The convenient, metal-free reduction of imines that contain an inexpensive and removable chiral auxiliary allowed for the synthesis of the immediate precursors of chiral active pharmaceutical ingredients (APIs). This protocol was carried out under batch and flow conditions to give the correspoding products in high yields with almost complete stereocontrol. In the presence of trichlorosilane, an inexpensive and nontoxic reducing agent, and an achiral Lewis base such as N,N-dimethylformamide, the formal syntheses of Rivastgmine, calcimimetic NPS R-568, and a Rho kinases inhibitor were successfully accomplished. For the first time, both the diastereoselective imine reduction and the auxiliary removal were efficiently performed in a micro- or mesoreactor under continuous-flow conditions, which paved the way towards the development of a practical process for the syntheses of industrially relevant, biologically active, enantiopure N-alkylamines.
Stereoselective metal-free reduction of chiral imines in batch and in flow mode. A convenient strategy for the synthesis of chiral Active Pharmaceutical Ingredients / D. Brenna, M. Benaglia, R. Porta, S.D. Fernandes, A.J. Burke. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1099-0690. - 2017:1(2017), pp. 39-44.
|Titolo:||Stereoselective metal-free reduction of chiral imines in batch and in flow mode. A convenient strategy for the synthesis of chiral Active Pharmaceutical Ingredients|
BRENNA, DAVIDE (Primo)
BENAGLIA, MAURIZIO (Secondo)
|Parole Chiave:||Amines; Chiral auxiliaries; Flow chemistry; Microreactors; Reduction|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||2017|
|Data ahead of print / Data di stampa:||25-nov-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/ejoc.201601268|
|Appare nelle tipologie:||01 - Articolo su periodico|