Studies On The Cyanosilylation Of Ketones

Cyanohydrins are versatile intermediates in the context of organic synthesis,especially, in asymmetric synthesis. The addition of TMSCN to ketones is the mostdirect, efficient, and prevailing method. In this dissertation, the alternative activationstrategy, introducing phenolic N-oxides as additivies to readily accessible salen titaniumcatalyst, has been developed and applied to the asymmetric silylcyanation of ketones. 21 Chiral ligands and 14 achiral N-oxides were prepared and evaluated for theenantioselective addition of TMSCN to ketones. Under the optimized conditions, theadduct cyanohydrins were obtained in excellent yields (up to 96%) with goodenantioselectivities (up to 82% ee), utilizing salen-Ti(IV) complex (10 mol%) andachiral phenolic N-oxide (1 mol%) as additives. From the optimizing experiments interm of enantioselectivity, in this case, we know the followings as the facts. Thestructure of additives affected the reactivity and also affects in some degree theenantioselectivity. In a certain range of temperature, lowering the reaction temperatureresulted in a increase of ee value. The spatial matching rather than the electronic effectsmostly impacts the enantioselectivity and catalytic reactivity of salen ligands. According to the control experiments and the experiment phenomena, a possiblecatalytic cycle and a possible key intermediate are rationally proposed to illustrate theexperimental observations and the absolute configuration of the product. In addition, it was found that potassium carbonate was high effective asheterogeneous catalyst for cyanosilylation of carbonyl compounds. The optimalreaction conditions were achieved as following: for aldehydes, 3 mol% K2CO3, III四川大学硕士论文solvent-free, TMSCN1.2 eq. and for ketones, 30 mol% K2CO3, solvent-free,TMSCN1.2 eq. The catalyst gave the corresponding cyanohydrin trimethylsilyl ethersfrom 20 minutes to 24 hours with 62% to 99% yields without solvent at roomtemperature. Moreover, the use of heterogeneous catalysts allows a simplification of thepurification step to a simple filtration, separating the catalyst from the reaction media.