Ambiphilic Reactivity of SF₅‐Alkynes Applied to Regioselective and Stereodivergent Halogenation Reactions: An Experimental and Theoretical Case Study

Abstract

We explored the ambiphilic reactivity of SF5‐alkynes, and we proved they can act as both nucleophiles and electrophiles. We selected halogenation reactions as benchmark reactions and developed highly selective stereodivergent hydrohalogenation (I, Br, Cl, F) reactions of SF5‐alkynes. The stereochemistry is finely controlled thanks to the nature of the acids used (strong or soft) in the presence of halide source, while the high regioselectivity is governed by the strong polarization of SF5‐alkynes. Mechanistic studies supported by DFT calculations shed light on two different reaction mechanisms responsible of the excellent stereocontrol. This stereoselectivity was quantitatively rationalized with the ASM and EDA methods. A few dihalogenation reactions are reported and DFT calculations rationalize this cis‐stereoselectivity. Relative configuration of all the SF5‐haloalkenes was unambiguously determined by X‐ray diffraction. Noteworthy, several post‐functionalization reactions such as cross‐couplings, cyanation and reductions are described to strengthen the synthetic potential.

Recent advances in the chemistry and the application of SF5-compounds

“…These side products are obtained alongside the cationic complex 27 containing an SF5 counter ion in the reaction between 25 with 2 equivalents of SF4. In this work, Braun and co-workers reported the full characterization of the obtained complexes including 19 F, 31 P NMR and single X-ray crystallography. Remarkably, oxidative chlorination of 28b with trichloroisocyanuric acid (TCICA) results in chlorination of the SF5 anion and the anionic methyl group, along with the formation of a Rh-Cl complex with a chloride counter anion.…”

“…Simultaneously and independently, Bizet, Cahard and Miqueu reported the same year the regioselective and stereodivergent hydrohalogenation of SF5-alkynes with all the halogens (I, Br, Cl, F). 31 Once again, the regioselectivity is controlled thanks to the polarization of the SF5-alkyne with selective introduction of halides on the electro-positive Cβ.…”

“…The Z-dihalogenated olefins 57 are formed as major products whatever the nature of the halogens (scheme 23a). 31 Template for SYNTHESIS Thieme Noteworthy, with ICl, the iodine atom is selectively introduced on Cα and the chlorine atom on Cβ. The mechanism of the dibromation was also investigated by DFT calculation confirming that the reaction pathway involves the formation of a bromovinyl cation 59 rather than a bromonium cation, followed by the addition of Brfrom Br3 -the opposite side to that of SF5 mainly because it induces a strong steric repulsion (scheme 23b).…”