Fleming et al.
propensity10 for planar, nitrogen-coordinated dimers in the solid
state11 and solution12 (Figure 1). Strategies for asymmetric
alkylations of lithiated nitriles through addition of chelating
ligands therefore locate the source of chirality relatively remote
from the site of alkylation, typically resulting in a modest
preference for one enantiomer.13
(4, Figure 2). In contrast to lithium, several metals exhibit an
inherent preference for coordination to the formally anionic
carbon of metalated nitriles. Among the solid-state structures
of transition metal-bound alkylnitriles there is a roughly equal
preference for N-14 and C-metalation.15 The seminal heat-
induced interconversions of the crystalline ruthenium N- and
C-phenylsulfonylacetonitriles 3 and 4 (Figure 2) are illustrative,
with the preference for N- or C-coordination depending on the
phosphine ligand.16
FIGURE 1. Prototypical X-ray and solution structures of lithiated
nitriles.
A potentially more effective means of chiral induction with
metalated nitriles is to selectively alkylate C-metalated nitriles
in which the metal is directly bound to the stereogenic carbon
FIGURE 2. Diagnostic structures and 13C chemical shifts of N- and
C-metalated nitriles.
(6) (a) Dias, L. C.; de Marchi, A. A.; Ferreira, M. A. B.; Aguilar, A. M.
Org. Lett. 2007, 9, 4869. (b) Evans, A. D.; Cote, B.; Coleman, J. P.; Conell,
T. B. J. Am. Chem. Soc. 2003, 125, 10893. (c) Paterson, I.; Collett, A. L.
Tetrahedron Lett. 2001, 42, 1187. (d) Evans, A. D.; Dart, J. M.; Duffy, L.
J.; Yang, G. M. J. Am. Chem. Soc. 1996, 118, 4322. (e) Paterson, I.; Gibson,
R. K.; Oballa, M. R. Tetrahedron Lett. 1996, 37, 8585. (f) Evans, A. D.;
Dart, J. M.; Duffy, L. J.; Reiger, L. D. J. Am. Chem. Soc. 1995, 117, 9073.
(7) (a) Varseev, G. N.; Maier, M. E. Org. Lett. 2007, 9, 1461. (b) Ruano,
J. L. G.; Martin-Castro, A. M.; Tato, F.; Pastor, C. J. J. Org. Chem. 2005,
70, 7346. (c) Viteva, L.; Gospodova, T. Z.; Stefanovsky, Y.; Angelova, S.;
Gorrichon, L. Tetrahedron 2005, 61, 5855. (d) Chen, Y.-J.; Gao, L.-J.;
Murad, I.; Verstuyf, A.; Verlinden, L.; Verboven, C.; Bouillon, R.; Viterbo,
D.; Milanesio, M.; Haver, D. V.; Vanderwalle, M.; Clercq, P. J. D. Org.
Biomol. Chem. 2003, 1, 257. (e) Halim-Partogyan, K.; Besson, L.; Aitken,
D. J.; Husson, H.-P. Eur. J. Org. Chem. 2003, 268. (f) Viteva, L.;
Gospodova, T. Z.; Stefanovsky, Y.; Angelova, S.; Gorrichon, L. Tetrahedron
2002, 58, 3371. (g) Fujishima, T.; Zhaopeng, L.; Konno, K.; Nakagawa,
K.; Okano, T.; Yamaguchi, K.; Takayama, H. Bioorg. Med. Chem. 2001,
9, 525. (h) Fall, Y.; Fernandez, C.; Gonzalez, V.; Mourino, A. Synlett 2001,
1567. (i) Salomon, J. C.; Labadie, R. G. Molecules 2000, 5, 252. (j) Fall,
Y.; Fernandez, C.; Vitale, C.; Mourino, A. Tetrahedron Lett. 2000, 41, 7323.
(k) Chen, J.-Y.; Clercq, D. P.; Vandewalle, M. Tetrahedron Lett. 1996, 37,
9361. (l) Gmeiner, P.; Hummel, E.; Haubmann, C. Liebigs Ann. 1995, 1987.
(m) Reetz, T. M.; Kayser, F.; Harms, K. Tetrahedron Lett. 1994, 35, 8769.
