Glycine, Alkylidene

This method is complementary to the anti-selective Michael route to 3-substituted glutamates using 2-azaallyl anions derived from alkylidene protected glycine (see Section 1.5.2.4.1.1.). 

Durch Kondensation von Glycin-estern mit Carbonsaure-ester-imiden und Aldehyden bei an-schliebender katalytischer Hydrierung der primar gebildeten 4-Alkyliden-5-oxo-4,5-dihydro-imidazole erhalt man 4-substituierte 5-Hydroxy-imidazole (Bd. E5/1, S. 518, 519). 

Die gemeinsame Condensation von Glycin-ethylester, Carbonsaure-ethylester-imiden und Carbonyl-Verbindungen ffihrt zu 4-Alkyliden- bzw. 4-Aralkyliden-5-oxo-4,5-di-hydro-imidazolen, die durch Reduktion und Hydrolyse in N-Acyl-aminosaure-amide, N-Acyl-aminosauren oder in freie a-Aminosauren fibergeffihrt werden kon-nen2 ... 

Die Palladium-katalysierte Allylierung der Enolate von achiralem N-Alkyliden-glycin (s.S. 492) verlauft mit 3-Acetoxy-l-propen und optisch-aktiven, Phosphan-Liganden tra-genden Palladium-Katalysatoren2 stereoselektiv zum entsprechenden 2-(Diphenyl-me-thylenamino)-4-pen ten saure-Derivat3-5. 

W-Alkylidene derivatives of glycine esters are the preferred starting compounds for the synthesis of unnatural amino acids via the deprotonation/alkylation procedure. Enolate formation is achieved with a strong base (LDA, BuLi, or phosphazene bases such as 2- tert-butylimino)-2-(ethylamino)-l,3-dimethyl-l,3,2-diazaphosphinane) or by phase-transfer catalysis (tetraalkylammonium salts with NaOH or the latter method allows... 

Scheme 70 Chiral Auxiliaries Used in the Derivatization of Glycine Equivalents and Diastereoselective Alkylation of Chiral A -Alkylidene Amino Acid Derivatives ...

Alkylidene-2,5-dihydrooxazoles (183) are obtained by reaction of glycine Schiff bases with a-... 

Hierbei werden N-Acyl-glycine in Gegenwart von Acetanhydrid und Natriumacetat mit aromatischen Aldehyden zu 4-Alkyliden-5-oxo-4,5-dihydro-l,3-oxazolen (Azlactonen) kondensiert, deren saure und basische Hydrolyse zu a-Oxo-carbonsauren fiihrt (vgl. Bd. VIII, S. 447 Bd. XI/2, 306, 368) ... 

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). 

Alvarez-IbaiTa. C. Csaky. A.G. Martin. M.El. Quiroga. M.L. Study of the asymmetrie synthesis of (Z)-y-substituted-0(,P-didehydroglutamate.s from V-alkylidene-glycinates. Tetrahedron 1999. 55 (23). 7319-7330. Yanagisawa, A. Yamada. Y. Yamamoto. H. Effect of crown ethers on the regioselectivity of allylation of benzaldehyde with allylic barium reagents. Synlett 1997. (9). 1090-1092. 

For instance, N-benzoyl glycine (26, hippuric acid) can be transformed to a 4-alkylidene azlactone (27) by treatment of 26 and an aldehyde (a) with Ac20/Na0Ac via intermediate formation of the azlactone 25 and (b) with polyp hosphoric acid via intermediate formation of alkylidene hippuric acid (28). Under the conditions of (b), ketones can be used in the Erlenmeyer synthesis. 

Catalytic hydrogenation of the 4-alkylidene azlactones 27 affords the 4-alkyloxazolones 29, whose hydrolysis in acid medium renders amino acids 30 (formally a-alkylated glycines) and benzoic acid ... 

SCHEME 5.22 Stereoselective synthesis of pyrrolidines 112 by Fischer alkenyl carbene complexes 106 with A -alkylidene glycine enolates 107. 

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