musings on music and life

August 12, 2015

Sweet sweet acetate cocktails

Filed under: Chemistry — Tags: — sankirnam @ 12:36 pm

I remember that this paper was trending when I was at the NOS a few weeks ago. Everyone I talked to was extremely derisive about this paper, and upon examining it myself, I share the same sentiments.

acetate_cocktail

Ugh.

Firstly, there is no real novelty in this reaction – why was it accepted by JACS? The authors are just trying to do a template-directed meta-selective C-H arylation using the norbornene (NBE) template, with an amine as a directing group. Gaunt did a similar meta-selective C-H arylation back in 2009, except he used a pivalamide as the directing group, and diaryliodonium salts as the arylating agents under Cu(I)-Cu(III) catalysis. The authors are trying to do a Pd-catalyzed meta arylation in this case.

One of the major issues with doing C-H activation in a Pd(II)-Pd(IV) catalytic cycle is that it is an oxidative process, and therefore one needs a terminal oxidant, otherwise no reaction will occur. In academia, the most popular choices are Ag salts, due to their solubility and ability to selectively conduct outer-sphere electron transfer with other metals. BUT… as one can see above, this reaction uses superstoichiometric amounts of silver – 4.5 molar equivalents! So while this reaction may be fine in microscale in the research laboratory, it will never be scaled up. This is what I call the “Jin-Quan Yu” approach, since a lot of his chemistry also uses excess amounts of silver salts as oxidants.

But the “acetate cocktail” part…wow. This really shows that the unfortunate post-docs or graduate students who developed this reaction really have no idea what is going on. They just “Hail Mary’d” it, threw in everything possible to make it work, and prayed for the best. I remember Prof. Karl Christe (who was on my PhD committee at USC), made a very memorable statement after sitting through a mediocre PhD defense:

When the reaction doesn’t work, add some Lewis Acid. 

If it still doesn’t work, add some Lewis Base.

If it STILL doesn’t work, add some dirt and pray!

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