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Transformation of D ‐Serine to Highly Functionalized Cyclohexenecarboxylates in Study of Oseltamivir Synthesis
Author(s) -
Lai Joshua,
Fang JimMin
Publication year - 2012
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.201100637
Subject(s) - chemistry , sodium azide , aldehyde , alcohol , alkoxy group , nucleophile , ether , protecting group , acetal , medicinal chemistry , azide , stereochemistry , organic chemistry , catalysis , alkyl
In an attempted synthesis of oseltamivir, D ‐serine was used to prepare ( R )‐Garner aldehyde, which reacted with vinylzinc reagent to give an alcohol product predominating in the (1′ R ,4 S )‐isomer. After the alcohol was protected as p ‐methoxybenzyl ether, the N , O ‐acetal was hydrolyzed and oxidized to an aldehyde, which underwent Reformatsky‐type reaction with ethyl α‐(bromomethyl)acrylate by promotion of indium to give an addition product readily for ring‐closure metathesis to afford 3‐alkoxy‐4‐amido‐5‐hydroxy‐1‐cyclohexenecarboxylates. After activation of the 5‐hydroxy group as methanesulfonate, an attempted substitution reaction with sodium azide gave unexpectedly a cyclic carbamate via an intramolecular nucleophilic attack of the 4‐ tert ‐butoxycarbamate group.