Phosphonylation of 2-Amino- and 2-Amido-3-bromopyridines and 2-Amino-3-chloroquinoxalines with Triethyl Phosphite

The Tavs reaction of 2-amino- and 2-acylamido-3-bromopyridines I and 2 with triethyl phosphite in the presence of palladium acetate or chloride allows the synthesis of 2-amino- and 2-acylamidopyridine-3-phosphonates 3 and 4. A second ring nitrogen atom causes strong activation and leads to excellent yields in the phosphonylation of 2-amino-3-chloroquinoxalines. 2,3-Dichloroquinoxaline does not need a catalyst and undergoes double phosphonylation with sodium diethyl phosphite under Michaelis-Becker conditions. The results show an activating influence of pyridine nitrogen (-M) and deactivating influence of the amino group (+M). The reactivity of I and 2 in the Tavs coupling is compared with that of the 3-NH-2-bromopyridine position isomers and 2-bromoanilines and discussed in terms of the opposite effects of pyridine and amino(amido) nitrogen and different position of the N atoms towards the reaction site. The advantage of the Tavs reaction is the easy optimization because neither auxiliary ligands are required nor a base to trap the halide or a solvent. Triethyl phosphite itself acts as ligand and forms Pd-0{P-(OEt)(3)}(n), in the initial phase of the reaction. The structures of the products and the expected intramolecular N-H center dot center dot center dot O=P hydrogen bridging bonds were proven by solution NMR and by X-ray crystal structure analysis of single crystalline 3c. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)