was not obtained at all and 4 was recovered
even at elevated temperature (Scheme 2).15
(5) Varela, J. A.; Castedo, L.; Saa`, C. Org. Lett. 1999, 1, 2141.
(6) For our first report on the cationic rhodium(I)/modified-BINAP-
catalyzed inter- and intramolecular [2 + 2 + 2] cycloadditions, see: Tanaka,
K.; Shirasaka, K. Org. Lett. 2003, 5, 4697.
(7) (a) Tanaka, K.; Toyoda, K.; Wada, A.; Shirasaka, K.; Hirano, M.
Chem.sEur. J. 2005, 11, 1145. (b) Tanaka, K.; Nishida, G.; Ogino, M.;
Hirano, M.; Noguchi, K. Org. Lett. 2005, 7, 3119. (c) Tanaka, K.; Wada,
A.; Noguchi, K. Org. Lett. 2005, 7, 4737. (d) Tanaka, K.; Wada, A.;
Noguchi, K. Org. Lett. 2006, 8, 907. (e) Tanaka, K.; Takeishi, K.; Noguchi,
K. J. Am. Chem. Soc. 2006, 128, 4586. (f) Nishida, G.; Suzuki, N.; Noguchi,
K.; Tanaka, K. Org. Lett. 2006, 8, 3489. (g) Tanaka, K.; Sagae, H.; Toyoda,
K.; Noguchi, K. Eur. J. Org. Chem. 2006, 3575. (h) Tanaka, K.; Suzuki,
N.; Nishida, G. Eur. J. Org. Chem. 2006, 3917. (i) Tanaka, K.; Sagae, H.;
Toyoda, K.; Noguchi, K.; Hirano, M. J. Am. Chem. Soc. 2007, 129, 1522.
(j) Tanaka, K.; Suda, T.; Noguchi, K.; Hirano, M. J. Org. Chem. 2007, 72,
2243. (k) Tanaka, K.; Nishida, G.; Wada, A.; Noguchi, K. Angew. Chem.,
Int. Ed. 2004, 43, 6510.
Scheme 2
(8) For recent reviews of pyridine synthesis by transition-metal-catalyzed
[2 + 2 + 2] cycloadditions, see: (a) Chopade, P. R.; Louie, J. AdV. Synth.
Catal. 2006, 348, 2307. (b) Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004,
104, 2127. (c) Varela, J. A.; Saa`, C. Chem. ReV. 2003, 103, 3787.
(9) For pioneering work on the transition-metal-catalyzed [2 + 2 + 2]
cycloadditions of alkynes with nitriles, see: (a) Wakatsuki, Y.; Yamazaki,
H. J. Chem. Soc., Chem. Commun. 1973, 280. (b) Wakatsuki, Y.; Yamazaki,
H. J. Chem. Soc., Dalton Trans. 1978, 1278. (c) Bo¨nnemann, H.; Brinkmann,
R. Synthesis 1975, 600. (d) Bo¨nnemann, H. Angew. Chem., Int. Ed. Engl.
1978, 17, 505.
(10) For pioneering work on the Co-catalyzed [2 + 2 + 2] cycloadditions
of R,ω-diynes with nitriles and cyanoalkynes with monoalkynes, see: (a)
Naiman, A.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1977, 16,
708. (b) Brien, D. J.; Naiman, A.; Vollhardt, K. P. C. J. Chem. Soc., Chem.
Commun. 1982, 133. (c) Parnell, C. A.; Vollhardt, K. P. C. Tetrahedron
1985, 41, 5791.
Next, we attempted the intramolecular double [2 + 2 +
2] cycloaddition of bis-diynenitriles 9, which can be readily
prepared starting from known protected alkyne diol 716
(Scheme 3). Etherification of 7 followed by desilylation
Scheme 3
(11) Recent examples of pyridine synthesis through transition-metal-
catalyzed [2 + 2 + 2] cycloadditions: Co(I): (a) Fatland, A. W.; Eaton,
B. E. Org. Lett. 2000, 2, 3131. (b) Moretto, A. F.; Zhang, H.-C.; Maryanoff,
B. E. J. Am. Chem. Soc. 2001, 123, 3157. (c) Bonaga, L. V. R.; Zhang,
H.-C.; Maryanoff, B. E. Chem. Commun. 2004, 2394. (d) Bonaga, L. V.
R.; Zhang, H.-C.; Moretto, A. F.; Ye, H.; Gauthier, D. A.; Li, J.; Leo, G.
