Titanium mediated asymmetric aldol reaction with α-fluoropropionimide enolates

Aldol reaction utilising Evans N-(α-fluoropropyl)-2-oxazolidinones with TiCl₄ have been explored. Reactions of N-(α-fluoropropyl)-2-oxazolidinones with aliphatic aldehydes generated α-fluoro-β-hydroxy-aldol products with high diastereoselectivities. When (αR)- and (αS)-N-(α-fluoropropyl)-2-(4S)-oxazolidinones were explored as substrates they gave rise to identical aldol diastereoisomer products. Examination of the enolates formed in each case by ¹⁹F NMR, after treatment with TiCl₄, indicated that both preparations gave the same predominant enolate. This was assumed to be the E-enolate. The α-fluoro-β-hydroxy-aldol products were removed from the auxiliary either by alcoholysis or reduction and converted to the corresponding α,β-difluoro products by treatment with Deoxofluor™.     

An unexpected result from the reaction of hydroxymethyl-2-oxazolidinones with isocyanates

The reaction of hydroxymethyl-2-oxazolidinones with 4-chlorophenyl isocyanate and phenyl isocyanate was studied. It was established that the investigated hydroxymethyl-2-oxazolidinones can react with isocyanates either at the NH group alone or at the NH and OH groups.     

Synthesis of 2-oxazolidinones from (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol

A series of isomeric 2-oxazolidinones has been synthesized from (1S, 2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 579–584, April, 2006.     

Pseudo-C3-symmetric trisoxazolines as ligands in copper catalyzed enantioselective Diels-Alder reaction

Air- and water-stable chiral catalyst trisoxazolines4-6 /Cu(ClO(4))(2)[middle dot]6H(2)O have been used in the Diels-Alder reaction of cyclopentadiene with acryloyl-2-oxazolidinones or ketoesters. The reaction is carried out in air and up to 82% ee was achieved.     

A novel highly stereoselective synthesis of chiral 5- and 4,5-substituted 2-oxazolidinones

A novel highly stereoselective synthesis of chiral mono- and bicyclic 4- and 4,5-substituted 2-oxazolidinones starting from β-keto esters was developed. After bioreduction with S. cerevisiae the resulting homochiral β-hydroxy esters are transformed into their hydrazides. Treatment with NaNO₂/H⁺ then furnishes 2-oxazolidinones in high e.e. (∼99%) and d.e. (>99%). The ring formation proceeds via a highly concerted sextet rearrangement with full retention of configuration at the stereocentres. Enantiopure 1,2-amino alcohols can subsequently be obtained by saponification of the 2-oxazolidinone products.     

Mass spectra of a series of 3-halo-2-oxazolidinones

The mass spectra of a series of 3-chloro and 3-bromo alkyl substituted 2-oxazolidinones have been investigated and compared with the mass spectra of the corresponding alkyl substituted-2-oxazolidinones. Fragmentation of the 2-oxazolidinone ring system has been found to be significantly influenced by: (1) the presence of an alkyl substituent, (2) the position, number and size of the alkyl substitutents, and (3)replacement of the N? H bond by N? CI and N? Br.     

Versatile synthons for optically pure alpha-amino aldehydes and alpha-amino acids: (+)- and (-)-4,5-dialkoxy-2-oxazolidinones

Both enantiomers of trans-5-benzyloxy-4-methoxy- (BMOx) and trans-4,5-dimethoxy-2-oxazolidinones (DMOx), which are readily accessible from simple 2-oxazolone heterocycles, represent good candidates for a new class of chiral synthons for use in the preparation of optically pure alpha-amino aldehydes and alpha-amino acids, respectively.     

Synthesis of 2-oxazolidinones from beta-lactams: stereospecific total synthesis of (-)-cytoxazone and all of its stereoisomers

The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxazolidinones, is described for the first time. In this approach, 2-oxazolidinones are prepared in stereomerically pure form from 3-hydroxy beta-lactams by a ring-opening-cyclization isomerization process. Application of this methodology to the total synthesis of the cytokine modulator, (-)-cytoxazone, and its three stereoisomers is demonstrated. [reaction: see text].     

3-Aryl-2-oxazolidinones through the palladium-catalyzed N-arylation of 2-oxazolidinones

[reaction: see text] 3-Aryl-2-oxazolidinones are obtained in good yields through the palladium-catalyzed N-arylation of 2-oxazolidinones with aryl bromides. The nature of aryl bromides, phosphine ligands, bases, and solvents strongly affects the reaction outcome.     

Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by tetrabutylammonium fluoride

By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various carboxylative cyclizations of the propargylic amines having internal alkynes with CO₂ proceeded to afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated 2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile and CO₂ by using TBAF as a catalyst.     

Nuclear magnetic resonace spectra of substituted oxazoles and oxazolidinones

During the synthesis of 2,5-disubstituted oxazoles and 4-oxazolidinones, NMR spectroscopy was utilized to obtain information on the structure, bonding and geometric isomerism in the various compounds. Long range couplings between substituents attached at C₂ and C₅ in both ring systems was of particular utility in this respect. The aromaticity of the oxazole ring is substantiated by the ability of the π system to transmit long range coupling through the ring and by the chemical shifts of the ring protons. Geometric isomers of the 4-oxazolidinones are identified by observing long-range cis and trans couplings of the order of 1·8 to 2·4 Hz.     

