About a year ago, Sigma-Aldrich signed an exclusive licensing agreement with the University of Illinois, Urbana-Champaign. The technology developed by Dr. Martin Burke and coworkers involves the use of caged boronic acids called MIDA boronates in Suzuki cross-coupling reactions. The technology enabled historically challenging and even impossible couplings to take place. I was really excited to see the MIDA Boronates were recently featured in an article in Chem and Engineering News entitled: "New Way To Protect Unstable Boron Reagents"!

The article can be found at Chem and Engineering News (you will need to login as a user). 

Written by: Louis-Charles Campeau Ph. D.
Senior Research Chemist
Process Research & Development
Merck FrosstCentre for Therapeutic Research

For over a century, the rules that govern electrophilic aromatic substitution have been guided by the high Friedel-Crafts-type selectivity.  Electron-rich substituents direct ortho/para and electron deficient direct meta.  The Gaunt group at University of Cambridge has developed a new copper-catalyzed direct arylation reaction which, in contrast, selectively substitutes arenes at the meta position from an amido group.  This reactivity gives access to a wide variety of substitution patterns which can be challenging to synthesize otherwise.  Generally speaking, the reactions demonstrate higher efficency with electron-rich or neutral arenes rather than electron-deficient arenes. 

 
Phipps, R. J.; Gaunt, M. J. Science, 2009, 323, 1593

Written By: Mark Redlich, Ph.D.

Due to limitations with cost and stability of triflates, alternative electrophilic coupling partners for cross-coupling reactions are continually being researched.  I recently came across a communication in Organic Letters which details the use of imidazolylsulfonates as electrophilic coupling partners.  These products show significantly improved shelf-stability versus the corresponding triflates, and better reactivity than the tosylates or mesylates.  The imidazolylsulfonates are easily prepared from the phenol and a slight excess of 1,1’-sulfonyldiimidazole and the successive Suzuki or Negishi couplings proceeded in good to excellent yields.  An added benefit to using the imidazolylsulfonates is the degradation of the imidazolesulfonic acid byproduct in aqueous or acidic conditions to form imidazole and sulfuric acid; this eliminates the formation of potentially genotoxic alkyl or aryl sulfonates from any residual sulfonic acid, a potential which exists when triflic, methanesulfonic, or toluenesulfonic acids are the byproduct.

Albaneze-Walker, J. et al. Org. Lett. 2009, 11, 1463.

Written By: Mark Redlich, Ph.D.

Here is a communication in JACS I recently came across that highlighted the metal-free cross-coupling of unfunctionalized heterocycles.  The reaction is mediated by a stochiometric quantity of a hypervalent iodine(III) reagent and displays a broad substrate scope under mild conditions. Interestingly, the methodology allows for the selective cross-coupling of two arenes that have closely related structures to give the mixed biaryls in high yield and regioselectivity without any detectable oligomerization.

Kita, Y. et al. J. Am. Chem. Soc. 2009, 131, 1668.