(n) Schlessinger, H. R.; Graves, D. D. Tetrahedron Lett. 1987, 28, 4385.
(o) Fleming, I.; Hill, M. H. J.; Parker, D.; Waterson, D. J. Chem. Soc.,
Chem. Commun. 1985, 318. (p) Maigrot, M.; Mazaleyrat, J.-P.; Welvart,
Z. J. Org. Chem. 1985, 50, 3916. (q) Okawara, T.; Harada, K. J. Org. Chem.
1972, 37, 3286.
(8) For chiral auxiliaries bearing an adjacent nitrile group see: (a)
Partogyan-Halim, K.; Besson, L.; Aitken, D. J.; Husson, H.-P. Eur. J. Org.
Chem. 2003, 268. (b) Cativiela, C.; Diaz-de-Villegas, D. M.; Galvez, A. J.;
Lapena, Y. Tetrahedron 1995, 51, 5921. (c) Cativiela, C.; Diaz-de-Villegas,
D. M.; Galvez, A. J. J. Org. Chem. 1994, 59, 2497. (d) Hanamoto, T.;
Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1986, 27, 2463. (e) Maigrot,
N.; Mazaleyrat, J.-P.; Welvart, Z. J. Org. Chem. 1985, 50, 3916.
(9) (a) Fleming, F. F.; Shook, B. C. Tetrahedron 2002, 58, 1. (b)
Arseniyadis, S.; Kyler, K. S.; Watt, D. S. Org. React. 1984, 31, 1.
(10) C-Lithiated nitriles, although rare, have been characterized by
crystallography in a lithiated cyclopropanea and were identified as fluxional
species in solutionb for a lithioacetonitrile-chiral ligand complex. (a) Boche,
G.; Harms, K.; Marsch, M. J. Am. Chem. Soc. 1988, 110, 6925. (b) Scott,
R.; Granander, J.; Hilmersson, G. J. Am. Chem. Soc. 2004, 126, 6798.
(11) Boche, G. Angew. Chem., Int. Ed. 1989, 28, 277.
Magnesiated nitriles, such as 517 (Figure 2), exhibit a dis-
tinctive preference for coordination to carbon as reflected in
the diagnostic solution 13C NMR shifts. Experimentally, mag-
nesiated nitriles exhibit alkylation selectivities consistent with
a preference for coordination to carbon.18 As a standard point
(14) For N-metalated nitriles, see: (a) Tanabe, Y.; Seino, H.; Ishii, Y.;
Hidai, M. J. Am. Chem. Soc. 2000, 122, 1690. (b) Murahashi, S.-I.; Take,
K.; Naota, T.; Takaya, H. Synlett 2000, 1016. (c) Triki, S.; Pala, J. S.;
Decoster, M.; Molinie´, P.; Toupet, L. Angew. Chem. Int. Ed. 1999, 38,
113. (d) Hirano, M.; Takenaka, A.; Mizuho, Y.; Hiraoka, M.; Komiya, S.
J. Chem. Soc., Dalton Trans. 1999, 3209. (e) Yates, M. L.; Arif, A. M.;
Manson, J. L.; Kalm, B. A.; Burkhart, B. M.; Miller, J. S. Inorg. Chem.
1998, 37, 840. (f) Ja¨ger, L.; Tretner, C.; Hartung, H.; Biedermann, M. Chem.
Ber. 1997, 130, 1007. (g) Zhao, H.; Heintz, R. A.; Dunbar, K. R. J. Am.
Chem. Soc. 1996, 118, 12844. (h) Murahashi, S.-I.; Naota, T.; Taki, H.;
Mizuno, M.; Takaya, H.; Komiya, S.; Mizuho, Y.; Oyasato, N.; Hiraoka,
M.; Hirano, M.; Fukuoka, A. J. Am. Chem. Soc. 1995, 117, 12436. (i)
Hirano, M.; Ito, Y.; Hirai, M.; Fukuoka, A.; Komiya, S. Chem. Lett. 1993,
2057. (j) Mizuho, Y.; Kasuga, N.; Komiya, S. Chem. Lett. 1991, 2127. (k)
Schlodder, R.; Ibers, J. A. Inorg. Chem. Soc. 1974, 13, 2870. (l) Ricci, J.
S.; Ibers, J. A. J. Am. Chem. Soc. 1971, 93, 2391.
