Photoinduced electron transfer (PET) promoted oxidative activation of 1-(N-Benzyl-N-methylglycyl)-(S)-prolinol: development of novel strategies towards enantioselective syntheses of α-amino acids, their N-methyl derivatives and α-hydroxy acids employing (S)-prolinol as a recyclable chiral auxiliary

Abstract

PET activation of 1-(N-benzyl-N-methylglycyl)-(S)-prolinol (1) in dry acetonitrile, utilizing 1,4-dicyanonaphthalene (DCN) as a light-harvesting electron-acceptor and methyl viologen (MV⁺⁺) as an electron-transfer mediator, leads to the formation of 3-[benzyl(methyl)amino]perhydropyrrolo[2,1-c][1,4]oxazin-4-one (3). When this photolysis is carried out in aqueous acetonitrile, exclusively 3-hydroxyperhydropyrrolo[2,1-c][1,4]oxazin-4-one (4) is produced. The formation of 3 can be rationalized in terms of intramolecular cyclization of the in situ generated iminium cation intermediate (2) by the OH moiety of (S)-prolinol, while 4 is generated by hydrolysis of 2 followed by acetalization. Nucleophilic alkylation of 3 and 4, using Grignard reagents and allyltrimethylsilane/TiCl₄, provides 12a-d & 15 and 17a-c & 21, respectively, in a highly stereoselective manner. Hydrolysis of the resultant amides (12, 15, 17, and 21) provides α -amino acid derivatives (14) and α -hydroxy acids, respectively, in optically active form, along with the recovered (S)-prolinol chiral auxiliary in its recyclable form.