W. Clark Still

This intermediate was then transformed into a key enone substrate over the course of five steps including Rubottom oxidation, TBS protection of the secondary alcohol, and formation of the exocyclic alkene via a selenoxide rearrangements.

Subsequent removal of the TBS protecting group and Sarett oxidation of the resulting secondary alcohol completed the total synthesis of racemic periplanone B.

Notably, this instance of acyclic stereocontrol is consistent with the Cram-Felkin-Anh model for the addition of nucleophiles to an aldehyde bearing an existing stereocenter in the alpha position.

Next, cleavage of the triethylsilyl (TES) protecting groups was achieved in the presence of para-toluenesulfonic acid; the resulting free secondary alcohols then engaged the ketone in a spontaneous cyclization reaction to form the thermodynamic spiroketal linkage.

Finally, hydrolysis of the methyl ester under basic conditions furnished the sodium salt of monensin, completing the synthesis of this challenging natural product.

[6] In this procedure, transmetalation of the organotin group can be achieved chemoselectively at low temperature using n-butyllithium to form an alpha-lithiated ether that undergoes the desired 2,3-sigmatropic rearrangement.

Treatment of this compound with two equivalents of n-butyllithium at low temperature resulted in transmetalation, initiating a double 2,3-sigmatropic rearrangement to give the bis-homoallylic alcohol product in 79% yield.

[1] Prior to this report, column chromatography using silica gel as a stationary phase had already been established as a valuable method for the separation and purification of organic compounds.

After optimizing this procedure, Still compiled a table correlating column diameter, volume of eluant, amount of sample, and typical fraction size, providing a useful guide for application of this technique in the laboratory.

Today, flash column chromatography is one of the most important methods for the purification of organic compounds, especially when working on a small scale (< 50 mg) where the techniques of recrystallization and distillation are impractical.

In an effort to make molecular modeling more accessible to practicing organic chemists, Still developed the integrated software program MacroModel in 1986 in association with Columbia University.