Benzophenone glycinate Schiff base

In 1989, O Donnell and coworkers successfully utilized cinchona alkaloid-derived chiral quaternary ammonium salts for the asymmetric synthesis of a-amino acids using tert-butyl glycinate benzophenone Schiff base 1 as a key substrate [5]. The asymmetric alkylation of 1 proceeded smoothly under mild phase-transfer... 

Quaternary Ammonium Salt-Mediated Asymmetric Direct Aldol Reaction of Glycinate Benzophenone Schiff Base with 3-Phenylpropanal Under Phase-Transfer Conditions [6] (p. 145)... 

Michael Addition of Benzhydryl Glycinate Benzophenone Schiff Base to Methyl Vinyl Ketone [37] (p. 143)... 

A solution of benzhydryl glycinate benzophenone Schiff base (0.12 mmol) and catalyst (1.2 pmol, 1 mol%) in diisopropyl ether (4 mL) was degassed with argon... 

A-(Diphenylmethylene)glycine t-butyl ester (t-butyl glycinate-benzophenone Schiff base) (171) is a reactive prochiral nucleophile and a-allyl-a-amino acids can be prepared by allylation and hydrolysis of the allylated product. Asymmetric allylation of 171 with cinnamyl acetate (41) afforded 172 regioselec-tively with high % ee when the reaction was carried out in presence of achiral phosphite P(OPh)3, and a ehiral phase-transfer catalyst of alkaloid [0-allyl-(9-anthracenylmethyOcinchonidinium iodide] [65,66]. 

A few years later Maruoka and coworkers [52] investigated the influence of ultrasonic irradiation on an asymmetric phase-transfer alkylation of glycinate-benzophenone Schiff base catalyzed by a chiral C2-symmetric ammonium salt (lmol%) in toluene and 50% KOH aqueous solution (Scheme 21.22). In this case sonication also significantly enhanced the reaction rate and reduced the reaction time from 8 to 1 h. Moreover, the enantioselectivity of the product was comparable with those obtained in the reaction with conventional stirring. 

Recently, Lamaty and coworkers [70] demonstrated asymmetric phase-transfer catalyzed alkylation of fert-butyl glycinate-benzophenone Schiff base under solvent-free ball milling conditions (Scheme 21.33). The reaction proceeds with different alkylating agents in the presence of the cinchonidine-derived ammonium salt (10mol%) with very high yields (91-97%). This protocol reduces the reaction time however, the enantioselectivity (36-75% ee) is lower compared to conventional method with solvents (>90% ee) [71]. 

More recently, catalytic asymmetric allylations of imines and imine derivatives in aqueous media have been studied. An /V-spiro C2-symmetrical chiral quaternary ammonium salt (5,5)-I-Br (,S, .S )-()-Np-NAS-Br] has been evaluated in the allylation of glycine tert-Bu ester benzophenone Schiff base [Ph2C=NCH2COOCMe3] for synthesis of both natural and unnatural a-amino acids (Eq. 11,45).76... 

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). ... 

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 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. 

The glycinate Schiff base of benzophenone 17 was also shown to be a suitable Michael donor for the asymmetric 1,6-addition to the activated dienes 44 having ketones, esters, and sulfones as substituents. Using Corey s phase-transfer catalyst, 16, the corresponding allylated products 47 were obtained as a single E-isomer with high enantioselectivity (from 92 to 98% ee). The synthetic utility of this reaction... 

Using a IM KOH aq solution, it is possible to perform the asymmetric alkylation of the benzophenone glycine Schiff base with benzyl bromide using 10 mol% of 15 at room temperature, as shown in Figure 14. 

O Donnell reported the asymmetric alkylation of the Schiff base of tert-h xty glycinate using TV-benzylcinchonium chloride (Scheme 3.26b, [151]). This process, which works for methyl, primary alkyl, allyl, and benzyl halides (Table 3.11), is noteworthy because the substrate is acyclic and because monoalkylation is achieved without racemization under the reaction conditions. The observed chirality sense may be rationalized by assuming an jE fO)-enolate and Jt-stacking of the benzophenone rings of the enolate above the quinoline ring on the catalyst, and approach of the electrophile as before. 

Required Schiff base substrates were also prepared in solvent-free ball-mill conditions by mechanochemical transimination reaction. Grinding of an equimolar amount of the methyl ester of glycine hydrochloride and benzophenone imine for 3 h exclusively produced Schiff base (Scheme 2.60). Aqueous washing eliminated ammonium chloride, and the pure product was obtained without recrystallization in nearly quantitative yield. The reaction time was reduced to 3h compared with one night for the synthesis in solution. 

To a suspension of 0.5 mmol Ni(II) complex of Schiff base arising from glycine and (5 )-o-[iV-(Af-benzylprolyl)amino]-benzophenone in 2.0 mL DMF was added 0.525 mmol 3-(fran -3 -methylpropenoyl)oxazolidin-2-one the mixture was stirred at ambient temperature for 10 min. Then 10 /u.L DBU (0.07 mmol) was added, and the reaction was monitored by TLC. After the reaction completed ( 15 min), the mixture was poured into 80 mL icy 5% aqueous acetic acid and stirred with a glass bar to initiate crystallization of the product. The crystalline product was filtered off, thoroughly washed with water, and dried in vacuo to afford > 98% of the addition products. The diastereomeric isomers were isolated by silica gel column chromatography (acetone/chloroform, 1/4), in a ratio of 2.4 to 1. 

Table 8 Box-calcium complex-catalyzed [3-1-2] cycloaddition reactions of glycine Schiff bases derived from benzophenone with a,p-unsaturated carbonyl compounds...

The Schiff s base derived from ethyl glycinate and benzophenone has been alkylated under both anhydrous and phase transfer conditions yielding, after hydrolysis, a-amino acids. Under phase transfer conditions, alanine, a-aminobutyric acid, valine, leucine and phenylalanine were prepared in 91%, 86%, 61%, and 55% yields, based on starting imine. 

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