Oxazoline derivative

Oxazoline Derivatives. Two papers dealing with the preparation of 4-ethoxy-carbonyl-2-oxazolines (457) and their hydrolysis to the ethyl esters of A -formyl-/S-hydroxy-amino-acids (458) have appeared (literature duplication ). Neighbouring-group participation involving intermediates like (459) is postulated for the alkaline hydrolysis. 

Irradiation of (460) and chromatography of the product on silica gel gave (461). That (462) is the photochemical product, which rearranges on contact with silica gel, was shown by i.r. spectroscopy. 

When nitriles are heated with a,jS- or a,y-amino-alcohols, respectable yields (60—85%) of 2-substituted A -oxazolines and 5,6-dihydro-4 T-l,3-oxazines (463) are obtained. Catalytic amounts of zinc or cadmium salts appear necessary for good yields. 

Heating iV-acylated jS-hydroxamines with solid zinc acetate gives A -oxazolines (464) with retention of configuration. A 1 1 complex of oxa-zoline and zinc acetate is obtained which is decomposed by treatment with water. 

The copper-catalysed reaction of allyl isocyanide with ketones and aldehydes gives 4-vinyl-2-oxazoline derivatives (465) in good yields. With activated olefins, as in a -unsaturated nitriles and esters, 5-vinyl-l-pyrroline derivatives are obtained (466). A copper complex is proposed as intermediate. 

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The mechanism of the asymmetric alkylation of chiral oxazolines is believed to occur through initial metalation of the oxazoline to afford a rapidly interconverting mixture of 12 and 13 with the methoxy group forming a chelate with the lithium cation." Alkylation of the lithiooxazoline occurs on the less hindered face of the oxazoline 13 (opposite the bulky phenyl substituent) to provide 14 the alkylation may proceed via complexation of the halide to the lithium cation. The fact that decreased enantioselectivity is observed with chiral oxazoline derivatives bearing substituents smaller than the phenyl group of 3 is consistent with this hypothesis. Intermediate 13 is believed to react faster than 12 because the approach of the electrophile is impeded by the alkyl group in 12. 

Meyers has demonstrated that chiral oxazolines derived from valine or rert-leucine are also effective auxiliaries for asymmetric additions to naphthalene. These chiral oxazolines (39 and 40) are more readily available than the methoxymethyl substituted compounds (3) described above but provide comparable yields and stereoselectivities in the tandem alkylation reactions. For example, addition of -butyllithium to naphthyl oxazoline 39 followed by treatment of the resulting anion with iodomethane afforded 41 in 99% yield as a 99 1 mixture of diastereomers. The identical transformation of valine derived substrate 40 led to a 97% yield of 42 with 94% de. As described above, sequential treatment of the oxazoline products 41 and 42 with MeOTf, NaBKi and aqueous oxalic acid afforded aldehydes 43 in > 98% ee and 90% ee, respectively. These experiments demonstrate that a chelating (methoxymethyl) group is not necessary for reactions to proceed with high asymmetric induction. 

Investigation- of oxazoline derivatives using infrared spectroscopy and pK measurements showed that the amino forms 178 and 179... 

Hayashi et al. [18] have synthesized two diastereoisomers of 2,2 -bis[4-(alkyl)oxazol-2-yI]-l,T-binaphthyl,bis(oxazoline) derivatives possessing both binaphthyl axial chirality and carbon centered chirality (structures 9 and 10, Scheme 5). 

The more difficult problem of protecting the carbonyl group can be accomplished by conversion to a oxazoline derivative. One example is the 4,4-dimethyl derivative, which can be prepared from the acid by reaction with 2-amino-2-methylpropanol or with 2,2-dimethylaziridine.269... 

