Research

Overview of our Research Programme

We develop new organic reactions and catalysts to enable efficient syntheses of complex and valuable molecules, such as natural products and pharmaceutical agents. All of this activity is underpinned by a core interest in organophosphorus and organosilicon chemistry.

Highlights of Recent Research

Organophosphorus Chemistry: The Catalytic Appel Reaction

The Appel reaction is one of the most widely used and important phosphorus(V)-based nuclephilic substitution reactions. Originally developed during the 1960s, it is used in laboratories around the world on a daily basis for the conversion of alcohols into alkyl halides. Unfortunately, activation of the alcohol occurs at the expense of a stoichiometric phosphorus reagent and oxidant (usually PPh3 in combination with CCl4). This results in the production of triphenylphosphine oxide as a by-product.

We have developed the first Appel reaction which is catalytic with respect to phosphorus (below left) by employing oxalyl chloride as as consumable reagent and chlorine source. This results in a substantial improvement in the atom efficiency of the transformation as CO2 and CO now replace triphenylphosphine oxide as by-products.


As part of this study have carried out some molecular modelling on the chlorination of methanol using Ph3PCl2. Shown below is the B3LYP/6-31+G* transition structure for the Arbuzov reaction in which the C-Cl bond is formed and triphenylphosphine oxide is eliminated.

Ts pic

To read more about our work in this area please refer to publications 17, 18, 20, 21, 23, 25 and 26.

Applications In Natural Product Synthesis: Chlorosulfolipids.

The chlorosulfolipids are a fascinating class of natural products that provide challenges for stereoselective carbon-chlorine bond construction. In order to access the polychlorinated stereochemical arrays present in these targets we developed a catalytic deoxydichlorination reaction (below).

dichlorination hi res

The incorporation of this reaction into an iterative epoxidation/chlorination protocol (see below) has allowed us to complete a synthesis of the protein kinase inhibitor malhamensilipin A. See publication 30 for more details.

mal

Organosilicon Chemistry: Practical Catalytic Reductive Alkylation of Amines Using Carboxylic acids

We have developed an alternative to classical reductive amination reactions in which carboxylic acids are used in place of aldehydes. This transformation exploits dual reactivity of phenylsilane, which is used for amidation and then, upon the addition of catalyst, reduction. For more details see publication 28.

amination

 

 

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