Organic isocyanates are versatile intermediates that provide access to a wide range of reactions.However,an efficient strategy to generate isocyanates from simple starting materials and control their reactivity has be...Organic isocyanates are versatile intermediates that provide access to a wide range of reactions.However,an efficient strategy to generate isocyanates from simple starting materials and control their reactivity has been a formidable,long-standing challenge.Herein,we develop a novel palladium-catalyzed carbonylative approach thatmerges hydroaminocarbonylation with Lossen rearrangement to achieve alkenyl isocyanates,allowing for the rapid synthesis of isoquinolones that are of interest in synthetic organic and medicinal chemistry.For the first time,mechanistic studies disclose that N-alkyloxylamides are generated as key intermediates and undergo a rearrangement process similar to that of like hydroxamic esters,ultimately delivering isocyanates,which represents a new type of Lossen rearrangement.The success of this reaction is attributed to the tamed sterically hindered O-substituent of hydroxylamines,which efficiently suppresses the side reactions and facilitates the Lossen rearrangement.展开更多
基金the National Key R&D Program of China(grant no.2023YFA1507500)the National Natural Science Foundation of China(grant nos.21925111,22350008 and 22301289)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB0450301).
文摘Organic isocyanates are versatile intermediates that provide access to a wide range of reactions.However,an efficient strategy to generate isocyanates from simple starting materials and control their reactivity has been a formidable,long-standing challenge.Herein,we develop a novel palladium-catalyzed carbonylative approach thatmerges hydroaminocarbonylation with Lossen rearrangement to achieve alkenyl isocyanates,allowing for the rapid synthesis of isoquinolones that are of interest in synthetic organic and medicinal chemistry.For the first time,mechanistic studies disclose that N-alkyloxylamides are generated as key intermediates and undergo a rearrangement process similar to that of like hydroxamic esters,ultimately delivering isocyanates,which represents a new type of Lossen rearrangement.The success of this reaction is attributed to the tamed sterically hindered O-substituent of hydroxylamines,which efficiently suppresses the side reactions and facilitates the Lossen rearrangement.
