A quantitative reactivity scale for electrophilic fluorinating reagents

Abstract

Through kinetic studies we provide a quantitative reactivity scale for ten electrophilic fluorination reagents.

The Electrophilic Fluorination of Enol Esters Using SelectFluor: A Polar Two‐Electron Process

“…It is important to considert hese results in the context of recent studies that imply that similar polar two-electron mechanismsa re in operation fort he fluorination of enamines, [22] stabilised carbanions, [22] and 1,3-dicarbonyl species. [23] The carbanions in particulara re more electron rich than the enol ester substrates considered here, andt he enamines would also be expectedt ob em ore electron rich. The enol forms of the 1,3dicarbonyl compounds considered by Sandford and Hodgson possibly have similar nucleophilicities to the enol esters considered here, butu nfortunately the nucleophilicities of these species have not yet been measured.…”

“…[19][20][21] Reagent 1 is one of the more reactive electrophilic fluorinating reagents, as judged from recentk inetic studies. [22,23] Steroid-like structures are often fluorinated using 1 via the corresponding (di)enol ester intermediates (Scheme 1), typically under very mild conditions;a lthough 1 is ultimately prepared from elemental fluorine,t he use of this bench-stable solid is more convenientt han the direct deployment of fluorine gas, [24] and requires no special glassware or apparatus.I na ddition, 1 offers advantages over expensive XeF 2 [25,26] or hazardoush ypofluorites; [27,28] the latter often requirec ryogenic temperatures which have associated cost, safety,a nd environmental implications.D espite the significant utility and widespread application of 1,there is only alimited understanding of the underlying reactionm echanismsi nm any of thesef luorination reactions. In particular, there are many examples in which ar eaction through ap olar two-electronm echanism is proposed, and a correspondings et of examples in which ar eaction via radical intermediatesi sp osited.…”

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…[104,105] Thef ormation of the pyridyl radical cation is consistent with NÀFt ransfer reagents proceeding through an N-centered radical rather than the fluorine radical pathway under SET conditions.T he nature of N-fluoropyridinium as an [F + ] transfer reagent has been proposed in studies by the groups of Hodgson and Mayr, but continues to be amatter of debate. [106] Thep rocess has been proposed to proceed through either: 1) aradical process involving successive single-electron transfers or 2) apolar two-electron mechanism, formally aS N -type reaction mechanism with pyridine as the nucleofuge (Scheme 30). [107] In both mechanistic situations,i ti sc lear that the organic or transition-metal-centered nucleophiles are oxidized and formally transfer fluorine through oxidative fluorination processes.H owever,i nvestigations into mechanisms are often restricted to classic kinetic experiments including UV/ Visa nd radical clock experiments,t hus limited to reaction rates which are likely slower than these stepwise SET radical processes.…”

One‐bond 1J(15N─19F) spin–spin coupling constants of cationic fluorinating reagents: Insights from DFT calculations

“…Concerning the existence of a relationship between the fluorinating strength of the compound and the 1 J ( 15 N─ 19 F) SSCC, recently, the reactivity of several fluorinating reagents was put on a common scale by Rozatian et al They introduced an experimentally determined reactivity scale covering eight orders of magnitude. Measured on this scale, the reactivity of some of the compounds investigated here, and also included in the study of Rozatian et al, is 7 >> 5 > 6 >> 10 > 11 . Comparing this order of reactivities with either the experimental or computed coupling constants, we note the lack of a clear correlation.…”

“…Orbital contributions to the SSCC shows a complex electronic pattern which is responsible for the negative sign of the reduced one‐bond K (N─F) SSCC and therefore for the positive, contrary to expectations, sign of 1 J ( 15 N─ 19 F). The calculated J SSCC show a very good correlation with the N─F bond length of the molecule, whereas no clear correlation can be found with the reactivity scale defined in Rozatian et al…”