Studies towards the Organocatalytic ‘Dialled In’ Synthesis of Chiral, Non-Racemic Aziridines, and Amino Acids, Containing Multiple Isotopic Labels

Within this thesis, a highly effective one-pot methodology (based around the use of the organocatalyst pyridinium triflate) has been developed for the highly cis-selective synthesis of N-aryl 3-aryl-aziridine-2-carboxylates as racemates in yields of up to 80 %. This methodology has been extended by the use of a highly acidic C2 symmetric 3,3’- anthracenyl functionalised BINOL triflylphosphoramide organocatalyst, which allows for the formation of the desired cis- N-aryl 3-aryl-aziridine-2-carboxylates in an effective and highly enantioselective manner (affording the desired materials in yields of up to 81 %, and e.e.s of >99 %). Utilising the methodology developed within the first part of the thesis, enantio- and isotopically enriched cis- N-aryl 3-aryl-aziridine-2-carboxylates have been synthesised in a regioselective manner; with deuterium selectively introduced at the C2, and/or C3 positions of the aziridine ring with generally >90 % isotopic enrichment. Further to this, these aziridines have been submitted to ring opening methodologies in order to produce enantiomerically enriched a-amino acid derivatives bearing regioselectively introduced deuterium labels (with generally >90 % isotopic enrichment), in yields of up to 97 %, and e.e.s of up to 97 %, Finally, these methods have been combined in order to synthesise 5 target molecules consisting of functionalised enantioenriched a-amino acid derivatives bearing multiple isotopic labels including deuterium, 15N, and 18O, in what has become known as the ‘Dialled In’ methodology.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2012

Author dc:creator

• Thurston, Sean

Language dc:language

en