Now showing 1 - 4 of 4
- PublicationCoupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivativesA continuous flow process is presented that couples a Curtius rearrangement step with a biocatalytic impurity tagging strategy to produce a series of valuable Cbz-carbamate products. Immobilized CALB was exploited as a robust hydrolase to transform residual benzyl alcohol into easily separable benzyl butyrate. The resulting telescoped flow process was effectively applied across a series of acid substrates rendering the desired carbamate structures in high yield and purity. The derivatization of these products via complementary flow-based Michael addition reactions furthermore demonstrated the creation of β-amino acid species. This strategy thus highlights the applicability of this work towards the creation of important chemical building blocks for the pharmaceutical and speciality chemical industries.
- PublicationExploiting Biocatalysed Processes for Telescoped Curtius Rearrangement Reactions in Flow Mode(University College Dublin. School of Chemistry, 2021)
;0000-0002-6890-6023The Curtius rearrangement of carboxylic acids i in the presence of benzyl alcohol was performed as a continuous flow process, enabling a safer and easier scale-up process. Inline purification processes, involving immobilized CALB and a mixture of A-15/A-21, were exploited to afford clean Cbz-carbamate product ii. An excess of benzyl alcohol was required to drive the reaction to completion. Therefore, immobilized CALB was employed to chemoselectively transform the residual benzyl alcohol into easily separable benzyl butyrate iv. To demonstrate the versatility of the products, the Cbz-carbamate ii was further derivatized into alkylated Cbz-carbamate v and ß- amino acids vi. 387
- PublicationTandem Continuous Flow Curtius Rearrangement and Subsequent Enzyme-Mediated Impurity TaggingThe use of continuous flow as an enabling technology within the fine chemical and pharmaceutical industries continues to gain momentum. The associated safety benefits with flow for handling of hazardous or highly reactive intermediates are often exploited to offer industrially relevant and scalable Curtius rearrangements. However, in many cases the Curtius rearrangement requires excess nucleophile for the reaction to proceed to high conversions. This can complicate work procedures to deliver high-purity products. However, tandem processing and coupling of the Curtius rearrangement with an immobilized enzyme can elegantly facilitate chemoselective tagging of the residual reagent, resulting in a facile purification process under continuous flow.
Scopus© Citations 10 45
- PublicationFunctional Group Interconversion Reactions in Continuous Flow ReactorsAn overview of the current uptake of continuous flow techniques for various functional group interconversion reactions is presented. Besides highlighting a variety of prominent examples and their main features, this review provides insights into specific reaction classes, such as oxidations, reductions, rearrangements as well as different C-H functionalization processes. While this review can only include key examples from the last decade, the reader will find a solid foundation of important transformations along with further references to inform and appreciate the opportunities arising from modern synthesis technologies such as flow synthesis.
Scopus© Citations 4 157