Professor Phil Baran and coworkers have developed a new reagent, N-Hydroxytetrachlorophthalimide (ALD00564), which provides a cheap, scalable, and safe synthetic alternative to highly used transformations like allylic oxidations, as well as Negishi and Suzuki–Miyaura type cross-coupling reactions. In these cases, this reagent obviates the requirement for toxic reagents or precious metals, thereby lending itself to application on scale and in industrial applications.2
TCNHPI-derived esters readily undergo cross-coupling with aryl zinc reagents1 and are ideal coupling partners for Suzuki coupling reactions.4
The proposed step-wise mechanism of the electrochemical allylic oxidation of an olefin by TCNHPI is described below:2
a) TCNHPI undergoes deprotonation with pyridine to afford tetrachlorophthalimido N-oxyl anion.
b) Anion undergoes anodic oxidation to afford tetrachlorophthalimido N-oxyl radical species.
c) Olefin compound (I) undergoes hydrogen abstraction, thus regenerating TCNHPI back and a stable allylic radical (II).
d) Allylic radical (II) reacts with electrochemically generated t-BuOO (from t-BuOOH) to afford allylic peroxide (III).
e) Removal of t-BuOH from (III) affords enone (IV).
In sum, ALD00564 is a cheap, scalable stoichiometric reagent that enables important transformations such as allylic oxidation as well as the Ni-catalyzed cross-coupling of carboxylic acids to boronic acids. These last are so well represented commercially that this technology (and reagent) will force a rethink in how molecules of all sizes and complexity are designed and synthesized.
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