The Sceptical Chymist | ACS: Synthetic catalysts, not different, just better

Published in Chemistry

I spent the early part of my first day in the metal-mediated reactions session. I particularly enjoyed a presentation by Andy Thomas from Scott Denmark’s group at UIUC, on rapid-injection NMR studies of Suzuki reaction intermediates.

Immediately after lunch I took a little bit of a trip down memory lane to attend the session on Lewis base catalysed asymmetric transformations and see a presentation by my PhD advisor Alan Spivey. It was genuinely fascinating to see the most recent achievements in areas that I spent a large chunk of my life battling. It’s gratifying to see some of these things really starting to work out. The presentation immediately following this was by Adam Kamlet from Pfizer. He described the use of a chiral DMAP catalyst to effect a dynamic kinetic resolution of a series of tetrazole containing prodrugs. The juxtaposition of these two talks really brings home that these studies are more than just an academic exercise, and I think it’s fair to say that Alan’s talk has inspired some future experiments for Adam.

In the second part of the afternoon I moved to hear Matt Sigman talk on the use of big data in physical organic chemistry. The topic really gets to the heart of what I believe many who work on new reaction methodology would like to do: correlate simple physical parameters of catalysts/ligands to reaction outcomes like rate and selectivity. As Matt pointed out early in his talk it’s all about trying to understand the outliers and all too often these results end up buried in supporting information or ignored altogether. This is of course not the recommended course of action.

Matt was talking in an award symposium (The ACS award for creative work in synthetic organic chemistry) honouring Scott Miller. In his award address, Scott spoke about his development of low molecular weight peptide catalysts for a whole variety of asymmetric reactions. I particularly enjoyed his definition of a complex molecular environment (a widely used term) as “any system in which your current reaction design isn’t working”.

A question Scott posed towards the end of his talk had me thinking for a while. I tried to tweet about this but wasn’t easy to explain in 140 character bursts, so I’ll try again here: In the early 2000s Miller and his group reported peptide catalysts for the phosphorylation of meso myo-inositol-derived triol ($). They were able to identify catalysts for selective functionalization of either the 1- or the 3-hydroxyl groups, a fantastic achievement and my inspiration for the somewhat tongue-in-cheek title of this post (a play on the title of a review article from Nature in 1991).

What they didn’t develop — possibly because they weren’t trying — was a catalyst to phosphorylate the 5-hydoxyl group. This would be a meso-to-meso transformation and thus, Miller suggested, wouldn’t have been considered of interest by the editors of leading journals, despite being possibly the most challenging transformation. I wouldn’t have rejected it of course as I was only a PhD student at the time (notice how I squirmed out of that one?). I do think he’s right though and I agreed with another editor (from a top journal that I won’t name) such a transformation would likely have been rejected without review!

Well, it’s Monday morning here in San Diego, so it’s time to head off to some more sessions – I hope it’s as enjoyable as yesterday.


Stephen Davey (Chief Editor, Nature Reviews Chemistry)

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