Selectfluor® Radical Dication (TEDA^2+.) – A Versatile Species in Modern Synthetic Organic Chemistry

Abstract

In radical processes involving Selectfluor®, TEDA 2 + * (N-(chloromethyl)triethylenediamine) is often generated after an electron or fluorine transfer step. This is a highly reactive species that displays different and unique reactivity when compared to Selectfluor®: It can act as a hydrogen atom transfer (HAT), halogen atom transfer (XAT), or aminating reagent, as well as a powerful single electron oxidant. Despite this versatility, the use of TEDA 2 + * in synthetic processes remains highly underexplored. This minireview, which covers recent applications of TEDA 2 + * to promote a wide range of C-heteroatom and CÀ C bond formations, aims to highlight the potential of this interesting species in organic chemistry. Particular attention is paid to mechanistic aspects involving how TEDA 2 + * is generated and the different reactivity patterns that it can display. TEDA 2 + * as Hydrogen Atom Transfer (HAT) ReagentThe direct functionalization of CÀ H bonds is one of the most attractive strategies for preparing synthetically useful chemicals out of abundant and cheap feedstocks. [4] A key challenge in CÀ H functionalizations is to achieve the selective activation of a given CÀ H bond. Hydrogen atom transfer (HAT) reactions represent a powerful strategy to achieve this goal. [5] One of the main applications of TEDA 2 + * in synthetic organic chemistry is its use as a HAT reagent to facilitate the formation of a wide range of C-heteroatom and CÀ C bonds. Although there are no precise measurements of the properties of TEDA 2 + * as a HAT reagent, based on its reactivity and structure, it can be compared to other amine-based HAT reagents, e. g. quinuclidine. This means that it can selectively activate hydridic CÀ H bonds with BDE � 100 kcal/mol. Csp 3 À F Bond FormationIn 2012, Lectka reported one of the first examples of the use of TEDA 2 + * in HAT processes (Scheme 1). [6] This straightforward fluorination methodology, which enabled the formation of CÀ F bonds from aliphatic, allylic or benzylic CÀ H bonds, required a Cu I catalyst, a radical precursor -N-hydroxyphthalimide (NHPI), a phase transfer catalyst (KB(C 6 F 5 ) 4 ), and Selectfluor® to proceed. Although several mechanistic studies were carried out to [a

Efficient cleavage of tertiary amide bonds via radical–polar crossover using a copper(ii) bromide/Selectfluor hybrid system

“…It should be noted here that Selectuor can be activated by photoirradiation, where the generated cation radical A is responsible for the hydrogen atom abstraction (HAA) during the C-H activation of various hydrocarbons. 25,26 Interestingly, acyl uoride 2a was also obtained when the reaction was triggered via photoirradiation (Scheme 3b). However, when compared to the photoirradiation approach, the CuBr 2 /Selectuor system showed higher efficiency, which suggests that the role of the copper species may not be that of an initiator, but that of a catalyst involved in the amide-cleavage process.…”

Catalytic C(sp3)–F bond formation: recent achievements and pertaining challenges

“…[28][29][30] These include fluorinating agents with nucleophilic, electrophilic and/or radical character, such as DAST, Selectfluor® (F-TEDA) and NFSI, which are able to mediate several types of fluorination reactions. [31][32][33][34][35][36] The discovery of such reagents represents a milestone in fluorination chemistry, and has subsequently led to the design of a great deal of new fluorination procedures. As such, a large portion of the modern catalytic methods to synthesise C(sp 3 )-F bonds typically utilise these "easy-to-handle" fluorinating agents.…”

“…nucleophilic, electrophilic, and radical fluorination. [31][32][33][34][35][36] In contrast to nucleophilic reactions, which are generally accepted to involve fluoride ions (F − ), electrophilic reactions are not thought to occur via the formation of formal fluoronium cations (F + ), which are unlikely to be formed due to their instability and the energy required to their formation. 17 For electrophilic fluorination, fluorine transfer is proposed to occur via two possible mechanisms; (i) single electron transfer (SET), or (ii) S N 2 nucleophilic substitution, in which a nucleophilic substrate attacks the fluorine atom, yielding the R-F bond.…”

Cationic DABCO-based Catalyst for Site-Selective C−H Alkylation via Photoinduced Hydrogen-Atom Transfer

“…[7] Among them, tertiary amine-derived cationic aminium radicals have recently been gaining attention as efficient HAT mediators. [8][9] The highly electrophilic nature of these radicals enables the selective abstraction of a hydrogen atom from hydridic C−H bonds. While aminium radicals derived from quinuclidine and its derivatives have been used for efficient HAT from substrates bearing C−H bonds adjacent to a heteroatom, [8] the more electrophilic dicationic aminium radical derived from Selectfluor ® can even abstract hydrogen atoms from the unactivated C−H bonds of hydrocarbons (Figure 1A).…”

“…While aminium radicals derived from quinuclidine and its derivatives have been used for efficient HAT from substrates bearing C−H bonds adjacent to a heteroatom, [8] the more electrophilic dicationic aminium radical derived from Selectfluor ® can even abstract hydrogen atoms from the unactivated C−H bonds of hydrocarbons (Figure 1A). [9] Moreover, these methods sometimes show unique site-selectivity among C−H bonds with similar BDEs. [10] Despite these attractive features, the use of dicationic aminium radicals as HAT mediators has been limited to fluorination and a few other oxidative transformations, as this radical is mainly generated in situ from a (supra)stoichiometric amount of Selectfluor ® , which is known as a fluorine-atom transfer reagent and/or a strong oxidant.…”