Glycine Tert-butyl Ester Research Articles

Diastereoselective Synthesis of Functionalized 5-Amino-3,4-Dihydro-2H-Pyrrole-2-Carboxylic Acid Esters: One-Pot Approach Using Commercially Available Compounds and Benign Solvents.

A novel three-step four-transformation approach to highly functionalized 5-amino-3,4-dihydro-2H-pyrrole-2-carboxylic acid esters, starting from commercially available phenylsulfonylacetonitrile, aldehydes, and N-(diphenylmethylene)glycine tert-butyl ester, was developed. The one-pot strategy delivered this class of amidines bearing, for the first time, three contiguous stereocenters, in good to high yield and diastereoselectivity. The entire sequence was carried out using diethyl carbonate and 2-methyl tetrahydrofuran as benign solvents, operating under metal-free conditions. The process could be conveniently scaled-up, and the synthetic utility of the products was demonstrated.

Synthesis and application of novel carbohydrate-based ammonium and triazolium salts

The synthesis of nine new carbohydrate-based quaternary ammonium salts and two new triazolium salts starting from d-glucose has been accomplished. Our synthesis utilized the regio- and stereoselective ring opening reaction of 2,3-anhydro sugars by nucleophilic reagents to afford the key intermediates. In these new types of phase transfer catalysts, the ammonium and triazolium functions are directly attached to the carbohydrate scaffold in different positions (2-, 3-, 6-positions of the sugar). The efficiency of the altrose- and glucose-based quaternary salts were tested in the alkylation of N-(diphenyl) methylene glycine tert-butyl ester with benzyl bromide. To our knowledge this is the first example when sugar-based quaternary ammonium or triazolium salts were used successfully as phase transfer catalysts. The enantiomeric recognition ability of the synthesized salts towards racemic Mosher’s acid silver salt was also investigated by 19F NMR spectroscopy.

Enantioselective C-C Bond Formation Enhanced by Self-Assembly of Achiral Surfactants.

The use of achiral surfactant assemblies as a reaction platform for an alkylation reaction resulted in a high enantiomeric excess. Dilauryldimethylammonium bromide (DDAB) vesicles were modified with cholesterol to promote alkylation of N-(diphenylmethylene)glycine tert-butyl ester (DMGBE) with benzyl bromide, resulting in high conversion (∼90%) and high enantioselectivity (up to 80%). The R-enantiomer was formed on using the DDAB vesicles, whereas the use of phospholipid liposomes prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) produced an excess of the S-enantiomer. Considering the chemical structures of the reaction substrates and amphiphiles as well as the membrane structures and properties of DDAB vesicles and DOPC liposomes, it is suggested that the enantiomeric excesses result from the location of the quaternary amine of the amphiphiles and the DMGBE at the outer surface of the membrane. We show that the enantioselective reaction at the surface of the self-assembly could be regulated by adjusting the chemical structures and resulting membrane properties of the self-assembly.

Liposomes Can Achieve Enantioselective C-C Bond Formation of an α-Amino Acid Derivative in Aqueous Media.

We first report that a highly enantioselective C–C bond formation reaction was achieved with liposomes in aqueous media. Alkylation of N-(diphenylmethylene)glycine tert-butyl ester (DMGBE) with benzyl bromide was conducted in the presence of cetyltrimethylammonium bromide micelles, resulting in a high conversion of DMGBE but little enantiomeric excess (e.e.) of the product. The same reaction was then carried out in 1,2-dioleoyl-sn-glycero-3-phosphocholine liposome suspensions, where the e.e. values were high (at least 90 % (S)), indicating that the liposome membranes can behave as the promoter of the enantioselective reaction. Changing the type of lipid to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine to form a more ordered bilayer membrane lowered the reaction conversion but still maintained high e.e.% , that is, >90 (S), regardless of lipid chirality. It is indicated that multiple interactions between the DMGBE intermediate and lipid molecules promoted the migration of the intermediate into the interior of the membrane, whose bottom side (Si face) could be free for alkylation. These results suggest that liposomes can promote and regulate the alkylation of amino acid derivatives.

