Rhodium catalysed asymmetric Suzuki reaction with polyconjugated allylic alcohol derivatives.

C-C bond formations are the cornerstone of organic chemistry.

Suzuki couplings are one of the most frequently performed reaction in the pharmaceutical industry synthesise these C-C bonds - both in early and late-stage drug development.

The classic Suzuki coupling involves the reaction of two sp2-hybridised carbon centres with a palladium catalyst which results in the formation of a somewhat flat planar product.

With an increase in interest of pivoting towards drug molecules with more 3-dimentional space projection due to its benefits to the pharmacodynamics and pharmacokinetics of the resulting drug candidate, the need for a broadly applicable sp2-sp3 Suzuki coupling is highly sought after.

While switching to a more saturated system has its benefits to the therapeutic effects of the drug candidate, the innate properties of a saturated system means that chiral centres could arise when the carbon centre has 4 different substituents attach to the carbon atom.

Although traditional palladium catalysed sp2-sp3 Suzuki coupling reactions has demonstrated its ability to stereoselectivity couple chiral components together, these reactions often proceed with either prochiral or stereopure starting material.

The simultaneous resolution of racemic starting material and coupling of the resulting upgraded starting material has not been reported for Pd-catalysed Suzuki couplings to the best of our knowledge.

Previous work in the Fletcher group has demonstrated rhodium's ability to catalyse dynamic kinetic asymmetric transformations and its applications to Suzuki couplings to give sp2-sp3 coupled products with high enantiomeric excess when starting from racemic electrophiles.

The aim of this project is to explore other systems where these Rh-catalysed DyKAT could be applied to in order to convert racemic starting material into enantiopure product.

More specifically, the expansion of the substrate scope for a Rh-catalysed asymmetric allylic substitution of vinyl ethylene carbonates to conjugated allylic phosphates/ acetates.

The development of this reaction would allow for the DyKAT substitution in allylic substrates containing polyene moieties such as derivatives of Retinol and terpenoids.

Additionally, mechanistic investigations will be conducted to elucidate the mechanism in which the Rh catalyse the substrate in question. This project falls within the EPSRC Catalysis research area.