Oxazolidinones schemes

Asymmetric conjugate addition of lithium amides to alkenoates has been one of the most powerful methods for the synthesis of chiral 3-aminoalkanoates. High stereochemical controls have been achieved by using either chiral acceptors as A-enoyl derivatives of oxazolidinones (Scheme 4) 7 7a-8 chiral lithium amides (Schemes 5 and 6),9-12 or chiral catalysts.13,14... 

Due to the presence of an electron-withdrawing group on the dipolarophile, these processes are classified as type 1 reactions. The process involves the transference of charge from the dipole to the dipolarophile. When catalyzed by metallic compounds, coordination of the dipolarophile is highly desired. Usually, coordination of a nitrone to the Lewis acid is more feasible than coordination of a carbonyl compound. For this reason, alkenes that enable a bidentate coordination to the Lewis acid, such as 3-alkenoyl-oxazolidinones (Scheme 5), have been frequently employed as a model system to smdy the metal-catalyzed 1,3-dipolar cycloaddition... 

Alkylene carbonate may also react with a hydroxoalkylamine to create a cyclization reaction [260] that affords oxazolidinones (Scheme 7.17). 

The a-amination of aldehydes and subsequent reduction to form oxazolidinones (Scheme 7.6) was developed by the Jorgensen group [7]. In the presence of 10 mol% L-proline as catalyst a variety of aldehydes reacted with azodicarboxylates, 3a and 3a, affording the oxazolidinones 7 after subsequent reduction with borohydride and cyclization. Selected examples of the synthesis of products 7, which were obtained in yields up to 92% and with enantioselectivity up to 95% ee, are shown in Scheme 7.6. 

A method has been developed for a one-pot procedure from an amino acid to an oxazolidinone (Scheme 2.3). The sequence can be run at scale.11... 

H)-Oxazolones give hydroxy ketones on alkaline hydrolysis lithium aluminum hydride reacts at the C=N bond to form the corresponding 2-oxazolidinones (Scheme 17). 

A wider range of possibilities of preparing cyclic derivatives is offered by the presence of carboxyl and a-amino groups in the molecule. Substituted 5-oxazolinone (Scheme 4.23) is prepared by refluxing with TFA anhydride, and substituted 5-oxazolidinone (Scheme 4.24)by reaction with (halogenated) acetone [117,118]. Thiohydantoins are formed by reaction with isothiocyanate (Scheme 4.25). If R is methyl or phenyl, then the corresponding methyl- or phenylthiohydantoin is produced. Thiohydantoins are usually not volatile enough and for the purposes of GC analyses must be further modified, e.g., by trimethylsilylation [119,120]. 

Recently, Oppolzer s group reported on the synthesis and use of a new sulfinylating agent,107 the /V-sulfinyl sultam 82, as part of a broad program on the use of the versatile bornane-10,2-sultam 81 in asymmetric synthesis.108 The condensation of p-TolSOCI with 81 in THF, using dimethylaminopyridine (DMAP) as catalyst, gave the /V-(p-tolylsulfinyl)bornane- 10,2-sultam as a 6.2 1 diastereomeric mixture. Crystallization of the mixture from E O/hexane afforded pure 82 in 77% yield. X-ray analysis showed the absolute configuration at the sulfinyl sulfur to be (/ ). The reaction has been shown to be kinetically controlled, in contrast to the results obtained when n-BuLi was used instead of DMAR In the latter case, the reaction was under thermodynamic control, in accord with the result obtained by Evans with iV-sulfinyl oxazolidinone (Scheme 25). 

An asymmetric synthesis of the aminocyclopentitol has been achieved from an acylated oxazolidinone (Scheme 38).110 Thus, the acylated oxazolidinone 295 was subjected to boron triflate-catalyzed condensation with 3-butenal to yield the syn aldol product 297 in 63% yield. Similarly, the A-acyloxazoI idineth ione 296 delivered the aldol adduct 298 in 75% yield when enolized with TiCl4-(—)-sparteine and then... 

The control of the C8 stereocenter was achieved by alkylation directed by an auxiliary at C7 involving Oppolzer sultams, Enders hydrazones and Evans oxazolidinones (Scheme 5 l-IIl, resp.). Either the corresponding propionate [14, 37] or propionaldehyde [13, 16] equivalents were alkylated with an alkyl iodide representing the principal part of the northern half of epothilones (Scheme 5 1, II), or C-8 of a sui-table chain was methylated diastereoselec-tively (Scheme 5 III, IV). 

A synthesis of Staurosporine, was facilitated by BOM protection of a phthal-imide and an oxazolidinone [Scheme 8.153].342 Both BOM groups were removed by hydrogenolysis to the corresponding -hydroxymethyl derivatives whereupon treatment with sodium methoxide expelled formaldehyde to release the desired product in 92% overall yield. 

For the synthesis of A -Fmoc-protected A-alkyl annino acids a multistep procedure has been proposed that relies on reduction of the corresponding oxazolidinones (Scheme 5). Overall yields are usually excellent despite the stericaUy hindered annino group. 

Retrosynthetic analysis leads a new strategy in the synthesis of the ABC core using a Bradsher cycloaddition [83]. Cleavage of the resulting oxazolidinone ( Scheme 22) and a subsequent series of reactions gave a suitably substituted tricyclic core, which can be used in the synthesis of the pentacyclic skeleton ABCDE. 

C (SchemeJAllb). Carbonate-protected hydroxylamines undergo equally efficient rearrangements in DMSO or THF, but while transformations run in THF allow for the isolation of the initial a-oxygenated product, reactions run in DMSO lead to the conversion of these products to the corresponding oxazolidinones (Scheme 14.11c). ... 

Nucleophilic attack by cyanide ion (NaCN in MeCN) on hexafluoro-acetone (2 equiv.) leads to the formation of 2,2,5,5,-tetrakis(trifluoromethyl)-4-oxazolidinone (Scheme 38 R p, R f = CF )/ and this reaction has been extended to other fluoroketones (see Table 3) to provide fluorinated 4-... 

The reaction conditions play a key role for having a 100 % selectivity. The temperature must be kept below 408 K at higher temperatures the conversion rate was increased but the selectivity was drastically decreased because of the occurrence of reaction (6.16) which drove other concurrent conversions of glycerol [105] to afford oxazolidinones (Scheme 6.16). 

In many cases the diastereoselectivities obtained using Davies SuperQuat are higher than the ones obtained using Evans oxazolidinones (Scheme 2.46). 

Chiral Auxiliaries in Aldol Reaction Asymmetric aldol reactions ntilizing chiral auxiliaries have emerged as one of the most reliable methods in organic synthesis. Both syn-and anti-selective aldol reactions have been developed over the years. The field of asymmetric i yn-aldol reactions has been largely advanced by Evans since his development of dibntylboron enolate aldol chemistry based on amino acid-derived chiral oxazolidinones (Scheme 2.109) [9]. 

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