Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie¹
• Thomas S. Moody^2,3
• Megan Smyth²
• Scott Wharry²
• Marcus Baumann¹

• ¹School of Chemistry, University College Dublin, D04 N2E2, Ireland
• ²Almac Group Ltd., Craigavon BT63 5QD, United Kingdom
• ³Arran Chemical Company, Athlone, Co. Roscommon N37 DN24, Ireland

A 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.

Read the publication that featured this abstract