Enolate anions, glycin

An intriguing enantioselective preparation of substituted quaternary 1,4-benzodiazepin-2-one scaffolds has been reported by Carlier et al. <03JA11482>. Enantioselective alkylation is used to prepare chiral products 64 (e.g. R = H R = Me, PhCH2 R = Me2CH) from non-racemic glycine-derived 1,4-benzodiazepinones. If the N1 substituent is sufficiently large (e.g. an isopropyl group) then the stereochemistry at the 3-position of the 3-substituted 1,4-benzodiazepinones is transmitted to the product despite the loss of chirality at C-3 on intermediate enolate anion formation. 

Another amino acid synthesis is called the azlactone synthesis. Remember from before that an azlactone is an oxazolone (see 95). When glycine (52) is converted to its AT-benzoyl derivative (112 known as hippuric acid) by reaction with benzoyl chloride, treatment with acetic anhydride (AC2O) gives the azlactone 113. This is the reaction presented in the preceding section (see compormd 95). Compound 110 has the common name of hippuric acid azlactone. As with the thiohydantoin, the -CH2- unit in 113 is susceptible to an enolate anion condensation reaction with aldehydes (Chapter 22, Section 22.7.2), and reaction with 2-methylpropanal in the presence of pyridine gives azlactone 114. Catalytic hydrogenation of the alkene unit (Chapter 19, Section 19.3.2) and acid hydrolysis lead to the amino acid leucine (55). 

A typical reaction that uses an amino acid derivative involves initial conversion to an enolate anion. This nucleophilic species is then reacted with an alkyl halide or a carbonyl derivative. An example that produces a new amino acid is the reaction of the ethyl ester of n-benzyl glycine with lithium diisopropylamide to give the enolate. Subsequent reaction with the mixed anhydride shown below proceeded with displacement of acetate to give /.22J.13 Acid hydrolysis generated a P-keto amino acid, which decarboxylated under the reaction conditions to give 4-oxo-5-aminopen-tanoic acid 1.156, also known as 5-aminolevulinic acid). 

Trifluoroalamne cannot be prepared by alkylation of a glycine anion with tri-fluoromethyl halides, since these electrophiles are not able to alkylate enolates. Other approaches have been reported using various substrates, but none is really satisfying. The three main ones are ... 

Flash photolysis and laser flash photolysis are probably the most versatile of the methods in the above list they have been particularly useful in identifying very short-lived intermediates such as radicals, radical cations and anions, triplet states, carbenium ions and carbanions. They provide a wealth of structural, kinetic and thermodynamic information, and a simplified generic experimental arrangement of a system suitable for studying very fast and ultrafast processes is shown in Fig. 3.8. Examples of applications include the keton-isation of acetophenone enol in aqueous buffer solutions [35], kinetic and thermodynamic characterisation of the aminium radical cation and aminyl radical derived from N-phenyl-glycine [36] and phenylureas [37], and the first direct observation of a radical cation derived from an enol ether [38],... 

The last step of an efficient protocol for the one-pot synthesis of biologically important (Z)-y-substituted-a, P-didehydroglutamates 21 starting from A-alkylidene-glycinates 19, involves the C-alkylation of intermediate alkaline dienolates 20 in THE. However, capture of 20 with an excess of electrophiles, such as Mel, failed even in the presence of DMPU as an anion activator. The generation of "naked enolates by using 18C6 allowed for a smooth and efficient reaction (Eq. 19). 

Unsaturated a-Amino-acids.—A general route to a-vinyl-a-amino-acids is based upon Stork s approach to substituted glycines (see ref. 288 etc.) and uses the enolate of the Schiff s base formally derived from benzaldehyde and methyl a-aminocrotonate (Scheme 54). ° -Vinylglycine itself cannot be prepared by this method as addition of water to the intermediate anion gives pure E) starting material. a-Vinylalanine has been obtained in good yields by a somewhat different approach from the enolate of alanine methyl ester and rrans-phenyl-2-... 

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