[Zurück]

H. Kalaus, M. Draskovits, C. Stanetty, M.D. Mihovilovic:
"N‑Heterocyclic carbene controlled dehomologation of aldoses - structure-reactivity relations of substrate and catalyst";
Poster: 15th European Training Course on Carbohydrates, Wageningen; 24.06.2018 - 28.06.2018; in: "Summer Course Glycosciences", (2018), 1 S.

Despite being regularly referred to as Nature´s largest chiral pool, actually, only a small number of carbohydrates are readily available at reasonable scale and cost. In our research, we aim to develop new synthetic methodology for the interconversion of carbohydrate derivatives focusing on the aldehyde moiety as uniting feature.[1]
In this light, carbohydrates have recently been reported as sacrificial feedstock for the N-heterocyclic carbene (NHC) catalyzed formylation of activated double bonds (Stetter reaction).[2] Based on this report we set out to investigate and establish an NHC-controlled dehomologation of sugar derivatives by interception of the putative mechanism.
Initial experiments with 3-O-benzyl-D-glucose delivered the aspired proof of concept, however, a critical follow-up elimination towards 2-deoxy-lactone was also identified. The selectivity between these two main reactions is currently in the focus of our attention. Addressing the presumable relevance of the relative stereochemistry, we prepared several epimeric structures of 3-O-benzyl-D-glucose and combined them with a series of N-aryl-thiazolium based catalysts with varying electronic and steric properties.
Detailed analysis of the reactions in a time-resolved and quantified fashion revealed important features of substrates and catalysts for the targeted selectivity and resulted in the first finding of a perfect match between substrate and catalyst structure. Striking selectivity for the intercepted dehomologation and a strong suppression of undesired lactone formation could be accomplished. The results of this study will further fuel our mechanistic considerations and the development of the NHC-controlled dehomologation of aldoses towards a more general and practical synthetic solution.