At the beginning of this project, the Fellow expanded upon the preliminary results already obtained in the Host Laboratory in enantioselective arylative cyclizations of alkynes tethered to a Z-allylic phosphate, to give enantioenriched chiral tetrahydropridines (Scheme 1). The Fellow successfully expanded the scope of the reaction to encompass a range of diverse examples, and this was published in Angew. Chem. Int. Ed. 2017, 56, 8216.
Inspired by these results, the Fellow decided to investigate whether electrophiles other than Z-allylic phosphates could be used, and he discovered that the method could be used for the enantioselective synthesis of highly functionalized chiral cyclopentenones by reaction of arylboronic acids with malonate esters tethered to an alkyne (Scheme 2). This work was published in Angew. Chem. Int. Ed. 2018, 57, 9122.
After these highly encouraging results, the Fellow also found that alkyne-tethered amides were also applicable to this chemistry and they produces highly functionalized pyrroles (Scheme 3). Pyrroles are highly important structures found in many naturally occurring and biologically active compounds. At the time of writing, this work is currently being prepared for publication.
Dissemination Activities:
At the time of writing, two papers have been published in a leading general chemistry journal while the remaining results are currently being prepared for publication as a communication. There are some final experiments which need to be completed, and this is being done by colleagues of the Fellow. We anticipate this will be completed in the next month or two, with manuscript submission to follow shortly thereafter. This work has also been presented in research seminars in industry and at conferences within the UK and internationally.
Training and Career Progression of the Fellow:
When the Fellowship began, the Fellow had expertise in gold mediated chemistry, and medicinal chemistry rather than in the development of new organic reactions using nickel catalysis, which is the main area of this project. Therefore, the Fellow had to learn new skills and gain new knowledge, but did this very successfully. At the end of this project, the Fellow is now highly trained in this area. Currently, the Fellow is searching for a new postdoctoral/research scientist position to consolidate his skills in preparation for an independent research career.
