Andrew N. French

Iodine electrophiles in stereoselective reactions: recent developments and synthetic applications

The regio- and stereocontrolled functionalisation of carbon-carbon double bonds bears enormous potential in organic synthesis. This area has been extensively studied and reviewed as alkenes are amongst the most important starting materials for synthetic chemists, accessible in many varieties and in large quantities. We focus in this tutorial review only on recent developments using iodine electrophiles for the functionalisation of alkenes although transition-mediated reactions and functionalisations with chalcogen electrophiles also play an important role. New synthetic applications using this methodology showing scope and limitations of iodine-mediated processes also within the context of other electrophilic reactions are highlighted.

Chiral Hypervalent Organo-Iodine(III) Compounds

A series of ortho-substituted chiral hypervalent iodine reagents has been synthesized utilizing a zirconium-mediated iodoacylation reaction, which was followed by a stereoselective reduction, methylation, and an oxidation/ligand-exchange sequence. The evaluation of these new compounds as stereoselective electrophilic reagents towards alkenes and ketones is reported. Enantioselectivities as high as 65% have been achieved in the dioxytosylation of styrene and of up to 40% in the oxytosylation of propiophenone. X-ray structure analysis and ab initio calculations on a hypervalent iodine salt have been used to develop a model for rationalizing the stereoselectivities in these reactions with chiral hypervalent iodine reagents. In this model, high enantiomeric excess in the reaction correlates with the relative population of a conformation in which a methyl group on the asymmetric carbon atom is in the axial position. This work provides new opportunities for the synthesis of new and more efficient chiral hypervalent iodine reagents for stereoselective synthesis.

Clean, Green Chiral Reactions—Just Add a Salt

An ammonium iodide salt can perform selective organic oxidation reactions and replace more toxic metal catalysts. Chirality—literally handedness—refers to the mirror-image, or left-right asymmetry of objects like shoes and gloves. Like our hands, many chemical compounds (and most biomolecules) exist as enantiomers, which, relative to each other, have mirror-image arrangements of substituents around an atom (typically carbon or nitrogen). In many cases, pharmaceuticals must have a specific chirality in order to be active, but making pure chiral compounds is difficult and costly. Traditionally, chemists have relied on reagents for controlling chirality that contain heavy metals (1), the presence of which can lead to toxicity issues. A relatively new alternative is the use of nonmetal catalysts called organocatalysts. On page 1376 of this issue, Uyanik et al. (2) report a more “green” organocatalytic reaction that also uses an iodine reagent to closes rings in a molecule during an oxidation step.