ADDITION AGAINST THE GRAIN

Abstract

WITH THE HELP of zinc reagents, chemists have found a way to circumvent rules that govern additions to chiral carbonyl compounds, a fundamental reaction in organic synthesis. The work, presented on March 24 at the ACS national meeting in San Francisco, could lead to more efficient syntheses of pharmaceuticals. In compounds in which a carbonyl group is next to a hydroxyl stereocenter that has a protecting group, time-honored models predict the chirality of the new stereocenter that arises after adding a carbon nucleophile to the carbonyl, converting it to a second hydroxyl. If the protecting group is small, the Cram chelation model predicts that the product will be a syn-diol (both hydroxyls on the same side). Bulky protecting groups, in contrast, obstruct chelation, leading to an anti-diol (hydroxyls on opposite sides) per the Felkin-Anh model. Using these predictive models has a drawback—chemists sometimes choose protecting groups that suit the carbonyl addition reaction but aren’t ...