A stereoselective, catalytic strategy for the in-flow synthesis of advanced precursors of rasagiline and tamsulosin.
The diastereoselective, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, was investigated to afford immediate precursors of chiral APIs (Active Pharmaceutical Ingredients). The carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol. By this metal-free approach, the formal synthesis of rasagiline and tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. The results of these explorative studies represent a new, important step towards the development of automated processes for the preparation of enantiopure biologically active compounds.
Dipartimento di Chimica, Universita' degli Studi di Milano, via Golgi 19, 20133 Milano, Italy.
Davide
D
Brenna
Dipartimento di Chimica, Universita' degli Studi di Milano, via Golgi 19, 20133 Milano, Italy.
Margherita
M
Pirola
Dipartimento di Chimica, Universita' degli Studi di Milano, via Golgi 19, 20133 Milano, Italy.
Laura
L
Raimondi
Department of Chemistry and Chemistry Center of Évora, University of Évora, Rua Romão Ramalho, 59, 7000 Évora, Portugal.
Anthony J
AJ
Burke
Dipartimento di Chimica, Universita' degli Studi di Milano, via Golgi 19, 20133 Milano, Italy. Electronic address: maurizio.benaglia@unimi.it.
Maurizio
M
Benaglia
D000588:Amines / Q000737:chemistry; D002384:Catalysis; D007097:Imines / Q000737:chemistry; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry*; D000077409:Tamsulosin
D000588:Amines; D007097:Imines; D007189:Indans; D013449:Sulfonamides; C031967:rasagiline; D000077409:Tamsulosin
Active pharmaceutical ingredients; Chiral amines; Flow chemistry; Flow reactors; Metal-free catalysis; Reduction; Stereoselective synthesis