Acylboronates Enter the Mix?

Just a few days removed from the great Synthesis Machine debate of '15, a new paper has appeared that prompts me to wonder: might other protected boronates work in this chemistry?

The Bode group, now at ETH-Zurich, discloses in JACS ASAPs some intriguing bifunctional acylboronates. Much like their MIDA boronate cousins, these, too, are stabilized by an N,O-chelating ligand, demonstrate a shelf-life of several months, and are easily prepared in one step from their potassium trifluoroborate salts.

Do you suppose these reagents could survive the strongly basic aqueous conditions used for MIDA deprotection and subsequent cross-coupling? The authors, comparing MIDA-acylboronates against NOF-acylboronates under aqueous hydrolysis conditions, claim:

"In all cases, the bidentate, monofluoroacylboronates were much more stable than the MIDA variants and should be sufficiently stable* for most applications." 

If this holds true, one could imagine capping Burke's automated syntheses with carboxylic acid derivatives without resorting to bulky t-Bu esters or exotic silyl-protected esters.

*Now I'm just brainstorming, but could catalytic conditions be found to transmetalate the acylboronate to, say, Rh or Pt? 

Friday Fun - Jobs from the Future

Who wants to help me construct a job description for the brave new world of automated synthesis?
Leave your suggestion in the comments, and I'll modify our advert as needed...

March 13, 2025 - Automated Synthesis Engineer

Our company seeks a motivated individual to work in our growing Automated Synthesis division.

Experience: Qualified candidates should have 5+ years previous experience in chemistry, mechanical engineering, or robosynthesis. Ideally, you'll have completed 10 (or more) previous multi-step total syntheses using 3D-Flow ModuloChem-XLs.

Software: Candidate should feel comfortable using the IBM SynBlox suite for fragment assembly, exploring GDB-23 for potential lead molecules, and assessing synthetic feasibility using the OPRD Engyn iPhone 9 app.

Special skills: Our synthesizers often require adjustments, thus experience in a trade - plumbing, welding, electrical - would be highly valued. Candidates interested in creating holographic "how-to" vidlets especially encouraged to apply.

Source: Burke Lab historical archives

WWWTP? Cover Art Conformations

Like everyone else in the chemblogosphere, I spent a fair amount of time mulling over what the new Burke Science paper holds in store for synthetic chemistry. Did anyone check out the cover art?

Images, from top R, clockwise: Heathcock et.al., JACS 1995;
Burke et.al., Science Supporting Information; Chris Brown Photography

I've stared at that picture a looong time. Funny - the Lego blocks seem intended to symbolize how Burke's new system renders synthesis highly modular...perhaps that it's even child's play. 

The asterisk in each line drawing (at right) represents where the artist holds the secodaphnane core. The entire structure, as pictured, is "flipped" such that it the two syn methyl groups (red and green in Burke's representation) should be touching the table. That conformation gives me twitches; nothing's quite where it should be in 3D space! I almost wonder if it's not hooked up quite right...

Sometimes, molecules make for capricious photo subjects. But I can't grok the way that one looks. Anyone else agree?