Transition Metal Catalyzed Reactions for Forming Carbon–Oxygen and Carbon–Carbon Bonds

Amanda Birgitte Sølvhøj

Research output: Book/ReportPh.D. thesisResearch

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Abstract

Dehydrogenative ester formation with a ruthenium NHC complex A new atom-economical methodology for synthesizing esters by the dehydrogenative coupling of primary alcohols was developed. The reaction is catalyzed by the ruthenium N-heterocyclic carbene complex RuCl2(IiPr)(p-cymene). By screening the effect of different additives, solvents and loadings on the selfcondensation of pentanol, the optimal reaction conditions were found to be 2.5 mol % of RuCl2(IiPr)(p-cymene), 4.5 mol % of PCy3 and 10 mol % of KOH in refluxing mesitylene, which gave the ester in nearly quantitative yield by GC analysis. The substrate scope was shown to include a range of different straight-chain and branched primary aliphatic alcohols, which reacted to give the corresponding esters in moderate to excellent yields. Condensation of diols also proceeded well, giving the corresponding lactones in good yields. Benzylic alcohols could be used as substrates, but the yields were generally poor due to decarbonylation of the substrate as a considerable side reaction. Some preliminary mechanistic investigations were performed. The results of these confirmed that the reaction is indeed dehydrogenative with the liberation of two moles of hydrogen per formed mol of ester as assumed. Furthermore a disproportionation mechanism (Tishchenko) could be ruled out due to the fact that free aldehydes did not enter the catalytic cycle. Fast deuterium/hydrogen exchange in the reaction with benzyl alcohol points towards a ruthenium dihydride species being the catalytically active species. A catalytic cycle consistent with these findings, as well as with previous knowledge about this particular catalytic system, was proposed. 2.5 % [Ru] 4.5 % PCy3 10 % KOH mesitylene iPr N N iPr Ru Cl Cl R OH R O R O 2 + 2 H2 [Ru] = iii Synthesis of Anti Zigzag-[5]-phenylene A new member of the family of [5]-phenylenes, named Anti Zigzag-[5]-phenylene, was synthesized and characterized. The desired target molecule was synthesized in ten steps from the commercially available starting material 1,2-dibromobenzene in an overall yield of 0.5 %. Six of the ten steps had not been performed before and six new compounds were isolated and characterized in the process. The target molecule was characterized by HRMS and proton NMR. Br Br 10 steps 0.5 % Manganese catalyzed radical formation of styryl derivatives A new method for the formation of styryl derivatives by the reaction of ether and hydrocarbon radicals with -bromostyrenes was serendipitously discovered and subsequently optimized. By screening of various radical initiators and transition metal salts the best conditions were found to involve addition of three to four equivalents of Me2Zn to a solution of -bromostyrene, using the radical precursor as solvent, in the presence of 10–12 % of MnCl2, and refluxing overnight in the presence of air. A simple acidic workup and purification by chromatography yielded the products in moderate to good yield. The radical precursor can be a cyclic or acyclic ether or even a cycloalkane, although the latter gives only poor conversion. The -bromostyrene can be substituted with electrondonating or electronwithdrawing substituents in the para position without affecting the yield of the reaction remarkably. The reaction is quenched when TEMPO is added, which confirms that the reaction occurs by a radical mechanism. The reaction is believed to be initiated by the formation of a methyl radical from the reaction of Me2Zn with oxygen. The methyl radical abstracts a hydrogen from the radical precursor and the resulting radical then adds to the -bromostyrene, which subsequently eliminates a bromo radical and forms the product.
Original languageEnglish
PublisherDepartment of Chemistry, Technical University of Denmark
Publication statusPublished - 2015

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