Synthesis of Fmoc-protected (S)-3,5-Dibromophenylalanine in the Presence of a Phase Transfer Catalyst or a Chiral Catalyst

Herein we present two methods of catalytic asymmetric synthesis of (S)-3, 5-dibromo phenylalanine. One approach is to use asymmetric alkylation reaction starting from diphenylimine glycine tert-butyl ester and 3, 5-dibromobenzyl bromide, with O-allyl-N-9-anthracene methyl bromide cinchonine as phase-transfer catalyst, the (S)-3, 5-dibromo phenylalanine derivative was obtained (up to 94.9% ee). The optimized conditions of asymmetric phrase transfer catalytic alkylation are explored. Another method is to employ asymmetric hydrogenation starting from 2-acetylamino-3-(3, 5-dibromophenyl) acrylic acid, with bis (1, 5-cyclooctadiene) rhodium (I) trifluoromethanesulfonate and (R)-N-diphenylphosphinoN-methyl-1-[(S)-2-dip-henylphosphino) ferrocenyl]ethylamine [(R)-methyl BoPhoz] as chiral catalyst. (S)-3, 5-Dibromo phenylalanine hydrochloride was obtained after hydrolysis. By Fmoc protection, Fmoc-(S)-3, 5-Dibromo phenylalanine was obtained (up to 94.7% ee). By comparison of the two methods, the first one gives higher overall yield and a little bit better selectivity, and is more suitable for the synthesis of other chiral dihalo-substituented phenylalanine derivatives.

Synthesis of chiral polymers containing thioetherified cinchonidinium repeating units and their application to asymmetric catalysis

A thiol-ene reaction of dithiol and two equivalents of cinchonidine afforded a thioetherified cinchonidine dimer. The dimer was treated with benzyl bromide to give a quaternary ammonium dimer. An ion exchange reaction of the cinchonidinium dimer and disodium disulfonate gave polymers containing chiral quaternary ammonium repeating units in their main-chain structures. Another type of chiral polymer was synthesized by quaternization polymerization. Repeated quaternization reactions between the thioetherified cinchonidine dimer and dihalides yielded chiral polymers containing cinchonidinium structures in their main chains. Both of these chiral polymers were successfully used as catalysts for the asymmetric alkylation of N-diphenylmethylene glycine tert-butyl ester. The chiral cinchonidinium polymers explored in this study showed excellent catalytic activity in asymmetric alkylation reactions and were reused several times without loss of activity.

Synthesis of cinchonidinium salts containing sulfonamide functionalities and their catalytic activity in asymmetric alkylation reactions

Various kinds of 4-(bromomethyl)benzenesulfonamides were prepared as quaternization reagent of cinchonidine. Cinchonidinium salts obtained from the quaternization of cinchonidine with 4-(bromomethyl)benzenesulfonamide showed highly enantioselective catalytic activity in the asymmetric benzylation of N-(diphenylmethylene)glycine tert-butyl ester. The corresponding phenylalanine derivative was obtained in high yield with a high level of enantioselectivity, up to 98% ee.

(L)-(Trimethylsilyl)alanine synthesis exploiting hydroxypinanone-induced diastereoselective alkylation

A new and efficient synthesis of (L)-(trimethylsilyl)alanine (TMSAla) with suitable protection for use in Solid Phase Peptide Synthesis (SPPS) has been accomplished starting from glycine tert-butyl ester and using hydroxypinanone as chiral inductor. The silylated side chain was introduced by alkylation of the Schiff base intermediate with iodomethyl(trimethylsilane) at -78 °C. Among the different synthetic routes that were tested including several chiral inductors and different Schiff bases, this strategy was selected and afforded (L)-TMSAla in good chemical overall yield with 98 % ee.

Synthesis of chiral quaternary ammonium polymers for asymmetric organocatalysis application

Main-chain chiral quaternary ammonium polymers have been synthesized using cinchonidine or 10,11-dihydrocinchonidine as a chiral source. Since the quinuclidine moiety of cinchonidine is easily quaternized with halide to form cinchonidinium salt, the quaternized reaction (Menshutkin reaction) was applied to the dimeric compound of cinchonidine and dihalide. The quaternization polymerization between cinchonidine dimer and dihalide smoothly occurred to afford the chiral polymers containing cinchonidinium salt structure in its main-chain. This atom economical addition polymerization was also applied to dimer of 10,11-dihydrocinchonidine. The corresponding chiral quaternary ammonium polymers were found to perform as polymeric organocatalysts for enantioselective benzylation of N-diphenylmethylene glycine tert-butyl ester to afford the desired (S)-phenylalanine derivative in high yields and high enantioselectivities (up to 95% ee).

