PINDY: A novel, pinene-derived bipyridine ligand and its application in asymmetric, copper(I)-catalyzed allylic oxidation

Article abstract of DOI:10.1021/ol006111k

(matrix presented) The title bipyridine ligand (+)-6(PINDY), prepared in five steps from (-)-β-pinene, forms a stable complex with CuCl₂ (8) that has been characterized by X-ray crystallography to reveal an unusual geometry at Cu. Triflate 9 proved to catalyze asymmetric allylic oxidation (10 → 11; rt, ～30 min, 49-75% ee).

Full text of DOI:10.1021/ol006111k

ORGANIC
LETTERS
2
000
Vol. 2, No. 20
047-3049
PINDY: A Novel, Pinene-Derived
Bipyridine Ligand and Its Application in
Asymmetric, Copper(I)-Catalyzed Allylic
Oxidation†
3
Andrei V. Malkov, Marco Bella,‡,§ Vratislav Langer, and Pavel Ko cˇ ovsk y´ *
‡
|
,‡
Department of Chemistry, UniVersity of Glasgow, Glasgow G12 8QQ, U.K., and
Department of Inorganic EnVironmental Chemistry, Chalmers UniVersity of
Technology, 41296 G o¨ teborg, Sweden
p.kocoVsky@chem.gla.ac.uk
Received May 26, 2000
ABSTRACT
The title bipyridine ligand (+)-6(PINDY), prepared in five steps from (−)-â-pinene, forms a stable complex with CuCl
by X-ray crystallography to reveal an unusual geometry at Cu. Triflate 9 proved to catalyze asymmetric allylic oxidation (10 f 11; rt, ∼30 min,
9−75% ee).
2
(8) that has been characterized
4
2
Transition metal complexes with sp -nitrogen as the ligating
(-)-â-pinene, and its application in asymmetric allylic
oxidation.
1
atom(s) constitute an important class of chiral catalysts in
which substituted oxazolines and bisoxazolines play the
2
The C -symmetrical ligand (+)-6 was synthesized via
annulation of the pyridine ring to a building block originating
from the chiral pool (Scheme 1): (-)-â-Pinene (-)-1 was
2
prime role. By contrast, 2,2′-bipyridyl and 1,10-phenan-
3
throline received much less attention in asymmetric catalysis
owing to the difficulties associated with their conversion into
oxidized (OsO
to produce (+)-nopinone (+)-2 (64%),
converted into oxime 3 (NH OH‚HCl, pyridine, ethanol).
4 4 3 2
, NaIO , Me NO, t-BuOH, H O, 80 °C, 2 h)
chiral molecules.4
-12
Herein, we report on an expedient
14,15
which was
13
16
synthesis of the bipyridine ligand 6 (PINDY), derived from
2
Reduction of the latter oxime with powdered iron in the
†
Dedicated to Professor Otakar Cˇ ervinka on the occasion of his 75th
birthday.
(5) Botteghi, C.; Schionato, A.; Chelucci, G.; Brunner, H.; K u¨ rzinger,
A.; Obermann, U. J. Organomet. Chem. 1989, 370, 17.
(6) (a) Hayoz, P.; von Zelewsky, A. Tetrahedron Lett. 1992, 33, 5165.
(b) Fletcher, N. C.; Keene, F. R.; Ziegler, M.; Stoeckli-Evans, H.; Viebrock,
H.; von Zelewsky, A. HelV. Chim. Acta 1996, 79, 1192. (c) Mamula, O.;
von Zelewsky, A.; Bark, T.; Bernardinelli, G. Angew. Chem., Int. Ed. 1999,
38, 2945. For an overview, see: (d) Knof, U.; von Zelewsky, A. Angew.
Chem., Int. Ed. 1999, 38, 303.
‡
University of Glasgow.
Exchange student from the Department of Chemistry, University of
§
Rome “La Sapienza”, Italy.
|
Chalmers University of Technology.
(
1) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley &
Sons: New York, 1994.
2) For a recent overview, see: Pfaltz, A. Acta Chem. Scand. 1996, 50,
89.
