Lithiation—Borylation Methodology

: Applications in the Synthesis of Polypropionate Fragment and Polyfluoromethylation Reactions of Organoboronic Esters

Abstract

The thesis describes the applications of lithiation–borylation methodology in
polypropionate synthesis and the synthesis of organofluorine compounds.
Firstly, an efficient method for the synthesis of polypropionate fragments based on building block assembly strategy using lithiation–borylation reaction has been
developed. Benzoate ester 302 can react with boronic ester 347 efficiently via lithiationborylation reaction and subsequent oxidation to afford alcohol 353 in good yield and with excellent diastereoselectivity, which can be applied in the synthesis of polypropionate fragment 358, a key intermediate of 6-deoxyerythronolide. Some limitations, such as substrate control and O-migration, were observed in the reaction process.

Secondly, we extensively explored the introduction of difluoromethyl and
monofluoromethyl groups by lithiation–borylation reaction with organoboronic esters. The difluoromethylation and monofluoromethylation reactions proved to
be very challenging due to the instability of in situ generated fluorinated carbanion 417 or 423. Generally, the formation of boronate complex 419 or 424 was not detected. Additionally, we proposed some other strategies for the future work.

Date of Award	7 May 2019
Original language	English
Awarding Institution	University of Bristol
Supervisor	Varinder K Aggarwal (Supervisor) & Chris L Willis (Supervisor)