89378-60-9Relevant academic research and scientific papers
Efficient dynamic kinetic resolution of secondary alcohols with a novel tetrafluorosuccinato ruthenium complex
van Nispen, Sjoerd F.G.M.,van Buijtenen, Jeroen,Vekemans, Jef A.J.M.,Meuldijk, Jan,Hulshof, Lumbertus A.
, p. 2299 - 2305 (2007/10/03)
Dynamic kinetic resolution (DKR) of a series of secondary alcohols has been conducted with a novel dinuclear ruthenium complex, bearing tetrafluorosuccinate and (rac)-BINAP ligands as the racemization catalyst. Novozym 435 has been used as the enzyme, and isopropyl butyrate as the acyl donor. Five substrates underwent DKR successfully: an aliphatic and an aromatic secondary alcohol, an aromatic alcohol with an electron-withdrawing substituent on the phenyl ring, an aromatic alcohol bearing an electron-donating substituent on the ring and a heteroaromatic secondary alcohol. The catalyst performed optimally at 70 °C. Typically the reaction reached complete conversion within 1 day with 0.1 mol % of racemization catalyst relative to the substrate. The addition of the ketone corresponding to the substrate stabilizes the active Ru complex and, therefore, increases the rate of the reaction.
Removal of the acyl donor residue allows the use of simple alkyl esters as acyl donors for the dynamic kinetic resolution of secondary alcohols
Verzijl, Gerard K.M.,De Vries, Johannes G.,Broxterman, Quirinus B.
, p. 1603 - 1610 (2007/10/03)
The dynamic kinetic resolution of secondary alcohols using a lipase and a ruthenium catalyst as developed by Baeckvall required some improvements to make it suitable for its use in an industrial process. The use of p-chlorophenyl acetate as acyl donor is not desirable in view of the toxicity of the side product. We herein report that simple alkyl esters can be used as acyl donors if the alcohol or ketone residue formed during the enzymatic acylation is continuously removed during the reaction. The addition of a ketone speeds up the racemisation process and allowed us to reduce the amounts of enzyme and ruthenium catalyst. The scope of this method was explored and a suitable range of acyl donors found. Various benzylic and aliphatic alcohols were reacted using isopropyl butyrate or methyl phenylacetate as acyl donor and in most cases the ester was isolated in >95% yield and 99% ee. Furthermore, it was demonstrated that the alcohol by-products of the enzymatic resolution could be used as the hydrogen source in the asymmetric reductive transesterification of ketones.
