Hydroxy-oxazolines

The use of hydroxy oxazolines 26 in catalytic aryl transfer reactions was investigated subsequently (specifically, addition of BPhs to p-methoxybenzaldehyde in the presence of dimethyl poly(ethylene glycol) (DiMPEG) for details of this... 

Bolm found that chiral ferrocenyl hydroxy oxazoline 24 is also a good catalyst (88% ee). When the zinc species is prepared from a 1 2 mixture of diphenylzinc and diethylzinc, enantioselectivity is dramatically improved (97% ee) (Scheme 11) [36]. Extremely high enantioselectivity was also achieved by using planar chiral q5-cyclopentadienylrhenium tricarbonyl complex 25 [37]. 

Geifken has shown that the reaction of 2-hydroxycarbohydroxamic acids (261) with carbodi-imidazole (CDI) can lead to two products, depending upon the nature of substituents at C-2. The dioxazol-5-ones (262) may be converted into AT-hydroxy-oxazolines (263) by further reaction with CDI (c/. ref. 143). 

When the reaction is run with potassium fert-butoxide in THF at -5°C, one obtains (after hydrolysis) the normal Knoevenagel product (32), except that the isocyano group has been hydrated (16-65). With the same base but with DME as solvent the product is the nitrile (33). When the ketone is treated with 31 and thallium(I) ethoxide in a 4 1 mixture of absolute ethanol and DME at room temperature, the product is a 4-ethoxy-2-oxazoline (34). Since 33 can be hydrolyzed to a carboxylic acid and 34 to an a-hydroxy aldehyde, this versatile reaction provides a means for achieving the conversion of RCOR to RCHR COOH, RCHR CN, or RCR (OH)CHO. The conversions to RCHR COOH and to RCHR CN have also been carried out with certain aldehydes (R = H). 

In this aforementioned Heine reaction the initial ring opening takes place by iodide ions. Subsequent ring closure by S 2 displacement of iodide by reaction with the negative oxygen center then leads to the products. This process proceeds with double inversion at the same carbon atom, thus with net retention. Hydrolysis of these oxazolines gives j9-hydroxy-a-amino acids (Scheme 31) [1,38]. The stereochemical course of ring expansion is the same as that observed in Scheme 29. 

The aziridine-2-carboxaldehyde 56 can also serve as synthon for the synthesis of sphingosines, which are important biomembrane constituents [64]. One possible route involves the addition of an alanate to the aldehyde. In a later stage of this synthetic plan the aziridine can be opened, either via the intermediacy of an oxazoline or directly with dilute acid. Unfortunately, the reaction of aldehyde 56 with a vinylalanate has a poor diastereoselectivity of 3 2. Therefore, an alternative approach was considered, namely one involving the addition of a vinylzinc reagent to the aldehyde thereby employing our N-tritylaziridinediphenyl-methanol 51 as the chiral catalyst. Gratifyingly, only one diastereomer was obtained. Reductive removal of the trityl function, acetylation of the hydroxy... 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

Reports of [ 2 + 2] cycloaddition of nitrogen containing heterocycles to alkenes are so numerous that attention can be drawn here to only a few. Recent examples include the acetone-sensitized photoaddition of 4-oxazolin-2-one (248) to ethylene to give the cis-adduct 249,203 the photocycloadditions of N-substituted imidazoles to acrylonitrile204 and of N-methyl-4-hydroxy-quinol-2-one to cyclohexene,205 and the photoaddition of pentafluoro-pyridine to ethylene to give the 1 1- and 1 2-adducts 250 and 251,... 

The photocycloaddition of aliphatic and aromatic aldehydes with 2,4,5-trimethyloxazole (131) gave bicyclic oxetanes 132 in almost quantitative yields hydrolitic cleavage led selectively to erytro a-amino-P-hydroxy methyl ketones 133 <00CC589>. The oxazolium salt 134 was converted to the azomethine ylide 136 via electrocyclic ring opening of the oxazoline 135. Intramolecular cycloaddition afforded 137 in 66% overall yield which was transformed into the aziridinomitosene derivative 138 . 

The reaction of lithiated 2-(l-chloroethyl)-2-oxazolines (367) with nitrones led to the stereoselective synthesis of oxazolinyl-[1.2] oxazetidines (372a,b) which are important as precursors of o.-hydroxy-j3-amino acids (Scheme 2.160) (601). 

Lithiated chiral oxazolines have been shown to react with various electrophiles, generating a new asymmetric center with considerable bias. This process has led to the synthesis of optically active a-alkylalkanoic acids,47 n-hydroxy(methoxy)alkanoic acids,48 / -hydroxy(methoxy)alkanoic acids,49 n-substituted y-butyrolactones,50 and 2-substituted-l,4-butanediols (Fig. 2-4).50... 

When a chiral auxiliary is present in the oxazoline ring and the boron part is replaced with an achiral bicyclic system (46 bearing 9-BBN), erythro-j/-hydroxy esters (syn-53) can be obtained as the major product upon reaction of the eno-late with several aldehydes.37... 

The considerable Lewis acidity of bis(oxazoline)-copper(II) complexes held promise for catalyzing the ene reaction, a process that usually requires strong Lewis acids. Indeed, these catalysts effect a highly selective ene reaction between a variety of alkene partners and glyoxylate esters to produce a-hydroxy esters in good yield, Eq. 210 (245). The ene reaction between cyclohexene and ethyl glyoxylate proceeds in excellent diastereoselectivity and enantioselectivity, Eq. 211. As a testament to the Lewis acidity of these complexes, it is noteworthy that... 

Carbonyl alkylation and condensation reactions are always of great value in synthesis, and the formation of o-ANIS ALDEHYDE via 4,4-dimethyl-2-oxazoline, 2,2-DIMETHYL-3-PHENYLPROPION-ALDEHYDE via alkylation of the magnesio-enamine salt and threo-4-HYDROXY-3-PHENYL-2-HEPTANONE via a directed aldol... 

Synthesis of natural-type aminopolysaccharide having dibenzylchitin structure was achieved by the polymerization of a sugar oxazoline monomer, 1 having one hydroxy group at position 4 (Scheme 4) [9]. The polymerization was carried out with an acid catalyst in 1,2-dichloroethane solvent at reflux temperature. All the H-NMR, C-NMR, and IR spectra as well as elemental analysis data of the isolated polysaccharide supported that the polymerization proceeded by the stereoregular glycosylation to give (1 4)-... 

The polymerization using sugar oxazoline monomers is not limited to the synthesis of linear aminopolysaccharides as described above and can be extended to formation of a hyperbranched material. Synthesis of hy-perbranched aminopolysaccharide was achieved by acid-catalyzed polymerization of a sugar oxazoline monomer, 8, having two hydroxy groups at position 3 and 4, which can be considered as an AB2 monomer (Scheme 9) [12]. This is the first example of the synthesis of a hyper-... 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

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