3) For the rich coordination chemistry of bipyridine and phenathroline,
(
1
(7) (a) Chen, C.; Tagami, K.; Kishi, Y. J. Org. Chem. 1995, 60, 5386.
(b) Chen, C. Synlett 1998, 1311.
(
see, e.g.: (a) Reedijk, J. In ComprehensiVe Coordination Chemistry;
Wilkinson, G., Gillard, R. D., McCleverty, J. A., Eds.; Pergamon Oxford,
(8) Chelucci, G.; Pinna, G. A.; Saba, A. Tetrahedron: Asymmetry 1998,
9, 531.
1
987; Vol 2, p 73. (b) Lehn, J.-M. Supramolecular Chemistry; VCH:
Weinheim, 1995.
4) (a) Ito, K.; Tabuchi, S.; Katsuki, T. Synlett 1992, 575. (b) Ito, K.;
Yoshitake, M.; Katsuki, T. Tetrahedron 1996, 52, 3905.
(9) Kwong, H.-L.; Lee, W.-S.; Ng, H.-F.; Chiu, W.-H.; Wong, W.-T. J.
Chem. Soc., Dalton Trans. 1998, 1043.
(10) Rios, R.; Liang, J.; Lo, M. M.-C.; Fu, G. C. Chem. Commun. 2000,
377.
(
1
0.1021/ol006111k CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/31/2000

2
0
h). Stoichiometric, nickel(0)-mediated coupling of 5 (NiCl
Ph P, Zn, DMF, 60 °C, 18 h) furnished a mixture of the
reduction product 7 (32%) and the desired dimer (+)-6
2
,
3
Scheme 1
2
1,22
(
50%).
Refluxing (+)-6 (PINDY) with CuCl
2 2 2 2
‚H O in CH Cl -
EtOH for 12 h (Scheme 2) resulted in the quantitative
Scheme 2
2
3
formation of 8 (75% after recrystallization). Single-crystal
X-ray analysis of the latter complex revealed an unusually
distorted geometry at the metal center (Figure 1),24 which
may have interesting implications for its catalytic activity.25
17
presence of acetic anhydride (Fe, Ac
°
2
O, toluene, AcOH, 0
C, 10 min)1 led to enamide 4 (90%), which afforded the
chloropyridine derivative 5 (70%) under the conditions of
Vilsmeyer-Haack reaction (HCONMe , POCl , 0-5 °C, 1
8,19
2
3
(11) For other chiral pyridine derivatives, see, e.g.: (a) Chelucci, G.;
Pinna, G. A.; Saba, A. Tetrahedron: Asymmetry 1997, 8, 2571. (b) Chelucci,
G. Tetrahedron: Asymmetry 1997, 8, 2667. (c) Chelucci, G.; Medici, S.;
Saba, A. Tetrahedron: Asymmetry 1997, 8, 3183. (d) Chelucci, G.; Berta,
D.; Saba, A. Tetrahedron 1997, 53, 3843. (e) Nordstr o¨ m, K.; Macedo, E.;
Moberg, C. J. Org. Chem. 1997, 62, 1604. (f) Bremberg, U.; Rahm, F.;
Moberg, C. Tetrahedron: Asymmetry 1998, 9, 3437. (g) W a¨ rnmark, K.;
Stranne, R.; Cernerud, M.; Terrien, I.; Rahm, F.; Nordstr o¨ m, K.; Moberg,
C. Acta Chem. Scand. 1998, 52, 961. For a recent overview of chiral
pyridines, see: (h) Moberg, C.; Adolfsson, H.; W a¨ rnmark, K. Acta Chem.
Scand. 1996, 50, 195. (i) Canal, J. M.; G o´ mez, M.; Jim e´ nez, F.; Rocamora,
M.; Muller, G.; Du n˜ ach, E.; Franco, D.; Jim e´ nez, A.; Cano, F. H.
Organometallics 2000, 19, 966. For recent examples of bipyridine ligands
with planar chirality, see ref 10 and: (j) W o¨ rsdorf o¨ r, U.; V o¨ gtle, F.; Nieger,
M.; Waletzke, M.; Grimme, S.; Glorius, F.; Pfaltz, A. Synthesis 1999, 597.