A novel way to chiral 2-oxazolidinones: selenium-catalyzed cyclocarbonylation of 2-aminoethanols

Selenium-catalyzed cyclocarbonylation of 2-aminoethanols with CO under atmospheric pressure at 30 °C afforded 2-oxazolidinones in excellent yields without any other co-catalyst. The method was then applied to the syntheses of chiral 2-oxazolidinones and no racemization was detected.     

DMAP-catalyzed synthesis of 2-oxazolidinones from corresponding halohydrins using KOCN/DMF

We report facile and simple synthesis of a variety of 2-oxazolidinones from the corresponding halohydrins by reaction with KOCN in DMF catalyzed by DMAP. DMAP and temperature play key roles in enriching the yield of 2-oxazolidinones. A few examples in this Letter are applicable to pharmaceutically important processes.     

Stereoselective Lewis acid promoted Kharasch-type addition of 3-bromoacetyl-2-oxazolidinones to norbornadiene

Ytterbium trifluoromethanesulfonate promoted radical atom-transfer addition of 3-bromoacetyl-2-oxazolidinones to norbornadiene afforded stereoselectively the corresponding 5-exo-3-bromo-5-nortricycleneacetic acid derivatives in good yields. Following clean tri(trimethylsilyl)silane reduction of the bromides, 3-exo-nortricycleneacetic acid derivatives were obtained with excellent diastereoselectivities (90–96% de) when using the chiral 4-isopropyl- and 4-benzyl-substituted 2-oxazolidinone auxiliaries. The stereochemistry of the studied compounds was investigated by 1D and 2D NMR spectroscopy.     

The Dakin-West reaction of N-alkoxycarbonyl-N-alkyl-alpha-amino acids employing trifluoroacetic anhydride

The Dakin-West reaction of N-alkoxycarbonyl-N-alkyl-alpha-amino acids (1a-j) with trifluoroacetic anhydride in the presence of pyridine gave alpha-amido trifluoromethyl ketones (2a-j), in which probable intermediates were mesoionic 1,3-oxazolium-5-olates (munchnones). The diastereoselective reduction of 2a-f with NaBH4 gave the threo-aminoalcohols (5a-f), which may be explained by the Felkin-Anh model. This was confirmed by converting 5a-f into trans-5-trifluoromethyl-2-oxazolidinones (6a-f) in good yields.     

Conformationally rigid chiral [4+2]cycloadduct-based 2-oxazolidinones as new auxiliaries

Newly introduced enantiomerically pure [4+2]cycloadduct-based 2-oxazolidinones which are conformationally fixed by bicyclo[2.2.2] and [2.2.1] ring systems, serve well as exellent chiral auxiliaries in the Evans' asymmetric strategy.     

Ruthenium catalyzed selective synthesis of enol carbamates by fixation of carbon dioxide

Secondary amines react with carbon dioxide and terminal alkynes in the presence of a catalytic amount of 4-1,5-cyclooctadiene) (6-1,3,5-cyclooctatriene)ruthenium [Ru(COD)(COT)] and tertiary phosphine in toluene to give enol carbamates in good yields with high regio- and stereoselectivity. Cyclic enol carbamates, 5-methylene-2-oxazolidinones are obtained from N-substituted propargylamines and carbon dioxide in high yields.     

Chiral building blocks: enantioselective syntheses of benzyloxymethyl phenyl propionic acids

The synthesis of (2S)-2-benzyloxymethyl-3-(2-fluoro-4-methoxyphenyl)- propionic acid, (2S)-2-benzyloxymethyl-3-(2-fluoro-4-methylphenyl)propionic acid and (2S)-2-benzyl-oxymethyl-3-(2,4-dimethylphenyl)propionic acid has been achieved by TiCl4 mediated alkylation of the corresponding (4R)-4-benzyl-3-[3-(2-fluoro-4-methoxyphenyl-, 2-fluoro-4-methylphenyl-, 2,4- dimethylphenyl-)propionyl]-2-oxazolidinones, followed by hydrolysis of the chiral auxiliary. The stereochemistry of the alkylation reaction was confirmed by an X-ray crystal structure of (4R)-4-benzyl-3-[(2S)-2-benzyloxymethyl-3-(2- fluoro-4-methylphenyl)propionyl]-2-oxazolidinone.     

Enantioselective Synthesis of 3-Heterosubstituted-2-amino-1-ols by Sequential Metal-Free Diene Aziridination/Kinetic Resolution

A general protocol for the enantioselective synthesis of 3-heterosubstituted-2-amino-1-ols was developed based on metal- free intramolecular regio- and stereoselective diene aziridination and regioselective opening. Kinetic resolution of the resulting (1′-NR¹R² and 1′-SR)-4-oxazolidinones was performed using ABCs organocatalysts, expanding the application of this methodology.     

Pd（OAc）2／[mmim]I催化体系催化胺氧化羰化合成氨基甲酸酯、脲和2-噁唑啉酮

采用Pd(OAc)2/[mmim]I催化体系,在不同反应条件下可以将烷基胺、芳香胺及氨基醇(酚)一步转化为氨基甲酸酯、脲和2-噁唑啉酮.N-苯基氨基甲酸甲酯、二苯基脲及苯并-2-噁唑酮的催化转化频率分别为12417,17638和4114h-1.