Aryl glycines, synthesis

A convenient synthesis of aryl glycines from Grignard reagents, prepared via iodine-magnesium exchange, was performed by the reaction with N-Boc-iminomalonate (from diethyl mesoxalate and BocN=PPh3). The reaction... 

A mild and highly efficient one-pot synthesis of aryl glycines 618 from readily available serine derivatives 617 has been reported (Scheme 3.242) [650]. This method is based on the p-fragmentation of a primary alkoxy radical, generated on treatment of the serine derivative with PhI(OAc)2-l2, immediately followed by... 

Racemization is not encountered when 4-unsubstituted-5(477)-oxazolones or 4,4-disubstituted-5(477)-oxazolones are used as reagents. Indeed, 4-unsubstituted-5(47/)-oxazolones function as glycine synthons in the synthesis of A-acylglycyl-a-amino acids. For example, aminolysis of 2-(trifluoromethyl)-5(47/)-oxazolone with a-methylphenylalanine affords A-(trifluoroacetyl)glycyl-a-methylphenylalanine. 4,4-Disubstituted-5(4//)-oxazolones, readily available by alkylation of the monosubstituted derivatives, are very useful intermediates in the synthesis of peptides that incorporate ot,ot-disubstituted amino acids. As an example, 4-(aryl-methyl)-2-phenyl-4-(trifluoromethyl)-5(4//)-oxazolones 260 are key intermediates... 

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. ... 

Hinsberg oxindolc synthesis. Formation of oxindoles from secondary aryl amines and sodium bisulfite addition compound of glyoxal primary aryl amines give glycine or glycinamide derivatives. 

A one-pot MW-accelerated synthesis of selective glycine receptor antagonists 3-aryl-4-hydroxyquinolin-2(lH)-ones has been developed via amidation of malonic ester derivatives with anilines and subsequent cydization of the intermediate, ma-londianilides under solvent-free conditions (Scheme 8.71) [180]. 

Aryl-4-hydroxyquinolin-2(li-f)-ones, which are of pharmaceutical interest, were readily obtained in a one-pot procedure by formal amidation of malonic ester derivatives with an aniline then cyclization of the intermediate malondianilides (Scheme 10.103) [200]. The synthesis of Merck s glycine NMDA receptor or antagonist l-701,324 is illustrative. It can be prepared in one step by use of this procedure whereas the previously reported synthetic procedure comprises several reaction steps. 

Azomethinium salts are very versatile intermediates since they present an extremely electrophilic carbon for nucleophilic attack. High yields of these salts can be obtained in one step from a-amino acids via their tert-dcsmno derivatives Ethyl N-Benzylidene-glycinate has been used for the synthesis of a-amino acids and as an acyl carbanion equivalent A new reactive formaldehyde anion equivalent is lithium methylthioformaldine, (4,5-dihydro-5-methyl-l,3,5-dithiazin-2-yllithium A convenient synthesis of 2-alkyl- and 2-aryl-l,3-benzo-dithioles, which are precursors of acyl carbanion equivalents, has recently been published . 

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