Synthesis of Halo-Enol Phostones by Using DMAP-Catalyzed Halocyclization of Alkynylphosphonic Monoesters

A new class of non-benzo halo-enol phostones was synthesized by using a DMAP-catalyzed [DMAP = 4-(dimethylamino)pyridine] halocyclization reaction of 4-pentynylphosphonic monoesters with N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS) in CHCl3 at room temperature. DMAP was critical to the reaction system, as it greatly improved the yields of the desired products. The reaction showed high regioselectivity for six-membered ring products that were formed by a 6-exo-dig halocyclization, and no endo products were detected. However, this cyclization reaction exhibited no apparent stereoselectivity. For each substrate, two stereoisomers, one with the (Z) and the other with the (E) configuration were isolated. In addition, under the same conditions, the 3-butynylphosphonic monoesters did not undergo the cyclization, which indicates that the chain length between the triple bond and the phosphonyl group serves an important role in the reaction.