TAMING THE VINYL CARBOCATION

by BETHANY HALFORD

IN THE REALM OF REACTIVITY, THE VINYL CARBOCATION IS A BEAST SO FLEETING, SO KEEN TO COMBINE OR REARRANGE, THAT MANY HAVE DOUBTED THAT IT CAN BE TAMED TO CREATE MOLECULES IN A STEREOSELECTIVE WAY.

But by confining a vinyl carbocation within a bulky catalyst, chemists have now shown they can coax this wildly reactive intermediate to insert itself into a carbon-hydrogen bond in which one enantiomer of a chiral product is preferentially produced.

The enantioselective insertion comes from the collaboration of researchers in Hosea M. Nelson’s group at the California Institute of Technology, Matthew S. Sigman’s group at the University of Utah, and K. N. Houk’s group at the University of California, Los Angeles.

After screening dozens of catalysts, the chemists found a family of what’s called imidodiphosphorimidate organocatalysts designed by its developer to serve as general catalysts for a variety of asymmetrical transformations. This family was able to create and confine the vinyl cation in such a way that it would only react to form one of two possible enantiomers in a C–H insertion reaction. The chemists liken the catalyst to an enzyme in that it is able to exert stereocontrol over a highly reactive intermediate.

Houk and Sigman then modeled the behavior computationally to verify that the reaction is indeed going through the vinyl carbocation. “Now that chemists know these intermediates can be harnessed,” Sigman says, “they can be creative about what kind of molecules they make with this type of reaction.”

"The idea that carbocations as reactive as unstabilized vinyl cations could be engaged in highly enantioselective reactions would have seemed unlikely until recently," says Harvard University's Eric N. Jacobsen, who also develops new reactions. The work represents "a significant advance in asymmetric catalysis with highly reactive intermediates."

The chemists think the area is still rich for exploration. Sigman, who is currently chair of the Department of Chemistry at the U, says the information they’ve gleaned could help their team redesign the catalysts to be more practical. The chemists would also like to expand their substrates. In this work, the C–H insertion was an intramolecular transformation, in which the vinyl cation and the C–H bond were in the same molecule. They’d like to see the work extended to intermolecular reactions—in which the vinyl cation and the C–H bond it inserts into are on different molecules. <

Excerpted with permission from Chemical & Engineering News.

Copyright ©2022 by the American Chemical Society. The article, “Chemists tame the vinyl carbocation,” was first published in C&EN on December 8, 2022 and appeared in Volume 100, Issue 44.

Image credit: Science; Confined to an organic catalyst (space-filling model), this vinyl carbocation substrate (stick model) is poised to react stereoselectively.