Dedicated with much respect to awonderful frienda nd mentor,t he ProfessorsP rofessor,P rof.J ackD .Dunitz FRS

Recently, contemporaneous strategies to achieve the vicinal difluorination of alkenes via an I(I)/I(III) catalysis manifold were independently reported by this laboratory and by Jacobsen and co-workers. Both strategies proceed through a transient ArI(III)F species generated by oxidation of the ArI catalyst. Herein, an efficient synthesis of p-TolIF from p-TolI and Selectfluor is presented, together with a crystallographic and spectroscopic study. To mitigate safety concerns and simplify reaction execution, an HF-free protocol was devised employing CsF as a substitute fluoride source. The study provides insight into the initial I(I)→I(III) oxidation stage of the catalytic protocol using Selectfluor.

Contemporaneous reports describing the vicinal difluorination of olefins relying on I­(I)/I­(III) catalysis have augmented the arsenal of dihalogenation methods and provided a solution to this longstanding challenge in olefin functionalization. In both studies, success was contingent on the in situ generation of ArIF2 from a simple aryl iodide, HF source, and suitable terminal oxidant. The first report by Jacobsen and co-workers employed a resorcinol-derived aryl iodide/m-CPBA oxidant combination, while this laboratory relied on p-iodotoluene and Selectfluor. The complementarity of these approaches ensures that a wide variety of electronically distinct olefins are viable substrates for this transformation. This perspective describes our development of a catalytic difluorination of terminal olefins as a means to efficiently construct a hybrid, chiral bioisostere of the trifluoromethyl and ethyl groups in the broader context of molecular design and highlights key reports from other laboratories that accelerated the study.

The chromane nucleus is common to a plenum of bioactive small molecules where it is frequently oxidized at position 3. Motivated by the importance of this position in conferring efficacy, and the prominence of bioisosterism in drug discovery, an iodine(I)/iodine(III) catalysis strategy to access enantioenriched 3‐fluorochromanes is disclosed (up to 7:93 e.r.). In situ generation of ArIF2 enables the direct fluorocyclization of allyl phenyl ethers to generate novel scaffolds that manifest the stereoelectronic gauche effect. Mechanistic interrogation using deuterated probes confirms a stereospecific process consistent with a type IIinv pathway.

Herein detailed conformational analyses of β-fluorosulfides, -sulfoxides and -sulfones are disclosed, thus extending the scope of the fluorine gauche effect to the 3rd Period (X = SR, SOR, SO2R; φFCCS ≈ 60°).

A geminal difluorination of alkenes based on I­(I)/I­(III) catalysis is disclosed, which is compatible with a range of electronically and substitutionally diverse styrenes (27 examples, up to 89% yield). Employing inexpensive p-TolI as the organocatalyst, turnover is enabled by Selectfluor-mediated oxidation to generate the ArIF2 species in situ. Extension to include α-substituted styrenes bearing fluorine-containing groups is disclosed and provides an expansive platform for the generation of fluorine-rich architectures.

Understanding the role of boranes in hypervalent iodine chemistry will open up new reactivities which can be utilised in organic synthesis. Due to similar reactivities, λ3-iodanes have presented themselves as...

Herein, we describe a catalytic fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the mono-fluoromethyl unit and the C(sp3)–O bond of the ring are aligned in a synclinal relationship thereby engaging in stabilising hyperconjugative interactions with vicinal, electron-rich σ-bonds (σC–C→σ*C–F and σC–H→σ*C–O). This manifestation of the stereoelectronic gauche effect was established by X-ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class.