Oxazolines => nitrile oxides

Dihydrofuran (376) and 2,5-dihydrofuran (377) react with nitrile oxides to give furo[2,3-6 ]isoxazoles (378) and furo[3,4-rf]isoxazoles (379), respectively, as cycloadducts. The double bonds of furan, pyrrole and thiophene also react when the nitrile oxide is generated in situ. Thus furan and benzonitrile oxide gave (380), and with 2-methyl-2-oxazoline the cycloadduct (381) was obtained (71AG(E)810). These and related cycloadditions are discussed in Chapter 4.36. 

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. 

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). 

Dipolar cycloaddition of nitrile oxides to unsaturated five-membered carbocyclic and heterocyclic systems gives fused 1,2-oxazolines. Steric effects are apparently of far greater importance than electronic ones, especially with regard to the orientation of the dipolarophile towards the nitrile oxide in the cycloaddition reaction. Originally, only one... 

Oxazoline 7V-oxides are nitrile oxide equivalents that cycloadd to electron-poor dipolarophiles such as crotonates. Langlois and coworkers [346] introduced chirality into these reagents. While regio- and stereoselective cycloadditions were observed, the dural auxiliaries have not yet been removed. 

Addition to 1,3-dicarbonyl compounds. The CAN oxidation of these compounds in. he presence of allyltrimethylsilane results in C-allylation. The oxidative addition of 1.3-dicarbonyl compounds to alkenes to form dihydrofurans is a rather general reaction. - 2-Oxazolines. a-Nitro ketones form nitrile oxides, which are trapped by Jipolarophiles. 

Oxidation of N-O Compounds. The preparation of disub-stituted oxazolines from aldoximes has been accomplished via in situ nitrile oxide formation using Mn02 (eq 60). Oxidation of hydroxylamines and oximes to nitrones " and aldehydes/ ket- ones, respectively, has been found to occur upon treatment with Mn02 (eqs 61 and 62). 

In the other study [24], complexes containing heterocycles of a new type, namely, 2,3a-disubstituted 5,6-dihydro-3a//-[l,3]oxazolo[3,2-fe][l,2,4]oxadiazoles (6, Scheme 13.5), were prepared via the intermolecular platinum(II)-mediated DCA between coordinated nitriles in fran.y/aT-[PtCl2(R CN)2] and the oxazoline A-oxide C (Me)2CH20C(R )=N +(0 )(C -N ). With the exception of benzonitrile species, cycloaddition of oxazoline A-oxides to the platinum(II)-ligated nitriles proceeds diastereoselectively giving mixtures of enantiomers. The heterocyclic ligands in 6 were liberated by treatment with excess ethane-1,2-diamine [24]. 

Preparation of the diastereomerically pure platinum(II) complexes bearing tetrahydro-5,8-methanocyclohexa-[3, 2 4, 5][l,3]oxazolo[3,2-fc][l,2,4]oxadiazole ligands (7, Scheme 13.6) was accomplished via the intermolecular 1,3-DCA between enantiomerically pure camphor-derived oxazoline-A-oxides and the coordinated nitriles in frans -[PtCl2(R CN)2] [26], The reaction proceeds at 20-25 °C. Free heterocyclic species were liberated as single stereoisomers from the respective platinum(II) complexes by treatment with excess NaCN [26],... 

Olefins also undergo the Ritter reaction with nitriles in the presence of diphenyl diselenide, ammonium persulfate, and trifluoromethanesulfonic acid to produce oxazolines.When cyanamide is used, 2-aminooxazolines are obtained. The active electrophilic agent is phenylselenyl sulfate formed by oxidation of diphenylselenide with ammonium persulfate. The reaction is trans-stereospecific. 

Aldehydes are one of the most impotent synthons in organic chemistry. Many methods of preparation of formyl carboranes have been discussed previously (E. I. Rosemimd method, Sonn-Miller reaction/ reaction of dodecaborane with diacylal of propargyl aldehyde/ Swem Oxidation ). Since oxazolines are rather good reagents for the preparation of aldehydes and nitriles, we developed a method of preparation of carboranyl oxazolines (Scheme 9). 

Scheme 13.5 Platinum(II)-mediated dipolar cycloaddition of oxazoline -oxides to nitriles and liberation of free 2,3a-disubstituted 5,6-dihydro-3aH-[l,3]oxazolo[3,2-ii][l,2,4]oxadiazoles [24],...

The ahain-lengthening of carboxylic acids by three carbon atoms to y-keto aaida (or nitriles) by way of oxazoline-5-one anions have been described. The conversion of aldehydic cyanohydrins to a-hydroxy-N-t-butylcarboxamides followed by oxidation and hydrolysis constitutes h new general procedure for the preparation of a-ketoaoida. ... 

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