Professor Donald Craig



Natural products synthesis | Novel pericyclic processes | De novo synthesis of highly subsituted aromatics


The decarboxylative Claisen rearrangement

Recent work in the group has shown that exposure of allylic tosylacetates to sub-stoichiometric quantities of weak base (potassium acetate) and silylating agent (N,O-bis(trimethylsilyl-acetamide): BSA) causes in-situ silyl ketene acetal formation, [3,3]-sigmatropic rearrangement and decarboxylation; these transformations provide homoallylic sulfones in high yield in an overall decarboxylative Claisen rearrangement (dCr) reaction.

dCr mechanism 

Doubly allylic tosylmalonates can undergo tandem dCr reactions, where the first rearrangement takes place at ambient temperature, while the second frequently requires microwave irradiation.   These heptadiene products can be further elaborated to give access to densely functionalised aromatic systems.

Tandem dCr

Incorporation of the allylic moiety into a heteroaromatic ring leads to a dearomatising dCr.  Previous work within the group has shown that, in certain cases, the dearomatised product can be isolated and further synthetically manipulated, providing a facile route to 3-substituted furans from furfural derived species.

dearomatising dCr

Current invesigations include the expansion of the above chemistry to synthesise a range of cyclopentadiene-containing compounds, including oligomeric and polymeric materials.  An enantoioselective variant of the dearomatising dCr is being developed also.

Stereospecific ring opening of aziridines

We have previously shown that the ring opening of protected aziridines with sulfone stabilised carbanions , can give access to highly substituted piperidines and piperidones, structures commonly found in a vast range of biologically active compounds.

aziridine ring opening

We are currently exploring the reactivity of these piperidines towards nucleophilic and electrophilic attack and the application of this chemistry towards the synthesis of biologically important natural products.

Natural Product Synthesis

The group maintains a strong interest in the field of natural product synthesis, utilising methodology developed within the group.  Our recent synthesis of alstonerine included a regioselective, stereospecific ring opening of a trisubstituted aziridine; intramolecular Michael reaction, and a late-stage one-pot reduction-Pictet-Spengler cyclisation to give the polycyclic core.  Current targets include lepadiformine, which has been shown to exhibit cytotoxic activity against cancer cell lines, and the indole containing alkaloid hinckdentine A.
natural product targets