Reductions performed with Ti(IV) complexes of ligands based on bicyclo[2.2.2]octane diols 5 and 6 are effective catalysts in the reduction of prochiral ketones to optically active alcohols, with catecholborane as the reducing agent. Methyl ketones are favored and enantiomeric excesses (ee) of < or =98% have been achieved with acetophenone as the substrate. Several other substrates were tested, among them 2-octanone, which gave 2-octanol in 87% ee. Further details of the method were examined, for example, temperature, solvent composition, amount of molecular sieves (4 A), and catecholborane quality, as well as the sensitivity of the ligands towards acids. NMR spectroscopic methods were used to gain some insight into the complexes formed between the ligands and [Ti(OiPr)4]. A dimeric structure is proposed for the pre-catalyst.
The stereoselective reduction of the bicyclic diketone bicyclo[2.2.2]octane-2,6-dione, to the ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one, was used as a model reduction to optimize parameters involved in NADPH-dependent reductions in Saccharomyces cerevisiae with glucose as co-substrate. The co-substrate yield (ketoalcohol formed/glucose consumed) was affected by the initial concentration of bicyclic diketone, the ratio of yeast to glucose, the medium composition, and the pH. The reduction of 5 g l(-1) bicyclic diketone was completed in less than 20 h in complex medium (pH 5.5) under oxygen limitation with an initial concentration of 200 g l(-1) glucose and 5 g l(-1) yeast. The co-substrate yield was further enhanced by genetically engineered strains with reduced phosphoglucose isomerase activity and with the gene encoding alcohol dehydrogenase deleted. Co-substrate yields were increased 2.3-fold and 2.4-fold, respectively, in these strains.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.