Reactions of Glycine Derivatives

The GDC reaction of a benzylic C-H bond without an adjacent heteroatom is more challenging. Sinee benzylic carbocations can be generated under oxidative reaction conditions, asymmetric allqrlation is considered to be possible if the carbocations are trapped with chiral enamines or chiral metal enolates. 

In the case of Feng s reaction, it is interesting that a chiral Ni/Fe bimetallic system was essential to achieve high chemical yield and enantioselectivity (Table 7.1). The Fe-L 1 1 complex (2 mol%) gave high chemical yield without asymmetric induction. The reaction promoted by the Ni-Li 1 1 complex (10 mol%) alone was slower, while the ee was excellent. The authors 

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DOUBLE INSERTION IN REACTIONS OF GLYCINE DERIVATIVES REARRANGEMENT OF SYMMETRICAL ANHYDRIDES TO PEPTIDE-BOND-SUBSTITUTED DIPEPTIDES... 

Bagley MC, Brace C, Dale JW, Ohnesorge M, Phillips NG, Xiong X, Bower J (2002) J Chem Soc [Perkin 1] 1663 Belattar A, Saxton JE (1992) J Chem Soc [Perkin 1] 679 Bernardi L, Gothelf AS, Hazell RG, Jprgensen KA (2003) Catalytic asymmetric Mannich reactions of glycine derivatives with imines. A new approach to optically active alpha,beta-diamino acid derivatives. J Org Chem 68 2583-2591... 

Other hydrogen transfer reactions of glycine derivatives have been used to introduce functional groups at the a-position. For example, reactions with bromine or A -bromosuccinimide, fert-butyl perbenzoate in the presence of a copper catalyst, and tert-butyl hydroperoxide and formate, have been used to produce a-bromo-, benzoyloxy- and carboxy-substituted glycine derivatives, respectively (Scheme 2) [12-14]. 

Table 1. Relative rates of reaction of glycine derivatives with iV-bromosuccinimide NBS...

Owing to the importance of optically active amino acid derivatives and the lack of successful systems for catalytic asymmetric CDC reactions of glycine derivatives with p-keto esters, Wang and co orkers embarked on the study of enantioselective CDC reactions of secondary and tertiary amines for the synthesis of optically active a-alkyl a-amino acids. In the presence of a catalytic amount of Cu(OTf)2 and BOX ligand L2 as the chiral catalyst, in combination with DDQ as the stoichiometric oxidant, the reactions of glycine esters 47 with a-substituted p-keto esters 48 underwent smoothly to afford the desired products 49 in satisfactory yields, moderate dr and excellent ee (Scheme 2.17). 

El fazepam (80) not only is a tranquilizer, but also stimulates feeding in satiated animals. One of several syntheses involves reaction of benzophenone derivative with a glycine equivalent masked as an oxazolidine-2,5-dione (79). ... 

The reaction of propylamine derivatives (30) with EMME gave amino-methylenemalonates (31) in 80-84% yields (82MI7). Aminomethylene-malonates (32) were prepared in the exothermic reaction of glycine esters and EMME (77H1821). 

Arai et al. also reported another BINOL-derived two-center phase-transfer catalyst 31 for an asymmetric Michael reaction (Scheme 6.11) [8b]. Based on the fact that BINOL and its derivatives are versatile chiral catalysts, and that bis-ammonium salts are expected to accelerate the reaction due to the two reaction sites - thus preventing an undesired reaction pathway - catalyst 31 was designed and synthesized from the di-MOM ether of (S)-BINOL in six steps. After optimization of the reaction conditions, the use of 1 mol% of catalyst 31a promoted the asymmetric Michael reaction of glycine Schiff base 8 to various Michael acceptors, with up to 75% ee. When catalyst 31b or 31c was used as a catalyst, a lower chemical yield and selectivity were obtained, indicating the importance of the interaction between tt-electrons of the aromatic rings in the catalyst and substrate. In addition, the amine moiety in catalyst 31 had an important role in enantioselectivity (34d and 34e lower yield and selectivity), while catalyst 31a gave the best results. 

The very short reaction times required for the alkylation of substrate 11a with benzylic bromides using Nobin as an asymmetric phase-transfer catalyst are important for the synthesis of 18F-fluorinated amino adds for use in positron-emission tomography (PET)-imaging studies. Thus, Krasikova and Belokon have developed a synthesis of 2-[18F]fluoro-L-tyrosine and 6-[18F]fluoro-L-Dopa employing a (S)-Nobin-catalyzed asymmetric alkylation of glycine derivative 11a as the key step, as shown in Scheme 8.14 [29]. The entire synthesis (induding semi-preparative HPLC purification) could be completed in 110 to 120 min, which corresponds to one half-life of18 F. Both the chemical and enantiomeric purity of the final amino acids were found to be suitable for clinical use. 

A facile synthesis of (3R,5R)-dihydroxy-L-homoproline, an idulonic acid mimic, was realized using L-threonine aldolase-catalyzed reaction of glycine with an aldehyde derived from L-malic acid [96]. 

MA Freitas, RAJ O Hair, JAR Schmidt, SE Tichy, BE Plashko, TD Williams. Gas phase reactions of glycine, alanine, valine, and their N-methyl derivatives with the nitrosonium ion, NO+J Mass Spectrom 31 1086,1996. 

Fig. 8-16. Reaction of pyrogallol-derived free radicals with glycine (Wang and Huang, 1987).

Reaction of glycine cation equivalents with vinylsilanes leads to 3,7-unsaturated a-amino acid derivatives with high regio- and stereo-selectivity. Thus, chloroglycine derivative (165) reacts with ( )-3-tri-... 

Several recent examples serve to illustrate the potential of allyltributyltin for organic synthesis (Scheme 4). Baldwin and Easton have independently shown that glycine derivatives undergo efficient allylation reactions, providing an avenue for the preparation of non-natural amino acids [8]. Subsequently, addition of glycine-derived radicals to allyltributyltin was shown by Hamon to occur with stereoselectivity if the radical bears an ester chiral auxiliary [9]. An alternative method for the preparation of amino acid derivatives via allylation of carbamoyloxy radicals that are incorporated into an oxazolidin-2-one ring system was reported by Kano... 

Another approach to the synthesis of p hydroxy-a-amino acids is by aldol reaction of imines derived from amino adds. The benzophenone imine of glycine (7.102) undergoes highly enantioselective aldol addition with a range of aliphatic aldehydes, including (7.71) xmder phase-transfer conditions in the presence of the bromide salt of phase-transfer catalyst (7.103). A similar transformation is catalysed, in low to moderate ee, by the bimetallic catalysts developed by Shibasaki and CO workers. ... 

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