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New synthetic methods using single-electron processes

University of British Columbia

This thesis presents investigations of alkoxy and aminyl radical cyclizations onto silyl enol ethers, as well as the development of a new photoinduced electron transfer-promoted redox fragmentation of N-alkoxyphthalimides. We investigated alkoxy radical cyclizations onto silyl enol ethers as a method for the synthesis of alpha-oxygenated oxacycles. Cyclizations to form tetrahydrofurans displayed a high degree of chemoselectivity relative to competing 1,5-hydrogen atom transfer, fragmentation and cyclization pathways. The rate acceleration imparted by the silyl enol ether allowed for a highly chemoselective 6-exo cyclization, a difficult mode of alkoxy radical reactivity to access due to competing 1,5-hydrogen atom transfers. We next examined the applications of silyl enol ether acceptors for aminyl radical cyclizations and the factors that lead to high diastereoselectivity in these cyclizations. This methodology allows for the synthesis of the 2-hydroxymethylpyrrolidine core found in many polyhydroxylated alkaloid natural products. In the course of our synthesis of the alkaloid CYB-3, we found that the cyclization diastereoselectivity was dependent on a complex combination of sterics and olefin geometry. Alkyl- and aryl-substituted substrates cyclized with high selectivity regardless of olefin geometry or substitution pattern. When electronegative substituents were introduced alpha to the silyl enol ether, only Z-silyl enol ethers provided high cyclization diastereoselectivities. Finally, we report a new fragmentation reaction of N-alkoxyphthalimides mediated by visible light and a Ru(bpy)₃²⁺ photocatalyst. Our mechanistic data support a unique concerted intramolecular fragmentation process, initiated by a single electron transfer to the phthalimide from either the metal catalyst or directly from a tertiary amine additive. The redox fragmentation reaction was applied to aryl, allyl and lactol derivatives. We found that the reaction could be carried out under catalyst-free conditions, but the yields of many substrates were improved in the presence of Ru(bpy)₃²⁺. The redox fragmentation of N-alkoxyphthalimides was applied to the mild and selective redox fragmentation of sensitive nitrogen-containing heterocycles.

Text

2012-07-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/42847

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/