Mild and general methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides

Organic Letters

Volumn 9, Issue 9, 2007, Pages 1711-1714

  Littke, Adam ^a   Soumeillant, Maxime ^a   Kaltenbach III, Robert F ^a   Cherney, Robert J ^a   Tarby, Christine M ^a   Kiau, Susanne ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 CHLOROANILINE; 4-CHLOROANILINE; ANILINE DERIVATIVE; CHLORIDE; CYANIDE; LIGAND; PALLADIUM; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; SYNTHESIS;

ANILINE COMPOUNDS; CATALYSIS; CHLORIDES; CYANIDES; LIGANDS; MOLECULAR STRUCTURE; PALLADIUM;

EID: 34248328795     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol070372d     Document Type: Article

References (41)

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23. The type of zinc used (flakes vs dust) was largely irrelevant on small-scale reactions; however, we found it was essential to use fine zinc particles on larger scales to enable a homogeneous dispersion throughout the reaction medium under mechanical overhead stirring conditions.
24. 6.
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27. 2.
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35. 2.
36. As for all the nonquantitative reactions reported herein, the remainder of the mass balance was predominantly unreacted 5-chloroindole as in this example.
37. For example, attempted monocyanation of both 2,4- and 2,5-dichloropyridine yields a mixture of starting material, monocyanated pyridine (at the 2-position), and dicyanated pyridine.
38. For example, see: Erker, T.; Nemec, S. Synthesis 2004, 23-25.
39. 2 gives only a 32% yield of 2-cyano-3-methylthiophene for the cyanation of 2-chloro-3- methylthiophene.
40. 2 (43.9 mg, 0.374 mmol, 56 mol %) were charged successively to a 25 × 90 mm glass test tube equipped with a magnetic stir bar and a Teflon screw-cap. The test tube was evacuated and back-filled with nitrogen. DMAC (anhydrous, 99.8%, 3.6 mL) was added via syringe, and the resulting reaction mixture was stirred at room temperature for 20 min while performing 3 evacuation-nitrogen refill cycles. The reaction mixture was then heated to 95 °C over 45 min and held at that temperature for 14 h. The reaction mixture was then cooled to room temperature, diluted with acetonitrile. and filtered through a 45 μm HPLC syringe filter, and the supernatant was analyzed by HPLC. HPLC analysis indicated a solution yield of 97.8% of 4-aminobenzonitrile. For workup procedures used to obtain isolated yields, please refer to the Supporting Information.
41. Certain substrates such as 4-chlorostyrene and 2-chloro-m-xylene do not perform well under these cyanation conditions using either catalyst system.