Chemistry Seminary: Asymmetric Synthesis with Boronic Esters

Friday, April 14, 2017

11:00 AM-12:30 PM

Don Matteson, PhD, Washington State University

"Asymmetric Synthesis with Boronic Esters"

Boronic ester chemistry is an unusual approach to asymmetric synthesis that routinely provides 99% diastereoselectivity and, after replacement of the asymmetric boronic ester function, enantioselectivity. Typical syntheses begin with the addition of LiCHCl2 to the boron atom of a boronic ester of a chiral diol (1) followed by intramolecular rearrangement to form an -chloro boronic ester (2). Addition of an organometallic reagent and similar rearrangement then lead to an asymmetric alkylboronic ester (3). The boronic ester group of 3 can be replaced stereospecifically by OH from hydrogen peroxide, or, since 3 is itself an alkylboronic ester, the foregoing process can be repeated to form two adjacent stereocenters or more.The process outlined has been useful in the highly stereoselective synthesis of a few insect pheromones. However, the most important practical application has been the synthesis of -amido boronic esters, which enabled the discovery of "Velcade" (bortezomib) by Julian Adams. Velcade has extended the lives of hundreds of thousands of multiple myeloma sufferers, in some cases by a number of years. The difficulties in the discovery of the -amido boronic ester synthesis will be described, as well as some chemically related baffling behavior of the chemically related deboronation of the cyclic dimer of HOCH2B(OH)2 that I have been figuring out recently without the aid of students.

Contact Information

Hai-Feng (Frank) JI, PhD
215.895.2562
hj56@drexel.edu