Oxazolidines, reaction with

The related serine derived (4S)-4-methoxycarbonyl-3-(l-oxopropyl)-2-thiono-l,3-oxazolidine 11, and the cysteine derived (4A)-4-methoxycarbonyl-3-(l-oxobntyl)-2-thiono-1,3-thiazolidine 13, also serve as efficient chiral auxiliaries in boron- and tin(II)-mediated aldol condensations98. Thus, conversion of 11 into the boron or tin enolate, followed by reaction with 2-methylpropanal affords predominantly one adduct. Subsequent methanolysis and chromatographic purification delivers the syu-methyl ester in 98% ee. 

Chiral oxazolidines 6, or mixtures with their corresponding imines 7, are obtained in quantitative yield from acid-catalyzed condensation of methyl ketones and ( + )- or ( )-2-amino-l-phcnylpropanol (norephedrine, 5) with azeotropic removal of water. Metalation of these chiral oxazolidines (or their imine mixtures) using lithium diisopropylamide generates lithioazaeno-lates which, upon treatment with tin(II) chloride, are converted to cyclic tin(II) azaenolates. After enantioselective reaction with a variety of aldehydes at 0°C and hydrolysis, ft-hydroxy ketones 8 are obtained in 58-86% op4. 

Scheme 1.43 Test reaction with oxazolidine-thioether and thiazolidine-methanol ligands.

The same reaction with acetaldehyde produces carbene complex 34 with a saturated ring, i.e., an oxazolidin-2-ylidene ligand with the tosyl group replaced by methoxide. 

Chiral oxazolidine compounds have also been used as chiral auxiliaries for asymmetric Diels-Alder reactions. Adam et al.8 demonstrated the cycloaddition of optically active 2,3-dimethyl oxazolidine derivatives with singlet oxygen. As shown in Scheme 5-9, the reaction of chiral substrate 39 with singlet oxygen provides product 40 in high diastereomeric ratio. 

In the preparation of (2R,33, 7a3 )-2-phenyl-3-methyl-5-oxo-2,3,5,6,7,7a-hexahydropyrrolo-[2,T ]-oxazole 248, the reaction time is the most important parameter in the /ra r-halometallation. For instance, by stirring 246 with 1 or 2equiv of fer7-butyllithium in EtzO at — 78 °C for 30 min, 247 and the bicyclic lactam 248 were obtained as an equimolar mixture. The latter substance was isolated as a single product when the reaction time was increased to 120min for the reactions of 2-(2 -bromoethyl)oxazolidine 246 with fert-butyllithium (Scheme 36) <1996T10761>. 

The Michael addition reaction of the serine-derived oxazolidine 326 with ethyl acrylate gave two products. The major product of the reaction was found to be the bicyclic compound 327, which was formed in 27% yield, accompanied by the unsaturated ester 328. The Dess-Martin oxidation of 327 resulted only in formation of the elimination product, the 7,7a-dihydro-177, 377-pyrrolo[l,2-r ]oxazole 328 (Scheme 46) <2001JOC7555>. 

Saccharidic templates bearing an amino group in C-2, C-6, C-3, C-5. Generally, an amine located on non-anomeric position reacts similarly through the condensation reaction with carbon disulfide or thiophosgene, the preliminary formed isothiocyanate leads to spontaneous or base-induced cyclization into 1,3-oxazolidine- or l,3-oxazine-2-thiones, as previously mentioned. Several extensive studies are reported about the selective introduction of thionocarbamate moieties on carbohydrate scaffolds.3 22 23 320 34 38... 

Taguchi and coworkers175 studied the Lewis acid catalyzed asymmetric Diels-Alder reactions of chiral 2-fluoroacrylic acid derivatives with isoprene and cyclopentadiene. When a chiral l,3-oxazolidin-2-one and diethylaluminum chloride were used as the chiral auxiliary and the Lewis acid catalyst, respectively, a de of 90% was observed for the reaction with isoprene. The reaction with cyclopentadiene afforded a 1 1 mixture of endo and exo isomers with de values of 95% and 96%, respectively. The endo/exo selectivity was improved by using 8-phenylmenthol as the chiral auxiliary. Thus, the reaction... 

