Phenylglycine derivatives

Scheme 3.2 (5)-Phenylglycine-derived P-amino disulfide ligand for additions of ZnEt2 to aldehydes.

The sodium salt of the phenylglycine derivative (33) was investigated as an absorption promoter for the rectal absorption of beta-lactam antibiotics and insulin [80JAP(K)31040 81CPB1998, 81CPB2012], (Naphthothiazol-2-ylidene)malonates (1661 and 1662) were applied in silver halide photographic emulsions as sensitizer dyes [82JAP(K)54936]. 

When 2-anisidine, p-acetylaniline, 1,2-phenylenediamine, and 2-trifluro-methylaniline were used, the above procedure gave oifly monosubstituted or A-phenylglycine derivatives. 

By this process phenylglycine derivatives have been resolved by crystallization of the tartaric acid ammonium salts. The equilibration is induced at the amino ester stage by forming the configurationally labile imines with a catalytic amount of benzaldehyde or acetone (Table 11). 

In the asymmetric hydrogenation of the (R)-phenylglycine derivative (54) in the presence of an achiral catalyst the stereoselectivity was reported 89) to be low. The lactone (55) could subsequently be converted into (S)-aspartic acid 89). This reaction sequence is an example of the intramolecular transfer of chirality with subsequent disappearance of the original chiral center. 

Phenylglycine derivatives are key intermediates in the synthesis of vancomycin. 81-85 This amino add is also very useful for incorporation into oxazolidinones as a chiral aux-iliaryt45,47 48 53 86 87 and for modulating bioactivities of peptides and peptidomimeticsJ85,88 There are several possible approaches to the synthesis of phenylglycines, including the Strecker reaction and the Evans electrophilic azidation reaction.181 ... 

Recently, Maeda and coworkers utilized the (S, S) -le-catalyzed asymmetric alkylation of phenylglycine-derived Schiffbase 42 (R1 = Ph) for the stereoselective synthesis of a 4-hydroxy-2-phenylproline framework [27]. After hydrolysis and transesterification, the resulting (S)-49 was derivatized to its N-tosylate 50. Subsequent treatment of 50 with Br2 in CH2C12 resulted in the formation of y-lactone 51 with high diastereos-electivity this was then treated with NaH in methanol to give essentially pure (2 S,4R)-4-hydroxy-2-phenylproline derivative 52 in 80% yield from 50 (Scheme 5.25). 

Based on their fluorination protocol, Cahard and co-workers have elaborated a convenient synthesis of a-fluoro-a-phenylglycin derivatives [18]. For example, upon reaction with reagent 24 racemic nitrile 23 was converted into the fluorinated derivative 25 with 94% enantiomeric excess. The corresponding ester derivatives of 23 gave rise to somewhat lower ees. This difference was contributed to the fact that a-lithiated nitriles can be in equilibrium with axial-chiral lithio ketene imines of low racemization barriers thus leading to a potential dynamic kinetic resolution. 

A large series of A-phenylglycine derivatives (Table 9) was studied as electron donors in photoinduced free-radical polymerization [108]. A-Phenylglycine deriva-... 

Table 9. Structures, oxidation potentials of A -phenylglycine derivatives tested as electron donors.

More recently, quinonoidal spirolactones (LV), which can react with amino acid esters to give dipeptides, have been conveniently prepared via anodic oxidation of tyrosine derivatives (LIV) [Eq. (24)] [54]. Anodic phenolic coupling of tyrosine and phenylglycine derivatives to afford isodityrosine, dityrosine, and related compounds has also been recently reported [55]. 

Schering-Plough Corp, has used an oxazolidinone in its synthesis of the cholesterol adsorption inhibitor (+)-SCH 54016 (24) (Scheme 7) [51], Condensation of an acid chloride intermediate with the (7 )-phenylglycine-derived Evans auxiliary followed by reaction of the titanium enolate with -(4-methoxybenzyh-dene)anihne gave the intermediate 25. This was silylated and treated with TBAF, resulting in removal of the auxiliary and cyclization to form the 2-azetidinone ring. The stereochemistry was exclusively trans. The azetidinone was then converted to the bromide, followed by intramolecular alkylation to form SCH 50416 in > 99% ee. 

