2-Oxazolidinone synthesis

Lindsay KB, Ferrando F, Christensen KL, Overgaard J, Roca T, Bennasar M-L, Skrydstrup T (2007) Sml2-promoted radical addition reactions with N-(2-indolylacyl)oxazolidinones synthesis of bisindole compounds. J Org Chem 72 4181-4188... 

Watile RA, Bagal DB, Deshmukh KM, Dhake KP, Bhanage BM (2011) Polymer supported diol functionalized ionic liquids an efficient, heterogeneous and recyclable catalyst for 5-aryl-2-oxazolidinones synthesis from CO2 and aziridines under mild and solvent free conditions. J Mol Catal A 351 196-203... 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

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). 

The synthesis of the E-ring intermediate 20 commences with the methyl ester of enantiomerically pure L-serine hydrochloride (22) (see Scheme 9). The primary amino group of 22 can be alkylated in a straightforward manner by treatment with acetaldehyde, followed by reduction of the intermediate imine with sodium borohydride (see 22 —> 51). The primary hydroxyl and secondary amino groups in 51 are affixed to adjacent carbon atoms. By virtue of this close spatial relationship, it seemed reasonable to expect that the simultaneous protection of these two functions in the form of an oxazolidi-none ring could be achieved. Indeed, treatment of 51 with l,l -car-bonyldiimidazole in refluxing acetonitrile, followed by partial reduction of the methoxycarbonyl function with one equivalent of Dibal-H provides oxazolidinone aldehyde 52. 

Oxazolidinones are a new class of synthetic antimicrobial agents, which have activity against many important pathogens, including methicillin-resistant Staphylococcus aureus and others. Oxazolidinones (e.g. linezolid or eperezolid) inhibit bacterial protein synthesis by inhibiting the formation of the 70S initiation complex by binding to the 50S ribosomal subunit close to the interface with the 3OS subunit. 

Oxathiane dioxides lithiated 641 synthesis of 638, 647 Oxathiane oxides, synthesis of 352 Oxathiolane oxides, synthesis of 241 Oxaziridines 72, 254, 826 as optically active oxidizing agents 291 Oxazolidinones 826 Oxazolines 619, 788... 

Bolm et al. [106] have carefully studied the synthesis and the hganding ability of salen-like bis(sulfoximines). The chirahty which is indeed generally introduced via the use of chiral diamines in the salen series, is in sulfoximines present via the sulfur atom. They investigated the Diels-Alder cycloaddition between cyclopentadiene and acryloyl-2-oxazolidinones with various bis(sulfoximines) (see Scheme 42) and Cu(OTf)2 as the copper source [107]. 

The syntheses in Schemes 13.45 and 13.46 illustrate the use of oxazolidinone chiral auxiliaries in enantioselective synthesis. Step A in Scheme 13.45 established the configuration at the carbon that becomes C(4) in the product. This is an enolate alkylation in which the steric effect of the oxazolidinone chiral auxiliary directs the approach of the alkylating group. Step C also used the oxazolidinone structure. In this case, the enol borinate is formed and condensed with an aldehyde intermediate. This stereoselective aldol addition established the configuration at C(2) and C(3). The configuration at the final stereocenter at C(6) was established by the hydroboration in Step D. The selectivity for the desired stereoisomer was 85 15. Stereoselectivity in the same sense has been observed for a number of other 2-methylalkenes in which the remainder of the alkene constitutes a relatively bulky group.28 A TS such as 45-A can rationalize this result. 

The synthesis in Scheme 13.47 was also based on use of a chiral auxiliary and provided the TBDMS-protected derivative of P-D lactone in the course of synthesis of the macrolide portion of the antibiotic 10-deoxymethymycin. The relative stereochemistry at C(2)-C(3) was obtained by addition of the dibutylboron enolate of an A-propanoyl oxazolidinone. The addition occurs with syn anti-Felkin stereochemistry. 

Since 4 has a high inclusion ability for a wide variety of organic compounds 46), it might be useful for various reaction controls. For example, 4 was found to be useful for a selective synthesis of the P-lactam 89 from N,N-diisopropylaeetylformamide (88). Irradiation of 88 in benzene solution and in neat liquid has been reported to give the oxazolidinone derivative 90 exclusively in 86 and 65% yields, respectively, but not any 89 Control of the photocyclization of 88 has been attempted by irradiation... 

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]. 

Solution-phase enantioselective synthesis of 437 and 438 thus achieved was also translated into solid-phase synthesis <2002TL8981>. The oxazolidinone 441 prepared from L-tyrosine methyl ester via 440 was attached to Merrifield resin to produce 442. Resin-bound 442 was converted to 443 (Scheme 98). 

Nicolas, E., Russell, K. C., and Hruby, V. J. (1993). Asymmetric 1,4-addition of organo-cuprates to chiral a, b-unsaturated N-Acyl-4-phenyl-2-oxazolidinones A new approach to the synthesis of chiral b-branched carboxylic acids. J. Org. Chem. 58, 766—770. 

This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.11 The catalyst is derived from optically active 1,2-diphenylethylenediamine, the preparation of which (either antipode) was described in the preceding procedure. The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with cyclopentadiene,11 and acryloyl derivatives with benzyloxymethylene-cyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.11... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Although the synthesis of the oxazolidinone 159 appeared to be well established, the scale-up of the reaction gave poorly reproducible results. The synthesis was much more efficient using diphosgene and a catalytic amount of activated charcoal <06S885>. 

Combs and coworkers have presented a study on the solid-phase synthesis of oxa-zolidinone antimicrobials by microwave-mediated Suzuki coupling [38], A valuable oxazolidinone scaffold was coupled to Bal resin (PS-PEG resin with a 4-formyl-3,5-dimethoxyphenoxy linker) to afford the corresponding resin-bound secondary amine (Scheme 7.18). After subsequent acylation, the resulting intermediate was transformed to the corresponding biaryl compound by microwave-assisted Suzuki coupling. Cleavage with trifluoroacetic acid/dichloromethane yielded the desired target structures. 

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