Methylene oxazoline

Oxazoles.—Formation. ci)-Diazoacetophenone reacts with benzonitrile in the presence of trifluoromethanesulphonic acid to give 2,5-diphenyloxazole (514). Bi-, ter-, and quater-oxazoles have been synthesized from a-metallated isocyanides thus lithiobenzyl isocyanide (PhCHLiNC) and dimethyl oxazole-3,4-dicarboxylate afford compound (515). Stable methylene-oxazolines (516 R = Me or Ph) are obtained by heating the iminesHN=C(Ph)OCHRC=CH. The fluorinated oxazoline (518) results from the action of benzonitrile on the oxiran (517), and also from the reaction of bis(trifluoromethyl)carbene with the benzoylimine (CF3)2C=NCOPh/ Treatment of 2-acylamino-l-aryl-alkan-l-ols (519) under the conditions of the Pictet-Gams reaction, i.e. with phosphorus pentoxide in boiling toluene or xylene, results in cis- and trans-2-oxazolines (520), rather than isoquinolines, as claimed previously. The spiro-oxazolines (521 R = Me or Ph) are formed when the lithiated di-isocyanide CN—CH2CH2CHLi—NC is treated with acetone or benzophenone, respec-tively. ... 

Precursors 16 and 17 react to yield the alkynyl amide 18, which is converted into the 5-methylene oxazoline 19 (Scheme 16.1.3). Chlorination of 19 employs trichloroisocyanuric acid (TCIA) as the chlorinating agent to produce the mono-chlorinated oxazoline 20, which is converted into zoxamide (1) by acid-catalyzed hydrolysis. 

Zinc The 5-exo-dig cyclization of propargylic amide (210), mediated by Znl2, has been reported to produce the exo-methylene oxazoline (211). With = H and FeC as the reagent, oxazole (212) was obtained as a result of the final aromatization. ... 

Methylene thiirane is obtained by thermolysis of several spirothiirane derivatives which are formally Diels-Alder adducts of methylenethiirane and cyclopentadiene or anthracene <78JA7436). They were prepared via lithio-2-(methylthio)-l,3-oxazolines (c/. Scheme 121). A novel synthesis of the allene episulfide derivatives, 2-isopropylidene-3,3- dimethylthiirane (good yield) or its 5-oxide (poor yield), involves irradiation of 2,2,3,3-tetramethyl-cyclopropanethione or its 5-oxide (81AG293). Substituents on the thiirane ring may be modified to give new thiiranes (Section 5.06.3.9). The synthesis of thiirane 1-oxides and thiirane 1,1-dioxides by oxidation is discussed in Section 5.06.3.3.8 and the synthesis of 5-alkylthiiranium salts by alkylation of thiiranes is discussed in Section 5.06.3.3.4. Thiirene 1-oxides and 1,1-dioxides may be obtained by dehydrohalogenation of 2-halothiirane 1-oxides and 1,1-dioxides (Section 5.06.4.1.2). 

Scheme 61).22 149 150 152 229 230 The methylene-bridged bis(oxazoline)s (70) can afford either neutral copper complexes of the semicorrin type (72) or cationic copper complexes (73). Cyclopro-panation with copper complexes of type (70) shows similar stereochemistry to that with the corresponding copper semicorrin complexes.229-231 Alternatively, bis(oxazoline) ligand (71), bearing... 

Cyclization of. V-alkeny lam ides to 2-oxazolines was achieved in very mild conditions with fert-butyl hypoiodite <06OL3335>. The 5-exo-dig gold(I)-catalyzed cyclization of propargylic trichloroacetimidates 129 proceeded with remarkably efficiency under very mild conditions to give 4-methylene-4,5-dihydrooxazoles 130 in good yields. The mildness of the protocol was clearly responsible for the lack of isomerization of the final products to the corresponding, thermodynamically more stable, oxazoles <06OL3537>. 

Clark et al. (112) observed that aminoindanol-derived ligand 128 provides results superior to those found with other bis(oxazoline) ligands when the reactions are conducted on reasonable laboratory time scales (< 24 h), Eq. 95. This system was also moderately effective for methylene cycloalkenes. Methylenecyclopen-tene undergoes oxidation to provide a single regioisomer in modest yield and 43% ee, Eq. 96. 

