Oxazolidinones alcohols

Propargyl alcohol (332) and (328) react readily with isocyanates in the presence of a basic catalyst to give 4-methylene-2-oxazolidinones (334) and 4-methylene-2-imidazolinones (336), respectively (63JOC991). In the absence of sodium methoxide the intermediate methanes (333) and ureas (335) were obtained and on treatment with sodium methoxide underwent ring closure. Moderate to excellent yields were obtained. 

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 construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

Reaction of the glycol, 70, affords an oxazolidinone rather than the expected carbamate (71) on fusion with urea. It has been postulated that the urea is in fact the first product formed. This compound then undergoes 0 to N migration with loss of carbon dioxide reaction of the amino alcohol with the isocyanic acid known to result from thermal decomposition of urea affords the observed product, mephenoxolone (74) this compound shows activity quite similar to that of the carbamate. An analogous reaction on the glyceryl ether, 75, affords metaxa-lone (76). 

The optically active oxazolidinone derivative 3, readily obtainable from serine (see Appendix), is alkylated to give predominantly the cw-product98. The auxiliary is removed by acid hydrolysis to give the 2-amino alcohol. 

Oxidative carbonylation generates a number of important compounds and materials such as ureas, carbamates, 2-oxazolidinones, and aromatic polycarbonates. The [CuX(IPr)] complexes 38-X (X = Cl, Br, I) were tested as catalysts for the oxidative carbonylation of amino alcohols by Xia and co-workers [43]. Complex 38-1 is the first catalyst to selectively prepare ureas, carbamates, and 2-oxazolidinones without any additives. The important findings were the identity of the counterion and that the presence of the NHC ligand influenced the conversions. 2-Oxazohdinones were formed from primary amino alcohols in 86-96% yield. Complex 38-1 also catalysed the oxidative carbonylation of primary amines to ureas and carbamates. n-Propylamine, n-butylamine, and t-butylamine were transformed into the... 

The substituents direct the approach of the aldehyde. The acyl oxazolidinones can be solvolyzed in water or alcohols to give the enantiomeric (3-hydroxy acid or ester. Alternatively, they can be reduced to aldehydes or alcohols. 

The cycloberbine 339 derived from coptisine (65) was reduced with lithium aluminum tri-tert-butoxyhydride to afford the trans-alcohol 340 along with a small amount of the cis-alcohol (Scheme 62). Treatment of 340 with ethyl chloroformate effected C-8—N bond cleavage and simultaneous oxyfunc-tionalization at C-8 with the desired stereochemistry to produce the oxazolidinone 341. This was hydrolyzed with potassium hydroxide and then underwent N-methylation to give ( )-ochrobirine (343). Similarly, the ochrobirine analog 344 was also obtained from berberine (15) (171). 

The transformation of the cyano group could also introduce a new chiral center under diastereoselective control (Figure 5.13). Grignard-transimination-reduction sequences have been employed in a synthesis of heterocyclic analogues of ephedrine [81]. The preferential formation of erythro-/3-amino alcohols may be explained by preferential hydride attack on the less-hindered face of the intermediate imine [82], and hydrocyanation of the imine would also appear to proceed via the same type of transition state. In the case of a,/3-unsaturated systems, reduction- transimination-reduction may be followed by protection of the /3-amino alcohol to an oxazolidinone, ozonolysis with oxidative workup, and alkali hydrolysis to give a-hydroxy-/3-amino acids [83]. This method has been successfully employed in the synthesis L-threo-sphingosine [84]. 

Benzotetramisole 213 has been identified as an effective catalyst for kinetic resolution of sec-benzylic and propargylic alcohols 214 to give 215 in excellent enantioselectivity O60L1351 06OL4859>. The benzotetramisole-catalyzed kinetic resolution has been extended to 2-oxazolidinone 217 via enantioselective /V-acylation <06JA6536>. 

Cleavage of 2-oxazolidinones to amino alcohols. 2-Oxazolidinones and related heterocycles can be cleaved to Boc-amino alcohols by N-f-butoxycarbony-lation followed by treatment with a catalytic amount of Cs2CO, in CH,OH at 25°.3... 

