Blanc, Guilaine F.
New strategies for pinacol cross-couplings and alkenation reactions.
PhD thesis, University of Glasgow.
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The research described herein involves the study of new approaches to alkenation and pinacol cross-coupling.
The competition between modified Julia alkenation and Peterson alkenation was studied. Heterocyclic sulfides were oxidised to sulfones by dimethyldioxirane. Reactions between sulfones and aldehydes gave vinyl sulfones in good yields, rather than vinyl silanes, confirming that the Peterson alkenation is preferred in this system.
Pinacol cross-coupling between an aldehyde or ketone in solution and a more easily reduced aldehyde immobilised on resin was attempted, but proved unsuccessful. However, aldehydes bearing the salts of tertiary amines were found to be good substrates for pinacol homo-coupling giving diols. The formation of salt avoided unwanted reduction of the aldehyde to a primary alcohol.
A wide range of approaches to anisomycin using titanium reagents were investigated. These were based on the formation of the bond between C-3 and C-4 by alkylidenation of esters and ring-closing metathesis (RCM) or intramolecular alkylidenation or radical cyclization. The presence and position of the nitrogen atom proved an insurmountable obstacle to this strategy.
The solid-phase synthesis of 4-amino-ketones was achieved. Resin-bound esters were alkylidenated using a novel titanium reagent generated in situ by reduction of a thioacetal with a low valent titanium reagent. Treating the resulting enol ethers with acid gave ketones in good yield and high purity because of the switch in the nature of the linker from acid-stable to acid-sensitive (a chameleon catch strategy). Amino-ketones are potential precursors of pyrrolidines.
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