The reaction of α-stannylmethyllithium with esters

Ketonic compounds were prepared from esters using α-stannylmethyllithium as the reagent.     

A novel annulation reaction of N-substituted-2-nitrosoanilines with esters of α-isocyano acids. A one-pot,two-step route to 2-benzimidazole-substituted esters of α-amino acids

A BF₃-promoted α-addition of isocyanides to both nitrogen atoms of N-aryl-2-nitrosoanilines leads to stable BF₃-complexes of 3-N-hydroxy-(2-alkylimino)benzimidazole derivatives, which, after reduction with Zn in AcOH produce 1-N-aryl-2-alkylaminobenzimidazoles. This two-step annulation proceeds efficiently in a one-pot protocol with isocyanides derived from esters of α-amino acids. The chirality of the latter remains unaffected in the reaction.     

Synthesis of α,α-dideutero-β-amino esters

A straight forward entry to α,α-dideutero-β-amino esters starting from the corresponding imines and deuterated acetonitrile has been developed involving a two-step process.     

Transition-metal-free synthesis of multisubstituted N-arylindoles via reaction of arynes and α-amino ketones

A simple transition-metal-free protocol for the synthesis of indoles has been developed using aryne cycloaddition. The in situ-generated arynes couple with α-amino ketones through a one-step N-arylation–nucleophilic addition process under mild conditions and efficiently produce multisubstituted N-arylindoles.     

Copper-catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates: Synthesis of aryl/heteroaryl α-keto esters

A copper catalyzed Pummerer type reaction of α-thio aryl/heteroarylacetates is described for the first time. This transformation represents a new route to synthesize α-keto esters, which are important intermediates for pharmaceuticals and organic synthesis. The reaction proceeds via in situ generation of a thionium ion that undergoes hydrolysis to furnish α-keto esters in synthetically viable yields (up to 82%).     

Copper-catalyzed chemoselective cross-coupling reaction of thioamides and α-diazocarbonyl compounds: Synthesis of enaminones

The development of operationally simple and cost-effective methods for CC bond formation reactions are highly important in pharmaceutical, agrochemical and material research. In this article we describe the first copper-catalyzed cross-coupling reaction of thioamides with acceptor/acceptor-substituted and acceptor-only substituted α-diazocarbonyl compounds to yield enaminones. The reaction shows broad substrate scope in terms of thioamides and diazocarbonyl compounds. Primary, secondary and tertiary thioamides all give enanminones when reacted with α-diazodiesters, α-diazoketoesters, α-diazodiketones, α-diazoketoamides, α-diazoesteramides, α-diazoketosulfones and α-diazomonoketones.     

Synthesis of macrocyclic α-amino esters through the chemoselective hydrolysis of benzoxazinephanes

New meso-macrocyclic α-amino esters were synthesized through the chemoselective hydrolysis of azacyclophanes derived from l-tyrosine (benzoxazinephanes). The results showed that the alkyl chain of the ester determined the chemoselectivity of the reaction.     

Synthesis of unnatural N-glycosyl α-amino acids via Petasis reaction

A convenient and efficient protocol for the synthesis of unnatural N-glycosyl a-amino acids was developed.Condensation of 1,3,4,6-tetra-O-actyl-β-D-glucosamine hydrochloride,alkenyl boronic acid,and glyoxylic acid was achieved in CH_2C1_2 to give the derivatives of 2-(N-glycosyl)aminobut-3-enoic acid which may find applications in glycobiology research and medicinal chemistry.     

