Advertisement

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Synthesis

Phase Switching With Productive Tags

Boronic acid-based procedure for separating organic reaction products is more streamlined than predecessors

by Stu Borman
March 1, 2010 | A version of this story appeared in Volume 88, Issue 9

[+]Enlarge
Credit: Courtesy of Dennis Hall
Phase switching of blue-colored boronic acid-derivatized compound from organic (top layer) to aqueous sorbitol phase (bottom layer).
Credit: Courtesy of Dennis Hall
Phase switching of blue-colored boronic acid-derivatized compound from organic (top layer) to aqueous sorbitol phase (bottom layer).

A new synthetic approach uses phase switching to separate organic reaction products while saving a tag-removal step required in similar procedures. Traditional phase-switching systems like fluorous synthesis use tags that have to be installed and later removed. Dennis G. Hall and coworkers at the University of Alberta have now developed an alternative method (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200906710). A synthetic substrate derivatized with a boronic acid is reacted in organic solvent. Excess reagents and side-products are then removed by phase switching: The reaction mixture is exposed to a basic phase such as a solution of sorbitol, which forms a water-soluble complex with the hydrophobic boronic acid and its attached substrate but not with other components of the reaction mixture. Single or multiple reaction cycles are possible, after which the boronic acid is converted into a desired functional group. Oxidations, reductions, organometallic additions, and other reactions can be done this way. Hall and coworkers used the technique in a five-step synthesis of the drug ezetimibe, which required purification only at the end, owing to phase-switch purifications after each step.

Article:

This article has been sent to the following recipient:

0 /1 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.