Synthesis of esters of α-chloroacetoxy-β,β,β,-trichloroethylphosphonic acids

Summary The synthesis of 11 previously unreported dialkyl esters of -mono-, -di-, and -trichloroacetoxy-,,-trichloroethylphosphonic acids has been effected.     

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 new α,α,β,β-tetrafluoroesters

Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF₂CF₂CO₂Et, 1 in the presence of copper powder to give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and allyl acetate proceeded smoothly under thermal and radical conditions to give the corresponding adducts, which underwent elimination reaction to give β-vinyl and β-allyl α,α,β,β-tetrafluoroesters, CH₂CHCF₂CF₂CO₂Et, 4 and CH₂CHCH₂CF₂CF₂CO₂Et, 5, respectively. 1 also readily reacted with 1,5-hexadiene and 1-hexene with copper or palladium complex, followed by reduction to remove iodine to produce ω-alkenyl-α,α,β,β-tetrafluoroester CH₂CH(CH₂)₄CF₂CF₂CO₂Et 6 and α,α,β,β-tetrafluoroester C₄H₉CH₂CHICF₂CF₂CO₂Et.     

Synthesis of α-amino ketones

Summary A new method is described for synthesizing aromatic -amino ketones with the general formula , which is based on the condensation of azlactones with benzene in the presence of aluminum chloride.     

Diastereoselective synthesis of aliphatic α,α-difluoro-β3-amino esters via a sonocatalyzed Reformatsky reaction

(R)-2-Phenylglycine ethyl ester was found to be a cheap and effective auxiliary for the preparation of aliphatic α,α-difluoro-β(3)-amino esters via a Reformatsky reaction performed under sonication conditions. The products were obtained in good to high yield and ≥96:4 dr, thus providing a new stereoselective route to this under-represented class of compounds. A facile one-pot removal of the phenylglycine moiety and concomitant Boc protection subsequently afforded the corresponding Boc-protected β(3)-amino esters in excellent yield.     

Synthesis and reactions of α-fluoro-α-amino amides

N-((S)-1-Phenylethyl)halofluoroethanamides have been investigated as precursors to N-protected α-fluoro-α-amino amides by nucleophilic displacement of halide with nitrogen nucleophiles such as potassium phthalimide, sodium succinimide, sodium glutarimide, trimethylamine and sodium azide. With single diastereoisomers of the iodofluoroethanamide, clean inversion of configuration occurs at room temperature, but subsequent epimerisation may occur as a result of the liberated iodide. The α-fluoro-α-amino amides made underwent a wide variety of reactions depending on conditions, but in many cases the carbon-fluorine bond was compromised. However, reacting trimethylamine and N-((S)-1-phenylethyl)iodofluoroethanamide gave the corresponding α-fluorobetaine amide, and subsequent acidic hydrolysis led to α-fluorobetaine as the first example of an ‘unprotected’ α-fluoroamino acid.     

Synthesis of α,β-unsaturated γ-amino esters with a quaternary center by ruthenium-catalyzed codimerization of N-acetyl α-arylenamines and acrylates

Ruthenium-catalyzed highly selective codimerization of N-acetyl α-arylenamines with ethyl acrylates is reported. This codimerization reaction provides a new efficient method for the synthesis of α,β-unsaturated γ-amino esters with a quaternary center.     

A highly efficient method for the α,β-dehydrogenation of α-amino esters and α-amino-β-diesters

N-monochlorination of N-unprotected α-amino esters and α-amino-β-diesters was efficiently and very simply effected by using inexpensive effervescent sodium dichloroisocyanurate tablets for water disinfection in a biphasic organic solvent-water system. Subsequent dehydrochlorination provided α,β-didehydroaminoacid esters, whose hydrogenation would allow the starting compounds to be easily racemized.     

Synthesis of α,α-disubstituted α-amino esters: nucleophilic addition to iminium salts generated from amino ketene silyl acetals

Alkoxycarbonyl iminium species are prepared easily by the oxidation of tetrasubstituted amino ketene silyl acetals, and subsequent nucleophilic addition of Grignard reagents to the iminium salts gives α,α-disubstituted α-amino ester derivatives in moderate to good yields, in which aryl and ethynyl substituents are readily introduced.     

