Synthesis of Borylated Cyclobutanes via a Strain-Release 1,2-Metallate Rearrangement

Abstract

Cyclobutanes are important motifs in natural products and are increasingly found in medicinal chemistry since they can provide a defined spatial arrangement of substituents. This thesis describes a new route to 1,1,3-trisubstituted cyclobutanes using a novel strain-release boronate complex.
Specifically, reaction of lithiatedbicyclo[1.1.0]butane with a boronic ester furnished an intermediate boronate complex which was reacted with a broad set of electrophiles. The electrophile and boronic ester substituent effectively add across the highly strained C–C σ-bond of the bicyclo[1.1.0]butane, which acts as a conjunctive reagent. This modular three-component coupling occurs with excellent levels of diastereoselectivity generating 1,1,3-trisubstituted cyclobutanes, decorated with an array of functional groups. The thesis also describes an improved route to lithiated bicyclo[1.1.0]butane.

Date of Award	23 Jan 2019
Original language	English
Awarding Institution	University of Bristol
Supervisor	Varinder K Aggarwal (Supervisor)