Quest for a Symmetric [C–F–C]⁺ Fluoronium Ion in Solution: A Winding Path to Ultimate Success

Abstract

In this Account, we chronicle our tortuous but ultimately fruitful quest to synthesize a [C−F−C] + fluoronium ion in solution, thus providing the last piece of the organic halonium ion puzzle. Inspiration for the project can be traced all the way back to the graduate career of the corresponding author, wherein the analogy between a [C−H− C]+ "hydrido" bridge and a hypothetical [C−F−C] + bridge was first noted. The earliest attempt to construct a bicyclo[5.3.3]tridecane-based fluoronium ion (based on the analogous hydrido bridged cation) proved to be synthetically difficult. A subsequent attempt involving a 1,8-substituted naphthalene ring was theoretically nai ̈ve in retrospect, and it resulted in a classical benzylic carbocation instead. A biphenyl-based substrate, although computationally sound, proved to be kinetically untenable. At last, after some tweaking (including a dead-end detour into a fluoraadamantane skeleton), we finally achieved success with a highly rigid, semicage precursor based on the decahydro-1,4:5,8dimethanonaphthalene system. This strained substrate possessed a triflate leaving group to enhance its solvolytic reactivity. Detailed isotopic labeling and kinetic studies supported the generation of a symmetrical [C−F− C]+ bridge; interesting solution behavior allowed the manipulation of the rate-determining step for solvolysis depending on solvent nucleophilicity. After initial generation as a transient intermediate, the fluoronium ion was later produced as a stable species in solution and was fully characterized by 19 F, 1 H, and 13 C NMR, with the resultant species displaying evident C s symmetry through coordination of a molecule of SbF 5 . This remarkable ion proved stable to −30 °C. We also address a disagreement surrounding the nomenclature of fluoronium ions in particular and its potential impact upon the naming of onium ions in general. We strove to highlight the dangers of confusing the arbitrary concept of calculated partial charge with IUPAC nomenclature. Finally, we discuss future directions, for example, the synthesis of a fluoronium ion in which fluorine resides within an aromatic ring.

Hydrogen Bond and Other Lewis Acid–Lewis Base Interactions as Preliminary Stages of Chemical Reactions

“…The crystal structure of the fluoronium ion precursor was determined [ 50 ]; the structure of this ion taken from the Cambridge Structural Database, CSD [ 17 , 18 ] is presented in Figure 3 . The direct observation of the similar symmetrical [CFC] + ion was described recently [ 49 ], this is a stable species in solution and it was characterised by 19 F, 1 H, and 13 C NMR.…”

“…It was proved in numerous earlier and recent studies that the heavier halogen atom (Cl, Br, I) may be engaged in the hypervalent link in solution possessing formally positive charge. Such a link was usually doubted for the fluorine centre; the studies of Lectka and co-workers discussed here [ 49 , 50 ] are related to this challenge. However, it was evidenced only indirectly the occurrence of the fluoronium ion as a short-lived reaction intermediate [ 50 ].…”

“…They are designated later here as [LbXLb] + , where in further discussions Lb is replaced by the specific atomic centre while X marks the halogen. The second challenge concerns finding of the [LbXLb] + arrangement with fluorine, X = F, situated between the Lewis base sides since rather such systems with heavier halogens are known [ 49 ]. As concerns the latter challenge, the generation of a symmetrical fluoronium ion in solution was discussed, its existence was evidenced indirectly [ 50 ].…”

Close Amide NH···F Hydrogen Bonding Interactions in 1,8-Disubstituted Naphthalenes

“…The interaction of C–F bonds, especially in proteins, with proximate functional groups is a topic of lively interest and discussion. − Their importance in dictating protein structure and function is not yet fully answered, including the dilemma of whether such interactions themselves are due to propinquity, attractive interactions, or a combination thereof. Over the past several years we have investigated close interactions between C–F bonds and common organic functional groups in relatively small molecules that are often dictated by forced proximity, along with some measure of attraction and repulsion. − The case of the amide NH···F interaction is presumably one of the more interesting, due to the ubiquity of amide residues in proteins. Nevertheless, a search of the Cambridge Crystallographic Database (CCD) indicates only a few substantial interactions; most are self-evidently weak and long-range.…”