Pushing Back the Limits of Hydrosilylation: Unprecedented Catalytic Reduction of Organic Ureas to Formamidines

Abstract

Catalytic hydrosilylation of carbonyl functional groups is gaining an increasing interest in synthetic organic chemistry because it circumvents important limitations of the more classical hydrogenation or metal-hydride mediated reduction methodologies. Indeed, hydrosilanes are practical reducing agents because they have a mild reduction potential and are less sensitive to moisture than LiAlH4, DIBAL or NaBH4. Moreover, the slightly polar and weaker Si–H bond (bond dissociation energy (BDE) 92 kcal/mol in SiH4) [2] is easier to activate than the strong non-polar H–H bond (BDE 104 kcal/mol) and hydrosilylation reactions can be promoted using noble metal-free catalysts or organocatalysts under mild reaction conditions, without the need for high-pressure apparatus. As a result, catalytic hydrosilylation can achieve highly chemoand regio-selective transformations and recent examples include the reduction of carboxylic acids, esters (to ethers and aldehydes) and amides. Nonetheless, the methodology still has limitations and, so far, the catalytic hydrosilylation of organic ureas to formamidines remains unknown. Indeed, the C=O group in urea derivatives is the least electrophilic function within the series of carbonyl groups in aldehydes, ketones, esters, amides, carbonates, carbamates and ureas. This effect primarily results from strong resonance effects between the vacant π*C=O orbital and the vicinal nitrogen lone pairs in urea. As a result, strong reductants such as aluminoand boro-hydrides have been utilized so far for the reduction of urea derivatives to formamidines. However, they also lead to over-reduction to the aminal derivative, because the formamidine product is more easily reduced than the urea starting material. In 2011, Milstein and coworkers were the first to successfully promote the hydrogenation of organic ureas, utilizing tailor-made ruthenium catalysts. However, the ruthenium catalysts promote C–N over C–O bond cleavage and the resulting formamide intermediate is hydrogenated faster than the urea starting material, leading to the formation of methanol and free amines (Scheme 1).