Process Catalyst Mass Efficiency by Using Proline Tetrazole Column-Flow System.

Generally, organocatalysts are not decomposed during chemical transformation, which is different from traditional metal catalysts. To improve catalytic processes efficiency, various studies have been applied to flow synthesis for organocatalysis. Furthermore, many immobilized organocatalysts have been used for heterogeneous flow synthesis, which requires huge amounts of immobilized catalyst and requires several steps to prepare. We took advantage of organocatalysts with low-polarity organic solvent and developed a flow system through a packed-bed column with simply proline tetrazole (5-(2-pyrrolidinyl)-1H-tetrazole) for heterogeneous organocatalytic synthesis. Under ambient temperature, this heterogeneous organocatalyst continuous flow-column system with ketones as a donor provides aldol, Mannich, and o-nitroso aldol reactions in up to quantitative yields with excellent enantio- and chemoselectivity values. Our heterogeneous-flow synthesis provides extremely low process catalyst mass efficiency and continuous production without changing the packed-bed catalyst column.