Oxazolidinones, reaction with

The reaction has wide scope in respect of the dienophUe / -substituent. The representative less reactive dienophiles, crotonoyl- and cinnamoyl-oxazolidinone, react with cyclopentadiene at -15 °C and 25 °C for 20 h and 24 h giving cycloadducts in 99% ee and 96% ee, respectively. The 3-chloropropenoyl derivative also affords the adduct in high optical purity (96% ee) this adduct is transformed to 2-(methoxycar-bonyl)norbornadiene, a useful chiral building block. Thus, the 3-chloropropenoyl derivative can be regarded as a synthetic equivalent of an acetylene dienophile. 

The Diels-Alder reaction catalyzed by this chiral titanium catalyst 31 has wide generality (Scheme 1.53, 1.54, Table 1.22, 1.23). Acryloyl- and fumaroyl-oxazolidinones react with isoprene giving cycloadducts in high optical purity. 2-Ethylthio-l,3-buta-diene can also be successfully employed as the diene [42]. 

In a more recent study on 1,3-dipolar cycloaddition reactions the use of succi-nimide instead of the oxazolidinone auxiliary was introduced (Scheme 6.19) [58]. The succinimide derivatives 24a,b are more reactive towards the 1,3-dipolar cycloaddition reaction with nitrone la and the reaction proceeds in the absence of a catalyst. In the presence of TiCl2-TADDOLate catalyst 23a (5 mol%) the reaction of la with 24a proceeds at -20 to -10 °C, and after conversion of the unstable succinimide adduct into the amide derivative, the corresponding product 25 was obtained in an endojexo ratio of <5 >95. Additionally, the enantioselectivity of the reaction of 72% ee is also an improvement compared to the analogous reaction of the oxazolidinone derivative 19. Similar improvements were obtained in reactions of other related nitrones with 24a and b. 

The desilylacetylated qrcloadducts, produced from the reactions of trimethylsilyl-diazomethane with 3-crotonoyl-2-oxazolidinone or 3-crotonoyl-4,4-dimethyl-2-oxa-zolidinone, were transformed to methyl traws-l-acetyl-4-methyl-l-pyrazoline-5-car-boxylate through the reactions with dimethoxymagnesium at -20 °C. When the optical rotations and chiral HPLC data were compared between these two esters, it was found that these two products had opposite absolute stereochemistry (Scheme 7.39). The absolute configuration was identified on the basis of the X-ray-determined structure of the major diastereomer of cycloadduct derived from the reaction of trimethylsilyldiazomethane to (S)-3-crotonoyl-4-methyl-2-oxazolidi-none. 

We have found in our studies that the use of the lithium counter ion in the base is essential for successful reaction with regiochemical control and allows cyclization to proceed under mild thermal conditions. In contrast, use of sodium (NaH, NaN(SiMe3)2) or potassium (KH, KN(SiMe3)2) bases require elevated temperatures, and results in poor yields of the desired product, and a mixture of several by-products, including the regioisomeric 4-hydroxymethy-2-oxazolidinone,6 resulting from alternate processes. Thus, the lithium ion plays a very important role in the mechanism of this reaction. 

Water, which can be taken to a minimum by the use of molecular sieves, can produce a lactamide either through direct reaction with the aziridinone intermediate, or upon hydrolysis of oxazolidinone self-condensation products, previously obtained also in the presence of a strong non-nucleophilic base (H ) (ref. 17). The recently reported 0-self-alkylation compound H bears the (S,S)-configurations at the unreacted C-Br and newly formed C-0 bonds. The presence of bromine was expedient for the x-ray assessment of configuration at the two chiral centers of 11 which forms in high diastereoisomeric excess (ref. 5). 

Reaction progress kinetic analysis offers a reliable alternative method to assess the stability of the active catalyst concentration, again based on our concept of excess [e]. In contrast to our different excess experiments described above, now we carry out a set of experiments at the same value of excess [ej. We consider again the proline-mediated aldol reaction shown in Scheme 50.1. Under reaction conditions, the proline catalyst can undergo side reactions with aldehydes to form inactive cyclic species called oxazolidinones, effectively decreasing the active catalyst concentration. It has recently been shown that addition of small amounts of water to the reaction mixture can eliminate this catalyst deactivation. Reaction progress kinetic analysis of experiments carried out at the same excess [e] can be used to confirm the deactivation of proline in the absence of added water as well to demonstrate that the proline concentration remains constant when water is present. 

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. 

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-... 

Tamariz et al. reported the synthesis of mukonine (11) based on a regioselective Diels-Alder reaction of N-phenyl-4,5-dimethylidene-2-oxazolidinone (634) with methyl propiolate (635). The diene 634 was prepared in moderate yield from the condensation reaction of 2,3-butanedione (632) with phenyl isocyanate (633). In an optimized reaction procedure using drastic basic hydrolytic conditions (KOH/ MeOH), followed by methylation with dimethyl sulfate, the adduct 636, was... 

