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

Abstract

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-d 4 confirmed a radical pathway, which was underpinned by developing a radical−radical crosscoupling 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.

Thermal Formation of Metathesis-Active Tungsten Alkylidene Complexes from Cyclohexene

“…Thermal (often reversible) M–C bond cleavage in transition metal complexes has been explored and discussed since the mid 1950s, − especially with respect to catalytic reactions in which a metal–carbon bond is lost or formed (alkyl migration to a ligand, β hydride elimination, oxidative addition, etc.). Discussions of that nature continue today , and include the role of visible light and radical formation induced through the coordination of a ligand. , In short, thermal M–C bond cleavage can hide, unrecognized, in plain sight. The case for M–C bond cleavage in a metallacyclopentane can be built in part as a consequence of the fact that the carbon-based radical that is formed upon M–C bond cleavage in a metallacyclopentane cannot escape to the solution.…”

Access to 3‐Azetidines via Halogenation of Titanacyclobutanes

“…A control experiment wherein 4 a was reacted with 2‐iodomethyl‐naphthalene and then exposed to DCl afforded d ‐ 10 c along with d ‐2‐methylnaphthalene (i. e., d ‐ 12 ), thereby confirming alkyl Ti(IV) complex B as an intermediate (Scheme 2). We speculate that the path connecting 4 a to B involves coordination‐induced homolysis of the strained Ti−C σ‐bond in 4 a to generate A , a primary alkyl radical species that is stabilized by proximity to a persistent Ti(III) metalloradical center [31,32] . These results hint at the broad, albeit underdeveloped, synthetic utility of titanacyclobutanes.…”