C.; Maryanoff, B. E. J. Am. Chem. Soc. 2005, 127, 3473. (e) Heller, B.;
Sundermann, B.; Buschmann, H.; Drexler, H.-J.; You, J.; Holzgrabe, U.;
Heller, E.; Oehme, G. J. Org. Chem. 2002, 67, 4414. (f) Gutnov, A.; Heller,
B.; Fischer, C.; Drexler, H.-J.; Spannenberg, A.; Sundermann, B.; Sunder-
mann, C. Angew. Chem., Int. Ed. 2004, 43, 3795. (g) Gutnov, A.; Abaev,
V.; Redkin, D.; Fischer, C.; Bonrath, W.; Heller, B. Synlett 2005, 1188.
(h) Groth, U.; Huhn, T.; Kesenheimer, C.; Kalogerakis, A. Synlett 2005,
1758. (i) Hrdina, R.; Stara`, I.; Dufkova`, L.; Mitchel, S.; Cisarova`, I.; Kotora,
M. Tetrahedron 2006, 62, 968. Ru(II): (j) Yamamoto, Y.; Okuda, S.; Itoh,
K. Chem. Commun. 2001, 1102. (k) Yamamoto, Y.; Ogawa, R.; Itoh, K. J.
Am. Chem. Soc. 2001, 123, 6189. (l) Varela, J. A.; Castedo, L.; Saa`, C. J.
Org. Chem. 2003, 68, 8595. (m) Yamamoto, Y.; Kinpara, K.; Nishiyama,
H.; Itoh, K. AdV. Synth. Catal. 2005, 347, 1913. (n) Yamamoto, Y.; Kinpara,
K.; Ogawa, R.; Nishiyama, H.; Itoh, K. Chem.sEur. J. 2006, 12, 5618.
Ni(0): (o) McCormick, M. M.; Duong, H. A.; Zuo, G.; Louie, J. J. Am.
Chem. Soc. 2005, 127, 5030. (p) Takevec, T. N.; Zuo, G.; Simon, K.; Louie,
J. J. Org. Chem. 2006, 71, 5834.
furnished diyne monool 8. Dialkylation of malononitrile with
the corresponding tosylate of 8 furnished bis-diynenitrile 9a,
possessing a phenyl at each alkyne terminus, in high yield.
1296
Org. Lett., Vol. 9, No. 7, 2007

(diphenylphosphino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-
binaphthyl]19 as a ligand (entries 4 and 5). Furthermore, C2-
symmetric spirobipyridines 10f-h, possessing a six-membered
spiro skeleton, could be synthesized from bis-diynenitriles
9f-h in high yields using (R)-Segphos or (R)-H8-BINAP as
a ligand, although lower enantioselectivities were observed
(entries 6-8). Enantiopure (-)-10b was readily obtained by
recrystallization from CH2Cl2-pentane, and the absolute
configuration was determined to be S by the anomalous
dispersion method (Figure 1).
Table 1. Rh(I)+/(R)-Segphos or (R)-H8-BINAP
Complex-Catalyzed Enantioselective Double [2 + 2 + 2]
Cycloaddition of Bis-diynenitriles 9a-ha
Figure 1. ORTEP diagram of C2-symmetric spirobipyridine (S)-
(-)-10b.
Scheme 4 depicts a plausible mechanism for the selective
formation of (S)-(-)-10b. Enantioselectivity is determined
by preferential formation of metallacycle A, due to avoidance
(12) For pioneering work on the Rh-catalyzed [2 + 2 + 2] cycloadditions
of alkynes with nitriles, see: (a) Cioni, P.; Diversi, P.; Ingrosso, G.;
Lucherini, A.; Ronca, P. J. Mol. Catal. 1987, 40, 337. (b) Cioni, P.; Diversi,
P.; Ingrosso, G.; Lucherini, A.; Ronca, P. J. Mol. Catal. 1987, 40, 359.
(13) For examples of pyridine synthesis through [2 + 2 + 2] cycload-
ditions using stoichiometric amounts of transition metals, see: (a) Takahashi,
T.; Tsai, F.-Y.; Kotora, M. J. Am. Chem. Soc. 2000, 122, 4994. (b)
Takahashi, T.; Liu, Y.; Iesato, A.; Chaki, S.; Nakajima, K.; Kanno, K. J.
Am. Chem. Soc. 2005, 127, 11928. (c) Suzuki, D.; Tanaka, R.; Urabe, H.;
Sato, F. J. Am. Chem. Soc. 2002, 124, 3518. (d) Tanaka, R.; Yuza, A.;
Watai, Y.; Suzuki, D.; Takayama, Y.; Sato, F.; Urabe, H. J. Am. Chem.
