/l-Ketonitrile-Derived Protecting Groups of the Amino Function. Synthesis of Amino AlcoholsThe amino group of natural L-amino acid esters is protected by condensation with 2-oxocyclopentanenitrile (1) or 2-formyl-2-pheny~dtetonitrik (10). Only the ester group of the formed cyanoenamino esters 2 and 11 reacts with nucleophilic reagent!; such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes I and 2). Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid. This sequence of reactions allows to prepare derivatives of L-tyrosinol from (-)-L-tyrosine (see, e.g., Scheme 4 ) . Cyanoenamino esters 11 are readily methylated at the N-atom to give N-methylated cyanoenamino esters (Scheme 3 ) . This property is exploited on the way of a multistep procedure to obtain N-methylated amino alcohols homologous to natural (-)-(1 R,2S)-ephedrine.Introduction. -Nous avons deji d6crit [l] [2] la preparation des amino-alcools 4 a partir d'esters d'amino-acides naturels, dont la fonction amino est masquke sous forme cyanohamino dtrivt du 2-oxocyclopentanenitrile (1; schirna 1 ). La fonction ester des cyanotnamino-esters 2 (Z = OR3) peut subir diverses attaques nucltophiles qui ne modifient pas la configuration d'origine. Si le reactif nucleophile 'Nu' mis en jeu est un organomktallique (KMgX ou RLi), on obtient des cyanoenamino-alcools optiquement actifs 3 (R' = R2 = alkyle ou aryle), le groupe cyanotnamino restant inchangt [l]. Si 'Nu' est un amidure, l'esttx est transformi: en amide disubstitut 5 (Z = N R R ) avec conservation de l'activitk optique; il est ensuite possible d'acceder, par action du phenyllithium (PhLi), aux cetones ,aromatiques correspondantes 6 (Z = Ph), puis par action du NaBH, dans I'EtOH, aux alcools secondaires 3 (R' = H, R2 = Ph) [2]. L'tlimination du groupe protecteur 2-cyanocyclopent-1 -enyle (Ccp) effectuke par hydrolyse acide conduit finalement aux amino-alcools 4 et au reactif 1 (schPrna I ) . Ces rtactions s'effectuent sans racemisation [3].

No abstract

Synthesis of (–)‐(1R,2S)‐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 NaBH4 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 (–)‐(1R,2S)‐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.