Trading N and O: asymmetric syntheses of β-hydroxy-α-amino acids via α-hydroxy-β-amino esters

Both diastereoisomers of 2-amino-3-hydroxybutanoic acid and 2-amino-3-hydroxy-3-phenylpropanoic acid have been prepared from enantiopure α-hydroxy-β-amino esters via the intermediacy of the corresponding cis- and trans-aziridines. Aminohydroxylation of two α,β-unsaturated esters produced enantiopure 2,3-anti-α-hydroxy-β-amino esters in >99:1 dr. Subsequent epimerisation at the C(2)-position via a sequential oxidation/diastereoselective reduction protocol gave the corresponding enantiopure 2,3-syn-α-hydroxy-β-amino esters in >99:1 dr. These syn- and anti-substrates were then converted into the corresponding N-Boc protected cis- and trans-aziridines, respectively, via a three step reaction sequence: (i) hydrogenolysis and in situ N-Boc protection; (ii) OH-activation; and (iii) aziridine formation. Subsequent regioselective ring-opening of the C(3)-methyl-aziridines with Cl₃CCO₂H proceeded with inversion of configuration to give the corresponding 2-amino-3-trichloroacetate esters, whereas the analogous reaction with the C(3)-phenyl-aziridines resulted in rearrangement to the corresponding oxazolidin-2-ones with retention of configuration. In each case, hydrolysis of the products from these ring-opening reactions produced the corresponding enantiopure β-hydroxy-α-amino acids as single diastereoisomers.     

Investigation of the reaction of α-thioamides, α-esters and α-nitriles with N-halosuccinimides

Investigation of the reaction of α-thioamides, α-esters and α-nitriles with NBS and NCS is described. The scope of this stereoselective oxidative transformation to the β-haloacrylamides, β-acrylates and β-acrylonitriles has been determined. A mechanistic rationale to explain the observed differences in reactivity between the amide, ester and nitrile series is proposed.     

Synthesis of polysubstituted isoquinolines through cross-coupling reactions with α-alkoxytosylhydrazones

A Pd-catalyzed cross-coupling reaction of α-alkoxytosylhydrazones with sulfonates derived from salicyl aldehydes gives rise to protected 1,5-dicarbonyl compounds. Treatment with ammonium hydroxide readily transforms these alkenes into isoquinolines with diverse substitution patterns at positions 3 and 4. In a similar way, the employment of o-cyanononaflates in the coupling reaction, followed by treatment with an organometallic, provides isoquinolines that incorporate substitution also at position 1. The combination of both approaches represents a versatile method for the preparation of isoquinolines substituted at any position of the heterocyclic ring.     

Molecular recognition of α-amino acid esters with arylporphyrin zinc complexes

The recognition ability of 10 arylporphyrin zinc complexes with respect to glycine, -alanine, and leucine methyl esters in toluene at 20°C was studied by spectrophotometric titration. The formation of amino acid-porphyrin associates, depending on the substitution pattern in the macroring, was examined by ¹H NMR spectroscopy. The zinc complex with diarylporphyrin having hydroxy groups in the para positions of the benzene rings was found to be the best recognizing agent with respect to glycine methyl ester, while leucine methyl ester was recognized best by the complex with hydroxy groups in the ortho positions of the benzene rings.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004, pp. 1557–1562.Original Russian Text Copyright © 2004 by G. Mamardashvili, Storonkina, N. Mamardashvili.This revised version was published online in April 2005 with a corrected cover date.     

Photodecarboxylative additions of N-protected α-amino acids to N-methylphthalimide

Photoreactions involving N,N-dimethylated α-amino acid salts and N-methylphthalimide are dominated by photoreduction and acetone trapping. Only, N-phenyl glycinate underwent photodecarboxylative addition in a moderate yield of 30%. In contrast, N-acylated α-amino acid salts readily gave addition products in fair to high yields of 20-95%. Comparison experiments with N,N-dimethylacetamide and amino-/amido-containing phthalimides revealed the origin of the crucial electron-transfer step and the reactivity order NR₃ »  ? RCONR₂ was established.     

