Improved Access to Imidazole‐phosphonic Acids: Synthesis of D ‐manno‐Tetrahydroimidazopyridine‐2‐phosphonates

The D‐manno‐tetrahydroimidazopyridine‐2‐phosphonate 11 was prepared via a high‐yielding Pd(PPh3)4‐catalysed diphenylphosphonylation of the manno‐iodoimidazole 12, followed by transesterification to the diethyl phosphonate 14 and dealkylation, providing 11 in eight steps from the thionolactam 1 and in an overall yield of 15%. Alternatively, a more highly convergent synthesis based on the HgCl2/Et3N‐promoted condensation of the thionolactam 1 with the α‐aminophosphonate 24 in THF led to 11 in four steps and in the same overall yield. In the presence of HgCl2/Et3N, the thionolactam 1 reacted at 80° with 2‐methoxyethanol to provide 66% of a 64 : 36 mixture of the gluco‐ and manno‐iminoethers 29/30. Performing the reaction at 22° yielded preferentially the gluco‐isomer 29 (86%, 84 : 16).