Periodic Reporting for period 1 - TransNic (Enantioselective Nickel-Catalyzed trans-Carbometallative Couplings and Cyclizations)
Période du rapport: 2016-08-01 au 2018-07-31
The original objectives of this project were to:
(a) Define the scope and limitations of this method in producing a wide range of cyclic compounds.
(b) Develop variants of these reactions that are able to give products selectively as a single enantiomer (which is defined as a non-superimposable mirror-image form). The ability to produce compounds as single enantiomers is very important because the exact function of compounds within biological systems (e.g. if the compounds are to be used as medicines) often depends upon which mirror image they exist in.
The work in this project was highly successful, which led us to further develop and expand the chemistry in the same area. These new methods were successful in producing a wide range of cyclic products in good yields under mild reaction conditions, and at the time of writing, this research has been published in two articles in a leading general chemistry journal. The remaining work is being currently being prepared for publication (Scheme 1–3).
"
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.