Immobilization of Cinchona Quaternary Ammonium Salts as the Chiral Phase Transfer Catalysts on Multi-walled Carbon Nanotubes and Their Application in Enantioselective Alkylation

The pyrene-tagged cinchona quaternary ammonium salt, the chiral phase transfer catalysts (PTC-1), was synthesized and immobilized on multi-walled carbon nanotubes (MWCNTs). The new catalysts (PTC-1/MWCNTs) were employed in enantioselective alkylation of N-(diphenylmethyene)glycine tert-butyl ester. UV-Vis absorption spectra show the effect of different organic solvents on the adsorption and desorption of PTC-1 onto and from MWCNTs, respectively. The results show that 5.3 mg PTC-1 can be loaded on 10 mg MWCNTs in toluene, and 0.02025 mg PTC-1 was desorbed from 12.7 mg PTC-1/MWCNTs when washed by CHCl3. In the enantioselective alkylation of different halohydrocarbons with N-(diphenylmethyene)glycine tert-butyl ester using PTC-1/MWCNTs as a catalyst, the alkylating products were obtained with high yield and ee value. Furthermore, PTC-1/MWCNTs catalyst can be recovered and used repeatedly. PTC-1/MWCNTs as a new catalyst is effective in enantioselective alkylation of multiple halohydrocarbon.

Synthesis of main-chain chiral quaternary ammonium polymers for asymmetric catalysis using quaternization polymerization.

Main-chain chiral quaternary ammonium polymers were successfully synthesized by the quaternization polymerization of cinchonidine dimer with dihalides. The polymerization occurred smoothly under optimized conditions to give novel type of main-chain chiral quaternary ammonium polymers. The catalytic activity of the polymeric chiral organocatalysts was investigated on the asymmetric benzylation of N-(diphenylmethylidene)glycine tert-butyl ester.

Molecular design of chiral quaternary ammonium polymers for asymmetric catalysis applications

Repeated reaction between a chiral quaternary ammonium dimer and disodium disulfonate gave a chiral ionic polymer, which showed excellent catalytic activity in the asymmetric benzylation of N-diphenylmethylene glycine tert-butyl ester.

Thin film characterization and vapor sensing properties of a novel perylenediimide material

A novel N, N′-(glycine tert-butylester)-3,4,9,10-perylenediimide was chosen for the study of Langmuir–Blodgett (LB) thin film characterization and the sensing properties against selected volatile organic vapors. Different number of LB film layer was deposited onto a glass and quartz crystal substrate. The thin film fabrication process was monitored with UV–vis and quartz crystal microbalance (QCM) measurement techniques. The results indicated that absorbance increased linearly with the number of the layers on film. A similar linear relationship between frequency shift and number of the layers was observed by the QCM measurement. It can be concluded that high quality and uniform LB films were produced by using this novel perylenediimide material. Chloroform, toluene, benzene, ethyl alcohol and isopropyl alcohol vapors were selected to test this material's applicability in room temperature as a vapor sensor. This novel material showed a fast, large and reproducible response to chloroform and isopropyl alcohol vapor.

A powerful synergistic effect for highly efficient diastereo- and enantioselective phase-transfer catalyzed conjugate additions

An efficient, catalytic, diastereo- and enantioselective conjugate addition of N-(diphenylmethylene)glycine tert-butyl ester to β-aryl substituted enones was realized in the presence of 1 mol% of newly desired dinuclear N-spiro-ammonium salts, affording functionalized α-amino acid derivatives in 57-98% yields with high diastereoselectivity (up to 99:1 dr) and enantioselectivity (up to 96.5:3.5 er).

Enantioselective synthesis of ( S)-4-methyleneglutamic acid via tandem conjugate addition–elimination under phase-transfer catalytic conditions

An efficient enantioselective synthetic method for ( S)-4-methyleneglutamic acid is reported. Phase-transfer catalytic conjugate addition–elimination of the benzophenone imine of glycine tert-butyl ester in the presence of chiral Cinchona-derived catalysts give the corresponding conjugated addition products (>99% ee), which could be hydrolyzed to chiral ( S)-4-methyleneglutamic acid.

