New strategy developed for remote dihalogenation of alkenes

In a study published in Journal of the American Chemical Society, a team led by Prof. CHEN Qing'an from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences developed a phosphordiamidate-catalyzed strategy for the highly selective synthesis of 1,3-, 1,4- and 2,3-dihalogenation products, providing a new way for constructing complex organic halides.

Organic halides exhibit distinct biological activities and reactivity, making them indispensable in pharmaceutical development, energy materials, and functional molecule design. Their critical role in molecular innovation continues driving the development of new synthetic methodologies.

Although direct alkene halogenation represents a classical route to organic halides, conventional methods are limited to the formation of vicinal dihalides, which limits the structural diversity and synthetic utility of these compounds.

In this study, researchers developed a phosphordiamidate-catalyzed, directing-group-free strategy for remote dihalogenation of alkenes. Regioselective was achieved through an ester transposition process. Under mild conditions, the catalyst cooperated with NBS and SOCl₂ to generate active intermediates, which then reacted with allylic or homoallylic esters to afford 1,3-, 1,4-, and 2,3-dihalides with high efficiency and selectivity.

Researchers demonstrated broad substrate compatibility including various unactivated alkenes, along with good functional group tolerance such as cyano and hydroxyl groups. Gram-scale experiments supported the practicality of the strategy. Besides, the resulting products could undergo diverse derivatizations including cross-coupling and cyclization reactions, highlighting their potential utility in complex molecule construction and pharmaceutical synthesis.

"This work may inspire the development of transposition-induced remote difunctionalizations strategies," said Prof. CHEN.