Short aliphatic groups are prevalent in bioactive small molecules and play an essential role in regulating physicochemistry and molecular recognition phenomena. Delineating their biological origins and significance have resulted in...

An I(I)/(III) catalysis strategy to construct an enantioenriched fluorinated isostere of the iPr group is reported. The difluorination of readily accessible α‐CF3‐styrenes is enabled by the in situ generation of a chiral ArIF2 species to forge a stereocentre with the substituents F, CH2F and CF3 (up to 95 %, >20:1 vicinal:geminal difluorination). The replacement of the metabolically labile benzylic proton results in a highly preorganised scaffold as was determined by X‐ray crystallography (π→σ* and stereoelectronic gauche σ→σ* interactions). A process of catalyst editing is disclosed in which preliminary validation of enantioselectivity is placed on a structural foundation.

The success of saturated, fluorinated heterocycles in contemporary drug discovery provides a stimulus for creative endeavor in main group catalysis. Motivated by the ubiquity of isochromans across the bioactive small molecule spectrum, the prominence of the anomeric effect in regulating conformation, and the metabolic lability of the benzylic position, iodine(I)/iodine(III) catalysis has been leveraged for the stereocontrolled generation of selectively fluorinated analogs. To augment the current arsenal of fluorocyclization reactions involving carboxylic acid derivatives, the reaction of readily accessible 2‐vinyl benzaldehydes is disclosed (up to >95 : 05 d.r. and 97 : 03 e.r.). Key stereoelectronic interactions manifest themselves in the X‐ray crystal structures of the products, thereby validating the [CH2‐CHF] fragment as a stereoelectronic mimic of the [O‐CH(OR)] acetal motif.

This mild TCICA/KF oxidative fluorination approach provides controllable access to aryl-IF2 and aryl-IF4 compounds, thus allowing detailed structural studies.

Simple α-(bromomethyl)styrenes can be processed to a variety of 1,1-difluorinated electrophilic building blocks via I(I)/I(III) catalysis. This inexpensive main group catalysis strategy employs p-TolI as an effective organocatalyst when combined...