B.R.S.M. All this happened, more or less.

10Oct/124

Woodward Wednesday 5: t-Butyllithium?!

Although it's been a while I do intend to do at least one full size Woodward Wednesday post this month. In the mean time here's a short (but important) synthesis that you may not know about.[1]

Who do you think was the first person to publish the preparation of tert-Butyllithium? Some big shot organometallic or inorganic chemist? Not so much. As far as I can tell it was none other than legendary organic chemist R. B. Woodward (J. Am. Chem. Soc., 1941, 63, 3229)![2] Many before tried and failed, and indeed Woodward noted that the the reaction between lithium and tert-butyl chloride was quite slow, although he discovered that it was efficiently catalysed by a few mole percent of magnesium. Eventually, the reaction could be performed using just lithium, providing it was finely enough divided. This so-called 'lithium sand' was prepared using a classic piece of kit invented by a fellow Harvard chemist: the Hershberg Wire Stirrer. This allowed molten lithium (in mineral oil at 250 degrees) to be whipped up into fine pieces. The mixture could then be cooled, the oil washed off and the lithium quickly used before it had a chance to react with the nitrogen atmosphere used to exclude air. You might ask why Woodward spent time fiddling around with such a dangerous reagent that appeared to defy all attempts to force it into existence. As best as I can tell, the answer was sheer curiosity; not so much regarding the substance itself, but to see if it could be used to prepare the elusive tri-tert-butyl carbinol. Alas, the only reaction observed with hexamethylacetone was reduction. Still, despite recent bad press, tert-BuLi remains a very useful reagent, and has helped me out of a tight synthetic spot on a few occasions.

Etc

1. I'll probably do reserpine next, but I'm not too sure what to do after that. Please leave suggestions in the comments!

2. Although, by Woodward's own admission, a couple of papers by the father of organometallic chemistry Henry Gilman from the previous year do imply that tert-BuLi was successfully prepared and used.

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  1. I remember reading somewhere that t-BuLi could be recrystallized. I can’t find the reference now, but I feel pretty confident that few have repeated the procedure :)

    • Quite a few of my inorganic mates prefer to work with solid t-BuLi as “there’s no solvent to burn up”. Its amazing how being blessed with a glove box can change a chemist’s perspectives on things…

  2. How about doing one on his prostaglandin synthesis? One of my all-time favorites. Or colchicine…that’s a great one too.

  3. “This is a report of some work, interrupted by
    the war, which it seems desirable to publish”

    Here’s the follow up: http://pubs.acs.org/doi/abs/10.1021/ja01217a049


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