Efforts directed toward the synthesis of colchicine: application of palladium-catalyzed siloxane cross-coupling methodology.
[reaction: see text] Colchicine is an important and synthetically challenging natural product. The key synthetic step in this approach to the synthesis of colchicine involved a palladium-catalyzed cross-coupling reaction between 5-bromotropolone (4) and an aryl siloxane to form the aryl-tropolone bond. The coupling of a variety of highly functionalized aryl siloxane derivatives was investigated and optimized coupling conditions were developed. It was discovered that a palladium catalyst with a high degree of phosphine ligand coordination (5 equiv of phosphine/mol Pd) was necessary to efficiently couple aryl siloxanes with 5-bromotropolone (4). In addition, the coupling approach has provided a direct comparison between siloxane and boronic acid coupling technologies that demonstrated that aryl siloxanes and boronic acids produce similar yields of highly functionalized biaryl products.
Seganish
W Michael
WM
Department of Chemistry and Biochemistry, University of Maryland, College Park, 20742, USA.
Handy
Christopher J
CJ
DeShong
Philip
P
D031724:Bromus / Q000737:chemistry; D002384:Catalysis; D003078:Colchicine / Q000138:chemical synthesis* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry; D012833:Siloxanes / Q000737:chemistry*; D013237:Stereoisomerism; D014334:Tropolone / Q000737:chemistry
D003432:Cross-Linking Reagents; D012821:Silanes; D012833:Siloxanes; D010165:Palladium; D014334:Tropolone; D003078:Colchicine