©2018 by Ed Anderson Group.

New Synthetic Methods

We extended these studies to realise the first synthesis of yndiamides– alkynes with nitrogen atoms at both ends of the alkyne. Here we used a copper catalyzed coupling of dibromoenamides with amide nucleophiles to form yndiamides under mild conditions. These novel motifs underwent a wide range of transformations, accessing a variety of doubly-aminated heterocycles.

We have long-standing interests in the chemistry of heteroatom-substituted alkynes and alkenes, in particular ynamidesand their derivatives. The synthesis of ynamides can often be limited in the scope of the nitrogen and carbon substituents, and to address this we developed a scalable route to ynamides from dichoroenamides, which are readily accessed from the reaction of an amide with trichloroethene under basic conditions. This method overcomes many traditional limitations, such as the use of carbamates, ureas, and aryl sulfonamides.

These interesting alkynes are typically bench-stable, crystalline solids. They appear to display many similar properties to ynamides, as shown by a selection of transformations effected using transition metal, or Brønsted acid, catalysis.

We have recently developed interests in the synthesis and functionalization of bicyclo[1.1.1]pentanes (BCPs) – molecules that are of significant interest to the medicinal chemistry and agrochemical industries as surrogates for metabolically-susceptible para-substituted benzene rings. Often accessed under relatively harsh reaction conditions, we have developed an 'atom transfer radical addition' (ATRA) route to BCPs where the C–X bond of alkyl halides (typically iodides) undergoes addition across the strained central bond of tricyclo[1.1.1.01,3]pentane (TCP). Displaying broad functional group tolerance, this chemistry provides facile and scalable access to a wide variety of iodo-BCPs, which can undergo further functionalization at the resulting C–I bond.