C O M M U N I C A T I O N S
Table 1. Substrate Scope in the Nickel-Mediated Decarbonylative
Cross-Coupling of Cyclic Anhydrides
Acknowledgment. We thank Colorado State University, the
donors of the Petroleum Research Fund (administered by the
American Chemical Society), Merck, and Glaxo-SmithKline for
financial support. E.A.B. thanks Pharmacia for a graduate fellow-
ship. We thank Andrew Bolig and Professor Eugene Chen (CSU)
for assistance in the preparation of Ph2Zn.
Supporting Information Available: Experimental procedures and
spectral data for all new compounds (PDF). This material is available
References
(1) Diederich, F.; Stang, P. J. Metal-catalyzed Cross-Coupling Reactions;
Wiley-VCH: Weinheim, 1998.
(2) See, for example: Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew.
Chem., Int. Ed. 2001, 40, 4544.
(3) (a) Ca´rdenas, D. J. Angew. Chem., Int. Ed. 2003, 42, 384. (b) Terao, J.;
Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc.
2002, 124, 4222. (c) Menzel, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125,
3718. (d) Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller, M. Angew. Chem.,
Int. Ed. 2002, 41, 4056. (e) Netherton, M. R.; Fu, G. C. Angew. Chem.,
Int. Ed. 2002, 41, 3910. (f) Giovannini, R.; Studemann, T.; Devasagayaraj,
A.; Dussin, G.; Knochel, P. J. Org. Chem. 1999, 64, 3544. (g) Giovannini,
R.; Stu¨demann, T.; Dussin, G.; Knochel, P. Angew. Chem., Int. Ed. 1998,
37, 2387. (h) Nishimura, T.; Matsumura, S.; Maeda, Y.; Uemura, S. Chem.
Commun. 2002, 50. (i) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J.
Am. Chem. Soc. 2003, 125, 5646. (j) Lee, J.-Y.; Fu, G. C. J. Am. Chem.
Soc. 2003, 125, 5616.
(4) A single example involves the use of a phenethyl Grignard reagent as the
nucleophile, necessarily limited by its reactivity as well as the requirement
of a benzylic group to allow the organometallic to epimerize under the
reaction conditions: (a) Hayashi, T.; Konishi, M.; Fukushima, M.; Mise,
T.; Kagotani, M.; Tajika, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104,
180. (b) Hayashi, T. Cross-coupling reactions. In ComprehensiVe Asym-
metric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer-Verlag: Berlin, 1999; Vol. 2, p 887.
(5) Pd-catalyzed allylic alkylation and Heck reaction are also capable of
generating stereochemistry, although by different reaction manifolds;
see: (a) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395. (b)
Shibasaki, M.; Vogl, E. M. Heck Reaction. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-
Verlag: Berlin, 1999; Vol. 1, p 457. For arylzinc trapping of π-allyl nickel,
see: Takimoto, M.; Mori, M. J. Am. Chem. Soc. 2001, 123, 2895.
(6) A number of workers have reported cross-coupling reactions involving
organometallic nucleophiles with a stereocenter at the metal-bearing
carbon. In each case, however, the stereochemistry was generated prior
to cross-coupling. See: (a) Ye, J.; Bhatt, R. K.; Falck, J. R. J. Am. Chem.
Soc. 1994, 116, 1. (b) Boudier, A.; Knochel, P. Tetrahedron Lett. 1999,
40, 687. (c) Ho¨lzer, B.; Hoffmann, R. W. Chem. Commun. 2003, 732.
(7) (a) Trost, B. M.; Chen, F. Tetrahedron Lett. 1971, 12, 2603. (b) Yamamoto,
T.; Sano, K.; Yamamoto, A. J. Am. Chem. Soc. 1987, 109, 1092. (c)
Fischer, R.; Walther, D.; Kempe, R.; Sieler, J.; Scho¨necker, B. J.
Organomet. Chem. 1993, 447, 131. (d) Uhlig, V. E.; Fehske, G.; Nestler,
B. Z. Anorg. Allg. Chem. 1980, 465, 141. (e) Sano, K.; Yamamoto, T.;
Yamamoto, A. Bull. Chem. Soc. Jpn. 1984, 57, 2741.
a Isolated yield of analytically pure material. In every case, direct addition
product is not visible by 1H NMR in the unpurified reaction mixture (<5%).
Mass balance typically resides in reduced decarbonylated product. b Reaction
conducted in dioxane at 80 °C. c Reaction conducted using TMEDA (1.5
equiv), Ni(COD)2 (2 equiv). d Reaction conducted at 45 °C.
(8) (a) Castan˜o, A. M.; Echavarren, A. M. Tetrahedron Lett. 1990, 31, 4783.
(b) Castan˜o, A. M.; Echavarren, A. M. Tetrahedron Lett. 1993, 34, 4361.
(c) Castan˜o, A. M.; Echavarren, A. M. Organometallics 1994, 13, 2262.
(d) Scho¨necker, B.; Walther, D.; Fischer, R.; Nestler, B.; Bra¨unlich, G.;
Eibisch, H.; Droescher, P. Tetrahedron Lett. 1990, 31, 1257. (e) Fischer,
R.; Walther, D.; Kempe, R.; Sieler, J.; Scho¨necker, B. J. Organomet.
Chem. 1993, 447, 131.
(9) Bercot, E. A.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 174.
(10) Ph2Zn does not add to succinic anhydrides uncatalyzed at 66 °C after 5
h.
(11) Ni-CO bond strengths have been estimated to be anywhere from 28.3 to
47.1 kcal/mol; see: (a) Sunderlin, L. S.; Wang, D.; Squires, R. R. J. Am.
Chem. Soc. 1992, 114, 2788. (b) Ziegler, T.; Tschinke, V.; Ursenbach, C.
J. Am. Chem. Soc. 1987, 109, 4825. (c) Li, J.; Schreckenbach, G.; Ziegler,
T. J. Am. Chem. Soc. 1995, 117, 486.
Subjection of meso-dimethyl glutaric anhydride 31, to the
prescribed reaction conditions results in â-cross-coupled product
32, formed as a single diastereomer in 74% yield, eq 5. This
presumably proceeds via isomerization of δ-nickelalactone 33 to
γ-nickelalactone 35 by a â-hydride elimination/hydrometalation
sequence.15
(12) In theory, this reaction may be made catalytic in neocuproine-nickel
complex when conducted in the presence of 0.5 equiv of Ni-dppb
complex. However, under these conditions, the decarbonylated product 5
is formed along with the direct addition product 6 (1:1.5), suggesting that
transmetalation to intermediate 7 may be kinetically competitive with
decarbonylation/CO-sequestration.
(13) Alkyl iodides have been used as cross-coupling partners to nickelacycles
(see refs 8c-e), but Echavarren has shown that the reaction proceeds via
radical intermediates and does not generate stereochemistry; see ref 8c.
(14) Diarylzinc reagents formed in situ from aryllithium and ZnCl2 also
participate in this reaction; see Supporting Information for details.
(15) Subjection of glutaric anhydride to these reaction conditions provides 3-
and 4-phenylbutanoic acid in a 1:3.75 ratio, and 77% combined yield.
Apparently, cross-coupling is preferred at a primary C-Ni bond over a
secondary; between two secondary positions, the ring-contracted meta-
lacycle is favored.
In summary, we have developed a nickel-mediated decarbonyl-
ation/cross-coupling of meso anhydrides, which constitutes the first
example of an sp3(electrophile)-sp2(nucleophile) cross-coupling
reaction that generates stereochemistry. Efforts to expand the scope
and render the system catalytic in nickel are currently under way.
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