Development of a Hypervalent Iodine Promoted One Step Formation of Tri- and Tetrasubstituted Cyclobutanes with Defined Relative and Absolute Configuration

• Applicant: Dr. Simon Wübbolt
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2018 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 404573905

The aim of this project is the development of the hypervalent iodine promoted dimerisation of alkenes to achieve full control over the relative and absolute stereochemistry of the cyclobutane products. The Donohoe Group has shown that hypervalent iodine reagents oxidise electron-rich aromatic trans-alkenes in fluorinated solvents to radical cations, which subsequently undergo a [2+2] cyclisation with unoxidised trans-alkenes. This results in the formation of homo- or heterodimeric all-trans-cyclobutanes. By extension of the substrate scope and an enhanced screening of the reaction conditions (oxidant, solvent, temperature) we will explore the requirements for an alkene to become oxidised as well as the substitution pattern tolerated on the unoxidised alkene.The formation of all-trans-cyclobutanes shows that the initial geometry of the used trans-alkenes is retained in the corresponding products. Therefore, we plan to investigate the influence of the alkene geometries on the relative stereochemistry of the cyclobutane products. For this purpose, we will combine all kinds of alkene geometries with each other to see if their stereochemistry is retained. By optimising the reaction conditions, we aim to achieve control of the relative stereochemical outcome of the transformation.Furthermore, we will develop an asymmetric version of the cyclisation. Since one of the cyclisation partners is charged, a novel possibility to utilise a chiral counteranion is offered, because it can selectively form an ion pair with the formed radical cation. The chiral counteranion could be formed during the reaction from an employed chiral hypervalent iodine reagent or could be added separately. Finally, we aim to use our asymmetric methodology for the construction of key chiral cyclobutane motifs in natural products such as members of the Sceptrin family.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Timothy J. Donohoe, Ph.D.