Chiral active pharmaceutical ingredients, 18 725-726. See also Enantio- entries Chiral additives, 6 75—79 Chiral alcohols, synthesis of, 13 667-668 P-Chiral alcohols, synthesis of, 13 669 Chiral alkanes, synthesis of, 13 668-669 Chiral alkenes, synthesis of, 13 668—669 Chiral alkoxides, 26 929 Chiral alkynes, synthesis of, 13 668-669 Chiral ammonium ions, enantiomer recognition properties for, 16 790 Chiral ansa-metallocenes, 16 90 Chiral auxiliaries, in oxazolidinone formation, 17 738—739... 

N-(2-Hydroxypropyl)carbamates (8.139, Fig. 8.13,b) are prodrugs that resemble the A-(2-hydroxyphenyl)carbamates discussed above. Here, activation yielded the tranquilizer mephenoxalone (8.140, Fig. 8.13,b) and an alcohol or a phenol such as paracetamol. Other active oxazolidinones could be obtained by replacing the MeO group in 8.139 (Fig. 8.13, b) with another substituent. For this series, the mechanism of activation is not an intramolecular nucleophilic attack, but, rather, decomposition of the deprotonated carbamate group as shown in Fig. 8.7,b, Reaction b, with the intermediate isocyanate being trapped to form the oxazolidinone ring. 

The synthetic methods and chemical characterization data for the various polymeric materials to be discussed in this work have been reported elsewhere [6-8]. In some cases copolymerization of the unchlorinated oxazolidinone monomer with other common monomers such as acrylonitrile, vinyl chloride, styrene, and vinyl acetate, using potassium persulfate as an initiator, was performed. In other cases the unchlorinated oxazolidinone monomer was grafted onto polymers such as poly(acrylonitrile), poly(vinyl chloride), poly(styrene), poly(vinyl acetate), and poly(vinyl alcohol), again using potassium persulfate as an initiator. 

Poly(aorylonitrile-co-oxazolidinone), 2 = poly(vinyl aoetate-co-oxazolidinone), 3 = poly(acrylonitrile-g-oxazolidinone), 4 = poly(vinyl aoetate-g-oxazolidinone), 5 = poly(vinyl alcohol-g-oxazolidinone). Coatings were soaked in 3,000 mg/L free ohiorine. Time after ohiorination when biooidal effioaoy was measured. TABLE 2. Zones of inhibition of A/-Chioramine Poiymerio Biooidai Coatings on Fabric against Staphylococcus aureus. ... 

Poly(actylonitrile-co-oxazolidinone), 2 = poly(vinyl acetate-co-oxazolidinone), 4 = poly(vinyl acetate-g-oxazolidinone), 5 = poly(vinyl alcohol-g-oxazolidinone), 6 = poly(vinyl chloride-g-oxazolidinone). 

Finally, single bead FT-IR has been further exploited in many applications, such as the study of the tetrapropylammonium perrutherate (TPAP)-catalyzed oxidation of supported alcohols [167], the ring opening of a supported oxazolidinone [173], and the solid-phase synthesis of a benzimidazole [174]. 

In the reaction of the conformationally restricted epoxy alcohol 84 and methyl or benzyl isocyanate, the epoxy carbamate 85 was formed. Cycliza-tion of 85 in tetrahydrofuran in the presence of sodium hydride gave the oxazinone 86 in approximately 20% yield, and the oxazolidinone 87 (R = Me, CH2Ph) in 40-60% yield. The formation of the two products can be rationalized by different nucleophilic attacks on the urethane nitrogen. With increasing nucleophilicity of the nitrogen, the regioselectivity of the reaction is shifted toward the formation of 87 (92TL3009). 

A current limitation of the amination methodology is encountered with carbamate esters derived from 2° alcohols (that is, 22 and 24 in Scheme 17.14). With some notable exceptions, substrates in this class often give only small amounts ( 0-20%) of oxazolidinone, and instead afford the corresponding ketones in variable yields. A similar observation has been made by Doyle for C-H insertion reactions with 1-indanol diazo-... 

