Synthesis and use of new chiral DABCO derivatives for asymmetric fluorination

Thesis

In this thesis, the synthesis, reactivity and enantioselectivity of novel chiral Selectfluor Analogues were investigated.

Chapter 1: Discussed is a general introduction to Selectfluor as an achiral electrophilic fluorinating reagent and its role as an oxidant in a wide variety of transformations and summarises the aims and objectives of the project.

Chapter 2: The synthesis of chiral 2-monosubstituted, 2,3-disusbstituted and 2,5-disubstituted DABCO derivatives is described. We selected two strategies to prepare these chiral analogues of DABCO. Strategy A takes advantage of a large range of commercially available natural and unnatural amino acids. 2,3-Disubstituted DABCO motifs were prepared via a protocol of Sharpless in strategy B. Eleven chiral DABCO systems have been synthesized, six of which are novel compounds.

Chapter 3 describes the synthesis of novel chiral non-racemic Selectfluor analogues using F₂. Mono-fluorinated chiral DABCOs were found to be unstable at low temperature, however, quaternized derivatives of these chiral reagents induced stability1. The fluorination proved challenging with chiral DABCO derivatives having sterically demanding substituents.

Moreover, we have developed a practical and general process for the synthesis of novel chiral non-racemic Selectfluor using N-fluoropentachloropyridinium triflate 221. This methodology alleviates the need to handle F₂ gas.

In Chapter 4: An investigation into how chiral Selectfluor analogues compare to N-F derived cinchona alkaloids in term of reactivity and enantioselectivity. The reactivity of the chiral Selectfluor analogues was challenged with both activated and less activated substrates. The novel chiral Selectfluor analogues showed superior reactivity than the cinchona alkaloids. Moderate to excellent yields of the desired products were obtained for all of the substrates studied.

Authors: Ilupeju, JO

• Publication date: 2012
• DOI: 10.5287/ora-e2anjrkjo
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Synthetic organic chemistry
• Subjects: Chemistry & allied sciences