Solid-phase synthesis of oxazolidinones by cycloaddition of resin-bound epoxides with isocyanates

The first solid-phase synthesis of oxazolidinones by cycloaddition of resin-bound epoxides with isocyanates is described. Synthesis of the title compounds was achieved by alkylation of resin-bound carbamates with glycidyl tosylate, followed by cycloaddition of the resulting epoxides with isocyanates at elevated temperature in high yields and purity. Because N-aryloxazolidinones have been known to possess various biological activities, this method is useful from the viewpoint of drug discovery.     

Chemoselective opening of Vince lactam epoxide with nitrogen nucleophiles

Here is reported the chemoselective opening of the amide bond on a Vince lactam derivative with amines, without the cleavage of the epoxide-moiety, getting five new epoxides. Also reported is the rearrangement of the epoxides into the respective five new oxazolidinones with the use of BF₃·Et₂O. Crystal structures of some molecules and hydrogen bonding interactions are discussed.     

Direct catalytic synthesis of enantiopure 5-substituted oxazolidinones from racemic terminal epoxides

A venerable scaffold for asymmetric synthesis and drug development, chiral 5-substituted oxazolidinones are obtained in almost enantiomerically pure form (up to 99.9% ee) starting from racemic terminal epoxides. The salient features of this process include the very simple and convenient experimental protocol and the employment of a readily accessible catalyst and inexpensive, easily handled starting materials. An enantioconvergent approach for the total conversion of racemic epoxide into a single stereoisomeric oxazolidinone is also described.     

Novel stereoselective synthesis of functionalized oxazolidinones from chiral aziridines

Enantiomerically pure N-(R)-alpha-methylbenzyl-4(R)-(chloromethyl)oxazolidinones (4R)-5a-k were synthesized in one step and high yields from various aziridine-2-methanols (S)-2a-k by intramolecular cyclization with phosgene. The alpha-methylbenzyl substituent on the nitrogen was easily cleaved to give both enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a. (R)-7a was used for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a-j. We also applied the same methodology to prepare oxazolidinones 9a-c containing a heteroatom-substituted alkyl group at C-4 in high yields.     

Convenient synthesis of oxazolidinones by the use of halomethyloxirane, primary amine, and carbonate salt

[reaction: see text] Primary amines reacted with carbonate salts (Na2CO3, K2CO3, Cs2CO3, and Ag2CO3) and halomethyloxiranes in the presence of a base such as DBU or TEA to give oxazolidinones in high yields. The use of K2CO3 among these carbonate gave the best yield in this synthesis. A reaction mechanism was proposed that the oxazolidinone was obtained from an oxazinanone intermediate via a bicyclo[2.2.1] intermediate. The present reaction can be widely applied to convenient synthesis of useful N-substituted oxazolidinones and chiral oxazolidinones.     

Parallel kinetic resolution of racemic oxazolidinones using quasi-enantiomeric active esters

Racemic Evans’ oxazolidinones were efficiently resolved using a combination of quasi-enantiomeric profens. The levels of stereocontrol were high, leading to products with predictable configurations.     

Co(III) porphyrin/DMAP: an efficient catalyst system for the synthesis of cyclic carbonates from CO2 and epoxides

CoTPP(Cl)/DMAP was found to be a highly active catalyst system for the chemical fixation of CO₂ via reaction with epoxides. The corresponding cyclic carbonate products are produced in high yield and selectivity for a variety of terminal mono and disubstituted epoxides. 1,2-Disubstituted internal epoxides were also investigated as substrates and found to react with very high stereospecificity.     

Iodine-catalyzed direct allylation of chiral oxazolidinones by the amide-aldehyde-alkene condensation

An iodine-catalyzed direct allylation of chiral oxazolidinones with aldehydes and alkenes has been developed. The reaction proceeds, without use of any bases or metals, directly converted the 3-chiral oxazolidinones into N-allylated oxazolidinones. Additionally, the 3-chiral allylamine skeleton was constructed and the diastereomers were isolated by simple column chromatography.     

A readily synthesized and highly active epoxide carbonylation catalyst based on a chromium porphyrin framework: expanding the range of available beta-lactones

[reaction: see text] Catalytic carbonylation of epoxides to beta-lactones was effected by a highly active and selective bimetallic catalyst comprised of a chromium(III) porphyrin cation and a cobalt tetracarbonyl anion. The complex is readily synthesized from commercially available compounds in high yield. Carbonylation of numerous linear epoxides, as well as bicyclic epoxides derived from 8- and 12-membered hydrocarbons, proceeded with high activity, selectivity, and yield.     

Asymmetric synthesis of beta2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives

Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4-isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium beta-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2'-alkylacryloyl)-4-isopropyl-5,5-dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of beta-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of beta-amino-beta'-hydroxy N-acyl oxazolidinones.     

Asymmetric synthesis of vicinal amino alcohols via organocatalytic sequential α-amination/Grignard addition reactions of aldehydes

An organocatalytic sequential α-amination/Grignard addition reaction of aliphatic aldehydes is reported. The synthetically useful anti-vicinal amino alcohol derivatives were obtained in high yields and with high stereoselectivities. These derivatives could be easily transformed into oxazolidinones.     

