Totally Synthetic by Paul H. Docherty, 27 August 2007
Total Synthesis of Spirolaxine Methyl Ether
B. M. Trost, A. H. Weiss, Angew. Chem. Int. Ed. 2007, 46, 7664-7666.
I wasn’t sure about this paper when I started reading it - the introduction, in which the ketone and acetylene functional groups are compared and contrasted, seemed quite out-of-place. Surely most readers are well aware of the utility of the alkyene group, and of the transformations which may be be performed on it. Anyway, Trost’s route to this natural product is really quite nice, and relies on some smart alkynylation chemistry.
As can be seen from the reterosynthesis, they planned to use a ProPhenol catalysed alkynylation twice to impart hydroxyl stereochemistry and form C-C bonds. This method seems to work rather well - in the first case, the yields and ee (shown) were very good; in the second case, a more complex addition to an unsaturated aldehyde, the result was moderate but still impressive (52%, 5:1 d.r.).
Having done this trick twice, a final piece of alkynylation was used; attack into R-(+)-propylene oxide gave the final hydroxyl stereocenter required for the impressive spiroketalisation. This chemistry was first used by Utimoto, and has been investigated mechanistically by De Brabander last year. Their result speaks for itself - creation of two rings and a spiro-stereocenter in cracking yield (presumably as a single diastereoisomer).
Smart chemistry, nice read…