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Synthesis of substituted azetidines and spirocyclic diazetidines
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Pancholi, Alpa K. (2017) Synthesis of substituted azetidines and spirocyclic diazetidines. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3171613~S15
Abstract
Chapter 1 begins with an introduction to azetidines, including a discussion of the methodologies for their synthesis, their applications, relevance in natural products and as building blocks in medicinal chemistry. It then describes the development of a new asymmetric route to 2-substituted azetidin-3-ones using Enders’ SAMP/RAMP auxiliary. A one-pot process was developed involving the metalation of SAMP hydrazones of N-Boc-azetidin-3-one, alkylation and subsequent in situ hydrolysis to give the substituted products. Various bases and reaction conditions were explored to find optimal conditions for maximal yield and enantioselectivity. A representative range of electrophiles were screened including alkyl, allyl and benzyl halides and carbonyl compounds, producing enantioselectivities of up to 85% ee. Multiple substitution on the azetidin-3-one ring was briefly explored by repetition of the alkylation/hydrolysis sequence. Derivitisation by way of Pictet-Spengler reactions was used to confirm the absolute configuration at the newly created stereocentre.
Chapter 2 begins with an introduction to 1,2-diazetidines outlining methods for their synthesis, before introducing the relevance of these nitrogen spirocycles. This chapter then describes two routes for the synthesis of these novel spirocyclic 1,2- diazetidines by (i) formation of the diazetidine ring and (ii) functionalisation of a range of 3-methylene-1,2-diazetidines including differentially protected variants. The diazetidines were subjected to dichloro- and difluorocyclopropanation with the latter achieved in high yields. Additionally, reactions with tetracyanoethylene by way of highly asynchronous [2π+2π] cycloadditions proceeded in near quantitative yield. In this way, a range of novel 4,5-diazaspiro[2.3]hexane and 1,2- diazaspiro[3.3]heptane spirocycles were produced.
Chapter 3 details the experimental procedure and characterisation for all the novel compounds synthesised.
| Item Type: | Thesis or Dissertation (PhD) | ||||
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| Subjects: | Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica |
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| Library of Congress Subject Headings (LCSH): | Lactams, Electrophiles, Carbonyl compounds, Pharmaceutical chemistry | ||||
| Official Date: | September 2017 | ||||
| Dates: |
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| Institution: | University of Warwick | ||||
| Theses Department: | Department of Chemistry | ||||
| Thesis Type: | PhD | ||||
| Publication Status: | Unpublished | ||||
| Supervisor(s)/Advisor: | Shipman, Michael | ||||
| Sponsors: | Engineering and Physical Sciences Research Council | ||||
| Extent: | 210 leaves : illustrations | ||||
| Language: | eng |
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