Organic Chemistry Portal
Reactions >> Total Syntheses

Totally Synthetic by Paul H. Docherty, 29 May 2009

Total Synthesis of Arboricine

van Maarseveen, Hiemstra

M. J. Wanner, R. N. A. Boots, B. Eradus, R. de Gelder, J. H. van Maarseveen, H. Hiemstra, Org. Lett. 2009, 11, 2579-2581.

DOI: 10.1021/ol900888e

This paper from Holland is definitely a methodology paper with a bit of total synthesis to prove the point… The key step in the synthesis of Arboricine is an organocatalytic asymmetric Pictet-Spengler reaction - a useful approach described in an earlier publication. Using an elaborated BINOL-phosphoric acid catalyst, in rather low loading, van Maarseveen and Hiemstra were able to develop a rather useful yield and enantiomeric excess. By reducing the planiarity of the naphthalene moieties, the e.e. could be further enhanced.

With the vast majority of the compound complete, they group were left with only one more C-C bond forming reaction. This vinyl iodide-enolate coupling is based on work by Sole and Bonjoch back in 2004 and works reasonably well in this case. Whilst the yield was moderate, van Maarseveen and Hiemstra had their total synthesis complete in only five steps from known precursors. With only a deprotection remaining, this is a good job proving the utility of their method nicely. I look forward to seeing it used by other groups in the near future!