Coordination-Induced Radical Generation: Selective Hydrogen Atom Abstraction via Controlled Ti–C σ‑Bond Homolysis

A method for the generation of transient alkyl radicals
via homolytic
Ti–C bond cleavage was developed by employing a tailor-made
organotitanium half-cage complex. In contrast to established metal-mediated
radical initiation protocols via thermal or photochemical M–C
σ-bond homolysis, radical formation is triggered solely by coordination
of a solvent molecule (thf) to a titanium(IV) center. During the reaction,
the nonstabilized alkyl radical is formed along with a persistent
titanium(III) metalloradical, thus taming the former transient radical
(persistent radical effect). Radical coupling and hydrogen atom abstraction
(HAT) reactions have been explored not only experimentally but also
computationally and by means of kinetic analysis. Exploiting these
findings led to the development of selective HAT transformations,
for example, with 9,10-dihydroanthracene. Deuterium labeling studies
using selectively deuterated alkyls and 9,10-dihydroanthracene-d4 confirmed a radical pathway, which was underpinned
by developing a radical–radical cross-coupling reaction for
transferring the alkyl radical to a stable Sn-centered radical. To
set the stage for an application in organic synthesis, a 5-endo-trig radical cyclization based on our methodology was
established, and a dihydroxylated sesquiterpene was thus prepared
in high diastereomeric excess.