2-Oxazolidinone substitution

Scheme 10.38 Asymmetric hydrogenation of 2 oxazolidinone substituted pyridines.

The oxazolidinone-substituted olefin Ic (Scheme 3) constitutes another fortunate substrate for the diastereoselective synthesis of a chiral dioxetane , which is of preparative value for the enantiomeric synthesis of 1,2 diols . For example, the photooxygenation of the enecarbamate Ic produces the asymmetric dioxetane 2c in >95% jt-facial diastereoselectivity. The attack of the O2 occurs from the jt face anti to the isopropyl... 

A comparative study involving singlet oxygen, ozone, and 4-phenyl-1,2,4-triazoline-3,5-dione oxidation of chiral oxazolidinone substituted enecarbamates has shed light on the mechanistic intricacies of the oxidative cleavage of alkenyl double bonds.282... 

In recent years, a few stereoselective methods for the asymmetric hydrogenation of pyridines and related heterocycles have been developed <20050BC4171>. A chiral auxiliary method starts with an oxazolidinone-substituted pyridine which on reduction with H2/Pd(OH)2 in acetic acid affords the corresponding piperidine in good yield and high enantiopurity. The chiral auxiliary is cleaved during the reaction and can be recovered (Equation 100) <2004AGE2850>. 

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... 

Oxazolidinone-substituted siloxydiene 105b also is applicable in DA reactions with electron-deficient alkenes under slightly vigorous conditions (Scheme 10.108)... 

The stereochemistry of the ZnCl2-catalyzed [4 + 3] cycloadditions of chiral oxazolidinone-substituted oxyallyls with unsymmetrical disubstituted furans is controlled by the substitution pattern on the fiiran (13JOC1753). 

Trifluoromethyl substituted aldimines react with a-benzyloxyacetyl chloride in the presence of triethylamine to give the CF3 substituted azetidinones in 50 % yields Also, A-o -(trimethylsilyl)methyl imines undergo cycloaddition with the oxazolidinone substituted ketene 269 to give the [2-1-2] cycloadducts 270 with excellent diastereomeric... 

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. 

Vinyl epoxides are highly useful synthetic intermediates. The epoxidation of dienes using Mn-salen type catalysts typically occurs at the civ-olefin. Epoxidations of dienes with sugar-derived dioxiranes have previously been reported to react at the trans-olefin of a diene. A new oxazolidinone-sugar dioxirane, 9, has been shown to epoxidize the civ-olefin of a diene <06AG(I)4475>. A variety of substitution on the diene is tolerated in the epoxidation, including aryl, alkyl and even an additional olefin. All of these substitutions provided moderate yields of the mono-epoxide with good enantioselectivity. 

A nucleophilic attack of methanol in the a-position to a nitrogen atom can take place through an electrochem-ically generated iminium cation from substituted pyrrolidine [171,172], piperidine [173-180] or oxazolidinone [181,182] derivatives, as illustrated in Scheme 99 for A-carbomethoxypyrrolidine [163] and N-carbomethoxypiperidine [174]. 

Verma and Ghosh [72] desymmetrized a a-symmetric 3-dimethyl(phe-nyl)silyl substituted glutaric anhydride (127) with Evans oxazolidinone 128 (Scheme 32) as one of the key steps in their synthesis of (+)-preussin. 

---