Copper-catalyzed domino cyclization of propargylic alcohol with tosyl isocyanate to oxazolidinones

A copper-catalyzed domino cyclization of propargylic alcohols with tosyl isocyanate for the synthesis of oxazolidinones has been developed. Various propargylic alcohols with an aryl or alkyl substituents worked smoothly to afford the corresponding oxazolidinones in moderate to excellent yields.     

Palladium(II)-catalyzed tandem intramolecular aminopalladation of alkynes and conjugate addition. Synthesis of oxazolidinones, imidazolidinones, and lactams

[reaction: see text]Under the catalysis of a divalent palladium species, oxazolidinones, imidazolidinones, or lactams were conveniently obtained with high chemo- and stereoselectivity from the tandem intramolecular aminopalladation of alkynes, followed by insertion of alkenes, and protonolysis of the newly formed carbon-palladium bond.     

Catalytic regiodivergent kinetic resolution of allylic epoxides: a new entry to allylic and homoallylic alcohols with high optical purity

A novel regiodivergent kinetic resolution of a series of allylic epoxides with alkylzinc reagents is described. Results demonstrate the potential of chiral copper-phosphoramidite catalysts for enantiomer differentiation of allylic epoxides, allowing a chiral catalyst-stereoregulated synthesis of cyclic allylic and homoallylic alcohols with high optical purities.     

Guiding the nitrogen nucleophile to the middle: palladium-catalyzed decarboxylative cyclopropanation of 2-alkylidenetrimethylene carbonates with isocyanates

A palladium-catalyzed decarboxylative cyclopropanation of 2-alkylidenetrimethylene carbonates with isocyanates is described to form oxazolidinones of (1-aminocyclopropyl)methanols with high selectivity. The site of nucleophilic attack is directed by connecting the two reaction components and by employing an electron-deficient triarylphosphine ligand.     

The reaction of dichlorocarbene with β-ethanolamines stereospecific synthesis of epoxides

Optically pure β-ethanolamines were converted into epoxides in good yield and with high e.e. ( ?, 95%) by reaction with dichlorocarbene. By this method α-aminoacids were successfully converted into synthetically useful epoxides.     

N-heterocyclic carbene catalyzed domino cyclization of propargylic alcohols and benzoyl isocyanates

N-Hetereocyclic carbenes (NHCs) were found to be efficient catalysts for the cyclization of propargylic alcohols and isocyanates. Domino cyclization reactions were carried out using isopropyl-substituted imidazolium salt as a precatalyst, and a wide range of substituted oxazolidinones were obtained in high yields.     

Enantioselective epoxide polymerization using a bimetallic cobalt catalyst

A highly active enantiopure bimetallic cobalt complex was explored for the enantioselective polymerization of a variety of monosubstituted epoxides. The polymerizations were optimized for high rates and stereoselectivity, with s-factors (k(fast)/k(slow)) for most epoxides exceeding 50 and some exceeding 300, well above the threshold for preparative utility of enantiopure epoxides and isotactic polyethers. Values for mm triads of the resulting polymers are typically greater than 95%, with some even surpassing 98%. In addition, the use of a racemic catalyst allowed the preparation of isotactic polyethers in quantitative yields. The thermal properties of these isotactic polyethers are presented, with many polymers exhibiting high T(m) values. This is the first report of the rapid synthesis of a broad range of highly isotactic polyethers via the enantioselective polymerization of racemic epoxides.     

N,O-Acetals from Pivalaldehyde and Amino Acids for the α-Alkylation with Self-Reproduction of the Center of Chirality. Enolates of 3-Benzoyl-2-(tert-butyl)-1,3-oxazolidin-5-ones

The sodium salts of (S)-alanine, (S)-phenylalanine, (S)-valine, and (S)-methionine are condensed with pivalaldehyde to imines 5 . Cyclization by treatment with benzoyl chloride in cold CH₂Cl₂ gives mainly (4:1 to > 99:1) the (2S,4S)-4-alkyl-3-benzoyl-2-(tert-butyl)-1,3-oxazolidin-5-ones ( 6 ; cis-configuration) in high yields (85–95%). The oxazolidinones 6 and 7 are deprotonated with lithium diethylamide (LDEA) in tetrahydrofuran (THF) and alkylated (Mel, benzyl bromide) or hydroxyalkylated (benzaldehyde) to 4,4-disubstituted oxazolidinones 9 and 10 , respectively, with high diastereoselectivity (9:1 to 50:1; relative topicity ul). Hydrolysis of three of the oxazolidinones to amino acids of known configuration and optical purity indicates that little if any racemization occurs in the process.     

Synthesis,Characterization, Polymerization of Optically Active Terminal Epoxides and Episulfides Bearing Bulky Groups

A simple and efficient protocol was developed for the syntheses of optically active epoxides(2a-2d) via the reactions of epichlorohydrin with organometallic reagents with steric hindrance at low temperature. On this basis, episulfides(3a-3d) were obtained with high e.e. values by the reaction of the corresponding epoxides with NH₄SCN. The configuration of thiiranes was opposite to that of the corresponding epoxides. Then, epoxides 2a-2d were anionically polymerized and the poly-R-2a(or poly-S-2a) was proved to keep a stable one-handed helical conformation in solution. The oligomers[degree of polymerization(DP)=2-5] were obtained when the thiiranes(3a, 3b and 3c) were used to polymerize.