· (MW 786.07)
(catalyzes arylation of organozinc reagents;1 catalyzes carbon-carbon bond formation via stannyl enolates;2 catalyzes aromatic cyanomethylation and amination3)
Physical Data: mp 285-295 °C (yellow crystals from toluene).4
Preparative Method: prepared by stirring PdCl2 and P(o-Tol)3 in methanol at rt for 2 h.4,5
Arylation of Organozinc Reagents.
The coupling of organozinc reagents with electron-rich (eq 1) or electron-deficient (eq 2) aryl iodides proceeds in good yield with Pd catalysis.1 PdCl2[P(o-Tol)3]2 is superior to PdCl2(PPh3)2 (see Palladium(II) Chloride) and Tetrakis(triphenylphosphine)palladium(0) because biaryls are not produced during the reaction. This catalyst is not useful, however, for coupling organozinc compounds with vinyl iodides or triflates. Zinc-substituted aromatic ketones also react with aryl iodides under PdCl2[P(o-Tol)3]2 catalysis in excellent yield (eq 3).6 Enantiomerically pure, protected 3-aryl-a-amino acids can be prepared by coupling a protected zinc homoenolate with an aryl iodide under Pd catalysis (eq 4).7 The sterically smaller catalyst
PdCl2(PPh3)2 produces the desired product in only 15% yield.
Carbon-Carbon Bond Formation via Stannyl Enolates.
Tri-n-butyltin enolates, generated in situ by treatment of enol acetates with Tri-n-butyl(methoxy)stannane undergo PdCl2[P(o-Tol)3]2-catalyzed coupling with vinyl bromides (eq 5)2 or bromobenzene (eq 6).8 Although the reaction is sensitive to steric hindrance caused by substituents on the enol acetate, the number and position of substituents on the vinyl bromide does not have a serious effect on the product yield. The configuration of the alkenyl bromide is completely retained in the product.
Stannyl enolates, generated in situ from silyl enol ethers by Bu3SnF-mediated silyl/stannyl exchange, undergo PdCl2[P(o-Tol)3]2-catalyzed aldol reactions with aromatic (eq 7) and aliphatic aldehydes.9 The products are isolated as the hydroxy ketones. Tin enolates produced from silyl enol ethers can also be coupled with both electron-deficient (eq 8) and electron-rich aryl bromides with almost equal success.10 The silyl/stannyl exchange induced by Bu3SnF is useful only for silyl enol ethers of methyl ketones. The remarkable difference in reactivities may arise from the steric repulsion between the alkyl group(s) attached to the alkenic moiety and the approaching tributyltin fluoride. This relative reaction rate
phenomena has been utilized for the PdCl2[P(o-Tol)3]2-catalyzed chemoselective desilylation of silyl enol ethers (eq 9).11
Aromatic Cyanomethylation and Amination.
Aryl bromides react with cyanomethyltributyltin in the presence of PdCl2[P(o-Tol)3]2 catalyst to afford cyanomethylated products (eq 10).3 The aryl bromides can be substituted with methyl, methoxy, or chloro groups, but not p-electron withdrawing groups such as nitro. Bromobenzene can be aminated with N,N-diethylaminotributyltin (eq 11).12 The best catalyst is PdCl2[P(o-Tol)3]2 and the reaction also gives good yields with methyl substituted bromobenzenes.
- 1. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. TL 1986, 27, 955.
- 2. Kosugi, M.; Hagiwara, I.; Migita, T. CL 1983, 839.
- 3. Kosugi, M.; Ishiguro, M.; Negishi, Y.; Sano, H.; Migita, T. CL 1984, 1511.
- 4. Bennett, M. A.; Longstaff, P. A. JACS 1969, 91, 6266.
- 5. Heck, R. F. Palladium Reagents in Organic Synthesis, Academic: Orlando, 1985; p 18.
- 6. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. AG 1987, 99, 1193.
- 7. Jackson, R. F. W.; Wishart, N.; Wood, A.; James, K.; Wythes, M. J. JOC 1992, 57, 3397.
- 8. Kosugi, M.; Hagiwara, I.; Sumiya, T.; Migita, T. CC 1983, 344.
- 9. Urabe, H.; Kuwajima, I. TL 1983, 24, 5001
- 10. Kuwajima, I.; Urabe, H. JACS 1982, 104, 6831.
- 11. Urabe, H.; Takano, Y.; Kuwajima, I. JACS 1983, 105, 5703.
- 12. Kosugi, M.; Kameyama, M.; Migita, T. CL 1983, 927.
Ron J. Graham
The Ohio State University, Columbus, OH, USA
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