The development and implementation of continuous flow procedures for photochemical transformations

Photochemistry, the employment of light as traceless reagent, has been utilised in organic synthesis  for decades. It allows access to complex, highly functionalised molecules from simple starting  substrates that would be otherwise inaccessible by classical thermal means. However, the synthetic  method had drawbacks in that it is notoriously inefficient leading to low product yields and long  reaction times. Microfluidic technology or ‘continuous flow’ gives an answer to these problems whilst  offering extra advantages such as enhanced reaction safety, simpler reaction set up and the ability to  carry out multistep syntheses without excess user handling. Presented here is a thorough investigation  into the advantages and drawbacks of continuous flow, in the synthesis of both cyclobutane-based  and furan-based molecules. 

Chapter 2 reports the first application of a continuous flow procedure in the well-established dimerization of N-vinylcarbazole (NVC). The procedure was fully optimised using a Design of  Experiments (DoE) approach with varying factors including flow rate, lamp wavelength and catalyst  loading. This reaction was scaled from 1 mmol to 10 mmol with no additional complications and  minimal impact on the yield. The newly development continuous flow procedure was then applied to the synthesis of lignan-based cyclobutanes including the natural products magnosalin and pellucidin A, as well as a brief exploration into the dimerization of cyclic enamines. 

Chapter 3 further expands on the continuous flow dimerization procedure and reports the synthesis of novel bromocarbazole-based cyclobutanes. The commercially available bromocarbazoles were vinylated using an Ir-catalysed method and subjected to dimerization in both batch and continuous flow. This allowed for a comparison of the two procedures showing that the continuous flow synthesis had reduced reaction times, increased yields and an overall simpler reaction set up. The continuous flow procedure was also expanded to several other vinylcarbazoles with pre-installed functionalities such as hydroxyl, vinylethers and tert-butyl groups. Post-modification of the cyclobutanes was performed through Pd-catalysed Suzuki coupling and borylation reactions. 

Chapter 4 develops on previous work reported by the Kimber group into the synthesis of furan containing molecules. The two-step synthetic procedure was fully transferred from batch into a continuous flow set up. By telescoping the photooxidation step and Appel-type dehydration negating the use of pure O2 and the need to isolate the peroxide intermediate. Both the batch and continuous flow procedures were then applied to the synthesis of 2,5-diaryl furan motifs with functionalities including halogens, alkyls and trifluoromethyls. Post-modification allowed for the molecules to be installed with further boryl and aryl groups.