Design Of Highly Active Catalysts For Cyanosilylation Of Aldehydes

Cyanohydrins are versatile synthetic intermediates in organic chemistry owing to the hydroxyl and nitrile groups, especially in asymmetric synthesis. The addition of TMSCN to carbonyl compounds is one of the most effective methods.In this dissertation, the efforts were focused on developing highly efficient catalysts for cyanosilylation of aldehydes and exploring the mechanistic aspects in catalysis.Based on the concept of intramolecularly cooperative catalysis, a series of unsymmetric bifunctional Salen ligands bearing an appended Lewis base on the three-position of one aromatic ring were synthesized and applied to the cyanosilylation of aldehydes and TMSCN by the combination with Ti(Oi-Pr)4. It was found that the catalyst system based on the ligand in which diethylamino group is attached on the ligand framework exhibited high activity and asymmetric induction. In a low catalyst loading of 0.05 mol%, the quantitative conversion of benzaldehyde to the corresponding cyanosilylation product was found within 10 min. at ambient temperature, with a TOF (turnover frequency) up to 12000 h-1 and 77% ee. Notably, even at a high [aldehyde]/[catalyst] ratio up to 50000, the catalyst system also exhibited excellent activity. The catalyst system could be applied to the cyanosilylation of TMSCN with various aldehydes including aromatic, aliphatic andα,β-unsaturated aldehydes to give the corresponding cyanohydrins in excellent activity.According to the control experiments, we tentatively propose a synergistic mechanism wherein the central metal Ti(IV) is suggested to play a role of Lewis acid to activate aldehydes while the appended Lewis base to activate TMSCN.Quaternary ammonium base compound, as an efficient organocatalyst, was successfully applied in the cyanosilylation of aldehydes for the first time. The reactions can be conducted with 1:1 ratio of the two substrates under solvent-free condition to give corresponding racemic cyanohydrin trimethylsilyl ether products with TOF up to 3000000 h-1, to the best of our knowledge, which is the most effective catalyst. Notablely, quantitative product was obtained when the amount of benzaldehyde was scaled up to 53 g. The catalyst was compatible with a broad range of aromatic, heterocyclic, aliphatic, includingα,β-unsaturated, functionalized, liner, and branched aldehydes.Chiral quaternary ammonium base compounds derived from cinchonine were also used for asymmetric cyanosilylation of aldehydes. However, it is a pity that only racemic product was obtained with a 97% conversion after 15 min (S/C=100000/1). This indicates that the cation species did not participate in the nucleophilic attack process. NMR and IR analyses, in combination with control experiments suggest a possible catalytic cycle, in which more reactive pentacoordinate silicate was formed by coordination of OH- negative ion to the Si atom. As counter ion, the cation of quaternary ammonium base maybe just exists in the form of tight ion pair with negative ion by coulombic interaction and does not participate in the attack of nucleophile.