About the Project
Since the beginning of the last century, it has been known that a diverse array of Lewis-bases such as tertiary phosphines/amines, imidazoles and pyridines can act as nucleophilic catalysts. These catalysts promote a diverse range of transformations including the addition of alcohols to ketenes, the rearrangement of O-acylated enolates and the acylation of alcohols by acid anhydrides. Of these, the latter reaction has been of the greatest synthetic utility, largely due to the development of 4-N,N,-dimethylaminopyridine (DMAP). This highly active, commercially available (and inexpensive) catalyst promotes the acylation of primary, secondary and even tertiary alcohols, often several orders of magnitude faster than the corresponding uncatalysed reaction, and it has found such widespread use that it is treated as a general laboratory reagent by most organic chemistry research groups. Given the success of DMAP, it is perhaps surprising that the first example of a chiral variant for asymmetric synthesis was not reported until 1996.
In the last 23 years many chiral nucleophilic catalysts have been developed, however all suffer from one key problem: in order to maximise the potential for stereochemical information transfer, the location of chirality as close to the nucleophilic site is desirable. However, this is costly: steric bulk proximal to the endocyclic N-atom (in the case of DMAP) dramatically reduces nucleophilicity and activity. In general, the further the chiral units are from the nucleophilic site, the faster the catalysis, but the narrower the scope and the lower the reaction temperature required. Hindered substrates are usually problematic. Nucleophilic catalysis is thus not yet a solved problem.
This project intends to develop a completely new organocatalytic design concept which circumvents this activity-selectivity conundrum: providing catalysts capable of being highly nucleophilic while being able to bring bulky chiral units on the catalyst to bear on the reaction when needed. Applications in heterocycle synthesis, asymmetric C-C bond formation, peptide formation and other asymmetric transformations are envisaged.
This project would suit an enthusiastic European Union student with an interest in organic synthesis and catalysis keen on joining a vibrant group with state-of-the art facilities and equipment.. The student will have the opportunity to develop their skills in (training will be provided) the following core areas: organic synthesis, NMR spectroscopy, analytical HPLC, catalysis snd will automatically become a member of the Dublin Chemistry Graduate School. Students should have (or be about to obtain) a 2.1 degree or higher and be able to provide the names of two academic referees.
Students interested in undertaking a PhD in our group in this research area should register their interest as soon as possible. Informal enquiries can be made to Professor Stephen Connon ([email protected]).
‘Enantioselective catalysis by fluoride ions’, R. Craig, M. Litvajova, S. A. Cronin and S. J. Connon, Chem. Commun. 2018, 54, 10108.
‘Dynamic kinetic resolution of bis-aryl succinic anhydrides: enantioselective synthesis of densely functionalised butyrolactones’, R. Claveau, B. Twamley and S. J. Connon*, Chem. Commun. 2018, 54, 3231.
‘Enantioselective Alkylation of 2-Oxindoles Catalyzed by a Bifunctional Phase-Transfer Catalyst: Synthesis of (-)-debromoflustramine B’, R. Craig, E. Sorrentino and S. J. Connon*, Chem. Eur. J. 2018, 24, 4528
‘Direct, efficient NHC-catalysed aldehyde oxidative amidation: In situ formed benzils as unconventional acylating agents’, V. Kumar and S. J. Connon*, Chem. Commun. 2017, 53, 10212.
‘A practical aryl unit for azlactone dynamic kinetic resolution: orthogonally protected products and a ligation-inspired coupling process’, S. Tallon, F. Manoni and S. J. Connon*, Angew. Chem. Int. Ed. 2015, 54, 813
‘Catalytic asymmetric Tamura cycloadditions’, F. Manoni and S. J. Connon*, Angew. Chem. Int. Ed. 2014, 53, 2628.
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