u/hearhithertinystool

I do glycosylation chemistry with rather reactive anomeric moieties - donor sugar is hit with eq mmol 1M KHMDS (usually let them ride for far to short lost activation with my activator species (it’s an electron rich sulfonyl chloride that needs to be both a good electrophile first and then an even better leaving group so that my naked nucleophilic acceptor can safer carry about its mission - the main question is: outside of extensive VT-NMR I’d constantly running the risks of quenching my reaction by going through the septa’s continuously- is there a way to “roughly” ball park a reaction’s completion time without physically altering the flask? I’m open to anything - this optimization process has been rheee months of “are ya ready to publish yet???” From my PI

PLEASE this damn glycos has been my baby for the past two months and I’m finally at a great place optimization-wise, so I’m not looking for “leaps and bounds” of profound advice - I just wanna know things like “cannulation v syringe”; parafilm reagent flask as they are under a stream of Ar through a 20G needle as to not disturb the septa too much; blah blah blah; if you do sugar chem and specifically glycosylations then def hit me up and we can cry intermittently together -

To summarize:

When do we think a relatively nucleophilic sugar is reacted to ‘completion’ with a(n) moderately, electron-rich ArylSulfonyl chloride @-78°C

I have been holding it anywhere from 15-30-45min..1.5h but I think the main hold up is th addition of my acceptor and that not going to completion. The generation of the glycosyl sulfonate is super finicky and sensitive/prone to degradation so TLCing isn’t really an option outside of a complete test run to see if/when I check the activation stage anything is left at some arbitrary earlier and later time points (but that’s monosaccharide wasted that took time and reagents to make)

Thoughts? Sorry for the rant - just got back from the lab and I’m dead tired.
Cheers, tho!

- M