First C-H activation route to oxindoles using copper catalysis.
The preparation of 3,3-disubstituted oxindoles by a formal C-H, Ar-H coupling of anilides is described. Highly efficient conditions have been identified using catalytic (5 mol %) Cu(OAc)(2).H(2)O with atmospheric oxygen as the reoxidant; no additional base is required, and the reaction can be run in toluene or mesitylene. Optimization studies are reported together with a scope and limitation investigation based on variation of the anilide precursors. The application of this methodology to prepare a key intermediate for the total synthesis of the anticancer, analgesic oxindole alkaloid Horsfiline is also described.
Klein
Johannes E M N
JE
Department of Chemistry, University of York, Heslington, York, YO10 5DD, United Kingdom.
Perry
Alexis
A
Pugh
David S
DS
Taylor
Richard J K
RJ
D000813:Anilides / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D000078183:Oxindoles; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry
D000813:Anilides; D007211:Indoles; D000078183:Oxindoles; D013141:Spiro Compounds; C443722:horsfiline; C022960:2-oxindole; D003300:Copper