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

Phosphonylation of N-Heterocycles and Synthesis of Pyrido-Fused 1,3-Azaphospholes

“…11 The N-heterocyclic o-amino-or o-amido phosphonates, however, show a more differentiated behavior in the reactions with LiAlH 4 . 6,8 o-Aminopyridine-phosphonates 1a and 1b react with LiAlH 4 almost analogously to o-aminophenylphosphonates and preferably furnish o-aminopyridylphosphines 5 (yields 50-75%), accompanied, however, by small amounts of P-C bond cleavage products. In the reduction of 2-aminoquinoxaline-3-phosphonates 3 with LiAlH 4 the P-C bond cleavage becomes dominant and prevents the access of the corresponding primary phosphine under the usual reaction conditions (20 • C, Et 2 O or tetrahydrofuran (THF) as solvent; Scheme 3).…”

“…We have therefore explored the applicability of the Tavs ACID ESTERS SYNTHESIS 689 protocol to amino-substituted heteroaryl phosphonates, required as starting materials for heterocyclically anellated P C N azaphospholes, and present here a short overview on our recent work in this field. [6][7][8] …”

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

“…The characteristic 31 P resonances of 3a-f and 4a-f appear only marginally below those of 2-acylanilido- [15] and 2-anilinophosphonates [16] (δ = 16.5-20.4 vs. 18.3-22.6 ppm) and indicate thus close electronic similarity. The isomeric 3-acylamido-and 3-aminopyridine-2-phosphonates (δ = 11.3-12.3; 14.5 ppm) [18] absorb at markedly higher field, halfway to 2-aminoquinoxaline-3-phosphonates 7a,b, which by further electron release resonate in the range of δ = 9.4-9.8 ppm. The electronic effects are also reflected in the 13 C chemical shifts, which are strongly influenced by changes of the π-electron density.…”

“…We used the Tavs reaction to synthesize oamino(amido)benzenephosphonates as starting materials for benzo-fused P=C-N heterocycles [14][15][16] and recently demonstrated the applicability also to 3-amino-and 3-amido-2-phosphonopyridines, likewise used as building blocks for heterocycles. [17,18] Whereas N-secondary o-anilido phosphonates were obtained in high yields from triethyl phosphite and o-bromoanilides in the presence of anhydrous nickel bromide, [15] the cross coupling with N-basic obromoanilines and 3-amino-or 3-amido-2-bromopyridines requires palladium catalysts that are more tolerant towards other functional groups.…”

“…[18] In the isomers with bromine in 3-and the amino or amido group in 2-position the C-Br bond will not be activated by the pyridine nitrogen, but the ring N-atom is more remote to the catalyst metal and catalyst blockage less probable. This prompted us to explore if this makes these compounds comparable to 2-bromoanilides or -anilines, allows the use of Ni catalysts for the coupling of N-acyl-bromopyridines or leads to improved yields with Pd catalysts.…”