2 2
Figure 1. ORTEP diagram of 8‚CH Cl showing the atom labeling
scheme. Displacement parameters are shown at the 30% probability
level. H atoms are shown as spheres of arbitrary radius.
(
k) Djukic, J.-P.; Michon, C.; Maisse-Fran c¸ ois, A.; Allagapen, R.; Pfeffer,
M.; D o¨ tz, K. H.; De Cian, A.; Fischer, J. Chem. Eur. J. 2000, 6, 1064.
12) Chiral phenanthrolines: (a) Gladiali, S.; Chelucci, G.; Soccolini,
(
F.; Delogu, G.; Chiessa, G. J. Organomet. Chem. 1989, 370, 285. (b) Pe n˜ a-
Cabrera, E.; Norrby, P.-O.; Sj o¨ gren, M.; Vitagliano, A.; De Felice, V.; Oslob,
J.; Ishii, S.; O’Neill, D.; A° kermark, B.; Helquist, P. J. Am. Chem. Soc.
To explore the catalytic potential of copper complexes of
PINDY (6), we elected to study asymmetric allylic oxidations
1
996, 118, 4299. (c) Oslob, J. D.; A° kermark, B.; Helquist, P.; Norrby, P.-
O. Organometallics 1997, 16, 3015. Related nonchiral phenanthrolines: (d)
Hansson, S.; Norrby, P.-O.; Sj o¨ gren, M. P. T.; A° kermark, B. Organome-
tallics 1993, 12, 4940. (e) Sj o¨ gren, M. P. T.; Hansson, S.; A° kermark, B.
Organometallics 1994, 13, 1963. (f) Frisell, H.; A° kermark, B. Organome-
tallics 1995, 14, 561. (g) Sj o¨ gren, M. P. T.; Frisell, H.; A° kermark, B.
Organometallics 1997, 16, 942. (h) Hagelin, H.; A° kermark, B.; Norrby,
P.-O. Organometallics 1999, 18, 2884.
(18) The conversion of oximes into enamides has also been known to
occur in the presence of strong reducing agents, such as (AcO)2Cr or
(AcO)3Ti.19 However, in view of the cost of the former and the difficulties
associated with the availability of the latter reagent, none of them was
particularly suitable for large-scale operations.
(
13) PINene-Derived bipYridine.
(19) For the Ti(III) and Cr(II) reduction, see: (a) Boar, R. B.; McGhie,
J. F.; Robinson, M.; Barton, D. H. R.; Horwell, D. C.; Stick, R. V. J. Chem.
Soc., Perkin Trans. 1 1975, 1237. (b) Barton, D. H. R.; Bowles, T.; Husinec,
S.; Forbes, J. E.; Llobera, A.; Porter, E. A.; Zard, S. Z. Tetrahedron Lett.
1988, 29, 3343.
(20) For the method, see: Meth-Cohn, O.; Westwood, K. T. J. Chem.
Soc., Perkin Trans. 1 1984, 1173.
(21) For the method of R-chloropyridine dimerization, see ref 6a and
the following: (a) Dehmlow, E. V.; Sleegers, A. Liebigs Ann. Chem. 1992,
9, 953. (b) Brenner, E.; Schneider, R.; Fort, Y. Tetrahedron Lett. 2000, 41,
2881.
(22) Although this coupling is, a priori, amenable to a catalytic process,
reactions with sub-stoichiometric amounts (e.g., 10 mol %) of Ni(0) turned
out to lead predominantly to the reduction product 7.
(14) Brown, H. C.; Weissman, S. A.; Perumal, P. T.; Dhokte, U. P. J.
Org. Chem. 1990, 55, 1217.
15) (+)-Nopinone (+)-2 thus prepared from the commercially available
-)-â-pinene (-)-1 (Aldrich) exhibited [R]D +34.7 (c 4.0 MeOH). Since
the highest optical rotation reported for enantiopure nopinone is [R]D +39.9
0.3 (Grimshaw, N.; Grimshaw, J. T.; Juneja, H. R. J. Chem. Soc., Perkin
(
(
(
1
4
Trans. 1 1972, 50) or [R]D +40.52 (c 4.0 MeOH), our nopinone
corresponds to 86% ee.
