Oxazolidine derivatives

The threo- and erythro- some.r% (448), which are capable of condensing with carbonyl compounds to give five-membered heterocycles (449), can be 

A study of cyclization versus elimination in the oximes of Mannich bases has shown that pathways giving either the A -isoxazoline (452) or the unsaturated ketone oxime (453), can be selected according to reaction conditions.  

The product of the reaction between hydroxylamine and mesityl oxide was thought to be (454). It has now been shown that the products are the corresponding oximes, 3,3,5-trimethyl-5-hydroxyisoxazolidine (455), 3,5,5-trimethyl-A -isoxazoline (456), and derivatives corresponding to solvent addition across the double bond of (454). 

The reaction of a-chloro-oximes or the isomeric nitrosochlorides with 

Jacquier, F. Petrus, and J. Verducci, Bull. Soc. chim. France, 1972, 330, 

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Some reactions in which a preformed 1,3-oxazolidine ring is transformed into another oxazolidine derivative were described. A detailed study of the enantioselective reduction of A-tosyl-4-alkylidene-l,3-oxazolidin-2-ones under the catalysis of Rh salts and chiral ligands, was published <06T9237>. 

Oxidation of oxazolidine derivatives (275) gives isomeric pairs (A) and (B) of a-methoxy-substituted oxazolidine nitroxyl radicals (276a-d, f, g) and a,a-dimethoxy-substituted nitroxyl radical (276e) (Scheme 2.102) (515). 

In addition to the oxidative alkoxylation of 4H -imidazole and oxazolidine derivatives, the reaction was also used with other cyclic aldo-nitrones such as DMPO, derivatives of 3-imidazoline-3-oxide (228-232) (506), and derivatives... 

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. 

Independent proof of these assignments is obtained from chemical studies. In the g/Mco-derivative (54), the hydroxyl groups at C-2 and C-4 can be inverted stereospecifically via oxazolidine derivatives with the neighboring amino group, thus unequivocally proving the stereochemical relationships between C-2, C-3 and C-4 in compounds (54)— (56) 10). 

By the use of chiral oxazolidines derived from a chiral norephedrine and methyl ketones, an asymmetric aldol reaction proceeds in a highly enantioselective manner. In the case of ethyl or a-methoxy ketones, the corresponding anti aldol products were obtained with high diastereo- and enantioselectivities. A chiral titanium reagent, generated from... 

Unlike the 13C-NMR method, H-NMR spectra are not applicable to 3-alkylaldehydes. For 3-arylaldehydes, the chemical shifts of 2-H, 3 -H, and 5-H appear deshielded in oxazolidines derived from chiral aldehydes with configuration A, where Rz is the aryl group. 

More recendy the cis and trans isomers of the mosquito repellent CIC-4, a mixture of citronella isomers, have been separated by preparative hplc and bioassayed for effectiveness (23). Chiral-phase capillary gas chromatography and mosquito repellent activity of some oxazolidine derivatives of (+)-and (— )-citronellal have been studied to find structure—activity relationships (24). Several 2-alkyl- -acetyloxalidines have been synthesized and tested against mosquitoes, with further efforts using nmr to determine the rotational isomers of the more active N-acetyl-2,2-dimethyloxazolidine (25). 

The effect of the size of the acyl group on the barrier for isomer interconversion was examined (82JOC3890) in oxazolidine derivatives 103. The energy barrier, which amounts to 72.8 kJ mor when R = Me, decreases to 53.2 kJ mol when R is an adamantyl group. 

The generally accepted mechanism for anodic amide alkoxylation involves the formation and further reaction of an intermediate acylimmonium ion with a nucleophile. The oxidation of Af-methyl-2-hydroxyethylcarbamate was utilized in the synthesis of a 1,3-oxazolidine derivative in 60% yield.117... 

Analogous to the use of chiral acetals one can employ chiral N,O-acetals, accessible from a, -unsatu-rated aldehydes and certain chiral amino alcohols, to prepare optically active -substituted aldehydes via subsequent Sn2 addition and hydrolysis. However, the situation is more complicated in this case, since the N,0-acetal center constitutes a new stereogenic center which has to be selectively established. The addition of organocopper compounds to a, -ethylenic oxazolidine derivatives prepared from unsaturated aldehydes and ephedrine was studied.70-78 The (diastereo) selectivities were rather low (<50% ee after hydrolysis) in most cases, the highest value being 80% ee in a single case.73 There is a strong solvent effect in these reactions, e.g. in the addition of lithium dimethylcuprate to the ( )-cinnamaldehyde-derived oxazolidine (70 Scheme 28) 73 the (fl)-aldehyde (71) is formed preferentially in polar solvents, while the (S)-enantiomer [ent-71) is the major product in nonpolar solvents like hexane. This approach was utilized in the preparation of citronellal (80% ee) from crotonaldehyde (40% overall yield).78... 

Fused ring heterocycles, prepared by cyclization of substrates with a tethered nitrogen nucleophile, have been used in the synthesis of amino sugars and aminocyclitols. The examples shown in Table 28 make use of imidate-type functionality (equation 101) to insure nucleophilic attack by nitrogen. The bro-mocyclization of N,W-dialkylaminomethyl ethers of 2-cyclohexen-l-ol to form bicyclic oxazolidine derivatives has been reported also.228b... 

The stereoselective synthesis of /(-branched a-halocarboxylic acids containing two newly formed chiral centres (155) has been accomplished by a reaction consisting of 1,4-addition of dialkylaluminium chlorides to a,/(-unsaturated A -acyloxazolidinones (154) followed by quenching the intermediate aluminium enolate with /V-halosuccini-mides. The most efficient stereo-control was achieved with oxazolidines derived from glucosamine (154). Although /(-branched aliphatic a-halo carboxylic acids were synthesized stereo selectively, the highest stereoselectivity was observed for (3-aryl substrates.112... 

