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Title: Asymmetric synthesis of α-tertiary amines by combination of biocatalysis and organolithium-mediated rearrangements of ureas
Author: Zawodny, Wojciech
ISNI:       0000 0004 7656 5411
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2017
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Quaternary centres bearing a nitrogen atom are found in natural products and therapeutic agents but they represent a remarkably challenging synthetic motif to access when stereochemical control is required. This thesis details investigations into the development of an innovative approach that - by combining biocatalysis with organolithium chemistry - allows the synthesis of enantioenriched α-tertiary amines. The strategy relies on the initial enzymatic asymmetric synthesis of amines. Two complementary pathways were identified: deracemisation with amine oxidases or enantioselective reduction with imine reductases. The enantioenriched amines were converted to the corresponding N-benzyl-N'-aryl ureas and subsequent organolithium-mediated stereospecific aryl migration developed in the Clayden group were carried out to obtain α-tertiary amines. Various scaffold were investigated: 1,1-disubstituted 1,2,3,4-tetrahydroisoquinoline, 2,2-disubstituted azepane and 1,1-disubstituted 2,3,4,5-tetrahydro-1H-benzo[c]azepine derivatives were successfully synthesised. The methodology was extended to acyclic systems, giving 3-pyridyl-derived α-tertiary amines.
Supervisor: Turner, Nicholas Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: biocatalysis ; organolithium ; rearrangement ; alpha-tertiary amines ; asymmetric synthesis ; azepanes ; pyridines