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Synthesis of (+)‐Dumetorine and Congeners by Using Flow Chemistry Technologies
Author(s) -
Riva Elena,
Rencurosi Anna,
Gagliardi Stefania,
Passarella Daniele,
Martinelli Marisa
Publication year - 2011
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.201100300
Subject(s) - flow chemistry , enantiopure drug , chemistry , yield (engineering) , reagent , continuous flow , organic chemistry , metathesis , combinatorial chemistry , total synthesis , solvent , salt metathesis reaction , catalysis , enantioselective synthesis , biochemical engineering , materials science , polymerization , polymer , metallurgy , engineering
An efficient total synthesis of the natural alkaloid (+)‐dumetorine by using flow technology is described. The process entailed five separate steps starting from the enantiopure ( S )‐2‐ (piperidin‐2‐yl)ethanol 4 with 29 % overall yield. Most of the reactions were carried out by exploiting solvent superheating and by using packed columns of immobilized reagents or scavengers to minimize handling. New protocols for performing classical reactions under continuous flow are disclosed: the ring‐closing metathesis reaction with a novel polyethylene glycol‐supported Hoveyda catalyst and the unprecedented flow deprotection/Eschweiler–Clarke methylation sequence. The new protocols developed for the synthesis of (+)‐dumetorine were applied to the synthesis of its simplified natural congeners (−)‐sedamine and (+)‐sedridine.