Lithiation-Borylation Methodology: New Classes of Metal Carbenoid Precursors for the Iterative Homologation of Boronic Esters

  • Giorgia Casoni

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

The work described in this thesis details the development of new classes of metallated carbenoids to be used in the homologation of boronic esters. 2-Phenyl-azetidinium ylide, generated in situ by deprotonation of 2-phenylazetidinium triflate, reacted with boronic esters to give, after ring-opening 1,2-metallate rearrangement, γ-dimethylamino tertiary boronic esters. The process proved to be not stereospecific, owing to the configurational instability of the generated intermediated ylide, which presumably exists in equilibrium with the open chain carbene species. The use of enantioenriched α-sulfinyl benzoates as precursors to lithium and magnesium carbenoids for the stereoselective reagent-controlled homologation of boronic esters has also been developed. α-Sulfinyl benzoates could be synthesised in very high enantiopurity from racemic lithiated benzoates by transmetalation to the corresponding magnesiated benzoates followed by electrophilic trapping with enantiomerically pure Andersen’s sulfinate. Alternatively, the α-sulfinyl benzoates could be prepared by alkylation of methylene α-sulfinyl benzoate. The carbenoid precursors were subsequently employed in the homologation of boronic esters, a process that proved to be efficient using either t-BuLi or i-PrMgClžLiCl to trigger the sulfoxide−metal exchange, giving the homologated products in high yield and excellent stereofidelity. The development of one-, two- and three-carbon building blocks for the homologation of boronic esters enabling the introduction of diverse functional groups has also been investigated.
Date of Award25 Sept 2018
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorJonathan Knowles (Supervisor) & Varinder K Aggarwal (Supervisor)

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