Oxazolines spiro

Fused or spiro sugar oxazolines have been synthesized by treating D-fructopyranose or D-fructofuranose 1,2-0-acetonides with nitriles in triflic acid773 (Scheme 5.73). First the activation of the anomeric center takes place with simultaneous isopropy-lidene cleavage to form the oxocarbenium ion intermediate, which is attacked by the nitrile. The resulting nitrilium ion is then trapped by the hydroxyl group in an intramolecular Ritter-like reaction to yield the final product. 

Jew and Park achieved a highly enantioselective synthesis of (2S)-a-(hydroxy-methyljglutamic acid, a potent metabotropic receptor ligand, through the Michael addition of 2-naphthalen-l-yl-2-oxazoline-4-carboxylic acid tert-butyl ester 72 to ethyl acrylate under phase-transfer conditions [38]. As shown in Scheme 5.36, the use of BEMP as a base at —60 °C with the catalysis of N-spiro chiral quaternary ammonium bromide le appeared to be essential for attaining an excellent selectivity. 

Diastereoselective allylzincations of achiral cyclopropenone acetals, addressing the control of the relative configuration at the newly formed C-C bond (centers C3 and C4) and of chiral derivatives such as 20 (R = H), addressing chirality transmission through a spiro carbon center, have been investigated. In the presence of bis(oxazoline) ligands, enantioselective reactions of this kind can also be performed. ... 

Sasai s group [13] developed a series of bisnitrogen ligands with fused hetero spiro cyclic backbones, including spiro bis(isoxazoline) 11 and 12, spiro isoxazole-isoxazoline 13, spiro bis(oxazoline) 14, spiro bis(pyrazole) 15, and spiro bis(isoxazole) 16 (Figure 3). Ligands 11 [14] and 13 [15] exhibited excellent reactivity and enantioselectivity in the Pd-catalyzed oxidative cyclization reactions. 

By using Cu complexes of chiral spiro bis(oxazoline) ligand S, S,S)-23a as catalysts, the enantioselective catalytic insertion of a-diazoesters into N—H bond of aromatic amines was realized in high yields and high enantioselectivities (Scheme 43) [25b, 108]. The chiral spiro Cu catalysts have unique binuclear structures, as showing in Figure 6, which may address the excellent performance of the Cu-(S, S,S)-23a catalyst for this challenging reaction. With the Cu-catalyzed asymmetric N—H... 

Modifications to the parent bis(oxazoline) structure have been subsequently disclosed (Fig. 24). Spirobis(oxazoline) 34 derived from amino indanol catalyzes (10 mol %) the enantioselective cycloaddition between cyclopentadiene and acrylimide (-78 °C) in 96.3% ee (endo/exo=44 l) [90]. When the size of the spiro ring (e.g., cyclobutyl, -pentyl, -hexyl) is increased, the resulting structural change progressively degrades the reaction enantioselectivity, demonstrating a relation-... 

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. ... 

In sharp contrast to P,P ligand, the P,N ligands 16a and 16b having a terf-Bu oxazoline unit were found to be effective to give the spiro product 22c with (S) sense in excellent yields and good enantioselectivities (over 80% ee) along with... 

Spiro-0,N-heterocycIics, Excess oxalyl chloride added dropwise to a stirred ice-cooled suspension of adamantane-1-carboxamide in methylene chloride, and stirring continued ca. 2 hrs. at room temp. crude 2 -(l-adamantyl)oxazoline-4, 5 -dione hydrochloride (Y 55-78%) treated at room temp, with abs. ethanol -> l-ethoxyhomoadamantane-2-spiro-2 -oxazolidine-4, 5 -dione (Y 62%). Also with N-subst. amides s. T. Sasaki, S. Eguchi, and T. Toru, Tetrah. Let. 1968, 4135. 

Asymmetric domino cyclization of the unsaturated alcohol 71 proceeded smoothly to give the bicyclic compound 72 with 82% ee in 89% yield as a single diastereomer using a spiro bis(oxazoline) ligand which has a chiral spiro skeleton and two oxazoline rings. The reaction proceeds via the formation of 73 and 74 as oxypalladation products. BQ was used as a reoxidant [36],... 

A series of nineteen 5-spiroalkane and 5-spiro-4-piperi-dine derivatives of 2-eUnino-2-oxazoline-4-one were prepared. Three of these compounds showed characteristics CNS stimulants, while the rest were weak CNS depressants. Clinical evidence for the efficacy oighomeostan (43) as a minor tranquilizer has been reported. 

A most unusual result was encountered when the irradiation of 243 was carried out in pentane in the presence of both methanol and methyl trifluoro-acetate (excess).Under these conditions, the only cycloadducts observed consisted of a mixture of the two stereoisomers of 3-oxazoline, 260. This result suggests that 2-phenylazirinylidene (244) reacts with methanol to give mainly azirine 258, which is subsequently converted to nitrile ylide 259 (and thus cycloadduct 260) on further irradiation. The formation of 245 has been explained in terms of a photoinduced methoxy migration of 258 which competes with C-C bond cleavage of the azirine ring. Ciabattoni and Cabell have previously reported that 2-chloro-2/f-azirines undergo ready isomerization at room temperature via a 27r-electron azacyclopropenyl cation. A similar mechanism would rationalize the apparent photoconversion of azirines 258 and 245. The results obtained with this spiro azirine system indicate that cycloelimination of ethylene from 243 is much more efficient than C-C bond scis-... 

Li, S. Zhu, S.-R Xie,J.-H. Song, S. Zhang, C.-M. Zhou, Q.-L. Enantioselective hydrogenation of a-aryloxy and a-alkoxy a, 3-unsaturated carboxylic acids catalyzed by chiral spiro iridium/phosphino-oxazoline complexes. /. Am. Chem. Soc. 2010,132,1172-1179. 

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