4-Substituted-2-oxazolidinone

An important feature of this reaction is that in contrast to most other catalytic asymmetric Mannich reactions, a-unbranched aldehydes are efficient electrophiles in the proline-catalyzed reaction. In addition, with hydroxy acetone as a donor, the corresponding syn-l, 2-aminoalcohols are furnished with high chemo-, regio-, diastereo-, and enantioselectivities. The produced ketones 14 can be further converted to 4-substituted 2-oxazolidinones 17 and /i-aminoalcohol derivatives 18 in a straightforward manner via Baeyer-Villiger oxidation (Scheme 9.4) [5]. 

Catalysed aerobic epoxidation of the styrene-cobalt complex, followed by the addition of trimethylsilyl isothiocyanate, yields 4-phenyloxazolidine-2-thione 123 <96TL7315>. The 4-substituted 2-oxazolidinone 124 undergoes a "chromium Reformatsky" reaction with aldehydes RCHO (R = i-Pr or Ph) in the presence of chromium(ll) chloride and lithium iodide to give mainly the unusual anti-aldol products 125 in excellent dia,stereomeric excess and yield <97TL4,387>. 

Ketone 16 can be prepared from glucose in 6 steps without extensive chromatography purification (Scheme 10.5).78. V-Aryl-substituted oxazolidinone-containing ketone 18 can be synthesized... 

The diastereoselective synthesis of a d ipeptide i sostere 221 was performed, through an organocopper mediated anti-SN2 reaction on substituted oxazolidinone 220 <020L1055>. 

The intramolecular Michael addition of A -tosylcarbamates 194 afforded selectively tram substituted oxazolidinones 195 <03H(60)1173>. 

Oxazolidinone-Substituted Carbanions. Oxazolidinone-substituted organostannanes readily undergo transmetalation with alkyllithium reagents to the organolithium derivatives which then can undergo nucleophilic addition reactions. -Substituted oxazolidinones can act in this capacity as both a nitrogen source and source of chirality (eq 60). Although the a-stereoselection... 

The Evans aldol reaction of chiral, crotonyl-substituted oxazolidinones had proven effective for the asymmetric synthesis of hydroxypropionates... 

The reactions of (5)-5-hydroxymethyl-2-pyrrolidinone (236) with phosgene or phosgene dimer (trichloromethylchloroformate) in the presence of pyridine afforded (+)-(S)-3,5-dioxo-perhydropyrrolo[l,2-c]oxazole (243) in moderate yield <92H(33)619>. In a similar manner, tri-substituted oxazolidinones have been obtained <84EUP128120>. 

Desymmetrization of AT-Boc-protected serinol has been achieved in good yield and high enantiomeric excess (ee > 99%) by acylation with PPL in vinyl acetate (Fig. 19) (26). The product has been exploited as an intermediate in different ways to prepare (4R)- and (4S)-substituted oxazolidinones known as Evans auxiliaries. These compounds have important tasks as asymmetric inductors for synthesis. 

A substituted oxazolidinone (XXIV) which had the pharmacological spectrum of a major tranquilizer was reported in a clinical study to worsen psychosis and no beneficial effect was noted. The unusual, fluorinated aminoimidazoline (XXV) has been reported to have the pharmacological properties of a minor tranquilizer. ... 

Miller AW, Nguyen SB (2004) (Salen)chromium (III)/DMAP an efficient catalyst system for the selective synthesis of 5-substituted oxazolidinones from carbon dioxide and aziridines. Org Lett 6 2301-2304... 

FIGURE 11 Exemplary catalytic processes for the selective formation of 5- and 4-substituted oxazolidinones using CO2 as reagent [95,96]. DMAP, dimethylaminopyridine. 

Willis et al reported an enantioselective direct aldol reaction for the synthesis of protected aryl P-hydroxy-a-amino acids catalyzed by chiral Mg (I I) complexes (Scheme 4.12) [12]. A catalyst system composed of 10 mol% of Mg(Cl04)2,11 mol% of (S,S)-Ph-Pybox (35), and diisopropylethylamine generated an enolate of a chiral glycine equivalent derived from isothiocyanate-substituted oxazolidinone (33). The... 

A hydrogen-bond-mediated asymmetric [4,l]-annulation/rearrangement cascade of stable sulfur ylides and nitroolefins has been developed in the presence of a C2-symmetric chiral urea catalyst This reaction provides a facile route to enantioenriched 4,5-substituted oxazolidinones with excellent stereocontrol (up to more than 95 5 dr and 97 3 er). The stereocontrolled modes and mechanism have been proposed to explain the origin of this stereochemistry. 

Chiral acyl oxazolidinones also proved effective as auxiliaries on the acceptor component in asymmetric conjugate additions (Equation 17) [100]. Hruby reported a Cu-catalyzed 1,4-addition to phenyl-substituted acceptor 99 that proceeds with high diastereofacial selectivity to furnish 101 in 98 2 dr and 91 % yield. In these studies, low diastereomeric ratios were observed for the corresponding benzyl-substituted oxazolidinones. 

Pentafluorobenzyl bromide has been used in the derivatization of mercaptans [55] and phenols [36], m the analysis of prostaglandins [37], and in quantitative GC-MS [5S] 1,3 Dichlorotetrafluoroacetone is used for the derivatization of amino acids to the corresponding cyclic oxazolidinones and allows the rapid analysis of all 20 protein ammo acids [d] Pentafluorophenyldialkylchlorosilane derivatives have facilitated the gas chromatographic analysis of a wide range of functionally substituted organic compounds, including steroids, alcohols, phenols, amines, carboxylic acids, and chlorohydrms [4]... 

For the isoxazolines 284 substituted at position 3, ring-chain tautomerism is depicted by the equilibrium 284 and 285-287 (Scheme 103). In general the cyclic tautomers 284 are strongly preferred. The ring-opened forms exist in equilibrium with 284 in rare cases [95ZOB705 96AHC(66)1, p. 21]. The equilibrium of the oxazolidinones 288 [78MI1, p. 107] is affected by the nature of the solvent. 

Finally we have performed the Michael addition reactions of malononitrile and 3-(2-alkenoyl)-2-oxazolidinones in dichloromethane in the presence of the R,R-DBF0X/Ph-Ni(C104)2-31 20 and TMP (10 mol% each). Enantioselectivities were a little lower than 90% ee for acceptors having a variety of / -substituents. The best selectivity was 94% ee in the reaction of t-butyl-substituted acceptor (Scheme 7.50). 

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

Reck F, Zhou F, Girardot M, Kern G, Eyermann CJ, Hales NJ, et al. Identification of 4-substituted 1,2,3-triazoles as novel oxazolidinone antibacterial agents with reduced activity against monoamine oxidase A. J Med Chem 2005 48 499-506. 

In Entry 5, the aldehyde is also chiral and double stereodifferentiation comes into play. Entry 6 illustrates the use of an oxazolidinone auxiliary with another highly substituted aldehyde. Entry 7 employs conditions that were found effective for a-alkoxyacyl oxazolidinones. Entries 8 and 9 are examples of the application of the thiazolidine-2-thione auxiliary and provide the 2,3-syn isomers with diastereofacial control by the chiral auxiliary. 

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