Photochemical approaches to the synthesis of highly functionalised cyclobutanes

  • Mark Deeprose

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

A new method has been developed to obtain densely functionalised cyclobutanes, wherein α-halo maleimides undergo sensitised [2+2] photocycloaddition under UV (366 nm) conditions to give α-halocyclobutanes and cyclobutenes in a highly regioselective manner in up to 78% yields over multiple steps. The dehalogenation of the α-chloride, by visible-light photocatalysis, gives a tertiary cyclobutyl radical, leading to radical addition to a range of suitable substrates to form a quaternary carbon-carbon bond in a diastereoselective manner in up to 94% yields of the desired highly functionalised cyclobutane. The protocol shows broad functional group tolerance and the succinimide ring can be further functionalised regioselectively in a variety of ways. These results are discussed in Chapter 1.

A novel approach towards cyclobutyl spirocycles was developed. An alkyne tethered redox active ester was found to undergo a visible-light [2+2] photocycloaddition with a maleimide to give a cyclobutene containing a redox active tether using a novel thioxanthone sensitiser. Introducing a diboron source such as B₂cat₂, acts as a reductant and produces alkyl radical. The pertinent radical undergoes 5-exotrig cyclisation forming a cyclobutyl spirocycle which can trap out boron to give the desired functionalised cyclobutane. The development of this methodology is discussed in Chapter 2.

A total synthesis of albiflorin has been undertaken. The current proposed route was based on the protocol developed described in Chapter 1, and therefore has scalability and is transition-metal free. The synthetic route and methodology developed is discussed in Chapter 3.

The results in this thesis have been communicated: M. J. Deeprose, M. Lowe, A. Noble, K. I. Booker-Milburn, and V. K. Aggarwal, Org. Lett. 2022 24, 137- 141.
Date of Award21 Jun 2022
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorVarinder K Aggarwal (Supervisor) & Kevin I Booker-Milburn (Supervisor)

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