Premium
Synthèse d'homologues de la (–)‐‐(1 R ,2 S )‐norephedrine
Author(s) -
Lamant Maurice,
Guignard Alain
Publication year - 1987
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19870700507
Subject(s) - chemistry , lithium amide , phenyllithium , amide , amino acid , hydrolysis , stereochemistry , alcohol , ketone , enantiomer , diastereomer , lithium (medication) , alkyl , organic chemistry , enantioselective synthesis , catalysis , medicine , biochemistry , endocrinology
Synthesis of (–)‐(1 R ,2 S )‐Norephedrine Homologues The amino function of esters of some simple natural amino acids I is blocked in the form of a cyanoenamine by means of 2‐oxocyclopentanecarbonitrile, so that the corresponding cyanoenamino esters II are obtained. The reaction of a disubstituted lithium amide with II leeds to the cyanoenamino‐amides VI . The amide function present in VI is then transformed into an aromatic ketone by means of phenyllithium, to give the (benzoylalkyl)aminocyclopentenecarbonitriles VII . Reduction of Compounds VII with NaBH 4 in EtOH −80° affects only the keto function and leads to the [(α‐hydroxybenzyl)alkyl]amino‐cyclopentenecarbonitriles VIII . The amino function is then deprotected by acid hydrolysis to give the amino‐alcohols IX with yields close to 50%; in every amino‐alcohol IX , the erythro isomer, homologous to natural (–)‐(1 R ,2 S )‐norephedrine is the more abundant or the single product. All the polyfunctional compounds prepared conserve optical activity; it has been demonstrated that the amino‐alcohols IX are pure enantiomers and that no racemisation lakes place at any step of their synthesis.