The results obtained in the photostimulated Sj l reaction between carbanions from 2,4,4-trimethyl-2-oxazoline or 2,4-dimethylthiazole and 2-bromopyridine are also consistent with the incomplete formation of the carbanions in KNH2-NH3(ii ) system. In these cases, 2-aminopyri-dine is formed alongside the corresponding pyridyl-2-methylene oxazolinyl or thiazolyl substitution products (Wong et al. 1997). When the Sr I pathway is impeded by conducting the reaction in the dark or in the presence of di(tert-butyl) nitroxide, the ionic amination reaction dominates. 

The constrained bis(oxazolines) 9a and 9b can be constructed beginning with malononitrile 32 as shown by Ghosh and co-workers. Thus, treatment of 32 with anhydrous hydrochloric acid in dioxane, as shown by Lehn and co-workers, yielded imidate salt 33 (Fig. 9.9). Condensation of the imidate salt with commercially available (15,2/ )-l-aminoindan-2-ol afforded the conformationally constrained bis(oxazoline) inda-box 9a. Alkylation at the bridging methylene of 9a was carried out by Davies and co-workers.Treatment of 9a with lithium diisopropylamide followed by alkylation with methyl iodide afforded 9b. Alternatively, alkylation with diiodoalkanes incorporated ring systems at the bridging position (structures 34a-d). 

Many examples of the use of chiral Ca-symmetric bis(oxazoline) hgands have been presented here. Other examples include their use in various heteroannulations, one of which is shown in Figure 9.69. Here, the vinyl iodide, (Z)-3-iodo-2-methyl-2-propen-l-ol, 235 is condensed with 1,2-undecadiene to form the 3-methylene-2//-pyran derivative 237. " When this reaction was mn in the presence of 10 mol% of bis(oxazoline) Ugand 236 complexed with palladium(ll), 237 was produced in 70% yield with 79% ee. 

Asymmetric transfer hydrogenation.1 Bis(oxazolines) lacking a methylene bridge such as 3 are prepared by reaction of dimethyl oxalate with a-amino alcohols,... 

A solution of 2-(4,4-dimethyl-2-oxazolin-2-yl)-4 -trifluoromethylbiphenyl (3.5 g, 0.011 mole) in 60 mL 6 N hydrochloric acid was stirred at vigorous reflux for 2 hr. The reaction mixture was then cooled to room temperature and extracted with methylene chloride. The organic extracts were dried and concentrated under reduced pressure to yield a solid. Recrystallisation from ethyl ether/pentane afforded 4 -(trifluoromethyl)-2-biphenyl carboxylic acid, yield 86% (melting point 167-169°C). 

Rezanka analysed the fatty acid composition of several species of myxomycetes. In addition to the common fatty acids, polyunsaturated and methylene non-interrupted polyunsaturated fatty acids, for example, with 5, 9- and/or 5, 11-double bonds, were identified by GS-mass spectrometry of their corresponding oxazolines [25]. Multibranched polyunsaturated fatty acid and its four glycosides (50 -54) were isolated from seven different myxomycetes [26]. The absolute configurations of hydroxyl groups were determined by modified Mosher s method, and the glycosides were revealed to contain glucose, mannose, and rhamnose. It may be interesting that these fatty acid constituents contained by the seven species of myxomycetes were different (Table 1). 

While monitoring the conversion via 1H NMR spectroscopy, an intermediate 5-methylene-4,5-dihydrooxazole could be observed and accumulated up to 95% and this is the first direct and catalytic preparative access to such alkylidene oxazolines. 

In variants of the above processes, the bifunctional reactivity of 4-(dialkylamino-methylene)pyrazolin-5-thiones (155) (Scheme 25) and oxazolin-5-thiones (157) (Equation (45)) with a-halocarboxylic acids (or esters) was exploited for the synthesis of thieno[2,3-c]pyrazoles (156)... 

The methylene bridge in the fused oxazoline (203), 6-methyl-2//,6//-oxazolo[5,4,3-j/]quinolin-4-one, shows great stability towards acid cleavage, such as heating in 47% hydriodic acid. It is cleaved by oxidation, however, when treated with activated manganese dioxide in acetic acid (73JA5003). 

In the 8-hydroxy-2(l//)quinolinone (277) the bridge between the oxygen and the nitrogen is formed from methylene bromide giving the angular fused oxazoline ring (73JA5003). 

---