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

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 13-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.

Automated summary

This study presented a continuous flow process that coupled a Curtius rearrangement step with a biocatalytic impurity tagging strategy to produce a series of valuable Cbz-carbamate products. Immobilized CALB was used to transform residual benzyl alcohol into benzyl butyrate, resulting in the creation of desired carbamate structures with high yield and purity. Derivatization of the products through complementary flow-based Michael addition reactions demonstrated the ability to create 13-amino acid species, highlighting the potential applicability of this work in the pharmaceutical and specialty chemical industries.