Molecular Diversity

, Volume 18, Issue 4, pp 701–719 | Cite as

Catalytic enantioselective diversity-oriented synthesis of a small library of polyhydroxylated pyrans inspired from thiomarinol antibiotics

  • Raed M. Al-Zoubi
  • Dennis G. Hall
Full-Length Paper


A small library of 30 thiomarinol analogues was successfully synthesised using as a key step–a catalytic enantioselective tandem oxa[4+2] cycloaddition/aldehyde allylboration methodology. With this method, highly substituted \(\alpha \)-hydroxyalkyl dihydropyrans were assembled in a single three-component reaction utilizing three different enol ethers and a wide variety of aldehydes, such as aromatic, heteroaromatic, unsaturated and aliphatic aldehydes. In a second operation, a mild and direct method for reducing an acetal unit in the \(\alpha \)-hydroxyalkyl dihydropyrans was optimised without the need for protecting a nearby hydroxyl group. This procedure facilitated the synthetic sequence, which was completed by a dihydroxylation of the residual olefin of \(\alpha \)-hydroxyalkyl 2\(H\)-pyrans to provide the desired library of dihydroxylated pyran analogues reminiscent of the thiomarinol antibiotics. The relative stereochemistry of the resulting library compounds was demonstrated by X-ray crystallography on one of the analogues.

Graphical Abstract


Allylboration ATP mimics Combinatorial library  Enantioselective catalysis Hetero-Diels–Alder cycloaddition Pyrans 



The authors thank the Natural Sciences and Engineering Research Council (NSERC) of Canada and the University of Alberta for financial support of this research.

Supplementary material

11030_2014_9542_MOESM1_ESM.pdf (18.6 mb)
ESM 1 (PDF 19,012 kb)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of AlbertaEdmontonCanada

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