(
16) Identical with the known compound: (a) Hall, H. K. J. Org. Chem.
963, 28, 3213. (b) Quon, H. H.; Chow, Y. L. Tetrahedron 1975, 31, 2349.
c) Yokoyama, Y.; Yunokihara, M. Chem. Lett. 1983, 1245.
17) For the method, see: Burk, M. J.; Casy, G.; Johnson, N. B. J. Org.
Chem. 1998, 63, 6084.
1
(
(
3048
Org. Lett., Vol. 2, No. 20, 2000

one of the reactions that have not yet been developed at a
2
6
satisfactory level. The catalysts reported to date often
Scheme 3
2
6a
require several days to allow completion of the reaction
and, as a rule, the enantioselectivity does not exceed ∼80%
ee. To increase the reactivity of the Cu/PINDY catalyst,
triflate analogue 9 was generated from (+)-6 and Cu(OTf)
26
2
.
Complex 9 was then reduced in situ with phenylhydrazine
to the corresponding Cu(I) species. Oxidation of cyclohexene
(10b) with tert-butyl peroxybenzoate, carried out in the
presence of 1 mol % of the catalyst thus generated, proved
to be complete within e30 min at room temperature, giving
obtained with cyclopentene 10a (48% ee at rt and 59% ee
at 0 °C). Cycloheptene, on the other hand, exhibited a
(
(
S)-(-)-11b (96%, 49% ee). Improved enantioselectivity
55% ee) was observed at 0 °C, but the reaction required 5
3
0
27
28,29
substantially better enantioselectivity (62% ee at rt and 75%
h in this instance (Scheme 3).
Similar results were
30
ee at 0 °C). In all cases the reaction was significantly slower
at 0 °C (5-10 h).
(
23) For the preparation of Cu(II)-bipy complexes, see, e.g., ref 9 and
2
In conclusion, novel, C -symmetrical bipyridine ligand
the following: Bolm, C.; Ewald, M.; Zehnder, M.; Neuburger, M. A. Chem.
Ber. 1992, 125, 453.
(+)-6 (PINDY) has been prepared from (-)-â-pinene via a
de novo construction of the pyridine ring followed by Ni-
(0)-mediated dimerization. This ligand has been found to
form a stable complex with CuCl (8) that exhibits an unusual
2
geometry at Cu, as revealed by X-ray crystallography.
(
24) Crystallographic data for 8: C24H28Cl2CuN2‚CH2Cl2, M ) 563.85.
Crystals were obtained from solution of the complex in CH2Cl2, covered
by hexane and left at -18 °C for 2 days. They are orthorhombic, space
group P212121, a ) 10.3637(1) Å, b ) 3.6592(2) Å, c ) 17.9777(2) Å, V
3
-3
-1
)
2544.92(5) Å , Z ) 4, dcalc ) 1.472 g cm , µ ) 1.295 mm , 30160
reflections collected, 9036 unique (Rint ) 0.0198), with 8590 observed data
2
having I > 2σI, RF ) 0.0332 for the observed data and wR(F ) ) 0.0973
Triflate 9 proved to catalyze asymmetric allylic oxidation
for all data, Flack factor ) 0.003(7). The estimated error in C-C bond
lengths is in the range of 0.002-0.003 Å.
(10 f 11) with high efficiency and good enantioselectivity.
(
25) For a similar distortion, see ref 9. Several oxazoline-type Cu(II)
These promising results suggest that optimization of the
complexes have also been reported to exhibit distortion at Cu (although
not to the extend observed for 8). For a recent summary, see: (a) Evans,
D. A.; Miller, S. J.; Lectka, T.; von Matt, P. J. Am. Chem. Soc. 1999, 121,
31
counteranion and of the ligand may lead to a very efficient
3
2,33
catalytic system.
7
559. (b) Evans, D. A.; Barnes, D. M.; Johnson, J. S.; Lectka, T.; von
Matt, P.; Miller, S. J.; Murry, J. A.; Norcross, R. D.; Shaughnessy, E. A.;
Campos, K. R. J. Am. Chem. Soc. 1999, 121, 7582. (c) Evans, D. A.;
Johnson, J. S.; Olhava, E. J. J. Am. Chem. Soc. 2000, 122, 1635.
