Tin-catalyzed reductive coupling of amines with CO2 and H2

Reductive coupling of amines with CO2 and H-2 can be catalyzed by transition metals. However, functional group (FG) tolerance is improved when using auxiliary main group hydrides (instead of H-2), which makes them more suitable for the synthesis of functionalized molecules. Replacing auxiliary main group hydrides with frustrated Lewis pairs (FLPs) can, in theory, generate comparably selective hydrides in situ from H-2 activation. Herein, we report the selective N-formylation of amines via CO2 hydrogenation catalyzed by a series of R3SnX (R = alkyl, X = Cl, OTf, NTf2, ClO4) Lewis acids, which form an FLP with the amine substrate and/or 2,4,6-collidine. FLP dihydrogen activation leads to the in situ formation of an R3Sn-H species with excellent selectivity toward CO2 hydrogenation over other reducible FGs. Consequently, amines containing alkenes, amides, esters, and carboxylic acids can be N-formylated with CO2 and H-2. Increasing the steric bulk of the alkyl substituents prevents the redistribution of the R3SnX Lewis acid to R4Sn and R2SnX2, which is the primary cause of catalyst decomposition. Cy3SnOTf reached turnovers of >300 and amine conversions of up to 100%. In addition to synthesis, isolation, and testing of key intermediates for their reactivity, we identified an off-cycle intermediate by in operando H-1 NMR spectroscopy and therefore propose a mechanistic cycle. By avoiding the use of any transition metals or auxiliary main group hydrides, our procedure opens a pathway for developing transition-metal-free CO2 hydrogenation methods utilising hydrogen gas.

Automated summary

Selective N-formylation of amines via CO2 hydrogenation catalyzed by Lewis acids is an efficient and highly selective synthetic strategy, enabling high-yield conversion of amines with functionalities such as alkenes and amides while preventing catalyst decomposition. Increasing steric hindrance with alkyl substituents can enhance conversion rates and prevent undesired reactions.