Synthesis and decarboxylation of N-acyl-α-triphenylphosphonio-α-amino acids: a new synthesis of α-(N-acylamino)alkyltriphenylphosphonium salts

4-Phosphoranylidene-5(4H)-oxazolones 1 undergo hydrolysis in THF in the presence of HBF₄ at room temperature to give N-acyl-α-triphenylphosphonioglycines 3 (R² = H) in very good yields. 4-Alkyl-4-triphenylphosphonio-5(4H)-oxazolones 2 react with water in CH₂Cl₂/THF solution without any acidic catalyst at 0-5 °C in a few days yielding N-acyl-α-triphenylphosphonio-α-amino acids 3 (R² = Me) or α-(N-acylamino)alkyltriphenylphosphonium salt 4 (R² = CH₂OMe). α-Triphenylphosphonio-α-amino acids 3, on heating up to 105-115 °C under reduced pressure (5 mmHg) or on treatment with diisopropylethylamine in CH₂Cl₂ at 20 °C undergo decarboxylation to give the corresponding α-(N-acylamino)alkyltriphenylphosphonium salts 4, usually in very good yields.     

Catalysis of highly stereoselective Mannich-type reactions of ketones with α-imino esters by a pyrrolidine-sulfonamide. Synthesis of unnatural α-amino acids

The novel pyrrolidine-sulfonamide I has been prepared and used successfully to catalyze Mannich-type reactions between ketones and α-imino esters. The process is used to efficiently synthesize functionalized α-amino acid derivatives with excellent levels of regio-, diastereo-, and enantio-selectivity.     

Synthesis of α-fluoro-β-hydroxy esters by an enantioselective Reformatsky-type reaction

The first enantioselective Reformatsky-type reaction of ethyl iodofluoroacetate has been accomplished with alkyl aryl ketones. High diastereoselectivities and excellent enantioselectivities for the major diastereomer (93-95% ee) were achieved with large alkyl groups. For smaller alkyl groups the diastereoselectivities were moderate, but excellent enantioselectivities were obtained for both diastereomers (79-94% ee).     

Synthesis of α-fluoro-β-amino acids via the Reformatsky reaction of chiral N-tert-butylsulfinylimines with ethyl bromofluoroacetate

Treatment of chiral N-tert-butyl sulfinylimines with ethyl bromofluoroacetate in the presence of activated Zn dust in THF afforded the α-fluoro- β-amino acid derivatives in good yields(70-86%) and moderate diastereoselectivity(66:34-92:8).     

The use of two optically active N-sulfinyl α-imino esters in the stereoselective aza-Diels-Alder reaction

Diastereoselective aza-Diels-Alder (aza-DA) reactions of ethyl (S)-N-(tert-butanesulfinyl)iminoacetate (2a) and ethyl (S)-N-(p-toluenesulfinyl)iminoacetate (2b) with different dienes including activated, non-activated, cyclic, and acyclic dienes in the presence of Lewis acids are described. Reactions with 2a were found to be more selective. Reactions of unactivated dienes (acyclic and cyclic) with stoichiometric amounts of TMSOTf as Lewis acid afforded the aza-DA adducts in modest yields and in diastereoselectivities up to 99%. A strong preference for Re-approach was observed for 2a. Cyclic dienes gave the exo adducts as major products. For the aza-DA reaction with activated Danishefsky type dienes poor diastereoselectivities were observed. In these cases, the best results were obtained using stoichiometric amounts of BF₃·Et₂O as Lewis acid (up to 69% de, 76% yield). The absolute configurations of six of the addition products were established by chemical correlation with known compounds. Acidic cleavage of the sulfinyl group occurred without racemization to optically active non-proteinogenic α-amino acid ethyl esters.     

Regio- and diastereoselective Reformatsky reaction of chiral fluoroalkyl α,β-unsaturated N-tert-butanesulfinyl ketimines: Efficient asymmetric synthesis of β-fluoroalkyl β-vinyl β-amino esters

Highly regio- and diastereoselective Reformatsky reaction of stable, chiral fluoroalkyl α,β-unsaturated N-tert-butanesulfinyl ketimines was developed, which provided an efficient method for the asymmetric synthesis of structurally diverse β-tetrasubstituted β-fluoroalkyl β-vinyl β-amino esters in good yields and with excellent diastereoselectivities (dr up to 96:4).