Synthesis of functionally substituted unsymmetrical biaryls via a novel double metal catalyzed coupling reaction

Tetrahedron Letters

Volumn 39, Issue 40, 1998, Pages 7275-7278

  Miller, Joseph A ^a   Farrell, Robert P ^a  

^a NZ Legacy LLC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE;

ANALYTIC METHOD; ARTICLE; CATALYSIS; COUPLING FACTOR; DRUG SYNTHESIS; GAS CHROMATOGRAPHY; NONHUMAN; REACTION ANALYSIS; STOICHIOMETRY;

EID: 0032191520     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01587-1     Document Type: Article

References (8)

1. 1. Negishi, E.; King, A. O.; Okukado, N. J. Org. Chem. 1977, 42, 1821.
2. 2. Miller, J. A.; Farrell, R. P. Tetrahedron Letters, in press.
3. 3. The concept of "double metal catalysis" has been introduced previously: Negishi, E.; Okukado, N.; King, A. O.; Van Horn, D. E.; Spiegel, B. I.; J. Am. Chem. Soc. 1978, 100, 2254.
4. 4. Representative procedure [o-(p-tolyl)benzonitrile; entry 1]. A solution of anhydrous nickel acetylacetonate (0.15 g; 0.60 mmol; moisture content <1%) and zinc chloride (0.082 g; 0.60 mmol) in THF (3 mL) was sequentially treated at room temperature with water (11 μL; 0.60 mmol), triisopropylphosphite (0.31 mL; 1.3 mmol), and methylmagnesium chloride (0.62 mL; 1.1 mmol; 1.73 M in THF). The reddish brown solution was then treated with 2-chlorobenzonitrile (1.38 g; 10.0 mmol), heated to 55° C, and to it added p-tolylmagnesium chloride (7.32 mL; 12.3 mmol; 1.68 M in THF) over the course of 30 min. After the addition of the Grignard reagent was complete, the reaction was stirred at 55° C for an additional 15 min before a sample was withdrawn aand quenched in a mixture of toluene and 1 N HCl. GC analysis of the hydrolyzed organic phase (using dodecane as an internal reference standard) showed the presence of 8.2 mmol (82%) of o-(p-tolyl)benzonitrile, 0.58 mmol of 4,4′-dimethylbiphenyl, 0.08 mmol of 2,2′-dicyanobiphenyl, and 0.36 mmol (3.6%) remaining 2-chlorobenzonitile in the reaction mixture.
5. 2M reagents were added to the reactions generally ranged from 15-60 min, and was dictated by both the scale and exothermicity of the particular reaction.
6. 3 (20 mol%), and water (10 mol%) in THF was cooled to 0° C and treated with a solution of Vitride (5 mol%) in THF. The dark solution was then stirred at 0° C for 10 min.
7. 7. Perri, S. T.; Rice, P.; Moore, H. W. Org. Synth. 1990, 69, 220.
8. 8. For a review of these biaryl syntheses, see: Stanforth, S. P. Tetrahedron 1998, 54, 263.