Aryl glycines, substituted

Aryl -a-aminopropionic acids are obtained by reduction of azlactones with phosphorus and 50% aqueous hydriodic acid in glacial acetic acid. Many other reducing agents have been used. Reviews of this synthesis and related reactions have been made. The azlactones are conveniently prepared in good yields from aromatic aldehydes and N-acyl derivatives of glycine. Potassium carbonate has been found to be a superior catalyst for this condensation. Ketones cannot be substituted for the aromatic aldehydes. ... 

O Donnell et al have examined benzophenone-derived glycine acetate (85) as a glycine cation equivalent. Higher order mixed cuprates [R2Cu(CN)Li2] react with (85) to afford alkylated Schiff base (86) in moderate yields. The reaction is sensitive to reaction conditions and reduction competes with or-ganometallic addition. Hydrolysis of (86) provides access to aryl- or alkyl-substituted amino acids (87 Scheme 16). 

In the second route, the amidoxime esters (154), formed in situ by addition of a-substituted ethyl glycinates to arylcarbonitrile oxides, are reported to cyclize spontaneously to the 3-aryl-4/7-1,2,4-oxadiazin-6(5. -ones (155) (Scheme 21). Yields range from 12-73% <84JHC455>. 

As this reaction has not been extensively studied and not much mechanistic information is available, a tentative mechanism is outlined here. It is possible that the primary aryl amine has less steric hindrance than the secondary aryl amine during the substitution, hence substituted glycine is produced as the product. 

In addition to THIQs that could act as the typical substrates for the asymmetric CDC reactions, glycine derivatives were also well tolerated in this kind of transformation. Xie and Huang reported a facile approach to iV-aryl amino acid derivatives via the CDC reactions between Af-substituted glycine esters with unmodified ketones under the cooperative catalytic system consisting of Cu(0Ac)2 H20 and pyrrolidine. TBHP and DDQ were proved to... 

Couplings of aryl bromides to phenols have benefited from use of ligands 13 and 42. With 10% CUI/CS2CO3 and glycine ligand 13 (30%), several diaryl ethers such as 68-70 can be fashioned at 90 °C in dioxane. With ort/io-substitution in the halides, a higher temperature gives a better yield (see 68). Both activated and deactivated bromides can be used. Not unexpectedly, a bromide reacts exclusively over an aryl chloride. 

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