Conversion of 2 to the highly crystalline oxazolidinone 3 with phosgene has been described by Thornton who has employed this substance as a chiral auxiliary in asymmetric aldol reactions of its N-propionyl derivative. Kelly has also used an oxazoline derived from 3 as a chiral auxiliary in asymmetric alkylation of a glycolate enolate. Oxazolidinone 3 has also been prepared from 2 with diethyl carbonate in the presence of potassium carbonate. The conversion of 2 to the oxazolidinone 3 is accomplished using triphosgene in this procedure because of the high toxicity of phosgene. 

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. ... 

Further methods [205] successfully employed to synthesize fuUeropyrroUdines include acid-catalyzed [213] or thermal [214] desilylation of trimethylsilyl amino derivatives, tautomerization of a-aminoesters of immonium salts [215] and imines [216, 217], reaction with aldehydes in the presence of aqueous ammonia [218], reaction with oxazolidinone [204] or photochemical reaction with some amino derivatives [219-223], The reaction with amino acids and aldehydes was also carried... 

The amino acid derived chiral oxazolidinone 188 is a very commonly used auxiliary in Diels-Alder and aldol reactions. However, its use in diastereoselective 1,3-dipolar cycloadditions is less widespread. It has, however, been used with nitrile oxides, nitrones, and azomethine ylides. In reactions of 188 (R = Bn, R =Me, R = Me) with nitrile oxides, up to 92% de have been obtained when the reaction was performed in the presence of 1 equiv of MgBr2 (303). In the absence of a metal salt, much lower selectivities were obtained. The same observation was made for reactions of 188 (R = Bn, R = H, R = Me) with cyclic nitrones in an early study by Murahashi et al. (277). In the presence of Znl2, endo/exo selectivity of 89 11 and up to 92% de was observed, whereas in the absence of additives, low selectivities resulted. In more recent studies, it has been shown for 188 (R =/-Pr, R = H, R =Me) that, in the presence of catalytic amounts of Mgl2-phenanthroline (10%) (16) or Yb(OTf)3(20%) (304), the reaction with acyclic nitrones proceeded with high yields and stereoselectivity. Once again, the presence of the metal salt was crucial for the reaction no reaction was observed in their absence. Various derivatives of 188 were used in reactions with an unsubstituted azomethine ylide (305). This reaction proceeded in the absence of metal salts with up to 60% de. The presence of metal salts led to decomposition of the azomethine ylide. 

One of the problems related to the LA induced activation of a,p-unsaturated carbonyl compounds for the reaction with a nitrone is the competitive coordination of the nitrone and the a,(3-unsaturated carbonyl compound to the Lewis acid (Scheme 12.65). Calculations have shown that coordination of the nitrone to the LA is more feasible than a monodentate coordination of a carbonyl compound. However, this problem can be circumvented by the application of alkenes such as 3-alkenoyl-oxazolidinones, enabling abidentate coordination to the LA, which is favored over the monodentate coordination to the nitrone. 

The application of two different chiral ytterbium catalysts 263 and 264 for the 1,3-dipolar cycloaddition was reported almost simultaneously by two independent research groups in 1997 (372,373). In both reports, it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 225 and aUcenoyl oxazolidinones 241 with endo-selectivity (Scheme 12.84). In the first study, 20 mol% of the Yb(OTf)2-pyridine-bis(oxazo-line) complex 263 was used as the catalyst for reactions of several derivatives of... 

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 3-acyl-2(3F/)-oxazolones function as good dienophiles in cycloaddition reactions with cyclic 2,4-dienes such as cyclopentadienes and anthracenes. Thus, the thermal reaction of 3-acetyl-2(37/)-oxazolone with cyclopentadiene and the hexachloro and hexamethyl derivatives gives endo-cycloadducts exclusively. In particular, the chiral cycloadducts 221 and 223 derived from the diastereoselective Diels-Alder reactions of 3-(2-exo-alkoxy-l-apocamphanecarbonyl)-2(3/7)-oxazo-lones with hexamethylcyclopentadiene and 9,10-dimethylanthracene, respectively, are highly useful as chiral 2-oxazolidinone auxiliaries. The conformationally rigid roofed structures play a crucial role in affording excellent chiral induction (Fig. 5.54). 

TABLE 9.14 DIELS-ALDER REACTIONS OE A-ACYL OXAZOLIDINONES, 553 TABLE 9.15 DIELS-ALDER REACTIONS WITH VARIOUS DIENOPHILES, 553 TABLE 9.16 ENANTIOSELECTIVE ENE REACTIONS OF ETHYL GLYOXYLATE, 556... 

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