One of the best examples of the utility of enzymatic synthesis in catalyzing reactions that cannot be accomplished by any other route is the synthesis of substituted oxazolidine diesters. The oxazolidine ring is extremely water sensitive, the oxazolidine rapidly reverting back to the alkanolamine and aldehyde in the presence of water. Bis-oxazolidines have been used as hardeners for polymer coatings but the diester based on the hydroxyethyl oxazolidine and adipic acid cannot be synthesized directly with chemical catalysis because of the rapid rate of reaction of the oxazolidine ring with either the water from the esterification or the alcohol from transesterification. ... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Esters of -hydroxy- or )8-mercapto-AAs react with n-butyl isonitrile to give 5-substituted methyloxazoline (or thiazoline)-4-carboxylates in the presence of PdCla as a catalyst (74SC97). The enamine-protected AAs were also tranformed into oxazolidin-5-ones after reaction with alkyl chloroform-ates (Scheme 28) (75S724). 

Upon warming, these oxazolinyl-stabilized lithiooxiranes undergo an electrocyclic a-ring opening to give a-oxo-2-oxazolines after hydrolysis (Scheme 87). However, all attempts to quench the presumed oxazolidine enolate intermediates through reaction with electrophiles failed. 

The diastereoselectivity is reversed in the alkylation of the enolate derived from the structurally very similar bicyclic lactam, tetrahydro-3-phenyl-l//.577-pyrrolof 1,2-c]oxazol-5-one (3). Thus, the major diastereomer 4 produced has the tram relationship between the newly introduced substituent in the pyrrolidine ring and the fused oxazolidine ring residue11,12. Only active electrophiles such as iodomethane, 3-halopropenes or (halomethyl)benzenes react11,12. Base-catalyzed equilibration of the product obtained by reaction with 3-bromocyclohexene gives a 50 50 mixture of the cis- and rra s-diastereomers11. 

The flexibility of the gas-solid extraction method stems from the choice of many adsorbing phases, each offering a particular selectivity. It is possible to stabilise certain molecules that would normally decompose upon contact with the sorbent by incorporating into the sorbent a reagent that carries out a specific derivatisation. For example, aldehydes can be converted into oxazolidines, which are stable and desorbable compounds, by reaction with 2-hydroxymethylpiperidine. 

Oxazolidin-2-one (202) has been attached to poly(ethylenimine) (203) by Mannich reaction with formaldehyde (Scheme 97) (72NKK1179). The resultant polymer (204) was a... 

Employing the Mitsunobu reaction with diisopropyl azodicarboxylate and triphenyl-phosphine, aminoacylserine (in contrast to aminoacylthreonine) is converted into (ami-noacyl)oxazolidine-2-carboxylic acid. 54 By the same procedure a/Zo-threonine peptides are converted into the oxazoline derivatives, whilst the threonine peptides are apparently converted into the aziridines in good yields. 86 ... 

Access to the imino group of oxazolidine-4-carboxylic acid is even more sterically hindered when substitutions are performed at the C2 position. For such cases, the typical procedure is based on the conversion of the desired serine or threonine dipeptides with unprotected hydroxy groups into the oxazolidine rings by reaction with aldehydes or ketones,1139,1691 as described in Vol. E 22a, Section 2.3.2.4. 

In the case of copper(II) complexes, the reaction with acetaldehyde is believed to proceed by the steps shown in Scheme 38. The bis(oxazolidine)copper(II) complex (148 R = Me) has been characterized by X-ray analysis.486 Treatment of this complex with H2S in acid solution gives threonine. Synthetic procedures have been developed giving threonine in 95% yields.483... 

Aliphatic aldehydes and ketones react with aziridines to form relatively stable half aminals, eg, aziridine reacts with formaldehyde to form Ai-hydroxymethylaziridine [20276-43-1]. Half aminals can be converted to full aminals by reaction with a further secondary amine, isomerized to oxazolidines by the action of heat or used in a Mannich reaction for the ring aminomethylation of phenols, although this reaction gives only moderate yields (218-227). 

The phase-transfer-catalyzed asymmetric alkylation of 1 has usually been performed with achiral alkyl halides, and hence the stereochemistry of the reaction with chiral electrophiles has scarcely been addressed. Nevertheless, several groups have tackled this problem. Zhu and coworkers examined the alkylation of 1 with stereo-chemically defined (5S)-N-benzyloxycarbonyl-5-iodomethyl oxazolidine using 4d to prepare (2S,4R)-4-hydroxyornithine for the total synthesis of Biphenomycin. Unexpectedly, however, product 7 with a 2 R absolute configuration was formed as a major isomer, and the diastereomeric ratio was not affected by switching the catalyst to pseudoenantiomeric 2d and even to achiral tetrabutylammonium bromide (TBAB), indicating that the asymmetric induction was dictated by the substrate (Scheme 2.3) [21]. 

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