Glycerol derivatives in the hydrogen autotransfer reaction - Development of C-C and C-N bond forming reactions

Licentiate thesis, 2014

Glycerol (1,2,3-propanetriol) is obtained as a byproduct in the biodiesel industry. In the quest for more sustainable starting materials for organic synthesis, glycerol with its three alcohol functionalities is a promising candidate. Hydrogen autotransfer is a catalytic method that allows for the direct substitution of alcohols with a variety of nucleophiles to form new carbon-carbon and carbon-heteroatom bonds. In this work we have aimed at developing such procedures employing amine and enolate nucleophiles using glycerol derivatives as electrophiles. In the first part of this thesis, the coupling reaction of 1,3-propanediol with acetophenone was investigated. A mixture of alkylation products consisting of 1-phenylpentan-1-one and small amounts of 1-phenylbutan-1-one and propiophenone was obtained using [Ir(cod)Cl]2/PPh3 as the catalyst. In addition, transfer hydrogenation of acetophenone as well as the product 1-phenylbutan-1-one occurred in parallel. A maximum of 43% conversion of the starting material was obtained in these studies and the highest selectivity for alkylated product was 90%. The complexity of the product mixture is a result of the combination of a weak nucleophile that can act as hydrogen acceptor, as well as the basic conditions, allowing base-promoted E1cB elimination and retro-aldol reaction to occur. The use of anthranilamide, a slightly stronger nucleophile without the possibility of transfer hydrogenation, proved more successful with a 50% conversion using [Cp*IrCl2]2 as the catalyst. In the second part of this work, the amination of protected glycerol derivatives was examined. DL-Isopropylideneglycerol was aminated using [Ru(p-cymene)Cl2]2/dppf as the catalyst in quantitative conversion. A series of three aminated isopropylideneglycerol derivatives were prepared in good isolated yields. Deprotection of amino isopropylidenglycerol was achieved quantitatively under acidic conditions. Initial tests on the amination of the obtained amino diol gave low yields of diaminated product, preferably on the secondary alcohol. Amination of the secondary alcohol in 1,3-O-benzylideneglycerol was achieved using [Ru(p-cymene)Cl2]2/DPEPhos as the catalyst, with a moderate conversion of 55%. We are currently working on optimizing these initial results. Keywords: Glycerol, Sustainable precursors, Organic synthesis, Hydrogen autotransfer, Alkylation, Amination