Formylation or methylation: what determines the chemoselectivity of the reaction of amine, CO₂, and hydrosilane catalyzed by 1,3,2-diazaphospholene?

ABSTRACT: DFT computations have been performed to gain insight into the mechanisms of formylation/methylation of amines (e.g. methylaniline (1a)/2,2,4,4-tetramethylpiperidine (2a)) with CO₂ and hydrosilane ([Si]H₂, [Si] = Ph₂Si), catalyzed by 1,3,2-diazaphospholene ([NHP]H). Different from the generally proposed sequential mechanism for the methylation of amine with CO₂, i.e. methylation proceeds via formylation, followed by further reduction of formamide to give an N-methylated amine, the study characterized a competition mechanism between formylation and methylation. The chemoselectivity originates from the competition between the amine and [NHP]H hydride to attack the formyloxy carbon of [Si](OCHO)₂ (the insertion product of CO₂ into [Si]H₂). When the attack of an amine (e.g.1a) wins, the transformation affords formamide (1b) but would otherwise (e.g.2a) result in an N-methylated amine (2c). The reduction of formamide by [Si]H₂ or [NHP]H is highly unfavorable kinetically, thus we call attention to the sequential mechanism for understanding the methylation of amine with CO₂. In addition, the study has the following key mechanistic findings. The activation of CO₂ by [NHP]H establishes an equilibrium: [NHP]H + CO₂ ? [NHP]OCHO ? [NHP]⁺ + HCO₂^-. The ions play catalytic roles to promote formylation via HCO₂^- or methylation via[NHP]⁺ . In 1a formylation, HCO₂^- initiates the reaction, giving 1b and silanol byproducts. However, after the initiation, the silanol byproducts acting as hydrogen transfer shuttles are more effective than HCO₂^- to promote formylation. In 2a methylation, [NHP]⁺ promotes the generation of the key species, formaldehyde and a carbocation species (IM17⁺ ). Our experimental study corroborates our computed mechanisms.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC5849201 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature