Organometallic Methods for Forming and Cleaving Carbon-Carbon Bonds

Stig Holden Christensen

Research output: Book/ReportPh.D. thesisResearch

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Abstract

The retro-Grignard addition reaction has been revisited and the benzyl addition reaction was found to be a reversible transformation by using crossover experiments. The retro benzyl addition reaction was shown by the addition of benzylmagnesium chloride to di-t-butyl ketone followed by exchange of both the benzyl and the ketone moiety with another substrate. Similar experiments were performed with phenylmagnesium bromide and t-butylmagnesium chloride, but in these two cases the Grignard addition reaction did not show any sign of a reverse transformation.
The ring-opening of cyclic ethers with concomitant C-C bond formation was studied with a number of Grignard reagents. The transformation was performed in a sealed vial by heating to about 160 °C in an aluminum block or at 180 °C in a microwave oven. Good yields of the product alcohols were obtained with allyl- and benzylmagnesium halides when the ether was tetrahydrofuran or 3,3-dimethyloxetane. Lower yields were obtained with substituted tetrahydrofurans while no ring-opening was observed with tetrahydropyran. Only highly reactive allyland benzylmagnesium halides participated in the transformation while no reaction occurred with other alkylmagnesium halides.
Carbohydrates with protecting groups on all alcohol groups except the primary alcohol were prepared and subjected to the iridium catalyzed dehydrogenative decarbonylation reaction where primary alcohols are converted into the corresponding one carbon shorter products. Modest conversions were obtained when isopropylidene- or cyclohexylidene ketals were used as protecting groups, but the conversion rate was slow. Low conversion was obtained when the alcohols were protected by benzyl groups and the carbohydrates were unstable at the required temperatures.
The syngas evolved from the iridium catalyzed dehydrogenative decarbonylation reaction was consumed in a palladium catalyzed reductive carbonylation reaction in a two-chamber system setup. Carbohydrates were not found to be a viable syngas source because they did not liberate sufficient syngas. Carbohydrates were attached to several lipophilic anchors and performing the dehydrogenative decarbonylation with the anchor monools proceeded well, while the corresponding anchor triols were unstable at the elevated temperatures. Of the simple primary alcohols investigated, 2-(2-naphthyl)ethanol, hexane-1,6-diol and dodecane-1,12-diol were found to be the most promising syngas sources. A substrate scope for the reductive carbonylation of aryl bromides is currently under development by using hexane-1,6-diol as a syngas source.
The synthesis of the anticancer antibiotic tetrahydroisoquinoline alkaloid jorumycin progressed via a route consisting of a crucial aryne annulation step where an isoquinoline scaffold was prepared. The aryne annulation step was problematic and after several attempted modifications to the formerly optimized procedure; no further improvement was obtained. Gratifyingly, an alternative route was found for the formation of the isoquinoline scaffold and further optimization of this route is needed.
Original languageEnglish
PublisherDTU Chemical Engineering
Number of pages235
Publication statusPublished - 2014

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