Synthesis of α-alkyl- and α,α-dialkyl-β-phenyltryptamines

A new method was developed for the synthesis of -alkyl- and ,-dialkyl--phenyltryptamines based on alkylation of nitroalkanes with -phenyl-nor-gramine.     

Synthesis of esters of α-vinyloxyethylcarbamodithioic acid

Mono and diesters of 2-vinyloxyethylcarbamodithioic acid were synthesized by the reaction of (1-p-nitrophenyl)-2-vinyloxyethylaminoethanol with carbon disulfide. 3-[2-(Vinyloxyethyl)]-5-(4-nitrophenyl)-1,3-thiazolidine-2-thione was prepared and its structure was proved by X-ray diffraction analysis.     

Synthesis of cyclic α-amino ketones

Summary A simple method is described for synthesizing cyclic -amino ketones by intramolecular cyclization of azlactones under the action of aluminum chloride.     

New Synthesis of α-Bromo-α,β-Unsaturated Esters

A synthesis of α-bromo-α,β-unsaturated esters 2 from tert-butyl α-(trimethylsilyl)-α-bromoacetate (1) and carbonyl compounds is described.     

Synthesis of difluorinated pseudopeptides using chiral α,α-difluoro-β-amino acids in the Ugi reaction

2,2-Difluoro-3-(2-hydroxy-1 R-phenylethylamino)-3 S-phenylpropionic acid 3, obtained by a Reformatsky-type reaction of ethyl bromodifluoroacetate with (4R)-2,4-diphenyloxazolidine, was used as a classical carboxylic acid in the Ugi reaction to prepare various difluorinated pseudopeptides 5a-n. Compounds 5 were then deprotected by hydrogenolysis to furnish difluorinated pseudopeptides 6.     

Preparation of sugar derived β,β′-dihydroxy α,α-disubstituted α-amino acids

A novel strategy for the preparation of β,β′-dihydroxy α,α-disubstituted α-amino acids bearing a sugar moiety has been developed. The procedure is based on two Henry reactions: the first Henry reaction involves a sugar aldehyde and nitroethanol to furnish a sugar derived α-hydroxymethyl α-nitroalkanol while the second Henry reaction is between this nitro sugar and formaldehyde. This sequence provided the expected epimers of sugar derived α,α-dihydroxymethyl α -nitroalkanols, from which the corresponding β,β′-dibenzyloxy α-N-benzyloxycarbonylamino esters were easily obtained. All rights reserved.     

Diastereoselective synthesis of trans-trifluoromethyl-β-lactams and α-alkyl-β-trifluoromethyl-β-amino esters

The diastereoselective synthesis of β-lactams was examined from N-tosyl-1-chloro-2,2,2-trifluoroethylamine 3 and various nonactivated aliphatic acid chlorides in the presence of a Brønsted base. The mild reaction conditions allowed to get trifluoromethyl-β-lactams in good yields with high trans-diastereo selectivity. In addition, we also demonstrated that ring-opening of β-lactams easily provided α-alkyl-β-trifluoromethyl-β-amino esters.     

Synthesis of α-Cyano-β-fluoro-α-hydroxyesters

The ring opening fluorination of glycidic gem-cyanoesters was achieved by action of pyridine polyhydrofluoride at 25°C in dichloromethane. The regioselective nucleophilic substitution reaction allows the synthesis of a new class of fluorohydrins with OH, CN and CO₂R on the same carbon atom.     

Synthesis of Cyclic α'α'-Disubsituted-α-Alkyl-γ-Hydroxy-α,β-Enones from α-Phenylthio-α,β-Enones

Key reactions in a “two pot” synthesis of cyclic γ-hydroxy-αβ-enones (6) from α-phenylthioenones (1) are regioselective α-alkylation of the α-phenylthioenones (1) and [2,3]sigmatropic rearrangement of the sulphoxide (3).