The utilization of a-amino acids and their derived 6-araino alcohols in asymmetric synthesis has been extensive. A number of procedures have been reported for the reduction of a variety of amino acid derivatives however, the direct reduction of a-am1no acids with borane has proven to be exceptionally convenient for laboratory-scale reactions. These reductions characteristically proceed in high yield with no perceptible racemization. The resulting p-amino alcohols can, in turn, be transformed into oxazolidinones, which have proven to be versatile chiral auxiliaries. Besides the highly diastereoselective aldol addition reactions, enolates of N-acyl oxazolidinones have been used in conjunction with asymmetric alkylations, halogenations, hydroxylations, acylations, and azide transfer processes, all of which proceed with excellent levels of stereoselectivity. 

The phenylalanine-derived oxazolidinone featured here enjoys three practical advantages over the valine-derived oxazolidinone developed earlier in this laboratory. First, both the intermediate g-amino alcohol and the derived oxazolidinone are crystalline solids which can be purified conveniently by direct crystallization. Second, the oxazolidinone contains a UV chromophore which greatly facilitates TLC or HPLC analysis when it is employed as a chiral auxiliary. Finally, both enantiomers of phenylalanine are readily available, enabling stereocontrol in either sense simply by using the oxazolidinone derived from the appropriate enantiomer. 

N-Methylation of 3 and reduction of the crystalline oxazolidinone 4 with lithium aluminum hydride was found to give a superior yield of DAIB (5) and a more easily purified product than exhaustive methylation of 2 with methyl iodide and reduction of the quaternary methiodide with Super-Hydride. Recently, a modified version of DAIB, 3-exo-morpholinoisoborneol MIB), was prepared by Nugent that is crystalline and that is reported to give alcohols in high enantiomeric excess from the reaction of diethylzinc with aldehydes. ... 

In a special case, basic hydrolysis of 2-(trichloromethyl)oxazolines 329 gave the oxazolidinone 330 or the amino alcohol 331 depending on the reaction conditions as shown in Table 8.25 (Scheme 8.99). Formation of 330 is presumably the result of facile displacement of the trichloromethyl leaving group. 

Some enantiomerically pure substituted 2-oxazolidinones are excellent as chiral auxiliaries. From the pioneering studies 2 conducted in the early 1980 s of the uses of such auxiliaries has emerged what is perhaps the most widely used method today for the preparation of enantiomerically highly enriched a-alkylalkanoic acids, alcohols and aldehydes, that is, the alkylation of enolates from chiral 3-acylated 2-oxazolidinones followed by auxiliary removal2 59. The early work has been reviewed60-62. These enantiomerically pure cyclic imide auxiliaries have been used not only for alkylations but also in a plethora of a-functionalization reactions, such as diastereoselective aldol, a-hydroxylation, a-amination and Diels-Alder reactions and these are discussed elsewhere in this volume. 

The vicinal amino alcohols (S)-2-amino-3-methylbutanol [( -valinol, 1], (15, 2R)-2-amino-l-phenylpropanol [(1, 2S)-norcphcdrine, 4] and, to a lesser extent, the enantiomers of p-aminobenzenepropanol (phenylalanol, 7) have been most often used as starting materials for the preparation2-4-24,64 of enantiomerically pure 2-oxazolidinones (2,5 and 8, respectively, see... 

S)-2-Amino-3-methylbutanol [(S)-valinol] derived oxazolidinones, i.e., (S)-3-acyl-4-iso-propyl-2-oxazolidinones 1, have been used extensively for the preparation of a-alkylated acids, aldehydes and alcohols. The enolates are formed by deprotonation with lithium diisopropyl-amide or sodium hexamethyldisilazanide at low temperature in tetrahydrofuran. Subsequent addition of a haloalkane gives alkylation, which occurs from the Si-face2. The diastereoselectivities are usually good (>90 10), and the products are usually purified by flash chromatography and/or recrystallization (see Table 10). Additional examples of alkylation of 1 have been published5 l0 12- 20 22-29 39.44.-47,49.57.70-78... 

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