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Enantioselective Organophotocatalytic Telescoped Synthesis of a Chiral Privileged Active Pharmaceutical Ingredient
Author(s) -
Herbrik Fabian,
Sanz Miguel,
Puglisi Alessandra,
Rossi Sergio,
Benaglia Maurizio
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202200164
Subject(s) - enantioselective synthesis , active ingredient , continuous flow , chemistry , combinatorial chemistry , catalysis , alkylation , ingredient , flow chemistry , organic chemistry , biochemical engineering , bioinformatics , food science , engineering , biology
The continuous flow, enantioselective, organophotoredox catalytic asymmetric alkylation of aldehydes was studied, by using a homemade, custom‐designed photoreactor for reactions under cryogenic conditions. Going from microfluidic conditions up to a 10 mL mesofluidic reactor, an increase of productivity by almost 18000 % compared to the batch reaction was demonstrated. Finally, for the first time, a stereoselective photoredox organocatalytic continuous flow reaction in a fully telescoped process for an active pharmaceutical ingredient (API)synthesis was successfully achieved. The final process consists of four units of operation: visible light‐driven asymmetric catalytic benzylation under continuous flow, inline continuous work‐up, neutralisation and a final oxidative amidation step afforded the pharmaceutically active molecule in 95 % e.e.