Acknowledgment. We thank the University of Glasgow
and the University of Rome “La Sapienza” for financial
support.
(26) (a) Gokhale, A. S.; Minidis, A. B. E.; Pfaltz, A. Tetrahedron Lett.
1
995, 36, 1831. (b) Andrus, M. A.; Argade, A. B.; Chen, X.; Pamment, M.
G. Tetrahedron Lett. 1995, 36, 2945. (c) S o¨ dergren, M. J.; Andersson, P.
G. Tetrahedron Lett. 1996, 37, 7577. (d) Hamachi, K.; Irie, R.; Katsuki, T.
Tetrahedron Lett. 1996, 37, 4979. (e) Kawasaki, K.; Katsuki, T. Tetrahedron
Supporting Information Available: Experimental pro-
cedures for new compounds, analytical details for allylic
oxidation, and crystallographic characterization of 8 and
atomic coordinates. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
997, 53, 6337. (f) Clark, J. S.; Tolhurst, K. F.; Taylor, M.; Swallow, S. J.
Chem. Soc., Perkin Trans. 1 1998, 1167. (g) Sekar, G.; DattaGupta, A.;
Singh, V. K. J. Org. Chem. 1998, 63, 2961. (h) Kohmura, Y.; Katsuki, T.
Tetrahedron Lett. 2000, 41, 3941.
(
27) Practically identical results were obtained with the Cu(I) complex
generated directly from (+)-6 and the more expensive (CuOTf)2‚C6H6.
28) Since the starting (+)-nopinone (+)-2 was not enantiomerically pure
OL006111K
(
1
5
(
86% ee), the observed enantioselectivities might, in principle, be higher.
washed successively with a saturated aqueous KHCO3 solution, brine, and
water, and dried over MgSO4. Evaporation followed by chromatography
on silica gel (20 × 3 cm) with hexane/ethyl acetate (10:1) as eluent afforded
pure cyclohexenyl benzoate (S)-11b (194 mg, 96%; g49% ee). Chiral HPLC
analysis: Chiralpak AD, hexane-isopropyl alcohol (99.6:0.4), flow rate 1
mL/min, tR ) 12.6 min (minor), tS ) 13.8 min (major), UV detection at
220 nm.
However, the synthesis of ligand (+)-6 included several crystallizations,
which may have contributed to the increase of enantiomeric purity of the
final product. Although we failed to detect the opposite enantiomer in (+)-6
by chiral HPLC and by NMR spectroscopy [in the presence of Eu(hfc)3],
its ultimate precursor 5 was found to be of 95% ee by HPLC.
(
29) Typical Procedure for Allylic Oxidation Catalyzed by Cu(I)/
PINDY. A green solution of (+)-6 (21 mg, 0.06 mmol) and Cu(OTf)2 (18
mg, 0.05 mmol) in acetone (4 mL) was stirred under a nitrogen atmosphere
at 20 °C for 1 h. Phenylhydrazine (5.9 µL, 0.06 mmol) was then added,
and the color of the solution changed to red. After 10 min, cyclohexene
(30) The absolute configuration of the product was determined by
comparison of its optical rotation with the known values.26
(31) For the role of the counterion in Cu(I)- and Cu(II)-catalyzed
reactions, see, e.g., ref 25.
1
0b (0.52 mL, 5 mmol) was added, followed by the dropwise addition of
(32) Apparently, the reaction requires a trace of water since adding
molecular sieves resulted in a dramatic deceleration (though the enanti-
oselectivity remained essentially unaffected).
tert-butyl peroxybenzoate (0.2 mL, 1.0 mmol). The progress of the reaction
was monitored by TLC (hexane/ethyl acetate 9:1). Disappearance of the
peroxyester indicated the completion of the reaction. The solvent was
removed in a vacuum, and the residue was dissolved in CH2Cl2 (15 mL),
(33) Note that individual ligands26 have different “optimal substrates”;
in the case of PINDY it is 11c that gives the highest enantioselectivity.
Org. Lett., Vol. 2, No. 20, 2000
3049