Soc. 2005, 127, 7774.
(14) Synthesis of bipyridines and terpyridines by transition-metal-
catalyzed [2 + 2 + 2] cycloadditions: Co(I): (a) Varela, J. A.; Castedo,
L.; Saa`, C. J. Org. Chem. 1997, 62, 4189. (b) Varela, J. A.; Castedo, L.;
Saa`, C. J. Am. Chem. Soc. 1998, 120, 12147. (c) Varela, J. A.; Castedo, L.;
Maestro, M.; Mahia, J.; Saa`, C. Chem.sEur. J. 2001, 7, 5203. Ru(II): see
refs 11k and 11n.
(15) Recently, Yamamoto and co-workers reported that a cyanoalkyne
failed to react with 1-hexyne intermolecularly in the presence of [Cp*RuCl-
(cod)] catalyst, but intramolecular [2 + 2 + 2] cycloadditions of cyanodiynes
proceeded to give tricyclic pyridines in the presence of the same Ru catalyst,
although a diluted reaction condition or a slow addition is necessary. See
ref 11n.
(16) Pettus, T. R. R.; Schlessinger, R. H. Synth. Commun. 2002, 32, 3019.
(17) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. AdV. Synth. Catal. 2001, 343, 264.
a Reactions were conducted using [Rh(cod)2]BF4/ligand (0.01 mmol, 10
mol %), 9 (0.10 mmol), and CH2Cl2 (1.0 mL) at rt for 16-24 h. Ligand:
(R)-Segphos (entries 1-3 and 6), (R)-H8-BINAP (entries 4, 5, 7, and 8).
b Isolated yield. c Catalyst: 5 mol %.
Fortunately, the intramolecular double [2 + 2 + 2]
cycloaddition of bis-diynenitrile 9a, catalyzed by 10% [Rh-
(cod)2]BF4/modified-BINAP, proceeded to give the expected
C2-symmetric spirobipyridine 10a in almost quantitative
yield.15 Although the reaction proceeds intramolecularly, a
diluted reaction condition or a slow addition is not necessary.
The highest enantioselectivity was achieved by using (R)-
Segphos [(4,4′-bi-1,3-benzodioxole)-5,5′-diylbis(diphenylphos-
phine)]17 as a ligand (Table 1, entry 1).18 The enantiomeric
excess is dependent on the electronic nature of aromatic
substituents: an electron-withdrawing group furnished higher
selectivity than did an electron-donating group (entries 2 and
3). Not only aryl-substituted bis-diynenitriles but methyl-
substituted and terminal bis-diynenitriles could also partici-
pate in this process by using (R)-H8-BINAP [2,2′-bis-
(18) Results with other BINAP-type ligands: (R)-BINAP 58% ee, (R)-
tol-BINAP 56% ee, (R)-xyl-BINAP 51% ee, (R)-H8-BINAP 60% ee.
(19) Zhang, X.; Mashima, K.; Koyano, K.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Takaya, H. Tetrahedron Lett. 1991, 32, 7283.
Org. Lett., Vol. 9, No. 7, 2007
1297

11 provides the expected C2-symmetric spirobipyridine (S)-
(-)-10b.
Scheme 4
In conclusion, we have developed a cationic rhodium(I)/
modified-BINAP complex-catalyzed enantioselective in-
tramolecular double [2 + 2 + 2] cycloaddition of bis-
diynenitriles leading to enantioenriched C2-symmetric
spirobipyridine ligands. Further applications of the cationic
rhodium(I)/modified-BINAP complex-catalyzed enantiose-
lective double [2 + 2 + 2] cycloadditions to the synthesis
of various chiral spiro ligands are underway in our laboratory.
Acknowledgment. We thank Takasago International
Corporation for the gift of modified-BINAP ligands. This
work was partly supported by Kurata Memorial Hitachi
Science and Technology Foundation.
Supporting Information Available: Experimental pro-
cedures, compound characterization data (PDF), and X-ray
crystallographic file (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
of the steric interaction between a cyano group of 9b and
the PPh2 groups of (R)-Segphos. Insertion of the cyano group
followed by reductive elimination of rhodium gives monoan-
nulation product 11 and regenerates the rhodium catalyst.20
A subsequent intramolecular [2 + 2 + 2] cycloaddition of
OL070129E
(20) Because the first annulation and the second annulation proceed
simultaneously, the monoannulation product 11 could not be isolated.
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Org. Lett., Vol. 9, No. 7, 2007