Reactions promoted by hypervalent iodine reagents and boron Lewis acids

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 viable alternatives for many transformations dominated by transition metals whilst mitigating some of the associated drawbacks of metal systems. As showcased by recent reports, boranes can adopt a dual role in hypervalent iodine chemistry that surpasses mere activation of the hypervalent iodine reagent. Increased efforts to harness this potential with diverse boranes will uncover exciting reactivity with high applicability across various disciplines including adoption in the pharmaceutical sciences. This review will be relevant to the wider synthetic community including organic, inorganic, materials, and medicinal chemists due to the versatility of hypervalent iodine chemistry especially in combination with borane activation or participation. We aim to highlight the development of hypervalent iodine compounds including their structure, bonding, synthesis and utility in metal-free organic synthesis in combination with Lewis acidic boranes

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

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

Deconstructing the Catalytic, <i>Vicinal</i> Difluorination of Alkenes: HF-Free Synthesis and Structural Study of <i>p</i>‑TolIF₂

Recently, contemporaneous strategies to achieve the <i>vicinal</i> 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)­F₂ species generated by oxidation of the ArI catalyst. Herein, an efficient synthesis of <i>p</i>-TolIF₂ from <i>p</i>-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

The Sulfur–Fluorine <i>Gauche</i> Effect in Coinage-Metal Complexes: Augmenting Conformational Equilibria by Complexation

Controlling the rotation about unhindered C­(sp³)–C­(sp³) bonds by simple structural changes has obvious benefits in molecular design. While the avoidance of nonbonding interactions remains one of the cornerstones of acyclic conformational control, stabilizing stereoelectronic effects have the added benefit that conformer populations can be fine-tuned by augmenting or diminishing the central interaction. Strategies may include adjusting the oxidation state of a substituent or reversible formation of a complex to modulate MO levels. In the case of the sulfur–fluorine <i>gauche</i> effect, the propensity of the S–C–C–F motif to adopt a <i>synclinal</i> arrangement (Φ_FCCS = 60°), the conformer population distribution of the three dominant rotamers partitioned by 120° can be biased by oxidation of the S atom. Motivated by the importance of sulfur-based ligands in main structural chemistry, the sulfur–fluorine <i>gauche</i> effect was translated to an organometallic paradigm as a potential tool to achieve structural preorganization. This would allow the influence of coinage-metal complexation on conformer population to be initially assessed. The synthesis and characterization of a model gold­(I) and silver­(I) metal complex featuring a ligand system containing a freely rotatable SCCF motif is disclosed. In both complexes, the title stereoelectronic effect manifests itself in the expected conformation, with the <i>synclinal</i>-<i>endo</i> conformer being preferred. This was corroborated by X-ray crystallography and DFT analysis, and the molar fraction of rotamers was extrapolated from a detailed solution-phase NMR spectroscopic analysis. Complexation was found to reinforce the sulfur–fluorine <i>gauche</i> effect

The Sulfur–Fluorine <i>Gauche</i> Effect in Coinage-Metal Complexes: Augmenting Conformational Equilibria by Complexation

Controlling the rotation about unhindered C­(sp³)–C­(sp³) bonds by simple structural changes has obvious benefits in molecular design. While the avoidance of nonbonding interactions remains one of the cornerstones of acyclic conformational control, stabilizing stereoelectronic effects have the added benefit that conformer populations can be fine-tuned by augmenting or diminishing the central interaction. Strategies may include adjusting the oxidation state of a substituent or reversible formation of a complex to modulate MO levels. In the case of the sulfur–fluorine <i>gauche</i> effect, the propensity of the S–C–C–F motif to adopt a <i>synclinal</i> arrangement (Φ_FCCS = 60°), the conformer population distribution of the three dominant rotamers partitioned by 120° can be biased by oxidation of the S atom. Motivated by the importance of sulfur-based ligands in main structural chemistry, the sulfur–fluorine <i>gauche</i> effect was translated to an organometallic paradigm as a potential tool to achieve structural preorganization. This would allow the influence of coinage-metal complexation on conformer population to be initially assessed. The synthesis and characterization of a model gold­(I) and silver­(I) metal complex featuring a ligand system containing a freely rotatable SCCF motif is disclosed. In both complexes, the title stereoelectronic effect manifests itself in the expected conformation, with the <i>synclinal</i>-<i>endo</i> conformer being preferred. This was corroborated by X-ray crystallography and DFT analysis, and the molar fraction of rotamers was extrapolated from a detailed solution-phase NMR spectroscopic analysis. Complexation was found to reinforce the sulfur–fluorine <i>gauche</i> effect

The Sulfur–Fluorine <i>Gauche</i> Effect in Coinage-Metal Complexes: Augmenting Conformational Equilibria by Complexation

Controlling the rotation about unhindered C­(sp³)–C­(sp³) bonds by simple structural changes has obvious benefits in molecular design. While the avoidance of nonbonding interactions remains one of the cornerstones of acyclic conformational control, stabilizing stereoelectronic effects have the added benefit that conformer populations can be fine-tuned by augmenting or diminishing the central interaction. Strategies may include adjusting the oxidation state of a substituent or reversible formation of a complex to modulate MO levels. In the case of the sulfur–fluorine <i>gauche</i> effect, the propensity of the S–C–C–F motif to adopt a <i>synclinal</i> arrangement (Φ_FCCS = 60°), the conformer population distribution of the three dominant rotamers partitioned by 120° can be biased by oxidation of the S atom. Motivated by the importance of sulfur-based ligands in main structural chemistry, the sulfur–fluorine <i>gauche</i> effect was translated to an organometallic paradigm as a potential tool to achieve structural preorganization. This would allow the influence of coinage-metal complexation on conformer population to be initially assessed. The synthesis and characterization of a model gold­(I) and silver­(I) metal complex featuring a ligand system containing a freely rotatable SCCF motif is disclosed. In both complexes, the title stereoelectronic effect manifests itself in the expected conformation, with the <i>synclinal</i>-<i>endo</i> conformer being preferred. This was corroborated by X-ray crystallography and DFT analysis, and the molar fraction of rotamers was extrapolated from a detailed solution-phase NMR spectroscopic analysis. Complexation was found to reinforce the sulfur–fluorine <i>gauche</i> effect