Free and polymer-supported chiral lithium amides : synthesis and applications

Abstract

This dissertation deals primarily with applications of chiral lithium amides (free and polymer-supported) as bases in the synthesis of a-functionalized carbonyl compounds.

Two cyclic ketones, tropinone and 1,4-cyclohexanedione monoethylene ketal were deprotonated with several chiral bases in solution. Tropinone was deprotonated enantioselectively in up to 96-99% ee in the presence of LiC1 as the additive. This successful outcome was the result of extensive methodological studies. Nine chiral lithium amides and ten different additives were tested. The enolate was trapped with 2,2,2-trichloroethyl chloroformate. The complexation effect of a chiral amine to the lithium enolate of the cyclic ketone was studied. 1,4-Cyclohexanedione monoethylene ketal was deprotonated with two chiral lithium amides, and the corresponding lithium enolate was trapped with benzaldehyde to give the optically active aldol product.

Three methods for the synthesis of insoluble and soluble polymer-supported chiral amines were developed. The chiral lithium amides were successfully generated and they were applied as bases in the deprotonation of different carbonyl compounds, a ketone, and a -ketoester. The corresponding a-functionalized compounds were obtained in good yield and enantioselectively (where applicable). Two soluble polymer-supported chiral amino-alcohols were synthesized and used as a proton donor in diastereoselective, and enantioselective protonation of the lithium enolates derived from cyclic ketones. This is the first reported generation and application of novel, polymer-supported chiral lithium amides. Hopefully, the work presented in this thesis will lay the foundation of a new way of performing organic synthesis.