Oxazolidinones generation

The diastereoselectivity of the zinc iodide catalyzed reaction of the azetidinone I with the trimethylsilyl enolate derivatives of the chiral 3-(l-oxopropyI)oxazolidinones 6 was considerably lower (about 60 40), although independent generation of the zinc enolate, via exchange of the lithium enolate with zinc bromide, afforded the /9-Iactam carboximide derivatives in a ratio (RIS) 80 20177. 

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... 

With titanium enolates it was found that use of excess (3 equiv.) of the titanium reagent reversed facial selectivity of oxazolidinone enolates.140 This was attributed to generation of a chelated TS in the presence of the excess Lewis acid. The chelation rotates the oxazolidinone ring and reverses the facial preference, while retaining the Z-configuration syn diastereoselectivity. 

The conversion of azidoformates to fused-ring aziridines via the thermal generation of a nitrene has previously been reported. More recently, the photolytic conversion of a sugar-derived azidoformate has been used to prepare fused-ring aziridines <06JOC8059>. Photolysis of azidoformate 66 at 254 nm provides aziridine 67 in excellent yield. The resulting bicyclic aziridine was reduced to provide oxazolidinone 68 in 95% yield. Oxazolidinone 68 was subsequently converted to L-daunosamine. 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted important interest thanks to there various applications in different synthetic transformations. These simple structures, directly related to the well-documented Evans oxazolidinones, have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations (7V-enoyl derivatives), but mainly in condensation of their 7V-acyl derivatives on aldehydes. Those have shown interesting characteristics in anti-selective aldol reactions or combined asymmetric addition. Normally, the use of chiral auxiliaries which can accomplish chirality transfer with a predictable stereochemistry on new generated stereogenic centers, are indispensable in asymmetric synthesis. The use of OZTs as chiral copula has proven efficient and especially useful for a large number of stereoselective reactions. In addition, OZT heterocycles are helpful synthons that can be specifically functionalized. 

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]. 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

Padwa has shown that rhodium-catalyzed oxidation of indolyl carbamate 67 employing either Phl(OAc)2 or Phl=0 follows a path similar to that of the D-aUal carbamate (Scheme 17.26) [95]. In principle, indole attack of the putative rhodium-nitrene generates zwitterion 68, which is trapped subsequently by an exogenous nucleophile. Spiro-oxazolidinone products (for example, 69) are isolated as single diastereomers in yields ranging from 50 to 85%. As an intriguing aside, Padwa has found that certain carbamates react with Phl=0 in the absence of any metal catalyst to furnish oxazoHdinone products. This result may have implications for the mechanism of the rhodium-catalyzed process, although it should be noted that control experiments by Espino and Du Bois confirm the essential role of the metal catalyst for C-H amination [57]. 

Treatment with amines of the type 279 generated the intermediate oxazolidinone 280, which underwent thermal decarboxylative formation of the azomethine yhde. Subsequent in situ intramolecular cycloaddition formed the products 281 and 282 in 63% yield and in a 1 1.2 ratio for n=l. Replacing toluene for acetonitrile, for n = 2, gave comparable yields and an improved ratio of 1 2.1 in favor of 281 (Scheme 3.93). 

Anodic oxidation of the carbamates 17 and 23 in methanol, followed by reaction with chlorodiphenylphosphine affords the a-diphenylphosphinylcarbamates 20 and 25, from which the readily generated carbanions react with aldehydes to give the 4-phosphinyl-2-oxazolidinones 21 and 26. The removal of the diphenylphosphinyl group by a mild thermal treatment provides a route to the 2(3//)-oxazolones 22 and 27 (Fig. 5.6). ... 

The enantioselective amination of iV-acyl oxazolidinones has been studied as part of a general approach to the synthesis of arylglycines. In this case, the enolization is initiated by a chiral magnesium bis(sulfonamide) complex. The oxazolidinone imide enolates are generated using catalytic conditions (10 mol% of magnesium complex) and treated in situ with BocN=NBoc to provide the corresponding hydrazide. 20 mol% of iV-methyl-p-toluensulfonamide are added to accelerate the reaction (equation 117). 

Bromocyclization of the thiocarbamidate generated from f-butylisothiocyanate and 3-buten-2-ol gave oxazolidinone products with slight selectivity for the cis isomer (cis.trans 1.9 1),2271 while iodocycliza-tions of /V-sulfonylated carbamates gave somewhat higher stereoselectivity (equation 117).233... 

Less satisfactory results have been frequently encountered in the related asymmetric cycloaddition of a vinyl epoxide to an isocyanate as in Scheme 8E.30 [160]. The modest enantioselectivities of this process are indicative of the competitive intramolecular nucleophilic addition with enantioface exchange. When the oxazolidinone was generated from an achiral substrate, somewhat higher enantioselectiviites were obtained presumably due to superposition of the enantioselection obtained in the ionization step. 

Most traditional methods use hydrochloric acid solutions as the acid reagent for the hydrolysis or alcoholysis of fi-lactams. Methanolic solutions of trimethylchloro-silane are able to generate HCI in situ, and the trick has been employed successfully for the methanolysis of fi-lactams in a route to aspartic acid derivatives [60, 61] and 2-oxazolidinones[62], respectively. Recently the use of silica-supported acid reagent has been reported as a convenient alternative. The reagent (Si02-Cl) prepared from admixing silica gel and SOCl2 in dichloromethane and subjected to dryness, is able to run the methanolysis of (1-lactams at room temperature in 20 min [63]. 

N-Tosyl carbamates, such as 325, derived from allylic alcohols, undergo the Pd(II)-catalysed cyclization to furnish oxazolidinones 326 under 1 atm of CO439. Analogous Pd(II)-catalysed N-cyclization of allenic N-tosylcarbamates has generated the corresponding vinylpalladium intermediate that could be further alkylated440. 

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