3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P–C coupling, structure and conversion to pyrido[b]-anellated PC–N heterocycles

Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a–f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a–f, whereas nickel catalysts, although providing access to related anilido-2-phosphonates, proved inactive. Reduction of the aminophosphonate 2a with LiAlH4 afforded 3-amino-2-phosphinopyridine (3a), which was cyclocondensed with dimethylformamide dimethyl acetal (DMFA) via phosphaalkene intermediates 4a to the novel pyrido[b]-anellated 1,3-azaphosphole 5a. Reaction of amidophosphonates 2b–f with LiAlH4 did not result in the expected reductive cyclization, as shown by closely related anilido-2-phosphonates, but led to product mixtures containing N-secondary 3-amino-2-phosphinopyridines 3b–f as the main or major component. The conversion of 3b,d,e with DMFA to 5b,d,e provides first examples of N-substituted pyrido[b]-anellated azaphospholes. Structures were confirmed by multinuclear NMR and X-ray crystallography (for 2c, 3b).

Graphical abstract3-Amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters were synthesized by palladium catalyzed C–P cross-coupling of NH-functional 2-bromopyridines with triethyl phosphate and subsequently converted to novel pyrido-anellated PC–N heterocycles.Figure optionsDownload full-size imageDownload as PowerPoint slide