Glycine alkyl ester

In all cases it was reported that the trifluoromethyl group enhances the interaction in the prochiral ion pair, resulting in higher ee. The exception appears to be the asymmetric synthesis of a-amino acids via alkylation of the benzophenone Schiff base of glycine alkyl esters with allyl bromide, which produced a 56% ee with the trifluoromethyl-substituted catalyst compared to 66% with the unsubstituted catalysts TY-benzylcinchoninium chloride (3) or TY-benzylcinchonidinium chloride (4) (eq 5). ... 

In 1978, O Donnell and coworkers developed the benzophenone imines of glycine alkyl esters 4 as glycine anion equivalents, which have been found to be perfed to use in the phase-transfer catalysis [10]. An essential feature of this reaction system lies in the selective mono substitution of the starting Schiff base, the O Donnell substrate 4. This can be possible because of the significant difference in acidity of a-hydrogen between starting substrate 4 p/C,(DMSO) 18.7 (R=Et)] and a-monosubstituted produd S p/C,(DMSO) 22.8 (R=Et, E = Me), 23.2 (R=Et, E = CH2Ph)] [11]. This dramatic acidity difference makes it possible for selective formation of only monoalkylated product without concomitant production of undesired dialkylated produd or racemization. 

S,N-Ditrityl-L-cysteine diethylamine selt L-Tyrosine lower alkyl ester L-lsoleucine lower alkyl ester Benzyl-L-proline hydrochloride L-Leucine lower alkyl ester Ammonia Hydrogen chloride Glycine lower alkyl ester... 

Several syntheses of muraghtazar (3) have appeared in patents (Cheng et al.) and journals (Devasthale et al., 2005) (Scheme 8.3). Alkylation of 4-hydroxybenzaldehyde with the phenyloxazolemesylate 23, prepared readily from commercially available alcohol 22, yielded aldehyde 24, which was treated with glycine methyl ester under reductive amination conditions to provide secondary amine 25 in excellent yield. Reaction of amine 25 with 4-methoxyphenyl chloroformate followed by hydrolysis of the methyl ester afforded 3 in 94% yield. 

Allylic alkylations using a benzophenone imine of glycine methyl ester as a prochiral nucleophile and chiral phosphine ligands on palladium produced optical yields up to 57% (equation 354).436... 

Amino acid synthesis (8, 389). Alkylation of the aldimine (1) from glycine ethyl ester and /j-chlorobenzaldehyde under phase-transfer conditions offers a general route to amino acids. Either liquid-liquid phase-transfer or solid-liquid phase-transfer catalytic conditions are satisfactory with active halides, but alkylation with allylic halides and less active alkyl halides is best effected under ion-pair extraction conditions (6,41), with 1 equiv. of tetra-n-butylammonium hydrogen sulfate (76-95% yields).1... 

The Maruoka group recently reported an alternative concept based on a one-pot double alkylation of the aldimine of glycine butyl ester, 44a, in the presence of the chiral ammonium salt 29 as chiral phase-transfer catalyst (the principal concept of this reaction is illustrated in Scheme 3.18, route 2) [58], Under optimized reaction conditions products of type 43 were obtained in yields of up to 80% and with high enantioselectivity (up to 98% ee). A selected example is shown in Scheme 3.20. 

Scheme 8 Asymmetric alkylation of N-(diphenylmethylene)glycine isopropyl ester with benzyl bromide catalyzed by the dendronized catalysts shown in Fig. 25...

The synthesis of quaternary amino acids 86 have been shown using azlac-tones 85 as nucleophiles and the Trost ligand 39 under palladium [179] or molybdenum catalysis (Scheme 8) [180]. The allylic alkylation of glycine imino esters under biphasic conditions has also been achieved using a chiral phase-transfer catalyst in combination with an achiral Pd catalyst producing the unnatural amino acid derivatives [181]. 

The rearrangement products derived from aromatic and non-aromatic heterocyclic amines crystallize readily from the lower alcohols. Unlike those of many of the A-substituted glycosylamines, the crystals are not solvated. On the other hand, the ketose derivatives of aralkyl- and alkyl-amines, such as 2-phenylethylamine, ethanolamine, diethanolamine, glycine ethyl ester, and phenylalanine (see Table II), are hydrated or alcoholated, or both, and are difficult to isolate in pure crystalline form. The crystals which have been isolated were hygroscopic. Alcohols, aqueous alcohols, and water are the most commonly used solvents for crystallization. Acetone, ether, or benzene have been added to the alcoholic media in order to increase the yield of crystalline compound. The use of solvents that contain peroxides promotes decomposition of the crystals during storage. ... 

Pfister and co-workers129 recently prepared derivatives of the third possible thieno-l,2-thiazin-4-one. Methyl 2-chlorosulfonylthiophene-3-car-boxylate (161) with glycine methyl ester gave intermediate 162, which afforded 4- hydroxy- 3- methoxycarbonyl - 2 H - thieno [3,2-e] -1,2- thiazine 1,1 -dioxide (163) upon heating with base. Alkylation of 163 with methyl iodide/sodium hydride gave 164 which afforded a thieno-1,2-thiazine analog (165) of piroxicam (29) when heated with 2-aminopyridine (Scheme 6). 

KOH/kaolin combined with a chiral catalyst was used for asymmetric alkylation of glycine imine esters, and recycled for subsequent reactions without loss of activity over three times [55, 56]. 

Alkylations. There are reports on the alkylation of Al-acylhydroxylamines, 1,2,4-tricizole, and glycine methyl ester using DBU as base. In the last case, an a,N,Al-triallyl derivative results because of a [2.3]Stevens rearrangement. 

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