A characteristic feature of contemporary investigations in the held under consideration, is the interest in cycloaddition reactions of nitrile oxides with acetylenes in which properties of the C=C bond are modified by complex formation or by an adjacent metal or metalloid atom. The use of such compounds offers promising synthetic results. In particular, unlike the frequently unselec-tive reactions of 1,3-enynes with 1,3-dipoles, nitrile oxides add chemo-, regio-and stereoselectively to the free double bond of (l,3-enyne)Co2(CO)6 complexes to provide 5-alkynyl-2-oxazoline derivatives in moderate to excellent yield. For example, enyne 215 reacts with in situ generated PhCNO to give 80% yield of isoxazoline 216 (372). 

The oxazoline-derived P,N ligands can be classified into four groups according to structure phosphino-oxazolines phosphite- and phosphinite-oxazolines catalysts containing a P-N bond and structurally related non-oxazoline catalysts. 

A number of ligands have been synthesized which have structural similarities to the oxazoline-derived ligands. 

Ghosh et al.32 have demonstrated another bis(oxazoline) derivative chiral ligand 86 for asymmetric Diels-Alder reaction and obtained excellent results. Reaction of an equimolar mixture of chiral ligand 86 and Cu(C104)2 6H20 produces the aqua complex 87 (w being water molecule), which shows excellent catalytic power in asymmetric Diels-Alder reactions. As depicted in Scheme 5 27, the reaction of 88 with cyclopentadiene gives product 89 with more than 80% yield, over 99 1 diastereoselectivity and up to 99% ee. 

Although the first examples of hyperbranched polymers proposed by Flory involved condensation-type polymerization strategies, the first well-characterized hyperbranched example involved the ring-opening polymerization of 2-carboxylic-2-oxazoline derivatives. As early as 1988, Odian and Tomalia [2] reported the ring-opening polymerization of these derivatives to form random... 

In the case of acetylenic amides, the carbonyl oxygen atom turned out to be nucleoplilic enough to directly attack the coordinated triple bond, owing to the conjugation with the amide moiety. Thus, cGa-dialkyl substituted 2-ynylamides smoothly underwent oxidative cyclization-alkoxycarbonylation to afford new oxazoline derivatives in good yields (Eq. 44) [102,113]. 

It has been found that the electrochemically generated NO radical addes to the substituted olefins 81, and the radical species 81a formed is further oxidized to the cationic intermediate 81b which reacts with acetonitrile and yields 82 (Scheme 41). The anodic oxidation was carried out in a mixed solvent CH3CN-Et20 with NaNOa as a supporting electrolyte. The oxazoline derivatives 82 were isolated in 69-77% yield [103],... 

The polymerization of 1 mentioned above should be compared with the enzymatic synthesis of chitin reported by Kobayashi and coworkers, in which an oxazoline derivative of A, A -diacetylchitobiose, the repeating unit of chitin was polymerized in the presence of chitinase enzyme via ring-opening addition process to give an artihcial chitin (Scheme 6) [5]. The method using an enzyme, however, may not enable synthesis of nonnatural-type aminopolysaccharide because the reaction catalyzed by chitinase enzyme is limited to the formation of (1 4)-P-glycosidic linkage. 

It should be noted that the 1,3-bifunctional starting compounds 4-7 are quite difficult to obtain. Moreover, the direction of acid-catalyzed cycliza-tion of 3-acylaminopropanols depends considerably on their structure. Thus, N-acylaminoalcohols 8 can be cyclized to give either 5,6-dihydro-4//-1,3-oxazinium salts 10 or 2-oxazoline derivatives 12 as well as mixtures thereof (82MI1, 82MI2 see also 78AHC1). 

Asymmetric allylic oxidation and benzylic oxidation (Kharasch-PSosnovsky reaction) are important synthetic strategies for constructing chiral C—O bonds via C—H bond activation.In the mid-1990s, the asymmetric Kharasch-Sosnovsky reaction was first studied by using chiral C2-symmetric bis(oxazoline)s. " Later various chiral ligands, based mainly on oxazoline derivatives and proline derivatives, were used in such asymmetric oxidation. Although many efforts have been made to improve the enantioselective Kharasch-Sosnovsky oxidation reaction, most cases suffered from low to moderate enantioselectivities or low reactivities. 

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. 

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