Stereospecifik katalytisk substitution av alkoholer: En grön lösning på en problematisk transformation inom kemin

Tidsperiod: 2012-01-01 till 2014-12-31

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 1 900 000 SEK

When substitution of the hydroxyl group of an alcohol is performed in traditional synthesis, the alcohol is first converted into a more reactive ester or halide in an extra synthetic step. Besides lowering the atom efficiency, the intermediates are often carcinogenic. Alternatively, the one-step Mitsunobu reaction can be used but this reaction suffers from significant waste generation. An additional method is the metal-catalyzed alkylation of amines with alcohols, where the alcohol temporally is dehydrogenated. This method has many advantages but suffer from generating full racemization of the product.We intend to develop a transition metal catalyzed stereospecific substitution of the hydroxyl group in alcohols by a variety of nucleophiles with only water as side product. Our hypothesis is: to achieve stereospecificity the C-O bond should be weakened, but not cleaved, in the absence of a nucleophile. Mechanistic studies of how the metal-oxygen coordination affects the C-O bond weakening will be performed by 13C NMR and IR spectroscopy. There is little understanding of the activation of a C-O bond of alcohols. We have found certain metals that do not cleave the C-O bond in the absence of nucleophile that will be the starting point of our studies. Another more challenging aspect to be considered is regioselectivity in a polyol. A vision is to develop an atom economic and general methodology where polyols in biomass with stereocenters can be used in efficient synthesis.