Decarboxylative Radical Additions to Vinyl Boronic Esters

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

This thesis details the development of novel decarboxylative radical addition reactions to vinyl boronic esters using photoredox catalysis, enabling the efficient and rapid access of functionalised alkyl boronic esters from abundant feedstock chemicals. Key to the success of these methodologies is the stabilised α-boryl radical intermediate generated upon radical addition to the vinyl boronic ester, which can undergo a range of terminating events to yield a diverse library of complex boronic ester products.

Firstly, the decarboxylative radical addition reaction of carboxylic acids to vinyl boronic esters was developed to directly access alkyl boronic esters using photoredox catalysis. The reaction was applied to a range of carboxylic acids, including α-amino, α-oxy and alkyl acids providing the corresponding boronic ester products in good to excellent yields. Moreover, the reaction could be applied to a range of substituted vinyl boronic esters. Mechanistic studies confirmed a radical-polar crossover mechanism, involving an unprecedented single-electron reduction of the α-boryl radical to the corresponding α-boryl anion, which is subsequently protonated.

Having set the stage for photoredox-mediated decarboxylative radical additions to vinyl boronic esters, we demonstrated that we could trap the α-boryl anion with an electrophile tethered to the vinyl boronic ester, enabling the synthesis of highly functionalised, polysubstituted cyclopropyl boronic esters. Mechanistic studies supported a radical-polar crossover mechanism involving an intramolecular SN2 cyclisation to yield the cyclopropane.

Finally, to introduce further molecular complexity into these molecules, a decarboxylative conjunctive cross-coupling of vinyl boronic esters with carboxylic acids and aryl iodides using metallaphotoredox catalysis was developed. Trapping of the intermediate α-boryl radical with an aryl nickel complex enabled a cross-coupling event to yield complex benzylic boronic ester products. A range of α-amino acids, mainly secondary amino acids, and tertiary α-oxy acids with aryl iodides were successfully employed and the methodology was applied to the synthesis of four sedum alkaloid natural products.
Date of Award29 Sep 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorVarinder K Aggarwal (Supervisor)

Cite this

Decarboxylative Radical Additions to Vinyl Boronic Esters
Mega, R. S. (Author). 29 Sep 2020

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)