Carbamates are widely used as pharmaceuticals and agrochemicals, such as fungicides and insecticides. However, industrial syntheses of carbamates typically require toxic starting materials, such as phosgene derivatives or isocyanates. An alternative route to access carbamates involves the dehydrogenation of formamides to generate isocyanates in situ, which can then react with alcohols to form carbamates. This is an atom-efficient method, H2 is the only byproduct, and the use of formamides is advantageous since they are considerably less toxic, volatile, and flammable than isocyanates. Here, we report that the pincer-supported iron complex (iPrPNP)Fe(H)(CO) (iPrPNP- = N(CH2CH2PiPr2)2-) is an active catalyst for dehydrogenative synthesis of both N-alkyl and N-aryl substituted carbamates in up to 90% yield. This is the first example of dehydrogenative carbamate synthesis with a first-row transition metal catalyst and the first method that is compatible with N-alkyl formamides. Mechanistic studies indicate the formamide is dehydrogenated to a transient isocyanate that forms a highly stable adduct at iron. This adduct has been independently synthesized and characterized and was determined to be the resting state in catalysis. Stoichiometric experiments indicate that catalysis requires high temperatures in order to release the isocyanate from iron so that is can react with alcohol to generate carbamate. The relative reactivity of amines, alcohols, and thiols under these catalytic conditions was also examined to assess whether urea, carbamate, or thiocarbamate products can be selectively formed. Thiols were found to irreversibly bind to iron and are therefore not competent substrates. Competition studies with formamide, alcohol, and amine determined urea to be the kinetic product, but at higher temperatures a thermodynamic mixture of 3:1 urea and carbamate is formed.

Dehydrogenative synthesis of carbamates using a pincer-supported iron catalyst

ACS Fall 2021

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