Conway. S.J.. Miller, J.C., Howson, P.A., Clark. B.P. and Jane. D.E., Synthesis of phenylglycine derivatives as potent and selective antagonists of group III metabotropic glutamate receptors, Bioorg. Med. Chem. Lett.. 11. 777, 2001. 

We developed an alternative method based on the resolution of phenylglycine derivatives [22]. Accordingly, the racemic amine was reacted with a chiral auxiliary, namely the tosyl derivative of ( S)-(+)-methyl mandelate, followed by chromatographic separation of the two diastereomers formed and the subsequent hydrogenation of the separated compounds to ve the free amines with good enantiomeric excess (e.e. 94% ). 

Hence it was found that while valine-derived oxazolidinone 62 and phenylglycine-derived 67 gave good selectivity (for the syn diastereomer) norephedine-derived 66 did not. 

Using the optimum conditions (Table 28, entry 6), a variety of chiral secondary amines have been investigated. The results are shown in Table 29. The most effective auxiliary for preparation of the enantiomeric aldol (242b) is the phenylglycine-derived amine (Table 29, entry 8). 

Other interesting coinitiators (10.47) are phenylglycine derivatives (a carbon-centered radical is formed after electron transfer, proton transfer, and decarboxylation) and mercaptans (where a thiyl radical is generated). The role of the mercaptan and the design of newly reactive compounds based on the iniferter structure described above (10.42) have been outlined in Ref. [104]. 

In the (keto)coumarin/amine/ferrocenium salt system, the ferrocenium salt plays a crucial role that is rather complex. In a three-component photoinitiator system [238,239] consisting of a coumarin, an iron arene complex such as CpFe +Ar and a phenylglycine derivative as an amine, the first step of the photoreaction occurs between the dye and the complex according to an electron process. The amine reacts with the radical (created on the complex) through hydrogen abstraction. Therefore, no detrimental ketyl radicals are formed. 

Iron-arene complexes are known to exhibit extremely high photoactivity as initiators. Quantum efficiencies have been found to be greater than I in the photopolymerisation of dicyanate esters. Phenylglycine derivatives have been found to be excellent co-synergists for the iron-arene complexes when used in conjunction with dyes and amines. Complexes of various types have also been proposed. Maleic anhydride-THF complexes have been used for the photopolymerisation of oligourethane acrylates while metal-ion complexes of spiropyran copolymers undergo reversible polymer precipitation. Azo and polyazo initiators have been used to make butadiene-isoprene block copolymers while charge-transfer complexes of morpholine-chlorine induce the radical polymerisation of methyl methacrylate. The presence of zinc chloride enhances the... 

The reaction of protected glycines affords a-phenylglycine derivatives (Eq. 20) [63]. The intramolecular reaction of a-amino acid derivatives provides... 

Electrophilic substitution of 108 with CO2 afforded the phenylglycine derivative in 95 % yield with an er of 96 4. Interestingly, the opposite enantiomer of the phenylglycine derivative was accessed using methyl chloroformate as the electrophile, which provided the corresponding product with an er of 93 7. 

The aziridination and amidation reactions of imidoiodanes can be efficiently catalyzed by Rh(II) complexes [810-815]. Dirhodium(II) tetrakis[Al-tetrafluorophthaloyl-(S)-tcrt-leucinate], Rh2(S-TFPTTL)4, has been found to be an exceptionally efficient catalyst for enantioselective aminations of silyl enol ethers 661 with imidoiodane 662 to afford a-amido ketones 663 in high yields and with enantioselectivities of up to 95% ee (Scheme 3.265). The effectiveness of this catalytic protocol has been demonstrated by an asymmetric formal synthesis of (-)-metazocine [810]. This catalyst has also been used for the asymmetric synthesis of phenylglycine derivatives by enantioselective amidation of silylketene acetals with PhINTs [811]. 

Still and coworkers reported a second tricyclic system 45. This host was accessible in a single step from 46 and 47 (13% yield) and also showed exceptional enantiodis-crimination. For example, L-phenylglycine derivative 48 and its enantionier were bound in the ratio 160 1. with CDCI3 as solvent. ... 

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