Main-Chain Ionic Chiral Polymers: Synthesis of Optically Active Quaternary Ammonium Sulfonate Polymers and Their Application in Asymmetric Catalysis

A condensation reaction between quaternary ammonium halide and sulfonate was first successfully applied to the synthesis of the chiral polymers. Reaction of bis(quaternary ammonium halide) with disulfonate afforded a polymer containing ionic bonds in its main chain. The chiral ionic polymers were applied to the asymmetric benzylation of N-diphenylmethylidene glycine tert-butyl ester to prepare (S)-phenylalanine derivatives in high yield with a high level of enantioselectivity.

Designing Chiral Quaternary Ammonium Polymers: Novel Type of Polymeric Catalyst for Asymmetric Alkylation Reaction

Abstract Optically active polymers containing chiral quaternary ammonium salt structure in their main chain have been prepared by simple polycondensation reaction. These polymers were used as catalyst for asymmetric alkylation of N-diphenylmethylidene glycine tert-butyl ester.

Synthesis of Novel Chiral Phase-Transfer Catalysts and Their Application to Asymmetric Synthesis of α-Amino Acid Derivatives

To investigate the electronic and steric influences on enantioselectivities of asymmetric phase-transfer reactions, a series ofchiral quaternary ammonium salts were synthesized from cinchona alkaloids and 2-chloromethylbenzimidazole or 1-chloromethyl benzotriazole. Using one of the cinchonine-derived alkaloid catalysts, enantioselective alkylations of N-(diphenylmethylene) glycine tert-butyl ester were efficiently carried out with various alkyl halides to give products in high enantiomeric excess (94-99% ee).

Synthesis of [3-14C]-L-tryptophan and 5′-hydroxy-[3-14C]-L-tryptophan

The synthesis of selectively labeled [3-14C]-L-tryptophan and its derivative 5′-hydroxy-[3-14C]-L-tryptophan using chemical and multienzymatic methods is reported. The key intermediate for this synthesis, [3-14C]-DL-alanine was obtained from 14CH3I as a result of its condensation with N-(diphenylmethylene)glycine tert-butyl ester. Next, the mixture containing [3-14C]-DL-alanine, indole or 5-hydroxyindole has been converted to [3-14C]-L-tryptophan or 5′-hydroxy-[3-14C]-L-tryptophan, respectively, in a one-pot multienzymatic reaction using four enzymes: D-amino acid oxidase, catalase, glutamic-pyruvic transaminase and tryptophanase.

Synthetic Studies on (−)-Lemonomycin: An Efficient Asymmetric Synthesis of Lemonomycinone Amide

Asymmetric synthesis of lemonomycinone amide (2) was accomplished from readily accessible starting materials. Enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester (11) by 5-tert-butyldimethylsilyloxy-2,4-dimethoxy-3-methylbenzyl bromide (10) in the presence of Corey-Lygo's phase transfer catalyst [O-(9)-ally-N-(9'-anthracenylmethyl) cinchonidium bromide, 0.1 equiv] afforded, after chemoselective hydrolysis of the imine function (THF/H(2)O/AcOH), the substituted l-tert-butyl phenylalanate 13 in 85% yield. A Pictet-Spengler reaction of 14 with benzyloxyacetaldehyde (15) provided the 1,3-cis-disubstituted tetrahydroisoquinoline 16 in 85% yield as a single diastereomer. Coupling of hindered secondary amine 16 with amino acid 9 was accomplished under carefully controlled conditions to furnish the amide 22, which was in turn converted to hemiaminal 24. A hafnium triflate catalyzed conversion of hemiaminal to alpha-amino thioether followed by a silver tetrafluoroborate promoted intramolecular Mannich reaction of 26 afforded the tetracycle 27 in excellent overall yields. Debenzylation of 27 [Pd(OH)(2), H(2), MeOH, 0 degrees C], removal of N-Boc function (aqueous 3 N HCl, MeOH/H(2)O), and oxidation of hydroquinone to quinone [(NH(4))(2)Ce(NO(3))(6), H(2)O, rt] afforded the lemonomycinone amide 2 in 76% yield over three steps.