Use this URL to cite or link to this record in EThOS:
Title: Iterative reagent-controlled homologation of boronic esters
Author: Burns, Matthew
ISNI:       0000 0004 5354 9494
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
Availability of Full Text:
Access from EThOS:
This thesis is concerned with developing a protocol for the reagent-controlled iterative homologation of boronic esters. Initial work focused on the synthesis of the highly enantioenriched Grignard reagent (5)-261 generated from sulfoxide (-)-anti-250 using a sulfoxide ligand exchange reaction. Grignard reagent (5)-261 has been successfully applied in the homologation of boronic esters 175 and (R)-176. However, it was found that Grignard reagent (5)-261 did not possess sufficiently high reactivity to homologate the sterically more hindered boronic ester 177. We therefore explored the use of highly enantioenriched Iithio derivatives as reagents for the homologation of boronic esters. Methods to generate Iithiated benzoates through a sulfoxide ligand exc~ange reaction proved fruitless as competing deprotonation occurred instead. A successful protocol was ultimately found in utilising the tin - lithium exchange reaction. A twostep procedure was developed that enabled the synthesis of either enantiomer of stannane 328 in 99.9 : 0.1 e.r.. Subjecting stannane 328 to a tin - lithium exchange generated Iithiated benzoate 272 which proved to be a highly effective reagent for the iterative homologation of boronic esters. Using Iithiated benzoate 272 we were able to rapidly construct molecules with ten contiguous stereocentres through an iterative homologation sequence. By choosing to use either (5)-272 or (R)-272 we have developed a system where any diastereoisomer can be synthesised. To demonstrate the potential of the methodology we have synthesised boronic esters 339,350 and 353. We have shown that by controlling. the configuration of the stereoecentres along a branched carbon chain we are able to control the conformation of the carbon backbone in the solid state. The alternating syn-anti diastereoisomer 350 causes the molecule to adopt a linear conformation in the solid state in order to minimise destabilising syn-pentane interactions. The all syn diastereoisomer, boronic ester 353 was successfully synthesised using our methodology. Additionally, we have shown that the crystalline derivative 355, adopts a helical conformation in the solid state, again to minimise destabilising syn-pentane interactions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available