Palladium-catalyzed synthesis of 2-aminobenzoxazinones by aerobic oxidative coupling of anthranilic acids and isocyanides.
Isocyanides have emerged as valuable C1 building blocks in palladium catalysis. Their potential has, however, mainly been exploited for the synthesis of amidines and amidine-containing heterocycles. To illustrate the broader applicability of isocyanides, we have recently developed a novel oxidative coupling of diamines and isocyanides furnishing valuable guanidine-containing heterocycles. We here report the extension of this protocol to the coupling of anthranilic acids and isocyanides leading to medicinally relevant 2-aminobenzoxazinones. This is a particularly challenging substrate class for this reaction due to the possibility of undesired decarboxylative pathways and the susceptibility of the products to nucleophilic attack. Therefore, this work underlines the generality and broad potential of the oxidative coupling of bisnucleophiles and isocyanides, facilitating the further implementation of this chemistry in library design.
Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam , De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Tjøstil
T
Vlaar
Romano V A
RV
Orru
Bert U W
BU
Maes
Eelco
E
Ruijter
D048588:Benzoxazines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003486:Cyanides / Q000737:chemistry*; D015394:Molecular Structure; D058451:Oxidative Coupling; D010165:Palladium / Q000737:chemistry*; D062367:ortho-Aminobenzoates / Q000737:chemistry*
D048588:Benzoxazines; D003486:Cyanides; D062367:ortho-Aminobenzoates; D010165:Palladium