(15) For C-metalated nitriles, see: (a) Naota, T.; Tannna, A.; Kamuro,
S.; Murahashi, S.-I. J. Am. Chem. Soc. 2002, 124, 6842. (b) Naota, T.;
Tannna, A.; Murahashi, S.-I. J. Am. Chem. Soc. 2000, 122, 2960. (c)
Alburquerque, P. R.; Pinhas, A. R.; Krause Bauer, J. A. Inorg. Chim. Acta
2000, 298, 239. (d) Ruiz, J.; Rodr´ıguez, V.; Lo´pez, G.; Casabo´, J.; Molins,
E.; Miravitlles, C. Organometallics 1999, 18, 1177. (e) Ragaini, F.; Porta,
F.; Fumagalli, A.; Demartin, F. Organometallics 1991, 10, 3785. (f) Porta,
F.; Ragaini, F.; Cenini, S.; Demartin, F. Organometallics 1990, 9, 929. (g)
Ko, J. J.; Bockman, T. M.; Kochi, J. K. Organometallics 1990, 9, 1833.
(h) Cowan, R. L.; Trogler, W. J. Am. Chem. Soc. 1989, 111, 4750. (i) Del
Pra, A.; Forsellini, E.; Bombieri, G.; Michelin, R. A.; Ros, R. J. Chem.
Soc., Dalton Trans. 1979, 1862. (j) Lenarda, M.; Pahor, N. B.; Calligaris,
M.; Graziani, M.; Randaccio, L. J. Chem. Soc., Chem. Commun. 1978, 279.
(k) Schlodder, R.; Ibers, J. A.; Lenarda, M.; Graziani, M. J. Am. Chem.
Soc. 1974, 96, 6893. (l) Yarrow, D. J.; Ibers, J. A.; Lenarda, M.; Graziani,
M. J. Organomet. Chem. 1974, 70, 133.
(16) (a) Naota, T.; Tannna, A.; Murahashi, S.-I. Chem. Commun. 2001,
63. (b) Naota, T.; Tannna, A.; Murahashi, S.-I. J. Am. Chem. Soc. 2000,
122, 2960. For an analogous interconversion of palladium complexes, see:
Kujime, M.; Hikichi, S.; Akita, M. Organometallics 2001, 20, 4049.
(17) (a) Thibonnet, J.; Vu, V. A.; Berillon, L.; Knochel, P. Tetrahedron
2002, 58, 4787. (b) Thibonnet, J.; Knochel, P. Tetrahedron Lett. 2000, 41,
3319.
(18) (a) Fleming, F. F.; Zhang, Z.; Wei, G.; Steward, O. W. J. Org.
Chem. 2006, 71, 1430. (b) Fleming, F. F.; Zhang, Z.; Liu, W.; Knochel, P.
J. Org. Chem. 2005, 70, 2200. (c) Fleming, F. F.; Zhang, Z.; Wei, G.;
Steward, O. W. Org. Lett. 2005, 7, 447. (d) Fleming, F. F.; Zhang, Z.;
Knochel, P. Org. Lett. 2004, 6, 501.
(12) (a) Carlier, P. R.; Lo, C.; W.-S. J. Am. Chem. Soc. 2000, 122, 12819.
(b) Carlier, P. R.; Lucht, B. L.; Collum, D. B. J. Am. Chem. Soc., 1994,
116, 11602.
(13) (a) Carlier, R. P.; Lam, -F. W.; Wan, C. N.; Williams, D. I. Angew.
Chem., Int. Ed. 1998, 37, 2252. (b) Brunner, H.; Zintl, H. Monatsh. Chem.
1991, 122, 841. (c) Suto, Y.; Kumagai, N.; Matsunaga, S.; Kanai, M.;
Shibasaki, M. Org. Lett. 2003, 5, 3147. (d) Mi, Q. A.; Wang, Y. Z.; Jiang,
Z. Y. Tetrahedron: Asymmetry 1993, 4, 1957. (e) Soai, K.; Hirose, Y.;
Sakata, S. Tetrahedron: Asymmetry 1992, 3, 677. (f) Soai, K.; Mukaiyama,
T. Bull. Chem. Soc. J. 1979, 52, 3371.
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