The Olofsson Research Group

 

Research

VBX vinylations  -  Ar2IX arylations  - Synthesis of iodine(III) 

Topics:
- Synthesis of Hypervalent Iodine Reagents
- Development of Metal-Free Application Areas for Hypervalent Iodine Reagents
- Application of Developed Methodology in Total Synthesis of Natural Products

Metal-free vinylations with VBX

The novel vinylation reagents Vinylbenziodoxolones (VBX) were recently developed in our lab. We have demonstrated the utility of VBX by vinylation of carbon, sulfur and phosphorous nucleophiles under transition metal-free conditions. The reactions proceed with excellent chemo-, regio- and stereoselectivity, and surprisingly delivers internal alkens with thiols, whereas nitroalkanes and phosphine oxides give terminal alkenes.

 

 

 

 

Metal-free arylations with diaryliodonium salts

We have developed a wide range of transition metal-free arylations where diaryliodonium salts are employed as electrophilic arylation reagents with various nucleophiles, e.g. the efficient and highly cited synthesis of diaryl ethers by arylation of phenols at room temperature:

More recently, we have also reported two papers in Angew. Chem. Int Ed. on O-arylation of carbohydrates and a sequential one-pot synthesis and N-arylation of sodium nitrite and sodium azide:

We are currently exploring the novel reactivity observed with specially designed diaryliodonium salts, which undergo nucleophilic aromatic substitution rather than ligand coupling, to provide diarylated products with excellent atom economy after a subsequent intramolecular aryl transfer.

 

Mechanistic studies

Arylations with diaryliodonium salts under metal-free conditions have become very powerful synthetic methods in the last decade. To further expand the area, we have performed mechanistic studies in collaboration with theoretical chemists on O-arylation and chemoselectivity in reactions with unsymmetric salts. Our first mechanistic study involved asymmetric α-arylation of enolates:

Synthesis of hypervalent iodine reagents

Our most recent contribution to this area is the development of a novel type of iodine(III) reagent that we have abbreviated VBX (VinylBenziodoXolones). We demonstrated that these reagents have different reactivity from acyclic vinyl(aryl)iodonium salts, and VBX has already been succesfully applied by the research groups of Leonori and Nachtsheim.

We have developed several practical one-pot protocols towards diaryliodonium salts starting from aryl iodides and arenes. The oxidant of choice is mCPBA, which rapidly oxidizes the aryl iodide to iodine(III) intermediate. In the presence of an acid, the arene subsequently attacks this intermediate to form the diaryliodonium salt. The anion has an effect on the solubility and reactivity of the salt, and it is therefore of interest to develop routes to salts containing various anions.

When triflic acid (TfOH) is added to the reaction, diaryliodonium triflates are obtained in high yields, without the need for an anion exchange step. The reaction is fast and has a big substrate scope, leading to both symmetric and unsymmetric salts.

This protocol was subsequently extended to the reaction of molecular iodine with arenes. The method delivers symmetric diaryliodonium triflates in high yields and short reaction times, thus avoiding the need for expensive aryl iodides. The reaction can easily be performed on large scale.

Tosic acid (TsOH) can be employed in the same type of one-pot reaction, leading to diaryliodonium tosylates. The benefit of using tosic acid in some cases is that very electron-rich substrates are tolerated. In applications where the triflate anion is preferred to the tosylate, an in-situ anion exchange can be employed to obtain also electron-rich diaryliodonium triflates.

An alternative approach to diaryliodonium salts was subsequently developed. This sequential one-pot synthesis employs aryl iodides and arylboronic acids, which in the presence of mCPBA and BF3 deliver diaryliodonium tetrafluoroborates in a regiospecific manner, avoiding the EAS limitations of the two other protocols.

Previous work

Berit Olofsson's Post doc work at Bristol University and PhD work at KTH. PhD work   

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