Despite the similarity between compound 1 and (-)-swainsonine, a different retrosynthetic strategy was devised for the synthesis of (-)-swainsonine (Scheme 3).19 The ring rearrangement yielded the hydropyrrolidine 5, which was prepared from the precursor 6. The enantiometrically pure oxazolidine derivative 7 was a suitable chiral starting material, as it was efficiently synthesised from the diol 8. As with the synthesis of 1, a palladium (0) catalysed allylic amination was carried out in the presence of ligand L (Scheme 2)14 to give 7 with an ee of 97%, which was increased to >99% on recrystallisation with dichloromethane/hexane. 

Air drawn through a solid sorbent tube containing 2-(hydroxymethyl) piperidine on XAD-2 (450 mg/250 mg) oxazolidine derivative of acetaldehyde formed derivative desorbed into toluene under ultrasonic condition analyzed by GC-FID (NIOSH Method 2538, 1989 OSHA Method 68, 1988). 

Other Af-(trimethylsilyl)methylnitrogen compounds like carbodiimides give the corresponding anion which reacted with benzaldehyde to give 1,3-oxazolidine derivatives (almost 1-to-l mixture of regioisomers).335... 

The six optically active alkaloids ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, and the N-methylated N-methylephedrine and N-methylpseudoephedrine are described in detail in Reti s review (2). Two new alkaloids of related structure have since been identified in Ephedra species, namely, (9-benzoylpseudoephedrine (271) and the oxazolidine derivative ephe-droxane (272). The 4-quinolone derivative ephedralone, recently isolated from Ephedra alata (273), may be of similar biogenetic origin as the ephedrines. Ephedra species also contain macrocyclic alkaloids of more complex structure (275). The two major Ephedra alkaloids (—)-ephedrine and (+)-pseudoephedrine are diastereomers. (—)-Ephedrine has the erythro and (+)-pseudoephedrine has the threo configuration. 

In this chapter, oxazole and its derivatives are named and numbered as in Chemical Abstracts. Thus compound (6) is called 4,5-dihydrooxazole rather than 2-oxazoline or A2-oxazoline, (7) is 2,5-dihydrooxazole, the betaines (3) are named anhydro-5-hydroxy-oxazolium hydroxides and not oxazolium 5-oxides or oxazolium 5-olates, and the oxo derivatives (4) and (5) are 5(4//)-oxazolone and 5(2//)-oxazolone, respectively, the position of the extra hydrogen atom being indicated in parentheses. The fully saturated compound (8) is oxazolidine its oxo derivatives are named oxazolidinones and oxazolidinediones, e.g. compound (9) is 2-oxazolidinone and (10) is 4,5-oxazolidinedione. A formula such as (11) is not meant to imply that all the substituents are methyl groups it represents a general oxazolidine derivative and is used in place of the cumbersome expression (12 R-R = H, alkyl or aryl). 

Statine was synthesised from the oxazolidine derivative 201 obtained through a stereoselective conjugate addition of an hydroxymethyl group in a basic methanolic solution. The conjugate addition proceeded faster than the dehydroxymethylation<02OL1213>. 

Deng and Overman employed the aza-Cope-Mannich reaction in the enantios-elective total synthesis of (+)-preussin (21), a potent antifungal agent possessing a pyrrolidine skeleton8 (Scheme 1.6h). Conversion of the amino alcohol 22 to the oxazolidine derivative 23 was readily accomplished by reacting with decanal in hot benzene with removal of water using a Dean-Stark trap. Treatment of... 

Kennedy ER, O Connor PF, Gagnon YT. 1984. Determination of acrolein in air as an oxazolidine derivative by gas chromatography. Anal Chem 56 2110-2123. 

Analogues of the reagent of Step 1 were used by the author to prepare 1,3-oxazolidine derivatives by reacting oxirane derivatives with imines as illustrated in Eq.l and are described (3). 

In reactions with acyclic dienes, the stereoselection with the (S)-valinol-derived cro-tonate imides is only about 3 1, but diastereoselection is high with N-acyl oxazolidines derived from phenylalanine. The chiral auxiliary is cleaved by transesterification with lithium benzyloxide in 85-95% yield. ... 

Polyfluoroalk-2-ynoic acids 7 readily undergo an intermolecular-intrarnolecular Michael addition reaction with a variety of bifunctional azanucleophiles and o-phenylenediamine. to give the corresponding carboxylated and/or decarboxylated 2-(polyfluoroalkyl)imidazolidine (e. g, 8 and 9. respectively), thiazolidine, and oxazolidine derivatives in moderate to good yields. The products formed depend strongly on the reaction conditions employed. For example, the decarboxylated derivative 9 is only formed under reflux conditions. ... 

Also, thiazolidine derivatives have been reported to control an insect s energy metabolism through the inhibition of trehalase, an enzyme involved in the energy functions, especially in the insect-flight [217,218]. The affinity of trehazolin (a) for this enzyme has motivated workers to explore 2-aryl-iminothiazolidine/oxazolidine derivatives (comp, b. Fig. 37, Table 26) as its inhibitors [219]. 

Table 26 Physicochemical properties and trehalase inhibitory activities of 2-arylimino-thiazolidine/oxazolidine derivatives (comp, b, Fig. 37) [219]...

Diastereoselective Cy clopropanation and Alkylation of Chiral Oxazolidines Derived from Ephedrine. Ephedrine forms... 

Chiral titanocene derivatives can also be used as catalysts in asymmetric Diels-Alder reactions (Sch. 56 and 57). Collins reported that the asymmetric Diels-Alder reaction of oxazolidine derivatives and cyclopentadiene was effectively catalyzed by... 

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