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

Abstract

AbstractThe Tavs reaction of 2‐amino‐ and 2‐acylamido‐3‐bromopyridines 1 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 1 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 Pd0{P(OEt)3}n in the initial phase of the reaction. The structures of the products and the expected intramolecular N–H···O=P hydrogen bridging bonds were proven by solution NMR and by X‐ray crystal structure analysis of single crystalline 3c.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)