Blue Light-Promoted Cross-Coupling of α-Diazo Esters with Isocyanides: Synthesis of Ester-Functionalized Ketenimines

Abstract

A metal-free scalable synthesis of functionalized ketenimines from alkyl α-(aryl/heteroaryl)-α-diazoacetates and alkyl isocyanides induced by blue light irradiation has been developed. The reaction proceeds at room temperature without any photocatalyst and provides ketenimines in moderate to good yields. Density functional theory (DFT) calculations and the experimental study showed that aryl(alkoxycarbonyl)carbenes in both singlet and triplet states can react with isocyanides but only the reaction of the former leads to the smooth formation of ketenimines. The obtained ketenimines were used for the synthesis of functionalized amidines under mild metal-free conditions.

Transition metal-catalysed carbene- and nitrene transfer to carbon monoxide and isocyanides

“… 60 However, extending this to the transfer to isocyanides afforded the corresponding ketenimines in only low to moderate isolated yields (12–64%). 61 The authors mention that the low yields are partly caused by a low selectivity of the free carbene as they do observe by-product formation via carbene dimerization. Besides reaction of two diazo compounds into a ketazine and degradation of the triplet ketenimine via homolytical C–N single bond fragmentation was noted.…”

“…Besides reaction of two diazo compounds into a ketazine and degradation of the triplet ketenimine via homolytical C–N single bond fragmentation was noted. 61 Transition metals such as Pd under thermal conditions typically aid in the circumvention of these unwanted side reactions and higher yields for target ketenimine formation plus a broader substrate scope were observed, albeit under typically harsher conditions than room temperature. 56 …”

Iron‐Catalysed Carbene Transfer to Isocyanides as a Platform for Heterocycle Synthesis

“…A relatively underexplored reaction in this area is the TM‐catalysed carbene transfer to isocyanides (Scheme 1A). Although some isolated examples of metal‐free carbene transfer to isocyanides have been reported, [6] they are limited to difluorocarbene [6a] or accompanied by side reactions, such as carbene dimerization [6b] . The coupling of carbenes and isocyanides results in ketenimines, which are valuable building blocks in organic synthesis [7] .…”

Gold vs Light: Chemodivergent Reactivity of Diazoesters toward 2H-Azirine-2-carboxylic Acids

“…The highest yield of the O–H insertion product was achieved from a diazo compound substituted with an electron-donating methoxy group (product 4i ). In contrast, the introduction of a nitro group in a diazo compound resulted in the formation of a complex mixture of products ( 4j ), which is probably due to the involvement of a triplet carbene in the reaction . Finally, diphenyldiazomethane was also successfully used in the O–H insertion reaction (product 4k ).…”

“…In contrast, the introduction of a nitro group in a diazo compound resulted in the formation of a complex mixture of products (4j), which is probably due to the involvement of a triplet carbene in the reaction. 23 Finally, diphenyldiazomethane was also successfully used in the O−H insertion reaction (product 4k).…”