Modeling at this scale would not be possible without the fast but reliable R^(2)SCAN-3c from Stefan Grimme's group for geometries and frequencies and a well-optimized engine as ORCA 6 (FACCTs) - thanks for enabling projects like this! (7/7)

Additional thanks to the other oxoammonium pioneers involved in this work. This was a long journey! Jonas Rein, Matt Sigman, Song Lin and Scott Miller. (6/7)

This tells us that functional generality is not necessarily tied to mechanistic homology but can be achieved through more "versatile" catalysts, able to accomodate (but still strictly regulate) multiple activation modes. (5/7)

But that doesn't mean that the most general catalyst P7 is a one-trick-pony: different substrates that are desymmetrized by P7 don't necessarily do so via the same activation topology. They might "bind" with different hydrogen bond partners, following specific constraints of that substrate! (4/7)

Two big takeaways: yes, with flexible catalysts, increased preorganization and convergence towards a single activation mode follow the catalyst evolution. And we tracked this effect for almost every point change in the optimization, with atomistic resolution. (3/7)

I teamed up with baymate Soren Rozema and the rest of the chiral oxoammonium peptides team in what became the largest computational study I have ever directed (for now?) on the Miller/Lin/Sigman peptidyl oxoammonium catalyst for meso-diol desymmetrization (from www.science.org/doi/10.1126/...) (2/7)

Always such cool, elegant, useful and mechanistically comprehensive studies - really the best of reads! Very inspiring, congrats team :)

We were hoping to find a single catalyst that would prove general across ring sizes besides the different mechanistic paradigms - and luckily, we did. But, we were quite surprised when both DFT and X-Ray, counterintuitively, told us we were making the opposite enantiomer of the two ring sizes! [3/3]

...proved effective to synthesize strained medium-sized rings of two different sizes with perfect intramolecular selectivity. To the best of our knowledge, this is the first method to synthesize strained, congested seven-membered rings under mild conditions. [2/3]

Wondrous!

I don't know the origin, but I believe it must be a self-reinforcing loop - clarity ties well with familiarity, so people end up adopting what they read. Reading some robotic papers though, I miss some charm and would be willing to sacrifice a tad of "clarity" for readability. What do you think?

Most people know about Nicolaous's work, but the original reports are actually from Mascaretti! In here they do describe some workup techniques that you might find useful:
J. Org. Chem. 1994,59, 7259-7266

This should be the original reference, as far as I know:
Tet. Lett. 29, 52, 1988, 6893-6896