Ti‐Mediated Efficient Reductive Dehalogenation of Carbon–Halogen Bonds

Abstract

A mild and efficient methodology for the reductive dehalogenation of carbon-halogen bonds in both activated (allylic or benzylic) and non-activated halides with excess Ti III is thoroughly described. A detailed computational and experimental study corroborates that the reaction occurs via the allyl(benzyl) radical and allyl(benzyl)-Ti, which is protonated by a Brønsted acid, and proceeds regioselectively in the case of allylic derivatives. This synthetic method is compatible with a wide range of functional groups and reaction conditions, and thus presents a mild process for reductive dehalogenation in the field of organic synthesis.

Cp2TiCl: An Ideal Reagent for Green Chemistry?

“…In the seminal works reported by Nugent and Rajanbabu, it was observed that Cp 2 TiCl was a novel single-electron transfer species capable of generating a radical from an epoxide, which under different experimental conditions could give cyclization reactions, intermolecular additions, reductions, and deoxygenation reactions. From this moment, this SET was widely used in chemical synthesis, meeting if not all, at least many of the 12 principles reported for Green Chemistry.…”

“…The Cp 2 TiCl complex can interact with epoxides, ozonides, oxetanes, allylic and propargylic halides, saturated ketones, imines, α-haloketones, unactivated alkyl halides, and α,β-unsaturated and aromatic aldehydes and ketones to yield the corresponding carbon-centered radicals (Scheme ). As we have already mentioned, the way in which these carbon-centered radicals progress depends upon the reaction conditions.…”

“…These radicals can be trapped by electronic acceptors or by a second molecule of Cp 2 TiCl to generate an organometallic compound that can be added to electrophilic carbons. In both cases, the result is the formation of a new C–C bond either inter- or intramolecularly. ,, In this way, epoxides and unsaturated epoxides were the first functional groups used as substrates in Cp 2 TiCl-catalyzed C–C bond forming reactions, either inter- or intramolecularly, under sustainable and environmentally friendly conditions (Scheme ). This radical opening of epoxides using Cp 2 TiCl is a complementary methodology to anti-Markovnikov traditional methods.…”

Cp2Ti(III)Cl and Analogues as Sustainable Templates in Organic Synthesis

“…Thus alkanes were obtained from primary aliphatic halides, primary and secondary benzylic halides, and secondary allylic halides whereas primary allylic halides gave alkene derivatives (Scheme 5). 31…”

“…The regioselectivity obtained was again explained by the coordination of the Brönsted acid to the titanium atom of 16. 31…”