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, TheirN-Methyl Derivatives and α-Hydroxy Acids Employing (S)-Prolinol as aRecyclable 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.

Sequential two electron photooxidation of t-amines: generation of a regiospecific iminium cation and its application in organic synthesis

“…The design of 16 was conceived by considering its unique structural feature, a reactive α-amino ether functionality; highly suitable for stereoselective nucleophilic alkylation reactions, ease of hydrolysis of the resultant amides to produce α-amino acids and their N-methyl derivatives. the formation of the major diastereoisomer (17) is explained 33 by assuming back side attack of the -OH moiety of prolinol on the iminium cation, leading to preferred energy minimized transition state in an equatorial position (C) so as to produce the energetically favorable transbicyclic system as shown in Fig. 3 Nucleophilic ring opening of 16 either by alkyl Grignard reagent or alkyl trimethylsilane in the presence of TiCl 4 gives corresponding amides 17 with the diastereomeric ratio as indicated in the parentheses 33 .…”