The enantioselective, catalytic vicinal difluorination of alkenes is reported by II/IIII catalysis using a novel, C2‐symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIIIF2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF–amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Brønsted acidity. Selectivity reversal from the 1,1‐difluorination pathway (geminal) to the desired 1,2‐difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p‐TolI (up to >95 % yield).

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.

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.

Organocatalytic strategies for the programmed, catalytic oxidation of π-bonds through regioselective halogenation remain comparatively underdeveloped. The vicinal dichlorination of unactivated alkenes is a pertinent example, where stoichiometric reagents and prefunctionalization steps are often employed. This is surprising given the prominence of the 1,2-dichloro moiety in an array of bioactive natural products of both terrestrial and marine origin. Inspired by Willgerodt’s seminal discovery in 1886 that PhICl2 can be generated by passing Cl2(g) through iodobenzene, a catalytic vicinal dichlorination of unactivated alkenes has been designed on the basis of an I­(I)/I­(III) manifold. In situ generation of p-TolICl2 is achieved using Selectfluor and CsCl. Substrate scope, mechanistic delineation, and preliminary validation of an enantiomeric variant are established. Over a century after the initial discovery of the Willgerodt reagent (PhICl2), an operationally simple, catalytic alternative has been validated.

The enantioselective,catalytic vicinal difluorination of alkenes is reported by I I /I III catalysis using an ovel, C 2symmetric resorcinol derivative.C atalyst turnover via in situ generation of an ArI III F 2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF-amine complex. The HF:amine ratio employed in this process provides ah andle for regioselective orthogonality as af unction of Brønsted acidity.S electivity reversal from the 1,1-difluorination pathway( geminal) to the desired 1,2-difluorination (vicinal) is disclosed (> 20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF 3 unit that is pervasive in drug discovery (20 examples,upto94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to > 95 %yield).